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Sample records for profiling uncovers plasmid-induced

  1. Investigation of plasmid-induced growth defect in Pseudomonas putida.

    PubMed

    Mi, Jia; Sydow, Anne; Schempp, Florence; Becher, Daniela; Schewe, Hendrik; Schrader, Jens; Buchhaupt, Markus

    2016-08-10

    Genetic engineering in bacteria mainly relies on the use of plasmids. But despite their pervasive use for physiological studies as well as for the design and optimization of industrially used production strains, only limited information about plasmid induced growth defects is available for different replicons and organisms. Here, we present the identification and characterization of such a phenomenon for Pseudomonas putida transformants carrying the pBBR1-derived plasmid pMiS1. We identified the kanamycin resistance gene and the transcription factor encoding rhaR gene to be causal for the growth defect in P. putida. In contrast, this effect was not observed in Escherichia coli. The plasmid-induced growth defect was eliminated after introduction of a mutation in the plasmid-encoded rep gene, thus enabling construction of the non-toxic variant pMiS4. GFP reporters construct analyses and qPCR experiments revealed a distinctly lowered plasmid copy number for pMiS4, which is probably the reason for alleviation of the growth defect by this mutation. Our work expands the knowledge about plasmid-induced growth defects and provides a useful low-copy pBBR1 replicon variant. PMID:27287537

  2. Unexpected Novel Relational Links Uncovered by Extensive Developmental Profiling of Nuclear Receptor Expression

    PubMed Central

    Tavares, Raquel; Sachs, Laurent; Chaumot, Arnaud; Bardet, Pierre-Luc; Escrivà, Héctor; Duffraisse, Maryline; Marchand, Oriane; Safi, Rachid; Thisse, Christine; Laudet, Vincent

    2007-01-01

    Nuclear receptors (NRs) are transcription factors that are implicated in several biological processes such as embryonic development, homeostasis, and metabolic diseases. To study the role of NRs in development, it is critically important to know when and where individual genes are expressed. Although systematic expression studies using reverse transcriptase PCR and/or DNA microarrays have been performed in classical model systems such as Drosophila and mouse, no systematic atlas describing NR involvement during embryonic development on a global scale has been assembled. Adopting a systems biology approach, we conducted a systematic analysis of the dynamic spatiotemporal expression of all NR genes as well as their main transcriptional coregulators during zebrafish development (101 genes) using whole-mount in situ hybridization. This extensive dataset establishes overlapping expression patterns among NRs and coregulators, indicating hierarchical transcriptional networks. This complete developmental profiling provides an unprecedented examination of expression of NRs during embryogenesis, uncovering their potential function during central nervous system and retina formation. Moreover, our study reveals that tissue specificity of hormone action is conferred more by the receptors than by their coregulators. Finally, further evolutionary analyses of this global resource led us to propose that neofunctionalization of duplicated genes occurs at the levels of both protein sequence and RNA expression patterns. Altogether, this expression database of NRs provides novel routes for leading investigation into the biological function of each individual NR as well as for the study of their combinatorial regulatory circuitry within the superfamily. PMID:17997606

  3. Developing Guidance Material To Uncover a Mathematics Profile of Adult Participants on a Crane Course.

    ERIC Educational Resources Information Center

    Lindenskov, Lena

    This paper reports on a pilot study in the Danish "Profile in Mathematics" project implemented by the Directorate General for Employment, Placement and Vocational Training and the Ministry of Education. The pilot study develops and tests specific guidance materials to guide participants and teachers through a course for crane workers that teaches…

  4. Transcriptional Profiling Uncovers a Network of Cholesterol-Responsive Atherosclerosis Target Genes

    PubMed Central

    Nilsson, Roland; Noori, Peri; Maleki, Shohreh; Köhler, Marina; Hamsten, Anders; Tegnér, Jesper; Björkegren, Johan

    2008-01-01

    Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr−/−Apo100/100 Mttpflox/flox Mx1-Cre). Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins) at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies. PMID:18369455

  5. Expression profiling pre-diabetic mice to uncover drugs with clinical application to type 1 diabetes.

    PubMed

    Pang, Dimeng; Irvine, Katharine M; Mehdi, Ahmed M; Thomas, Helen E; Harris, Mark; Hamilton-Williams, Emma E; Thomas, Ranjeny

    2015-08-01

    In the NOD mouse model of type 1 diabetes (T1D), genetically identical mice in the same environment develop diabetes at different rates. Similar heterogeneity in the rate of progression to T1D exists in humans, but the underlying mechanisms are unclear. Here, we aimed to discover peripheral blood (PB) genes in NOD mice predicting insulitis severity and rate of progression to diabetes. We then wished to use these genes to mine existing databases to identify drugs effective in diabetes. In a longitudinal study, we analyzed gene expression in PB samples from NOD.CD45.2 mice at 10 weeks of age, then scored pancreatic insulitis at 14 weeks or determined age of diabetes onset. In a multilinear regression model, Tnf and Tgfb mRNA expression in PB predicted insulitis score (R (2)=0.56, P=0.01). Expression of these genes did not predict age of diabetes onset. However, by expression-profiling PB genes in 10-week-old NOD.CD45.2 mice, we found a signature of upregulated genes that predicted delayed or no diabetes. Major associated pathways included chromatin organization, cellular protein location and regulation of nitrogen compounds and RNA. In a clinical cohort, three of these genes were differentially expressed between first-degree relatives, T1D patients and controls. Bioinformatic analysis of differentially expressed genes in NOD.CD45.2 PB identified drugs that are predicted to delay or prevent diabetes. Of these drugs, 11 overlapped with drugs predicted to induce a human 'non-progressor' expression profile. These data demonstrate that disease heterogeneity in diabetes-prone mice can be exploited to mine novel clinical T1D biomarkers and drug targets. PMID:26366287

  6. Expression profiling pre-diabetic mice to uncover drugs with clinical application to type 1 diabetes

    PubMed Central

    Pang, Dimeng; Irvine, Katharine M; Mehdi, Ahmed M; Thomas, Helen E; Harris, Mark; Hamilton-Williams, Emma E; Thomas, Ranjeny

    2015-01-01

    In the NOD mouse model of type 1 diabetes (T1D), genetically identical mice in the same environment develop diabetes at different rates. Similar heterogeneity in the rate of progression to T1D exists in humans, but the underlying mechanisms are unclear. Here, we aimed to discover peripheral blood (PB) genes in NOD mice predicting insulitis severity and rate of progression to diabetes. We then wished to use these genes to mine existing databases to identify drugs effective in diabetes. In a longitudinal study, we analyzed gene expression in PB samples from NOD.CD45.2 mice at 10 weeks of age, then scored pancreatic insulitis at 14 weeks or determined age of diabetes onset. In a multilinear regression model, Tnf and Tgfb mRNA expression in PB predicted insulitis score (R2=0.56, P=0.01). Expression of these genes did not predict age of diabetes onset. However, by expression-profiling PB genes in 10-week-old NOD.CD45.2 mice, we found a signature of upregulated genes that predicted delayed or no diabetes. Major associated pathways included chromatin organization, cellular protein location and regulation of nitrogen compounds and RNA. In a clinical cohort, three of these genes were differentially expressed between first-degree relatives, T1D patients and controls. Bioinformatic analysis of differentially expressed genes in NOD.CD45.2 PB identified drugs that are predicted to delay or prevent diabetes. Of these drugs, 11 overlapped with drugs predicted to induce a human ‘non-progressor' expression profile. These data demonstrate that disease heterogeneity in diabetes-prone mice can be exploited to mine novel clinical T1D biomarkers and drug targets. PMID:26366287

  7. Comparative Epigenomic Profiling of the DNA Methylome in Mouse and Zebrafish Uncovers High Interspecies Divergence

    PubMed Central

    Zhang, Chi; Hoshida, Yujin; Sadler, Kirsten C.

    2016-01-01

    The DNA methylation landscape is dynamically patterned during development and distinct methylation patterns distinguish healthy from diseased cells. However, whether tissue-specific methylation patterns are conserved across species is not known. We used comparative methylome analysis of base-resolution DNA methylation profiles from the liver and brain of mouse and zebrafish generated by reduced representation bisulfite sequencing to identify the conserved and divergent aspects of the methylome in these commonly used vertebrate model organisms. On average, 24% of CpGs are methylated in mouse livers and the pattern of methylation was highly concordant among four male mice from two different strains. The same level of methylation (24.2%) was identified in mouse brain. In striking contrast, zebrafish had 63 and 70% of CpG methylation in the liver and brain, respectively. This is attributed, in part, to the higher percentage of the zebrafish genome occupied by transposable elements (52% vs. 45% in mice). Thus, the species identity was more significant in determining methylome patterning than was the similarity in organ function. Conserved features of the methylome across tissues and species was the exclusion of methylation from promoters and from CpG islands near transcription start sites, and the clustering of methylated CpGs in gene bodies and intragenic regions. These data suggest that DNA methylation reflects species-specific genome structure, and supports the notion that DNA methylation in non-promoter regions may contribute to genome evolution. PMID:27379160

  8. Uncovering the profile of mutations of transforming growth factor beta-induced gene in Chinese corneal dystrophy patients

    PubMed Central

    Hao, Xiao-Dan; Zhang, Yang-Yang; Chen, Peng; Li, Su-Xia; Wang, Ye

    2016-01-01

    AIM To uncover the mutations profile of transforming growth factor beta-induced (TGFBI) gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS Forty-two subjects (6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients) of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy (GCD) (including 3 families and 8 sporadic patients) and lattice corneal dystrophy (LCD) (including 2 families and 9 sporadic patients). The next phenotypes were corneal dystrophy of Bowman layer (CDB) (1 family and 1 sporadic patient) and epithelial basement membrane dystrophy (EBMD) (1 sporadic patient). Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient. CONCLUSION GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD. Our findings extend the mutational spectrum of TFGBI, and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population. PMID:26949635

  9. Gene expression profiling in hearts of diabetic mice uncovers a potential role of estrogen-related receptor γ in diabetic cardiomyopathy.

    PubMed

    Lasheras, Jaime; Vilà, Maria; Zamora, Mònica; Riu, Efrén; Pardo, Rosario; Poncelas, Marcos; Cases, Ildefonso; Ruiz-Meana, Marisol; Hernández, Cristina; Feliu, Juan E; Simó, Rafael; García-Dorado, David; Villena, Josep A

    2016-07-15

    Diabetic cardiomyopathy is characterized by an abnormal oxidative metabolism, but the underlying mechanisms remain to be defined. To uncover potential mechanisms involved in the pathophysiology of diabetic cardiomyopathy, we performed a gene expression profiling study in hearts of diabetic db/db mice. Diabetic hearts showed a gene expression pattern characterized by the up-regulation of genes involved in lipid oxidation, together with an abnormal expression of genes related to the cardiac contractile function. A screening for potential regulators of the genes differentially expressed in diabetic mice found that estrogen-related receptor γ (ERRγ) was increased in heart of db/db mice. Overexpression of ERRγ in cultured cardiomyocytes was sufficient to promote the expression of genes involved in lipid oxidation, increase palmitate oxidation and induce cardiomyocyte hypertrophy. Our findings strongly support a role for ERRγ in the metabolic alterations that underlie the development of diabetic cardiomyopathy. PMID:27062900

  10. Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

    PubMed Central

    Gómez Ravetti, Martín; Rosso, Osvaldo A.; Berretta, Regina; Moscato, Pablo

    2010-01-01

    Background Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive. Methodology/Principal Findings We have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity. Conclusions/Significance A transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation

  11. Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis.

    PubMed

    Tang, Xiaohu; Keenan, Melissa M; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J Will; Freedland, Stephen J; Murphy, Susan K; Chi, Jen-Tsan

    2015-04-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  12. Comprehensive Profiling of Amino Acid Response Uncovers Unique Methionine-Deprived Response Dependent on Intact Creatine Biosynthesis

    PubMed Central

    Tang, Xiaohu; Keenan, Melissa M.; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J. Will; Freedland, Stephen J.; Murphy, Susan K.; Chi, Jen-Tsan

    2015-01-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  13. Genome-Wide Uncovering of STAT3-Mediated miRNA Expression Profiles in Colorectal Cancer Cell Lines

    PubMed Central

    Zhang, Jufeng; Luo, Xia; Li, Huiming; Deng, Ling

    2014-01-01

    Colorectal cancer (CRC) is one of the most common malignancies resulting in high mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor which is frequently activated and aberrantly expressed in CRC. MicroRNAs (miRNAs) are a class of small noncoding RNAs which play important roles in many cancers. However, little is known about the global miRNA profiles mediated by STAT3 in CRC cells. In the present study, we applied RNA interference to inhibit STAT3 expression and profiled the miRNA expression levels regulated by STAT3 in CRC cell lines with deep sequencing. We found that 26 and 21 known miRNAs were significantly overexpressed and downexpressed, respectively, in the STAT3-knockdown CRC cell line SW480 (SW480/STAT3-siRNA) compared to SW480 transfected with scrambled siRNAs (SW480/siRNA-control). The miRNA expression profiling was then validated by quantitative real-time PCR for selected known miRNAs. We further predicted the putative target genes for the dysregulated miRNAs and carried out functional annotation including GO enrichment and KEGG pathway analysis for selected miRNA targets. This study directly depicts STAT3-mediated miRNA profiles in CRC cells, which provides a possible way to discover biomarkers for CRC therapy. PMID:25126546

  14. Gene expression profiles uncover individual identities of gnathal neuroblasts and serial homologies in the embryonic CNS of Drosophila

    PubMed Central

    Urbach, Rolf; Jussen, David; Technau, Gerhard M.

    2016-01-01

    The numbers and types of progeny cells generated by neural stem cells in the developing CNS are adapted to its region-specific functional requirements. In Drosophila, segmental units of the CNS develop from well-defined patterns of neuroblasts. Here we constructed comprehensive neuroblast maps for the three gnathal head segments. Based on the spatiotemporal pattern of neuroblast formation and the expression profiles of 46 marker genes (41 transcription factors), each neuroblast can be uniquely identified. Compared with the thoracic ground state, neuroblast numbers are progressively reduced in labial, maxillary and mandibular segments due to smaller sizes of neuroectodermal anlagen and, partially, to suppression of neuroblast formation and induction of programmed cell death by the Hox gene Deformed. Neuroblast patterns are further influenced by segmental modifications in dorsoventral and proneural gene expression. With the previously published neuroblast maps and those presented here for the gnathal region, all neuroectodermal neuroblasts building the CNS of the fly (ventral nerve cord and brain, except optic lobes) are now individually identified (in total 2×567 neuroblasts). This allows, for the first time, a comparison of the characteristics of segmental populations of stem cells and to screen for serially homologous neuroblasts throughout the CNS. We show that approximately half of the deutocerebral and all of the tritocerebral (posterior brain) and gnathal neuroblasts, but none of the protocerebral (anterior brain) neuroblasts, display serial homology to neuroblasts in thoracic/abdominal neuromeres. Modifications in the molecular signature of serially homologous neuroblasts are likely to determine the segment-specific characteristics of their lineages. PMID:27095493

  15. TMA Uncovers Medicare Mistakes.

    PubMed

    Sorrel, Amy Lynn

    2015-07-01

    The Texas Medical Association recently uncovered some major Medicare mistakes that show just why some physicians talk about leaving the federal program. Investigations and advocacy by TMA staff put Medicare on the path to a fix. PMID:26201065

  16. Uncovering the Math Curriculum

    ERIC Educational Resources Information Center

    Burns, Marilyn

    2014-01-01

    Teachers often express to Marulyn Burns their worry about the need to "cover the curriculum." In response, she draws on one of her favorite quotes: "You don't want to cover a subject; you want to uncover it." This quote is from "The Having of Wonderful Ideas and Other Essays on Teaching and Learning" by Eleanor…

  17. Uncovering Sexual Problems

    PubMed Central

    Cohen, May

    1977-01-01

    While patients frequently make it difficult for us to uncover their sexual concerns, a much greater difficulty is due to physicians' unwillingness to deal with this subject. Physicians need to acquire basic knowledge about human sexuality as well as skills in making patients feel comfortable and open. A non-judgmental attitude is essential. The physician will also be able to anticipate and prevent sexual distress by education. Expertise must be developed in differentiating those problems requiring referral for specialized sexual counselling from those which the family physician can handle. PMID:21304865

  18. Non-targeted profiling of semi-polar metabolites in Arabidopsis root exudates uncovers a role for coumarin secretion and lignification during the local response to phosphate limitation.

    PubMed

    Ziegler, Jörg; Schmidt, Stephan; Chutia, Ranju; Müller, Jens; Böttcher, Christoph; Strehmel, Nadine; Scheel, Dierk; Abel, Steffen

    2016-03-01

    Plants have evolved two major strategies to cope with phosphate (Pi) limitation. The systemic response, mainly comprising increased Pi uptake and metabolic adjustments for more efficient Pi use, and the local response, enabling plants to explore Pi-rich soil patches by reorganization of the root system architecture. Unlike previous reports, this study focused on root exudation controlled by the local response to Pi deficiency. To approach this, a hydroponic system separating the local and systemic responses was developed. Arabidopsis thaliana genotypes exhibiting distinct sensitivities to Pi deficiency could be clearly distinguished by their root exudate composition as determined by non-targeted reversed-phase ultraperformance liquid chromatography electrospray ionization quadrupole-time-of-flight mass spectrometry metabolite profiling. Compared with wild-type plants or insensitive low phosphate root 1 and 2 (lpr1 lpr2) double mutant plants, the hypersensitive phosphate deficiency response 2 (pdr2) mutant exhibited a reduced number of differential features in root exudates after Pi starvation, suggesting the involvement of PDR2-encoded P5-type ATPase in root exudation. Identification and analysis of coumarins revealed common and antagonistic regulatory pathways between Pi and Fe deficiency-induced coumarin secretion. The accumulation of oligolignols in root exudates after Pi deficiency was inversely correlated with Pi starvation-induced lignification at the root tips. The strongest oligolignol accumulation in root exudates was observed for the insensitive lpr1 lpr2 double mutant, which was accompanied by the absence of Pi deficiency-induced lignin deposition, suggesting a role of LPR ferroxidases in lignin polymerization during Pi starvation. PMID:26685189

  19. Non-targeted profiling of semi-polar metabolites in Arabidopsis root exudates uncovers a role for coumarin secretion and lignification during the local response to phosphate limitation

    PubMed Central

    Ziegler, Jörg; Schmidt, Stephan; Chutia, Ranju; Müller, Jens; Böttcher, Christoph; Strehmel, Nadine; Scheel, Dierk; Abel, Steffen

    2016-01-01

    Plants have evolved two major strategies to cope with phosphate (Pi) limitation. The systemic response, mainly comprising increased Pi uptake and metabolic adjustments for more efficient Pi use, and the local response, enabling plants to explore Pi-rich soil patches by reorganization of the root system architecture. Unlike previous reports, this study focused on root exudation controlled by the local response to Pi deficiency. To approach this, a hydroponic system separating the local and systemic responses was developed. Arabidopsis thaliana genotypes exhibiting distinct sensitivities to Pi deficiency could be clearly distinguished by their root exudate composition as determined by non-targeted reversed-phase ultraperformance liquid chromatography electrospray ionization quadrupole-time-of-flight mass spectrometry metabolite profiling. Compared with wild-type plants or insensitive low phosphate root 1 and 2 (lpr1 lpr2) double mutant plants, the hypersensitive phosphate deficiency response 2 (pdr2) mutant exhibited a reduced number of differential features in root exudates after Pi starvation, suggesting the involvement of PDR2-encoded P5-type ATPase in root exudation. Identification and analysis of coumarins revealed common and antagonistic regulatory pathways between Pi and Fe deficiency-induced coumarin secretion. The accumulation of oligolignols in root exudates after Pi deficiency was inversely correlated with Pi starvation-induced lignification at the root tips. The strongest oligolignol accumulation in root exudates was observed for the insensitive lpr1 lpr2 double mutant, which was accompanied by the absence of Pi deficiency-induced lignin deposition, suggesting a role of LPR ferroxidases in lignin polymerization during Pi starvation. PMID:26685189

  20. Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers.

    PubMed

    Creighton, Chad J; Fountain, Michael D; Yu, Zhifeng; Nagaraja, Ankur K; Zhu, Huifeng; Khan, Mahjabeen; Olokpa, Emuejevoke; Zariff, Azam; Gunaratne, Preethi H; Matzuk, Martin M; Anderson, Matthew L

    2010-03-01

    MicroRNAs (miRNA) regulate complex patterns of gene expression, and the relevance of altered miRNA expression to ovarian cancer remains to be elucidated. By comprehensively profiling expression of miRNAs and mRNAs in serous ovarian tumors and cell lines and normal ovarian surface epithelium, we identified hundreds of potential miRNA-mRNA targeting associations underlying cancer. Functional overexpression of miR-31, the most underexpressed miRNA in serous ovarian cancer, repressed predicted miR-31 gene targets including the cell cycle regulator E2F2. MIR31 and CDKN2A, which encode p14(ARF) and p16(INK4A), are located at 9p21.3, a genomic region commonly deleted in ovarian and other cancers. p14(ARF) promotes p53 activity, and E2F2 overexpression in p53 wild-type cells normally leads via p14(ARF) to an induction of p53-dependent apoptosis. In a number of serous cancer cell lines with a dysfunctional p53 pathway (i.e., OVCAR8, OVCA433, and SKOV3), miR-31 overexpression inhibited proliferation and induced apoptosis; however, in other lines (i.e., HEY and OVSAYO) with functional p53, miR-31 had no effect. Additionally, the osteosarcoma cell line U2OS and the prostate cancer cell line PC3 (p14(ARF)-deficient and p53-deficient, respectively) were also sensitive to miR-31. Furthermore, miR-31 overexpression induced a global gene expression pattern in OVCAR8 associated with better prognosis in tumors from patients with advanced stage serous ovarian cancer, potentially affecting many genes underlying disease progression. Our findings reveal that loss of miR-31 is associated with defects in the p53 pathway and functions in serous ovarian cancer and other cancers, suggesting that patients with cancers deficient in p53 activity might benefit from therapeutic delivery of miR-31. PMID:20179198

  1. Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport.

    PubMed

    Phirke, Prasad; Efimenko, Evgeni; Mohan, Swetha; Burghoorn, Jan; Crona, Filip; Bakhoum, Mathieu W; Trieb, Maria; Schuske, Kim; Jorgensen, Erik M; Piasecki, Brian P; Leroux, Michel R; Swoboda, Peter

    2011-09-01

    Cilia are ubiquitous cell surface projections that mediate various sensory- and motility-based processes and are implicated in a growing number of multi-organ genetic disorders termed ciliopathies. To identify new components required for cilium biogenesis and function, we sought to further define and validate the transcriptional targets of DAF-19, the ciliogenic C. elegans RFX transcription factor. Transcriptional profiling of daf-19 mutants (which do not form cilia) and wild-type animals was performed using embryos staged to when the cell types developing cilia in the worm, the ciliated sensory neurons (CSNs), still differentiate. Comparisons between the two populations revealed 881 differentially regulated genes with greater than a 1.5-fold increase or decrease in expression. A subset of these was confirmed by quantitative RT-PCR. Transgenic worms expressing transcriptional GFP fusions revealed CSN-specific expression patterns for 11 of 14 candidate genes. We show that two uncharacterized candidate genes, termed dyf-17 and dyf-18 because their corresponding mutants display dye-filling (Dyf) defects, are important for ciliogenesis. DYF-17 localizes at the base of cilia and is specifically required for building the distal segment of sensory cilia. DYF-18 is an evolutionarily conserved CDK7/CCRK/LF2p-related serine/threonine kinase that is necessary for the proper function of intraflagellar transport, a process critical for cilium biogenesis. Together, our microarray study identifies targets of the evolutionarily conserved RFX transcription factor, DAF-19, providing a rich dataset from which to uncover-in addition to DYF-17 and DYF-18-cellular components important for cilium formation and function. PMID:21740898

  2. Tensor GSVD of patient- and platform-matched tumor and normal DNA copy-number profiles uncovers chromosome arm-wide patterns of tumor-exclusive platform-consistent alterations encoding for cell transformation and predicting ovarian cancer survival.

    PubMed

    Sankaranarayanan, Preethi; Schomay, Theodore E; Aiello, Katherine A; Alter, Orly

    2015-01-01

    The number of large-scale high-dimensional datasets recording different aspects of a single disease is growing, accompanied by a need for frameworks that can create one coherent model from multiple tensors of matched columns, e.g., patients and platforms, but independent rows, e.g., probes. We define and prove the mathematical properties of a novel tensor generalized singular value decomposition (GSVD), which can simultaneously find the similarities and dissimilarities, i.e., patterns of varying relative significance, between any two such tensors. We demonstrate the tensor GSVD in comparative modeling of patient- and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV) tumor, mostly high-grade, and normal DNA copy-number profiles, across each chromosome arm, and combination of two arms, separately. The modeling uncovers previously unrecognized patterns of tumor-exclusive platform-consistent co-occurring copy-number alterations (CNAs). We find, first, and validate that each of the patterns across only 7p and Xq, and the combination of 6p+12p, is correlated with a patient's prognosis, is independent of the tumor's stage, the best predictor of OV survival to date, and together with stage makes a better predictor than stage alone. Second, these patterns include most known OV-associated CNAs that map to these chromosome arms, as well as several previously unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and protein expression consistently map to the DNA CNAs. A coherent picture emerges for each pattern, suggesting roles for the CNAs in OV pathogenesis and personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38-encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell transformation, and are correlated with a cell's immortality, and a patient's shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are correlated with DNA stability, and a longer survival. In Xq, PABPC5

  3. Tensor GSVD of Patient- and Platform-Matched Tumor and Normal DNA Copy-Number Profiles Uncovers Chromosome Arm-Wide Patterns of Tumor-Exclusive Platform-Consistent Alterations Encoding for Cell Transformation and Predicting Ovarian Cancer Survival

    PubMed Central

    Sankaranarayanan, Preethi; Schomay, Theodore E.; Aiello, Katherine A.; Alter, Orly

    2015-01-01

    The number of large-scale high-dimensional datasets recording different aspects of a single disease is growing, accompanied by a need for frameworks that can create one coherent model from multiple tensors of matched columns, e.g., patients and platforms, but independent rows, e.g., probes. We define and prove the mathematical properties of a novel tensor generalized singular value decomposition (GSVD), which can simultaneously find the similarities and dissimilarities, i.e., patterns of varying relative significance, between any two such tensors. We demonstrate the tensor GSVD in comparative modeling of patient- and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV) tumor, mostly high-grade, and normal DNA copy-number profiles, across each chromosome arm, and combination of two arms, separately. The modeling uncovers previously unrecognized patterns of tumor-exclusive platform-consistent co-occurring copy-number alterations (CNAs). We find, first, and validate that each of the patterns across only 7p and Xq, and the combination of 6p+12p, is correlated with a patient’s prognosis, is independent of the tumor’s stage, the best predictor of OV survival to date, and together with stage makes a better predictor than stage alone. Second, these patterns include most known OV-associated CNAs that map to these chromosome arms, as well as several previously unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and protein expression consistently map to the DNA CNAs. A coherent picture emerges for each pattern, suggesting roles for the CNAs in OV pathogenesis and personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38-encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell transformation, and are correlated with a cell’s immortality, and a patient’s shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are correlated with DNA stability, and a longer survival. In Xq

  4. Uncovering Black Womanhood in Engineering

    ERIC Educational Resources Information Center

    Gibson, Sheree L.; Espino, Michelle M.

    2016-01-01

    Despite the growing research that outlines the experiences of Blacks and women undergraduates in engineering, little is known about Black women in this field. The purpose of this qualitative study was to uncover how eight Black undergraduate women in engineering understood their race and gender identities in a culture that can be oppressive to…

  5. Profiles.

    ERIC Educational Resources Information Center

    School Arts, 1979

    1979-01-01

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

  6. Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.

    PubMed

    Banchereau, Romain; Hong, Seunghee; Cantarel, Brandi; Baldwin, Nicole; Baisch, Jeanine; Edens, Michelle; Cepika, Alma-Martina; Acs, Peter; Turner, Jacob; Anguiano, Esperanza; Vinod, Parvathi; Kahn, Shaheen; Obermoser, Gerlinde; Blankenship, Derek; Wakeland, Edward; Nassi, Lorien; Gotte, Alisa; Punaro, Marilynn; Liu, Yong-Jun; Banchereau, Jacques; Rossello-Urgell, Jose; Wright, Tracey; Pascual, Virginia

    2016-04-21

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to nucleic acids and highly diverse clinical manifestations. To assess its molecular heterogeneity, we longitudinally profiled the blood transcriptome of 158 pediatric patients. Using mixed models accounting for repeated measurements, demographics, treatment, disease activity (DA), and nephritis class, we confirmed a prevalent IFN signature and identified a plasmablast signature as the most robust biomarker of DA. We detected gradual enrichment of neutrophil transcripts during progression to active nephritis and distinct signatures in response to treatment in different nephritis subclasses. Importantly, personalized immunomonitoring uncovered individual correlates of disease activity that enabled patient stratification into seven groups, supported by patient genotypes. Our study uncovers the molecular heterogeneity of SLE and provides an explanation for the failure of clinical trials. This approach may improve trial design and implementation of tailored therapies in genetically and clinically complex autoimmune diseases. PAPERCLIP. PMID:27040498

  7. Uncovering blue diffuse dwarf galaxies

    NASA Astrophysics Data System (ADS)

    James, Bethan L.; Koposov, Sergey; Stark, Daniel P.; Belokurov, Vasily; Pettini, Max; Olszewski, Edward W.

    2015-04-01

    Extremely metal poor (XMP) galaxies are known to be very rare, despite the large numbers of low-mass galaxies predicted by the local galaxy luminosity function. This paper presents a subsample of galaxies that were selected via a morphology-based search on Sloan Digital Sky Survey images with the aim of finding these elusive XMP galaxies. By using the recently discovered XMP galaxy, Leo P, as a guide, we obtained a collection of faint, blue systems, each with isolated H II regions embedded in a diffuse continuum, that have remained optically undetected until now. Here we show the first results from optical spectroscopic follow-up observations of 12 of ˜100 of these blue diffuse dwarf (BDD) galaxies yielded by our search algorithm. Oxygen abundances were obtained via the direct method for eight galaxies, and found to be in the range 7.45 < 12 + log (O/H) < 8.0, with two galaxies being classified as XMPs. All BDDs were found to currently have a young star-forming population (<10 Myr) and relatively high ionization parameters of their H II regions. Despite their low luminosities (-11 ≲ MB ≲ -18) and low surface brightnesses (˜23-25 mag arcsec-2), the galaxies were found to be actively star forming, with current star formation rates between 0.0003 and 0.078 M⊙ yr-1. From our current subsample, BDD galaxies appear to be a population of non-quiescent dwarf irregular galaxies, or the diffuse counterparts to blue compact galaxies and as such may bridge the gap between these two populations. Our search algorithm demonstrates that morphology-based searches are successful in uncovering more diffuse metal-poor star-forming galaxies, which traditional emission-line-based searches overlook.

  8. Researchers Uncover Surprises about Celiac Disease

    MedlinePlus

    ... news/fullstory_159122.html Researchers Uncover Surprises About Celiac Disease Immune condition most common among people descended ... has revealed some surprising findings about who develops celiac disease in the United States. The study found ...

  9. Uncovering your hidden occupancy costs.

    PubMed

    Apgar, M

    1993-01-01

    Senior managers at large companies may not believe that they can have much impact on the "bricks and mortar" of their cost structure. They may even think that occupancy costs are too insignificant to worry about, too technical to analyze, and too fixed to control. But as real estate consultant Mahlon Apgar argues, occupancy costs can hurt a company's earnings, share value, and overall performance. On the other hand, every dollar saved drops straight to the bottom line. Shearson Lehman Brothers, for example, has found that it can save as much as $20 million annually by reducing occupancy costs in its branch offices and headquarters. Managing occupancy costs isn't easy. But it is timely. As companies strive to improve productivity by consolidating functions and downsizing staff, they are saddled with excess office space. Expansions abroad present completely different market conditions that put a premium on reducing occupancy costs. At the same time, the changing nature of work is challenging deeply held beliefs about the workplace, and, consequently, traditional expectations of office space are giving way to innovations that are less costly and more productive. To manage occupancy costs, managers must be able to identify their components, measure their impact, understand what drives them, and develop options to change them. Four basic tools help diagnose problems: a cost history, a loss analysis, a component analysis, and a lease aging profile. Understanding cost drivers like leasing, location, and layout can give executives the insights they need to reduce occupancy costs while improving the effectiveness of facilities to support day-to-day operations. PMID:10126151

  10. 'Mystery shoppers' can uncover ED weaknesses.

    PubMed

    2006-12-01

    One veteran "mystery shopper" has uncovered several common ED practices that can hurt patient satisfaction. You can learn from her observations to improve your ED's customer service: Be sure to let all of your patients know how long they might expect to wait before seeing a doctor. Wash your hands where the patient can see you, so they can be confident you are practicing good hygiene. Clearly explain all forms and discharge instructions to help ensure patient compliance. PMID:17209484

  11. Lead exposure at uncovered outdoor firing ranges

    SciTech Connect

    Goldberg, R.L.; Hicks, A.M.; O'Leary, L.M.; London, S. )

    1991-06-01

    Excessive lead exposure in shooting instructors at indoor firing ranges and covered outdoor firing ranges has been documented. The City of Los Angeles assessed exposure of its full-time shooting instructors at uncovered outdoor ranges via air monitoring and blood lead-level measurements. Results of these tests revealed that significant lead exposure and absorption can occur at outdoor firing ranges. The use of copper-jacketed ammunition may decrease air lead levels and decrease lead absorption by range instructors.

  12. Clinical role modelling: uncovering hidden knowledge.

    PubMed

    Davies, E

    1993-04-01

    Those responsible for the education of nurses are well aware of the need to reconcile the art and science of nursing so that future practitioners can be prepared to offer a humanistic and professional service to society. One way to assist students in this integration is to provide them with opportunities for role modelling as a means of discovering the knowledge embedded in clinical practice. A study of first-year undergraduate students undertaking a course which provides such opportunities in a number of practice settings was carried out to determine whether the observation of clinical role models does lead to knowledge discovery. The study, which used a grounded theory approach, indicated that the major aspect of nursing uncovered by the students through observation of clinical role models was that of provision of direct care. They articulated their values in relation to 'good' and 'bad' care and identified those attributes of nurses which they considered contributed to these care positions. In addition, they were able to recognize creativity and flexibility in practitioners and to relate these attributes to the ability to provide individualized, context-specific care. There was some uncovering of aspects of the nurse's role in maintaining their own professional competence, socializing neophytes into the profession and collaborating with the members of the multi-disciplinary health care team. PMID:8496511

  13. Uncovering the Hidden Decisions that Shape Curricula

    NASA Astrophysics Data System (ADS)

    Harlow, Danielle Boyd

    2010-10-01

    Developing explanatory models is a central practice to scientific inquiry. When students create and test explanatory models for scientific phenomenon, they develop content knowledge, knowledge of the nature of science, and creative thinking skills. Unfortunately, such instruction rarely occurs in K-12 science. This is, in part, because teachers do not have the opportunity to develop sophisticated understandings of the process of modeling, but also because teaching in this way requires teachers to make real-time instructional decisions that are responsive to students' ideas. This is challenging for teachers, especially because this decision process is often invisible. In this talk, I will highlight the importance of providing opportunities for sophisticated science thinking for our youngest learners and consider how uncovering the decisions that shape physics courses for teachers may benefit their future students.

  14. Uncovering the Architecture of Action Semantics

    PubMed Central

    Watson, Christine E.; Buxbaum, Laurel J.

    2014-01-01

    Despite research suggesting that stored sensorimotor information about tool use is a component of the semantic representations of tools, little is known about the action features or organizing principles that underlie this knowledge. We used methods similar to those applied in other semantic domains to examine the “architecture” of action semantic knowledge. In Experiment 1, participants sorted photographs of tools into groups according to the similarity of their associated “use” actions and rated tools on dimensions related to action. The results suggest that the magnitude of arm movement, configuration of the hand, and manner of motion during tool use play a role in determining how tools cluster in action “semantic space”. In Experiment 2, we validated the architecture uncovered in Experiment 1 using an implicit semantic task for which tool use knowledge was not ostensibly relevant (blocked cyclic word-picture matching). Using stimuli from Experiment 1, we found that participants performed more poorly during blocks of trials containing tools used with similar versus unrelated actions, and the amount of semantic interference depended on the magnitude of action similarity among tools. Thus, the degree of featural overlap between tool use actions plays a role in determining the overall semantic similarity of tools. PMID:25045905

  15. Uncovering Wolbachia Diversity upon Artificial Host Transfer

    PubMed Central

    Schneider, Daniela I.; Riegler, Markus; Arthofer, Wolfgang; Merçot, Hervé; Stauffer, Christian; Miller, Wolfgang J.

    2013-01-01

    The common endosymbiotic Wolbachia bacteria influence arthropod hosts in multiple ways. They are mostly recognized for their manipulations of host reproduction, yet, more recent studies demonstrate that Wolbachia also impact host behavior, metabolic pathways and immunity. Besides their biological and evolutionary roles, Wolbachia are new potential biological control agents for pest and vector management. Importantly, Wolbachia-based control strategies require controlled symbiont transfer between host species and predictable outcomes of novel Wolbachia-host associations. Theoretically, this artificial horizontal transfer could inflict genetic changes within transferred Wolbachia populations. This could be facilitated through de novo mutations in the novel recipient host or changes of haplotype frequencies of polymorphic Wolbachia populations when transferred from donor to recipient hosts. Here we show that Wolbachia resident in the European cherry fruit fly, Rhagoletis cerasi, exhibit ancestral and cryptic sequence polymorphism in three symbiont genes, which are exposed upon microinjection into the new hosts Drosophila simulans and Ceratitis capitata. Our analyses of Wolbachia in microinjected D. simulans over 150 generations after microinjection uncovered infections with multiple Wolbachia strains in trans-infected lines that had previously been typed as single infections. This confirms the persistence of low-titer Wolbachia strains in microinjection experiments that had previously escaped standard detection techniques. Our study demonstrates that infections by multiple Wolbachia strains can shift in prevalence after artificial host transfer driven by either stochastic or selective processes. Trans-infection of Wolbachia can claim fitness costs in new hosts and we speculate that these costs may have driven the shifts of Wolbachia strains that we saw in our model system. PMID:24376534

  16. NLM Grantee's "HealthMap" Helps Uncover Measles Vaccination Gap

    MedlinePlus

    ... of NLM NLM Grantee's "HealthMap" Helps Uncover Measles Vaccination Gap Inadequate vaccine coverage is likely a driving ... stop this and future measles outbreaks is through vaccination." The research indicates that vaccine coverage among the ...

  17. 20. UNCOVERED TEST CELL AT THE STATIC TEST TOWER ON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. UNCOVERED TEST CELL AT THE STATIC TEST TOWER ON THE WEST SIDE WHERE F-1 ENGINE WAS TESTED. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

  18. η Carinae Baby Homunculus Uncovered by ALMA

    NASA Astrophysics Data System (ADS)

    Abraham, Zulema; Falceta-Gonçalves, Diego; Beaklini, Pedro P. B.

    2014-08-01

    We report observations of η Carinae obtained with ALMA in the continuum of 100, 230, 280, and 660 GHz in 2012 November, with a resolution that varied from 2.''88 to 0.''45 for the lower and higher frequencies, respectively. The source is not resolved, even at the highest frequency; its spectrum is characteristic of thermal bremsstrahlung of a compact source, but different from the spectrum of optically thin wind. The recombination lines H42α, He42α, H40α, He40α, H50β, H28α, He28α, H21α, and He21α were also detected, and their intensities reveal non-local thermodynamic equilibrium effects. We found that the line profiles could only be fit by an expanding shell of dense and ionized gas, which produces a slow shock in the surroundings of η Carinae. Combined with fittings to the continuum, we were able to constrain the shell size, radius, density, temperature, and velocity. The detection of the He recombination lines is compatible with the high-temperature gas and requires a high-energy ionizing photon flux, which must be provided by the companion star. The mass-loss rate and wind velocity, necessary to explain the formation of the shell, are compatible with an luminous blue variable eruption. The position, velocity, and physical parameters of the shell coincide with those of the Weigelt blobs. The dynamics found for the expanding shell correspond to matter ejected by η Carinae in 1941 in an event similar to that which formed the Little Homunculus; for that reason, we called the new ejecta the "Baby Homunculus."

  19. η Carinae Baby Homunculus uncovered by ALMA

    SciTech Connect

    Abraham, Zulema; Beaklini, Pedro P. B.; Falceta-Gonçalves, Diego

    2014-08-20

    We report observations of η Carinae obtained with ALMA in the continuum of 100, 230, 280, and 660 GHz in 2012 November, with a resolution that varied from 2.''88 to 0.''45 for the lower and higher frequencies, respectively. The source is not resolved, even at the highest frequency; its spectrum is characteristic of thermal bremsstrahlung of a compact source, but different from the spectrum of optically thin wind. The recombination lines H42α, He42α, H40α, He40α, H50β, H28α, He28α, H21α, and He21α were also detected, and their intensities reveal non-local thermodynamic equilibrium effects. We found that the line profiles could only be fit by an expanding shell of dense and ionized gas, which produces a slow shock in the surroundings of η Carinae. Combined with fittings to the continuum, we were able to constrain the shell size, radius, density, temperature, and velocity. The detection of the He recombination lines is compatible with the high-temperature gas and requires a high-energy ionizing photon flux, which must be provided by the companion star. The mass-loss rate and wind velocity, necessary to explain the formation of the shell, are compatible with an luminous blue variable eruption. The position, velocity, and physical parameters of the shell coincide with those of the Weigelt blobs. The dynamics found for the expanding shell correspond to matter ejected by η Carinae in 1941 in an event similar to that which formed the Little Homunculus; for that reason, we called the new ejecta the 'Baby Homunculus'.

  20. Uncovering the Nutritional Landscape of Food

    PubMed Central

    Kim, Seunghyeon; Sung, Jaeyun; Foo, Mathias; Jin, Yong-Su; Kim, Pan-Jun

    2015-01-01

    Recent progresses in data-driven analysis methods, including network-based approaches, are revolutionizing many classical disciplines. These techniques can also be applied to food and nutrition, which must be studied to design healthy diets. Using nutritional information from over 1,000 raw foods, we systematically evaluated the nutrient composition of each food in regards to satisfying daily nutritional requirements. The nutrient balance of a food was quantified and termed nutritional fitness; this measure was based on the food’s frequency of occurrence in nutritionally adequate food combinations. Nutritional fitness offers a way to prioritize recommendable foods within a global network of foods, in which foods are connected based on the similarities of their nutrient compositions. We identified a number of key nutrients, such as choline and α-linolenic acid, whose levels in foods can critically affect the nutritional fitness of the foods. Analogously, pairs of nutrients can have the same effect. In fact, two nutrients can synergistically affect the nutritional fitness, although the individual nutrients alone may not have an impact. This result, involving the tendency among nutrients to exhibit correlations in their abundances across foods, implies a hidden layer of complexity when exploring for foods whose balance of nutrients within pairs holistically helps meet nutritional requirements. Interestingly, foods with high nutritional fitness successfully maintain this nutrient balance. This effect expands our scope to a diverse repertoire of nutrient-nutrient correlations, which are integrated under a common network framework that yields unexpected yet coherent associations between nutrients. Our nutrient-profiling approach combined with a network-based analysis provides a more unbiased, global view of the relationships between foods and nutrients, and can be extended towards nutritional policies, food marketing, and personalized nutrition. PMID:25768022

  1. Uncovering the Nucleus Candidate for NGC 253

    NASA Astrophysics Data System (ADS)

    Günthardt, G. I.; Agüero, M. P.; Camperi, J. A.; Díaz, R. J.; Gomez, P. L.; Bosch, G.; Schirmer, M.

    2015-11-01

    NGC 253 is the nearest spiral galaxy with a nuclear starburst that becomes the best candidate for studying the relationship between starburst and active galactic nucleus activity. However, this central region is veiled by large amounts of dust, and it has been so far unclear which is the true dynamical nucleus to the point that there is no strong evidence that the galaxy harbors a supermassive black hole co-evolving with the starburst as was supposed earlier. Near-infrared (NIR) spectroscopy, especially NIR emission line analysis, could be advantageous in shedding light on the true nucleus identity. Using Flamingos-2 at Gemini South we have taken deep K-band spectra along the major axis of the central structure and through the brightest infrared source. In this work, we present evidence showing that the brightest NIR and mid-infrared source in the central region, already known as radio source TH7 and so far considered just a large stellar supercluster, in fact presents various symptoms of a genuine galactic nucleus. Therefore, it should be considered a valid nucleus candidate. Mentioning some distinctive aspects, it is the most massive compact infrared object in the central region, located at 2.″0 of the symmetry center of the galactic bar, as measured in the K-band emission. Moreover, our data indicate that this object is surrounded by a large circumnuclear stellar disk and it is also located at the rotation center of the large molecular gas disk of NGC 253. Furthermore, a kinematic residual appears in the H2 rotation curve with a sinusoidal shape consistent with an outflow centered in the candidate nucleus position. The maximum outflow velocity is located about 14 pc from TH7, which is consistent with the radius of a shell detected around the nucleus candidate, observed at 18.3 μm (Qa) and 12.8 μm ([Ne ii]) with T-ReCS. Also, the Brγ emission line profile shows a pronounced blueshift and this emission line also has the highest equivalent width at this

  2. Uncovering Contents of Mentor Teachers' Interactive Cognitions during Mentoring Dialogues

    ERIC Educational Resources Information Center

    Hennissen, Paul; Crasborn, Frank; Brouwer, Niels; Korthagen, Fred; Bergen, Theo

    2010-01-01

    In the context of developing mentor teachers' use of supervisory skills, two consecutive studies were conducted, using stimulated recall. Firstly, with eight participants, an instrument was developed to categorize contents of interactive cognitions. Secondly, with 30 participants, the instrument was applied to uncover contents of mentor teachers'…

  3. Uncovering key data points to improve OR profitability.

    PubMed

    Stiefel, Robert A; Greenfield, Howard

    2014-03-01

    Using data analysis to target areas for performance improvement in the operating room (OR) involves: regularly monitoring key OR statistics, such as through use of a dashboard, determining the root causes of problems uncovered by the data analysis, making appropriate corrections and continuing to monitor performance. PMID:24701846

  4. Weaving Social Foundations through Dance Pedagogy: A Pedagogy of Uncovering

    ERIC Educational Resources Information Center

    Barr, Sherrie; Risner, Doug

    2014-01-01

    Today's dance educators enter classrooms populated by increasingly diverse students in which teachers' pedagogical knowledge necessitates heightened understandings of race, ethnicity, social class, gender, and sexuality. Uncovering taken-for-granted assumptions, dominant stereotypes, and educational structures that reproduce social…

  5. Uncovering Student Thinking in Mathematics: 25 Formative Assessment Probes

    ERIC Educational Resources Information Center

    Rose, Cheryl M.; Minton, Leslie; Arline, Carolyn B.

    2006-01-01

    Students learn at varying rates, and if a misconception in mathematics develops early, it may be carried from year to year and obstruct a student's progress. To identify fallacies in students' preconceived ideas, "Uncovering Student Thinking in Mathematics" offers educators a powerful diagnostic technique in the form of field-tested assessment…

  6. Uncovering diversity in the development of central noradrenergic neurons and their efferents.

    PubMed

    Robertson, Sabrina D; Plummer, Nicholas W; Jensen, Patricia

    2016-06-15

    Uncovering the mechanisms that underlie central noradrenergic neuron heterogeneity is essential to understanding selective subtype vulnerability to disease and environmental insult. Using recombinase-based intersectional genetic fate mapping we have previously demonstrated that molecularly distinct progenitor populations give rise to mature noradrenergic neurons differing in their anatomical location, axon morphology and efferent projection pattern. Here we review the findings from our previous study and extend our analysis of the noradrenergic subpopulation defined by transient developmental expression of Hoxb1. Using a combination of intersectional genetic fate mapping and analysis of a targeted loss of function mutation in Hoxb1, we have now uncovered additional heterogeneity based on the requirement of some noradrenergic neurons for Hoxb1 expression. By comparing the distribution of noradrenergic neurons derived from the Hoxb1 expression domain in wild-type and mutant mice, we demonstrate that Hoxb1 expression is required by a subset of neurons in the pons. Additional fate mapping, using a Hoxb1 enhancer element that drives Cre recombinase expression exclusively in rhombomere 4 of the hindbrain, reveals the existence of a subpopulation of noradrenergic neurons in the pons with more restricted axonal targets than the full Hoxb1-derived subpopulation. The unique projection profile of this newly defined subpopulation suggests that it may be functionally distinct. These analyses shed new light on the molecular determinants of noradrenergic identity in the pons and the overall complexity of the central noradrenergic system. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26612521

  7. Malignant Gastroduodenal Obstruction: Treatment with Self-Expanding Uncovered Wallstent

    SciTech Connect

    Gutzeit, Andreas Binkert, Christoph A.; Schoch, Eric; Sautter, Thomas; Jost, Res; Zollikofer, Christoph L.

    2009-01-15

    Purpose: To retrospectively evaluate the clinical effectiveness of a self-expanding uncovered Wallstent in patients with malignant gastroduodenal obstruction. Materials and Methods: Under combined endoscopic and fluoroscopic guidance, 29 patients with a malignant gastroduodenal stenosis were treated with a self-expanding uncovered metallic Wallstent. A dysphagia score was assessed before and after the intervention to measure the success of this palliative therapy. The dysphagia score ranged between grade 0 to grade 4: grade 0 = able to tolerate solid food, grade 1 = able to tolerate soft food, grade 2 = able to tolerate thick liquids, grade 3 = able to tolerate water or clear fluids, and grade 4 = unable to tolerate anything perorally. Stent patency and patients survival rates were calculated. Results: The insertion of the gastroduodenal stent was technically successful in 28 patients (96.5%). After stenting, 25 patients (86.2%) showed clinical improvement by at least one score point. During follow-up, 22 (78.5%) of 28 patients showed no stent occlusion until death and did not have to undergo any further intervention. In six patients (20.6%), all of whom were treated with secondary stent insertions, occlusion with tumor ingrowth and/or overgrowth was observed after the intervention. The median period of primary stent patency in our study was 240 days. Conclusion: Placement of an uncovered Wallstent is clinically effective in patients with malignant gastroduodenal obstruction. Stent placement is associated with high technical success, good palliation effect, and high durability of stent function.

  8. Uncovering beat deafness: detecting rhythm disorders with synchronized finger tapping and perceptual timing tasks.

    PubMed

    Dalla Bella, Simone; Sowiński, Jakub

    2015-01-01

    A set of behavioral tasks for assessing perceptual and sensorimotor timing abilities in the general population (i.e., non-musicians) is presented here with the goal of uncovering rhythm disorders, such as beat deafness. Beat deafness is characterized by poor performance in perceiving durations in auditory rhythmic patterns or poor synchronization of movement with auditory rhythms (e.g., with musical beats). These tasks include the synchronization of finger tapping to the beat of simple and complex auditory stimuli and the detection of rhythmic irregularities (anisochrony detection task) embedded in the same stimuli. These tests, which are easy to administer, include an assessment of both perceptual and sensorimotor timing abilities under different conditions (e.g., beat rates and types of auditory material) and are based on the same auditory stimuli, ranging from a simple metronome to a complex musical excerpt. The analysis of synchronized tapping data is performed with circular statistics, which provide reliable measures of synchronization accuracy (e.g., the difference between the timing of the taps and the timing of the pacing stimuli) and consistency. Circular statistics on tapping data are particularly well-suited for detecting individual differences in the general population. Synchronized tapping and anisochrony detection are sensitive measures for identifying profiles of rhythm disorders and have been used with success to uncover cases of poor synchronization with spared perceptual timing. This systematic assessment of perceptual and sensorimotor timing can be extended to populations of patients with brain damage, neurodegenerative diseases (e.g., Parkinson's disease), and developmental disorders (e.g., Attention Deficit Hyperactivity Disorder). PMID:25867797

  9. Metabolism of human insulin after subcutaneous administration: A possible means to uncover insulin misuse.

    PubMed

    Thomas, Andreas; Brinkkötter, Paul; Schänzer, Wilhelm; Thevis, Mario

    2015-10-15

    The misuse of insulin for performance enhancement in sport or as toxic agent has frequently been reported in the past. In contrast to synthetic insulin analogues, the administration of recombinant human insulin is hardly recognized by mass spectrometry. The present study was designed to uncover the misuse of recombinant human insulin for doping control purposes as well as for forensic applications. It is hypothesized that an altered metabolite profile of circulating insulin prevails after subcutaneous administration due to exposure of insulin to epidermal proteases. In vitro experiments with skin tissue lysates (S9 fraction and microsomes), different biological fluids (urine, serum, plasma) and recombinant human insulin were performed and the deriving metabolites were characterized by liquid chromatography coupled to high resolution mass spectrometry (HRMS). Afterwards, authentic blood samples of patients suffering from diabetes mellitus and a control group of healthy humans were analysed. Therefore, a method using protein precipitation, ultrafiltration and antibody-coated magnetic beads for purification with subsequent separation by nano-scale liquid chromatography coupled a Q Exactive mass spectrometer was applied. Several metabolites of insulin with C-terminally truncated sequences of the B-chain (and A-chain in minor extent) were identified within this study. Here, the DesB30 human insulin represents the major metabolite in all experiments. This metabolite is frequently found in urine samples due to degradation processes and, thus, disqualifies this matrix for the intended purposes. In contrast, blood samples do commonly not contain DesB30 insulin, which was corroborated by data obtained from the control group. In post-administration blood samples, minute but distinct amounts (approx. 50 pg mL(-1)) of DesB30 insulin were found and suggest the use of this analyte as potential marker for subcutaneous human insulin administration, supporting the attempts to

  10. High levels of cryptic species diversity uncovered in Amazonian frogs

    PubMed Central

    Funk, W. Chris; Caminer, Marcel; Ron, Santiago R.

    2012-01-01

    One of the greatest challenges for biodiversity conservation is the poor understanding of species diversity. Molecular methods have dramatically improved our ability to uncover cryptic species, but the magnitude of cryptic diversity remains unknown, particularly in diverse tropical regions such as the Amazon Basin. Uncovering cryptic diversity in amphibians is particularly pressing because amphibians are going extinct globally at an alarming rate. Here, we use an integrative analysis of two independent Amazonian frog clades, Engystomops toadlets and Hypsiboas treefrogs, to test whether species richness is underestimated and, if so, by how much. We sampled intensively in six countries with a focus in Ecuador (Engystomops: 252 individuals from 36 localities; Hypsiboas: 208 individuals from 65 localities) and combined mitochondrial DNA, nuclear DNA, morphological, and bioacoustic data to detect cryptic species. We found that in both clades, species richness was severely underestimated, with more undescribed species than described species. In Engystomops, the two currently recognized species are actually five to seven species (a 150–250% increase in species richness); in Hypsiboas, two recognized species represent six to nine species (a 200–350% increase). Our results suggest that Amazonian frog biodiversity is much more severely underestimated than previously thought. PMID:22130600

  11. Phylostratigraphic Profiles in Zebrafish Uncover Chordate Origins of the Vertebrate Brain

    PubMed Central

    Šestak, Martin Sebastijan; Domazet-Lošo, Tomislav

    2015-01-01

    An elaborated tripartite brain is considered one of the important innovations of vertebrates. Other extant chordate groups have a more basic brain organization. For instance, cephalochordates possess a relatively simple brain possibly homologous to the vertebrate forebrain and hindbrain, whereas tunicates display the tripartite organization, but without the specialized brain centers. The difference in anatomical complexity is even more pronounced if one compares chordates with other deuterostomes that have only a diffuse nerve net or alternatively a rather simple central nervous system. To gain a new perspective on the evolutionary roots of the complex vertebrate brain, we made here a phylostratigraphic analysis of gene expression patterns in the developing zebrafish (Danio rerio). The recovered adaptive landscape revealed three important periods in the evolutionary history of the zebrafish brain. The oldest period corresponds to preadaptive events in the first metazoans and the emergence of the nervous system at the metazoan–eumetazoan transition. The origin of chordates marks the next phase, where we found the overall strongest adaptive imprint in almost all analyzed brain regions. This finding supports the idea that the vertebrate brain evolved independently of the brains within the protostome lineage. Finally, at the origin of vertebrates we detected a pronounced signal coming from the dorsal telencephalon, in agreement with classical theories that consider this part of the cerebrum a genuine vertebrate innovation. Taken together, these results reveal a stepwise adaptive history of the vertebrate brain where most of its extant organization was already present in the chordate ancestor. PMID:25415965

  12. Genomic profiling of lower-grade gliomas uncovers cohesive disease groups: implications for diagnosis and treatment.

    PubMed

    Zhang, Chang-Ming; Brat, Daniel J

    2016-01-01

    Lower-grade gliomas (including low- and intermediate-grade gliomas, World Health Organization grades II and III) are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classified based on their presumed histogenesis as astrocytomas, oligodendrogliomas, or oligoastrocytomas. Although the histopathologic classification of lower-grade glioma has been the accepted standard for nearly a century, it suffers from high intra- and inter-observer variability and does not adequately predict clinical outcomes. Based on integrated analysis of multiplatform genomic data from The Cancer Genome Atlas, lower-grade gliomas have been found to segregate into three cohesive, clinically relevant molecular classes. Molecular classes were closely aligned with the status of isocitrate dehydrogenase (IDH) mutations, tumor protein 53 mutations and the co-deletion of chromosome arms 1p and 19q, but were not closely aligned with histologic classes. These findings emphasize the potential for improved definition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classification. PMID:26758195

  13. Multi-analyte profiling in human carotid atherosclerosis uncovers pro-inflammatory macrophage programming in plaques.

    PubMed

    Shalhoub, Joseph; Viiri, Leena E; Cross, Amanda J; Gregan, Scott M; Allin, David M; Astola, Nagore; Franklin, Ian J; Davies, Alun H; Monaco, Claudia

    2016-05-01

    Molecular characterisation of vulnerable atherosclerosis is necessary for targeting functional imaging and plaque-stabilising therapeutics. Inflammation has been linked to atherogenesis and the development of high-risk plaques. We set to quantify cytokine, chemokine and matrix metalloproteinase (MMP) protein production in cells derived from carotid plaques to map the inflammatory milieu responsible for instability. Carotid endarterectomies from carefully characterised symptomatic (n=35) and asymptomatic (n=32) patients were enzymatically dissociated producing mixed cell type atheroma cell suspensions which were cultured for 24 hours. Supernatants were interrogated for 45 analytes using the Luminex 100 platform. Twenty-nine of the 45 analytes were reproducibly detectable in the majority of donors. The in vitro production of a specific network of mediators was found to be significantly higher in symptomatic than asymptomatic plaques, including: tumour necrosis factor α, interleukin (IL) 1β, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), CCL5, CCL20, CXCL9, matrix metalloproteinase (MMP)-3 and MMP-9. Ingenuity pathway analysis of differentially expressed analytes between symptomatic and asymptomatic patients identified a number of key biological pathways (p< 10(-25)). In conclusion, the carotid artery plaque culprit of ischaemic neurological symptoms is characterised by an inflammatory milieu favouring inflammatory cell recruitment and pro-inflammatory macrophage polarisation. PMID:26763091

  14. Transcriptional profiles uncover Aspergillus flavus-induced resistance in maize kernels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxin contamination caused by the opportunistic pathogen A. flavus is a major concern in maize production prior to harvest and during storage, and also a concern in many other crops, such as peanuts, cottonseed, tree nuts, and rice. Although a number of resistant maize lines with low aflatoxin c...

  15. Breakpoint Analysis of Transcriptional and Genomic Profiles Uncovers Novel Gene Fusions Spanning Multiple Human Cancer Types

    PubMed Central

    Giacomini, Craig P.; Sun, Steven; Varma, Sushama; Shain, A. Hunter; Giacomini, Marilyn M.; Balagtas, Jay; Sweeney, Robert T.; Lai, Everett; Del Vecchio, Catherine A.; Forster, Andrew D.; Clarke, Nicole; Montgomery, Kelli D.; Zhu, Shirley; Wong, Albert J.; van de Rijn, Matt; West, Robert B.; Pollack, Jonathan R.

    2013-01-01

    Gene fusions, like BCR/ABL1 in chronic myelogenous leukemia, have long been recognized in hematologic and mesenchymal malignancies. The recent finding of gene fusions in prostate and lung cancers has motivated the search for pathogenic gene fusions in other malignancies. Here, we developed a “breakpoint analysis” pipeline to discover candidate gene fusions by tell-tale transcript level or genomic DNA copy number transitions occurring within genes. Mining data from 974 diverse cancer samples, we identified 198 candidate fusions involving annotated cancer genes. From these, we validated and further characterized novel gene fusions involving ROS1 tyrosine kinase in angiosarcoma (CEP85L/ROS1), SLC1A2 glutamate transporter in colon cancer (APIP/SLC1A2), RAF1 kinase in pancreatic cancer (ATG7/RAF1) and anaplastic astrocytoma (BCL6/RAF1), EWSR1 in melanoma (EWSR1/CREM), CDK6 kinase in T-cell acute lymphoblastic leukemia (FAM133B/CDK6), and CLTC in breast cancer (CLTC/VMP1). Notably, while these fusions involved known cancer genes, all occurred with novel fusion partners and in previously unreported cancer types. Moreover, several constituted druggable targets (including kinases), with therapeutic implications for their respective malignancies. Lastly, breakpoint analysis identified new cell line models for known rearrangements, including EGFRvIII and FIP1L1/PDGFRA. Taken together, we provide a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis. PMID:23637631

  16. Phylostratigraphic profiles in zebrafish uncover chordate origins of the vertebrate brain.

    PubMed

    Šestak, Martin Sebastijan; Domazet-Lošo, Tomislav

    2015-02-01

    An elaborated tripartite brain is considered one of the important innovations of vertebrates. Other extant chordate groups have a more basic brain organization. For instance, cephalochordates possess a relatively simple brain possibly homologous to the vertebrate forebrain and hindbrain, whereas tunicates display the tripartite organization, but without the specialized brain centers. The difference in anatomical complexity is even more pronounced if one compares chordates with other deuterostomes that have only a diffuse nerve net or alternatively a rather simple central nervous system. To gain a new perspective on the evolutionary roots of the complex vertebrate brain, we made here a phylostratigraphic analysis of gene expression patterns in the developing zebrafish (Danio rerio). The recovered adaptive landscape revealed three important periods in the evolutionary history of the zebrafish brain. The oldest period corresponds to preadaptive events in the first metazoans and the emergence of the nervous system at the metazoan-eumetazoan transition. The origin of chordates marks the next phase, where we found the overall strongest adaptive imprint in almost all analyzed brain regions. This finding supports the idea that the vertebrate brain evolved independently of the brains within the protostome lineage. Finally, at the origin of vertebrates we detected a pronounced signal coming from the dorsal telencephalon, in agreement with classical theories that consider this part of the cerebrum a genuine vertebrate innovation. Taken together, these results reveal a stepwise adaptive history of the vertebrate brain where most of its extant organization was already present in the chordate ancestor. PMID:25415965

  17. Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity

    PubMed Central

    Charlier, Caroline; Touchon, Marie; Chenal-Francisque, Viviane; Leclercq, Alexandre; Criscuolo, Alexis; Gaultier, Charlotte; Roussel, Sophie; Brisabois, Anne; Disson, Olivier; Rocha, Eduardo P. C.; Brisse, Sylvain; Lecuit, Marc

    2016-01-01

    Microbial pathogenesis studies are typically performed with reference strains, thereby overlooking microbial intra-species virulence heterogeneity. Here we integrated human epidemiological and clinical data with bacterial population genomics to harness the biodiversity of the model foodborne pathogen Listeria monocytogenes and decipher the basis of its neural and placental tropisms. Taking advantage of the clonal structure of this bacterial species, we identify clones epidemiologically associated with either food or human central nervous system (CNS) and maternal-neonatal (MN) listeriosis. The latter are also most prevalent in patients without immunosuppressive comorbidities. Strikingly, CNS and MN clones are hypervirulent in a humanized mouse model of listeriosis. By integrating epidemiological data and comparative genomics, we uncovered multiple novel putative virulence factors and demonstrated experimentally the contribution of the first gene cluster mediating Listeria monocytogenes neural and placental tropisms. This study illustrates the exceptional power of harnessing microbial biodiversity to identify clinically relevant microbial virulence attributes. PMID:26829754

  18. Uncovering Transcriptional Regulatory Networks by Sparse Bayesian Factor Model

    NASA Astrophysics Data System (ADS)

    Meng, Jia; Zhang, Jianqiu(Michelle); Qi, Yuan(Alan); Chen, Yidong; Huang, Yufei

    2010-12-01

    The problem of uncovering transcriptional regulation by transcription factors (TFs) based on microarray data is considered. A novel Bayesian sparse correlated rectified factor model (BSCRFM) is proposed that models the unknown TF protein level activity, the correlated regulations between TFs, and the sparse nature of TF-regulated genes. The model admits prior knowledge from existing database regarding TF-regulated target genes based on a sparse prior and through a developed Gibbs sampling algorithm, a context-specific transcriptional regulatory network specific to the experimental condition of the microarray data can be obtained. The proposed model and the Gibbs sampling algorithm were evaluated on the simulated systems, and results demonstrated the validity and effectiveness of the proposed approach. The proposed model was then applied to the breast cancer microarray data of patients with Estrogen Receptor positive ([InlineEquation not available: see fulltext.]) status and Estrogen Receptor negative ([InlineEquation not available: see fulltext.]) status, respectively.

  19. Uncovering Quantum Correlations with Time-Multiplexed Click Detection.

    PubMed

    Sperling, J; Bohmann, M; Vogel, W; Harder, G; Brecht, B; Ansari, V; Silberhorn, C

    2015-07-10

    We report on the implementation of a time-multiplexed click detection scheme to probe quantum correlations between different spatial optical modes. We demonstrate that such measurement setups can uncover nonclassical correlations in multimode light fields even if the single mode reductions are purely classical. The nonclassical character of correlated photon pairs, generated by a parametric down-conversion, is immediately measurable employing the theory of click counting instead of low-intensity approximations with photoelectric detection models. The analysis is based on second- and higher-order moments, which are directly retrieved from the measured click statistics, for relatively high mean photon numbers. No data postprocessing is required to demonstrate the effects of interest with high significance, despite low efficiencies and experimental imperfections. Our approach shows that such novel detection schemes are a reliable and robust way to characterize quantum-correlated light fields for practical applications in quantum communications. PMID:26207467

  20. Uncovering an Existential Barrier to Breast Self-exam Behavior

    PubMed Central

    Goldenberg, Jamie L.; Arndt, Jamie; Hart, Joshua; Routledge, Clay

    2008-01-01

    The present research applies an analysis derived from terror management theory to the health domain of breast examination, and in doing so uncovers previously unrecognized factors that may contribute to women’s reluctance to perform breast self-examinations (BSEs). In Study 1, when concerns about mortality were primed, reminders of human beings’ physical nature (i.e., creatureliness) reduced intentions to conduct BSEs compared to reminders of humans’ uniqueness. In Study 2, women conducted shorter exams on a breast model (an experience found to increase death-thought accessibility) when creatureliness was primed compared to a uniqueness and no essay condition. In Study 3, after a creatureliness prime, women performed shorter BSEs when a placebo did not provide an alternative explanation for their discomfort compared to when it did. Advances for theory and breast self-exam promotion are discussed. PMID:19255593

  1. Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity.

    PubMed

    Maury, Mylène M; Tsai, Yu-Huan; Charlier, Caroline; Touchon, Marie; Chenal-Francisque, Viviane; Leclercq, Alexandre; Criscuolo, Alexis; Gaultier, Charlotte; Roussel, Sophie; Brisabois, Anne; Disson, Olivier; Rocha, Eduardo P C; Brisse, Sylvain; Lecuit, Marc

    2016-03-01

    Microbial pathogenesis studies are typically performed with reference strains, thereby overlooking within-species heterogeneity in microbial virulence. Here we integrated human epidemiological and clinical data with bacterial population genomics to harness the biodiversity of the model foodborne pathogen Listeria monocytogenes and decipher the basis of its neural and placental tropisms. Taking advantage of the clonal structure of this bacterial species, we identify clones epidemiologically associated either with food or with human central nervous system (CNS) or maternal-neonatal (MN) listeriosis. The latter clones are also most prevalent in patients without immunosuppressive comorbidities. Strikingly, CNS- and MN-associated clones are hypervirulent in a humanized mouse model of listeriosis. By integrating epidemiological data and comparative genomics, we have uncovered multiple new putative virulence factors and demonstrate experimentally the contribution of the first gene cluster mediating L. monocytogenes neural and placental tropisms. This study illustrates the exceptional power in harnessing microbial biodiversity to identify clinically relevant microbial virulence attributes. PMID:26829754

  2. Uncovering Quantum Correlations with Time-Multiplexed Click Detection

    NASA Astrophysics Data System (ADS)

    Sperling, J.; Bohmann, M.; Vogel, W.; Harder, G.; Brecht, B.; Ansari, V.; Silberhorn, C.

    2015-07-01

    We report on the implementation of a time-multiplexed click detection scheme to probe quantum correlations between different spatial optical modes. We demonstrate that such measurement setups can uncover nonclassical correlations in multimode light fields even if the single mode reductions are purely classical. The nonclassical character of correlated photon pairs, generated by a parametric down-conversion, is immediately measurable employing the theory of click counting instead of low-intensity approximations with photoelectric detection models. The analysis is based on second- and higher-order moments, which are directly retrieved from the measured click statistics, for relatively high mean photon numbers. No data postprocessing is required to demonstrate the effects of interest with high significance, despite low efficiencies and experimental imperfections. Our approach shows that such novel detection schemes are a reliable and robust way to characterize quantum-correlated light fields for practical applications in quantum communications.

  3. Approaches to uncovering cancer diagnostic and prognostic molecular signatures

    PubMed Central

    Hong, Shengjun; Huang, Yi; Cao, Yaqiang; Chen, Xingwei; Han, Jing-Dong J

    2014-01-01

    The recent rapid development of high-throughput technology enables the study of molecular signatures for cancer diagnosis and prognosis at multiple levels, from genomic and epigenomic to transcriptomic. These unbiased large-scale scans provide important insights into the detection of cancer-related signatures. In addition to single-layer signatures, such as gene expression and somatic mutations, integrating data from multiple heterogeneous platforms using a systematic approach has been proven to be particularly effective for the identification of classification markers. This approach not only helps to uncover essential driver genes and pathways in the cancer network that are responsible for the mechanisms of cancer development, but will also lead us closer to the ultimate goal of personalized cancer therapy. PMID:27308330

  4. Uncovering cortical MEG responses to listened audiobook stories.

    PubMed

    Koskinen, M; Seppä, M

    2014-10-15

    Naturalistic stimuli, such as normal speech and narratives, are opening up intriguing prospects in neuroscience, especially when merging neuroimaging with machine learning methodology. Here we propose a task-optimized spatial filtering strategy for uncovering individual magnetoencephalographic (MEG) responses to audiobook stories. Ten subjects listened to 1-h-long recording once, as well as to 48 repetitions of a 1-min-long speech passage. Employing response replicability as statistical validity and utilizing unsupervised learning methods, we trained spatial filters that were able to generalize over datasets of an individual. For this blind-signal-separation (BSS) task, we derived a version of multi-set similarity-constrained canonical correlation analysis (SimCCA) that theoretically provides maximal signal-to-noise ratio (SNR) in this setting. Irrespective of significant noise in unaveraged MEG traces, the method successfully uncovered feasible time courses up to ~120 Hz, with the most prominent signals below 20 Hz. Individual trial-to-trial correlations of such time courses reached the level of 0.55 (median 0.33 in the group) at ~0.5 Hz, with considerable variation between subjects. By this filtering, the SNR increased up to 20 times. In comparison, independent component analysis (ICA) or principal component analysis (PCA) did not improve SNR notably. The validity of the extracted brain signals was further assessed by inspecting their associations with the stimulus, as well as by mapping the contributing cortical signal sources. The results indicate that the proposed methodology effectively reduces noise in MEG recordings to that extent that brain responses can be seen to nonrecurring audiobook stories. The study paves the way for applications aiming at accurately modeling the stimulus-response-relationship by tackling the response variability, as well as for real-time monitoring of brain signals of individuals in naturalistic experimental conditions. PMID

  5. Multiple omics uncovers host-gut microbial mutualism during prebiotic fructooligosaccharide supplementation.

    PubMed

    Kato, Tamotsu; Fukuda, Shinji; Fujiwara, Akemi; Suda, Wataru; Hattori, Masahira; Kikuchi, Jun; Ohno, Hiroshi

    2014-10-01

    Fructooligosaccharide (FOS), a prebiotic well known for its health-promoting properties, can improve the human gut ecosystem most likely through changes in its microbial composition. However, the detailed mechanism(s) of action of FOS in the modulation of the gut ecosystem remain(s) obscure. Traditional methods of profiling microbes and metabolites could barely show any significant features due to the existence of large interindividual differences, but our novel microbe-metabolite correlation approach, combined with faecal immunoglobulin A (IgA) measurements, has revealed that the induction of mucosal IgA by FOS supplementation correlated with the presence of specific bacteria. Furthermore, the metabolic dynamics of butyrate, L-phenylalanine, L-lysine and tyramine were positively correlated with that of these bacteria and IgA production, whereas p-cresol was negatively correlated. Taken together, our focused intraindividual analysis with omics approaches is a powerful strategy for uncovering the gut molecular network and could provide a new vista for understanding the human gut ecosystem. PMID:24848698

  6. Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis

    PubMed Central

    Rosenberg, Alan M.; Yeung, Rae S. M.; Morris, Quaid

    2016-01-01

    Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA) patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction). This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples. PMID:27244050

  7. Expanding the power of recombinase-based labeling to uncover cellular diversity.

    PubMed

    Plummer, Nicholas W; Evsyukova, Irina Y; Robertson, Sabrina D; de Marchena, Jacqueline; Tucker, Charles J; Jensen, Patricia

    2015-12-15

    Investigating the developmental, structural and functional complexity of mammalian tissues and organs depends on identifying and gaining experimental access to diverse cell populations. Here, we describe a set of recombinase-responsive fluorescent indicator alleles in mice that significantly extends our ability to uncover cellular diversity by exploiting the intrinsic genetic signatures that uniquely define cell types. Using a recombinase-based intersectional strategy, these new alleles uniquely permit non-invasive labeling of cells defined by the overlap of up to three distinct gene expression domains. In response to different combinations of Cre, Flp and Dre recombinases, they express eGFP and/or tdTomato to allow the visualization of full cellular morphology. Here, we demonstrate the value of these features through a proof-of-principle analysis of the central noradrenergic system. We label previously inaccessible subpopulations of noradrenergic neurons to reveal details of their three-dimensional architecture and axon projection profiles. These new indicator alleles will provide experimental access to cell populations at unprecedented resolution, facilitating analysis of their developmental origin and anatomical, molecular and physiological properties. PMID:26586220

  8. 77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-29

    ... AGENCY 40 CFR Parts 141 and 142 Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public Meeting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of public..., concerning information that may inform the regulatory review of the uncovered finished water...

  9. Using a diode laser to uncover dental implants in second-stage surgery.

    PubMed

    Yeh, Sam; Jain, Kamlesh; Andreana, Sebastiano

    2005-01-01

    A soft tissue diode laser offers an alternative technique for uncovering dental implants. This article presents two cases in which four dental implants were uncovered using a soft tissue laser. This technique provides an efficient and patient-friendly method to perform second-stage implant surgery, safely allowing a faster rehabilitative phase. PMID:16366049

  10. Invisible Milky Way Satellite Uncovered With Help from NERSC

    SciTech Connect

    2011-01-01

    Astronomers predict that large spiral galaxies, like our Milky Way, have hundreds of satellite galaxies orbiting around them. While a few satellites are visible, like the Magellanic Clouds, many other galaxies are too dim to see. Scientists suspect that these faint satellite galaxies are primarily comprised of mysterious "dark matter," which makes up 85 percent of all matter in the universe and so far remains undetected. Using supercomputers at the National Energy Research Scientific Computing Center (NERSC), Sukanya Chakrabarti, an assistant professor of physics at Florida Atlantic University, developed a mathematical method to uncover these "dark" satellites. When she applied this method to our own Milky Way galaxy, Chakrabarti discovered a faint satellite might be lurking on the opposite side of the galaxy from Earth, approximately 300,000 light-years from the galactic center. According to Chakrabarti, the dark satellite galaxies create disturbances in the cold atomic hydrogen gas at the edges of the spiral galaxy's disk, and these perturbations reveal the mass, distance and location of the satellite. With the help of NERSC systems, she successfully validated her method by analyzing the radio observations of the Whirlpool Galaxy, which has a visible satellite one-third of its size, and NGC 1512, which has a satellite one-hundredth its size. Her calculations correctly predicted the mass and location of both of the known satellite galaxies. http://www.lbl.gov/cs/Archive/news031411.html

  11. Uncovering Aberrant Mutant PKA Function with Flow Cytometric FRET.

    PubMed

    Lee, Shin-Rong; Sang, Lingjie; Yue, David T

    2016-03-29

    Biology has been revolutionized by tools that allow the detection and characterization of protein-protein interactions (PPIs). Förster resonance energy transfer (FRET)-based methods have become particularly attractive as they allow quantitative studies of PPIs within the convenient and relevant context of living cells. We describe here an approach that allows the rapid construction of live-cell FRET-based binding curves using a commercially available flow cytometer. We illustrate a simple method for absolutely calibrating the cytometer, validating our binding assay against the gold standard isothermal calorimetry (ITC), and using flow cytometric FRET to uncover the structural and functional effects of the Cushing-syndrome-causing mutation (L206R) on PKA's catalytic subunit. We discover that this mutation not only differentially affects PKAcat's binding to its multiple partners but also impacts its rate of catalysis. These findings improve our mechanistic understanding of this disease-causing mutation, while illustrating the simplicity, general applicability, and power of flow cytometric FRET. PMID:26997269

  12. Uncovering patterns of technology use in consumer health informatics

    PubMed Central

    Hung, Man; Conrad, Jillian; Hon, Shirley D.; Cheng, Christine; Franklin, Jeremy D.; Tang, Philip

    2014-01-01

    Internet usage and accessibility has grown at a staggering rate, influencing technology use for healthcare purposes. The amount of health information technology (Health IT) available through the Internet is immeasurable and growing daily. Health IT is now seen as a fundamental aspect of patient care as it stimulates patient engagement and encourages personal health management. It is increasingly important to understand consumer health IT patterns including who is using specific technologies, how technologies are accessed, factors associated with use, and perceived benefits. To fully uncover consumer patterns it is imperative to recognize common barriers and which groups they disproportionately affect. Finally, exploring future demand and predictions will expose significant opportunities for health IT. The most frequently used health information technologies by consumers are gathering information online, mobile health (mHealth) technologies, and personal health records (PHRs). Gathering health information online is the favored pathway for healthcare consumers as it is used by more consumers and more frequently than any other technology. In regard to mHealth technologies, minority Americans, compared with White Americans utilize social media, mobile Internet, and mobile applications more frequently. Consumers believe PHRs are the most beneficial health IT. PHR usage is increasing rapidly due to PHR integration with provider health systems and health insurance plans. Key issues that have to be explicitly addressed in health IT are privacy and security concerns, health literacy, unawareness, and usability. Privacy and security concerns are rated the number one reason for the slow rate of health IT adoption. PMID:24904713

  13. Uncovering space-independent communities in spatial networks

    PubMed Central

    Expert, Paul; Evans, Tim S.; Blondel, Vincent D.; Lambiotte, Renaud

    2011-01-01

    Many complex systems are organized in the form of a network embedded in space. Important examples include the physical Internet infrastucture, road networks, flight connections, brain functional networks, and social networks. The effect of space on network topology has recently come under the spotlight because of the emergence of pervasive technologies based on geolocalization, which constantly fill databases with people’s movements and thus reveal their trajectories and spatial behavior. Extracting patterns and regularities from the resulting massive amount of human mobility data requires the development of appropriate tools for uncovering information in spatially embedded networks. In contrast with most works that tend to apply standard network metrics to any type of network, we argue in this paper for a careful treatment of the constraints imposed by space on network topology. In particular, we focus on the problem of community detection and propose a modularity function adapted to spatial networks. We show that it is possible to factor out the effect of space in order to reveal more clearly hidden structural similarities between the nodes. Methods are tested on a large mobile phone network and computer-generated benchmarks where the effect of space has been incorporated. PMID:21518910

  14. Uncovering the Geometry of Barrierless Reactions Using Lagrangian Descriptors.

    PubMed

    Junginger, Andrej; Hernandez, Rigoberto

    2016-03-01

    Transition-state theories describing barrierless chemical reactions, or more general activated problems, are often hampered by the lack of a saddle around which the dividing surface can be constructed. For example, the time-dependent transition-state trajectory uncovering the nonrecrossing dividing surface in thermal reactions in the framework of the Langevin equation has relied on perturbative approaches in the vicinity of the saddle. We recently obtained an alternative approach using Lagrangian descriptors to construct time-dependent and recrossing-free dividing surfaces. This is a nonperturbative approach making no reference to a putative saddle. Here we show how the Lagrangian descriptor can be used to obtain the transition-state geometry of a dissipated and thermalized reaction across barrierless potentials. We illustrate the method in the case of a 1D Brownian motion for both barrierless and step potentials; however, the method is not restricted and can be directly applied to different kinds of potentials and higher dimensional systems. PMID:26524392

  15. Thermoinhibition uncovers a role for strigolactones in Arabidopsis seed germination.

    PubMed

    Toh, Shigeo; Kamiya, Yuji; Kawakami, Naoto; Nambara, Eiji; McCourt, Peter; Tsuchiya, Yuichiro

    2012-01-01

    Strigolactones are host factors that stimulate seed germination of parasitic plant species such as Striga and Orobanche. This hormone is also important in shoot branching architecture and photomorphogenic development. Strigolactone biosynthetic and signaling mutants in model systems, unlike parasitic plants, only show seed germination phenotypes under limited growth condition. To understand the roles of strigolactones in seed germination, it is necessary to develop a tractable experimental system using model plants such as Arabidopsis. Here, we report that thermoinhibition, which involves exposing seeds to high temperatures, uncovers a clear role for strigolactones in promoting Arabidopsis seed germination. Both strigolactone biosynthetic and signaling mutants showed increased sensitivity to seed thermoinhibition. The synthetic strigolactone GR24 rescued germination of thermoinbibited biosynthetic mutant seeds but not a signaling mutant. Hormone analysis revealed that strigolactones alleviate thermoinhibition by modulating levels of the two plant hormones, GA and ABA. We also showed that GR24 was able to counteract secondary dormancy in Arabidopsis ecotype Columbia (Col) and Cape Verde island (Cvi). Systematic hormone analysis of germinating Striga helmonthica seeds suggested a common mechanism between the parasitic and non-parasitic seeds with respect to how hormones regulate germination. Thus, our simple assay system using Arabidopsis thermoinhibition allows comparisons to determine similarities and differences between parasitic plants and model experimental systems for the use of strigolactones. PMID:22173099

  16. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms

    PubMed Central

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-01-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)—a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  17. Uncovering the mechanism(s) of deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Gang, Li; Chao, Yu; Ling, Lin; C-Y Lu, Stephen

    2005-01-01

    Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

  18. Uncovering aberrant mutant PKA function with flow cytometric FRET

    PubMed Central

    Lee, Shin-Rong; Sang, Lingjie; Yue, David T.

    2016-01-01

    SUMMARY Biology has been revolutionized by tools that allow the detection and characterization of protein-protein interactions (PPI). Förster resonance energy transfer (FRET)-based methods have become particularly attractive as they allow quantitative studies of PPIs within the convenient and relevant context of living cells. We describe here an approach that allows the rapid construction of live-cell, FRET-based binding curves using a commercially-available flow cytometer. We illustrate a simple method for absolutely calibrating the cytometer, validate our binding assay against the gold-standard isothermal calorimetry (ITC), and use flow cytometric FRET to uncover the structural and functional effects of the Cushing syndrome-causing mutation (L206R) on PKA’s catalytic subunit. We discover that this mutation not only differentially affects PKAcat’s binding to its multiple partners, but also impacts its rate of catalysis. These findings improve our mechanistic understanding of this disease-causing mutation, while illustrating the simplicity, general applicability and power of flow cytometric FRET. PMID:26997269

  19. Uncovering Cryptic Parasitoid Diversity in Horismenus (Chalcidoidea, Eulophidae)

    PubMed Central

    Hansson, Christer; Alvarez, Nadir; Benrey, Betty

    2015-01-01

    Horismenus parasitoids are an abundant and understudied group of eulophid wasps found mainly in the New World. Recent surveys based on morphological analyses in Costa Rica have quadrupled the number of named taxa, with more than 400 species described so far. This recent revision suggests that there is still a vast number of unknown species to be identified. As Horismenus wasps have been widely described as parasitoids of insect pests associated with crop plants, it is of high importance to properly establish the extant diversity of the genus, in order to provide biological control practitioners with an exhaustive catalog of putative control agents. In this study, we first collected Horismenus wasps from wild Phaseolus bean seeds in Central Mexico and Arizona to assess the genetic relatedness of three morphologically distinct species with overlapping host and geographical ranges. Sequence data from two nuclear and two mitochondrial gene regions uncovered three cryptic species within each of the three focal species (i.e., H. missouriensis, H. depressus and H. butcheri). The monophyly of each cryptic group is statistically supported (except in two of them represented by one single tip in which monophyly cannot be tested). The phylogenetic reconstruction is discussed with respect to differences between gene regions as well as likely reasons for the differences in variability between species. PMID:26352700

  20. Charting the Vasculome: Uncovering the Principles of Vascular Organization

    NASA Astrophysics Data System (ADS)

    Oppenheim, Jacob; Magnasco, Marcelo

    2014-03-01

    The efficient distribution of resources in any system requires a carefully designed architecture that is both space filling and efficient. While the principles of such networks are beginning to be uncovered in plants, they remain poorly elucidated in the case of higher animals. We have developed a high-throughput, easily implemented method of mapping vascular networks in mammalian tissue. By combining high resolution, rapid fluorescence blockface imaging with serial sectioning, we are able to map the vasculature of the rat liver at a resolution of 10 microns, revealing the structure above the level of the capillaries, constituting the largest vascular dataset yet assembled. We have developed algorithms for the efficient three-dimensional reconstruction from two-dimensional images, allowing skeletonization and investigation of its geometry and topology. We are able to calculate the scaling properties of these networks as well as the frequency of loops at each level. Using sophisticated topological tools, we are beginning to elucidate the principles of their organization. Ultimately, a greater understanding of vasculature is necessary for the success of efforts in synthetic and regenerative biology along with the better understanding of the growth and development of cancers.

  1. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms.

    PubMed

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-09-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)-a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  2. Uncovering steroidopathy in women with autism: a latent class analysis

    PubMed Central

    2014-01-01

    Background Prenatal exposure to increased androgens has been implicated in both polycystic ovary syndrome (PCOS) and autism spectrum conditions (ASC), suggesting that PCOS may be increased among women with ASC. One study suggested elevated steroidopathic symptoms (‘steroidopathy’) in women with ASC. As the symptoms are not independent, we conducted a latent class analysis (LCA). The objectives of the current study are: (1) to test if these findings replicate in a larger sample; and (2) to use LCA to uncover affected clusters of women with ASC. Methods We tested two groups of women, screened using the Autism Spectrum Quotient - Group 1: n = 415 women with ASC (mean age 36.39 ± 11.98 years); and Group 2: n = 415 controls (mean age 39.96 ± 11.92 years). All participants completed the Testosterone-related Medical Questionnaire online. A multiple-group LCA was used to identify differences in latent class structure between women with ASC and controls. Results There were significant differences in frequency of steroid-related conditions and symptoms between women with ASC and controls. A two-class semi-constrained model best fit the data. Based on response patterns, we identified the classes as ‘Typical’ and ‘Steroidopathic’. The prevalence of the ‘Steroidopathic’ class was significantly increased within the ASC group (ΔG2 = 15, df =1, P = 0.0001). In particular, we confirmed higher frequencies of epilepsy, amenorrhea, dysmenorrhea, severe acne, gender dysphoria, and transsexualism, and differences in sexual preference in women with ASC. Conclusions Women with ASC are at increased risk for symptoms and conditions linked to steroids. LCA revealed this steroidopathy despite the apparent underdiagnosis of PCOS. PMID:24717046

  3. Uncovering Multiple Populations in Globular Clusters with Washington Photometry

    NASA Astrophysics Data System (ADS)

    Geisler, Douglas; Cummings, Jeff; Villanova, Sandro; Carraro, Giovanni

    2015-01-01

    Globular Clusters (GCs), long considered as ideal Simple Stellar Populations, are now known to harbor a wide variety of chemical inhomogeneities. Multiple populations (MP) are being found in a growing number of Galactic globular clusters (GCs) via both photometric and spectroscopic techniques. Indeed, it has been suggested that a GC is an object that possesses MP. A definitive investigation of MP in GCs will undoubtedly provide a profound improvement in our understanding of their formation and evolution.However, most studies employ either high resolution VLT spectroscopy, HST photometry or inefficient filters from the ground. A ground-based photometric system which is both efficient and effective would be especially excellent for uncovering MP. We demonstrate that the Washington system meets these goals. The Washington C filter, in addition to being specifically designed for the purpose of detecting MPs, is both much broader and redder than competing UV filters, making it far more efficient at detecting MPs and much less sensitive to reddening and extinction.Our analysis of the well-studied GC NGC 1851 shows indeed that the C filter is both very efficient and effective at detecting its previously discovered MPs in the RGB and SGB, using relatively little telescope time on only a 1-meter telescope. Remarkably, we have also detected an intrinsically broad MS best characterized by two distinct but heavily overlapping populations that cannot be explained by binaries, field stars, or photometric errors. Detailed analysis shows that the MS distribution is in very good agreement with that seen on the RGB. This is the first time MPs in a MS have been discovered from the ground, and just as strikingly, using only a 1-meter telescope. The Washington system thus proves to be a very powerful tool for investigating MPs, and holds particular promise for extragalactic objects where photons are limited.

  4. Profil'-1 measuring complex

    SciTech Connect

    Andrianov, V.R.; Petrov, A.P.

    1985-04-01

    This paper describes the Profil'-1 hydroacoustic measuring complex. The complex provides documentary information on the bottom profile of reservoirs, the configuration and geometric dimensions of underwater trenches, the spatial position of pipes in uncovered or washedout trenches, the thickness of a layer covering underwater pipes, etc. The complex can also be used to solve other industrial problems such as hydraulic exploration and searching for sunken objects. The Profil'-1 complex is designed for use on board small craft under field conditions with periodic transportation from storage bases to the operating location and back. The complex uses an echo-pulse method for determining the distance and coordinates of objects with the aid of an ultrasonic transceiver in an aqueous medium. Structurally, the complex consists of four main units: a BA-1 vertical sounding antenna unit; a BAS-1 antenna scanning unit; a BFOS-1 signal shaping and processing unit, and a BR-1 recording unit. Use of the complex in pipeline construction and the oil and gas industry will provide a considerable economic gain by reducing the number of diver inspections of underwater pipelines.

  5. Management of Complicated Aortic Aneurysms Using Multiple Overlapping Uncovered Stents

    PubMed Central

    Zhang, Yongxue; Teng, Zhongzhao; Lu, Qingsheng; Zhao, Zhiqing; Bao, Junmin; Feng, Xiang; Feng, Rui; Chen, Zengsheng; Huang, Yuan; Sadat, Umar; Gillard, Jonathan H; Jing, Zaiping

    2014-01-01

    Abstract This study sought to report the mid-term outcome of a modified flow-diverting strategy in the treatment of complicated aortic aneurysms of different morphology. Historical data suggested aortic aneurysm expansion and rupture after endovascular treatment with current commercial flow-diverters, indicating the essentiality of further investigation of this technique prior to its large-scale clinical application. An alternative flow-diverting strategy using layer-by-layer assembled multiple overlapping uncovered stents was employed in this study. The treatment outcome in aneurysms of different morphology (saccular, fusiform, and dissecting) was assessed during a mid-term follow-up period. Of 42 patients enrolled in this study (30 male, mean age: 63.3 years), technical success was achieved in 40 cases. During an average follow-up period of 20.9 months, mean aneurysm diameter shrunk from 53.4 ± 13.6 mm to 48.8 ± 13.9 mm (P < 0.001), while stent-induced sac thrombosis ratio increased significantly (18.1 ± 14.9% to 93.6 ± 9.5%, P < 0.001). The majority of side branches (74/76 major visceral branches, 237/244 minor segmental arteries), covered by 3.3 stents on average, maintained their patency after stenting. Saccular aneurysms manifested the highest thrombus deposition speed (18/20 were totally thrombosed within 12 months) and most significant shrinkage (51.4 ± 13.3 mm pre-operatively vs 43.5 ± 10.2 mm during follow-up, P < 0.001) compared with fusiform and dissecting aneurysms. This modified flow-diverting strategy could be a feasible alternative in the management of complicated aortic aneurysms where vital branches need to be preserved. The treatment outcome may depend on the aneurysm type. Further studies with larger patient cohort and longer follow-up are required to substantiate these results. PMID:25501077

  6. Uncovering oral Neisseria tropism and persistence using metagenomic sequencing.

    PubMed

    Donati, Claudio; Zolfo, Moreno; Albanese, Davide; Tin Truong, Duy; Asnicar, Francesco; Iebba, Valerio; Cavalieri, Duccio; Jousson, Olivier; De Filippo, Carlotta; Huttenhower, Curtis; Segata, Nicola

    2016-01-01

    Microbial epidemiology and population genomics have previously been carried out near-exclusively for organisms grown in vitro. Metagenomics helps to overcome this limitation, but it is still challenging to achieve strain-level characterization of microorganisms from culture-independent data with sufficient resolution for epidemiological modelling. Here, we have developed multiple complementary approaches that can be combined to profile and track individual microbial strains. To specifically profile highly recombinant neisseriae from oral metagenomes, we integrated four metagenomic analysis techniques: single nucleotide polymorphisms in the clade's core genome, DNA uptake sequence signatures, metagenomic multilocus sequence typing and strain-specific marker genes. We applied these tools to 520 oral metagenomes from the Human Microbiome Project, finding evidence of site tropism and temporal intra-subject strain retention. Although the opportunistic pathogen Neisseria meningitidis is enriched for colonization in the throat, N. flavescens and N. subflava populate the tongue dorsum, and N. sicca, N. mucosa and N. elongata the gingival plaque. The buccal mucosa appeared as an intermediate ecological niche between the plaque and the tongue. The resulting approaches to metagenomic strain profiling are generalizable and can be extended to other organisms and microbiomes across environments. PMID:27572971

  7. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... water storage facilities. 141.714 Section 141.714 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for Cryptosporidium Treatment Technique Requirements § 141.714 Requirements for uncovered...

  8. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... water storage facilities. 141.714 Section 141.714 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for Cryptosporidium Treatment Technique Requirements § 141.714 Requirements for uncovered...

  9. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... water storage facilities. 141.714 Section 141.714 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced... water storage facilities. (a) Systems using uncovered finished water storage facilities must comply...

  10. ChiNet uncovers rewired rewired transcription subnetworks in tolerant yeast for advanced biofuels conversion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Conventional differential gene expression analysis is insufficient to dissect altered gene interactions for adapted transcription regulatory networks that impact downstream molecular responses. Here we present comparative chi-square network analysis (ChiNet), a computational method, to uncover rewir...

  11. Tumour-specific proline vulnerability uncovered by differential ribosome codon reading.

    PubMed

    Loayza-Puch, Fabricio; Rooijers, Koos; Buil, Levi C M; Zijlstra, Jelle; Oude Vrielink, Joachim F; Lopes, Rui; Ugalde, Alejandro Pineiro; van Breugel, Pieter; Hofland, Ingrid; Wesseling, Jelle; van Tellingen, Olaf; Bex, Axel; Agami, Reuven

    2016-02-25

    Tumour growth and metabolic adaptation may restrict the availability of certain amino acids for protein synthesis. It has recently been shown that certain types of cancer cells depend on glycine, glutamine, leucine and serine metabolism to proliferate and survive. In addition, successful therapies using L-asparaginase-induced asparagine deprivation have been developed for acute lymphoblastic leukaemia. However, a tailored detection system for measuring restrictive amino acids in each tumour is currently not available. Here we harness ribosome profiling for sensing restrictive amino acids, and develop diricore, a procedure for differential ribosome measurements of codon reading. We first demonstrate the functionality and constraints of diricore using metabolic inhibitors and nutrient deprivation assays. Notably, treatment with L-asparaginase elicited both specific diricore signals at asparagine codons and high levels of asparagine synthetase (ASNS). We then applied diricore to kidney cancer and discover signals indicating restrictive proline. As for asparagine, this observation was linked to high levels of PYCR1, a key enzyme in proline production, suggesting a compensatory mechanism allowing tumour expansion. Indeed, PYCR1 is induced by shortage of proline precursors, and its suppression attenuated kidney cancer cell proliferation when proline was limiting. High PYCR1 is frequently observed in invasive breast carcinoma. In an in vivo model system of this tumour, we also uncover signals indicating restrictive proline. We further show that CRISPR-mediated knockout of PYCR1 impedes tumorigenic growth in this system. Thus, diricore has the potential to reveal unknown amino acid deficiencies, vulnerabilities that can be used to target key metabolic pathways for cancer treatment. PMID:26878238

  12. Uncovering phenotypes of poor-pitch singing: the Sung Performance Battery (SPB).

    PubMed

    Berkowska, Magdalena; Dalla Bella, Simone

    2013-01-01

    Singing is as natural as speaking for humans. Increasing evidence shows that the layman can carry a tune (e.g., when asked to sing a well-known song or to imitate single pitches, intervals and short melodies). Yet, important individual differences exist in the general population with regard to singing proficiency. Some individuals are particularly inaccurate or imprecise in producing or imitating pitch information (poor-pitch singers), thus showing a variety of singing phenotypes. Unfortunately, so far there is not a standard set of tasks for assessing singing proficiency in the general population, allowing to uncover and characterize individual profiles of poor-pitch singing. Different tasks and analysis methods are typically used in various experiments, making the comparison of the results across studies arduous. To fill this gap we propose here a new tool for assessing singing proficiency (the Sung Performance Battery, SPB). The SPB starts from the assessment of participants' vocal range followed by five tasks: (1) single-pitch matching, (2) pitch-interval matching, (3) novel-melody matching, (4) singing from memory of familiar melodies (with lyrics and on a syllable), and (5) singing of familiar melodies (with lyrics and on a syllable) at a slow tempo indicated by a metronome. Data analysis via acoustical methods provides objective measures of pitch accuracy and precision in terms of absolute and relative pitch. The SPB has been tested in a group of 50 occasional singers. The results indicate that the battery is useful for characterizing proficient singing and for detecting cases of inaccurate and/or imprecise singing. PMID:24151475

  13. Uncovering phenotypes of poor-pitch singing: the Sung Performance Battery (SPB)

    PubMed Central

    Berkowska, Magdalena; Dalla Bella, Simone

    2013-01-01

    Singing is as natural as speaking for humans. Increasing evidence shows that the layman can carry a tune (e.g., when asked to sing a well-known song or to imitate single pitches, intervals and short melodies). Yet, important individual differences exist in the general population with regard to singing proficiency. Some individuals are particularly inaccurate or imprecise in producing or imitating pitch information (poor-pitch singers), thus showing a variety of singing phenotypes. Unfortunately, so far there is not a standard set of tasks for assessing singing proficiency in the general population, allowing to uncover and characterize individual profiles of poor-pitch singing. Different tasks and analysis methods are typically used in various experiments, making the comparison of the results across studies arduous. To fill this gap we propose here a new tool for assessing singing proficiency (the Sung Performance Battery, SPB). The SPB starts from the assessment of participants' vocal range followed by five tasks: (1) single-pitch matching, (2) pitch-interval matching, (3) novel-melody matching, (4) singing from memory of familiar melodies (with lyrics and on a syllable), and (5) singing of familiar melodies (with lyrics and on a syllable) at a slow tempo indicated by a metronome. Data analysis via acoustical methods provides objective measures of pitch accuracy and precision in terms of absolute and relative pitch. The SPB has been tested in a group of 50 occasional singers. The results indicate that the battery is useful for characterizing proficient singing and for detecting cases of inaccurate and/or imprecise singing. PMID:24151475

  14. The polychaete, Perinereis nuntia ESTs and its use to uncover potential biomarker genes for molecular ecotoxicological studies.

    PubMed

    Rhee, Jae-Sung; Won, Eun-Ji; Kim, Ryeo-Ok; Choi, Beom-Soon; Choi, Ik-Young; Park, Gyung Soo; Shin, Kyung-Hoon; Lee, Young-Mi; Lee, Jae-Seong

    2012-01-01

    The polychaete, Perinereis nuntia, has been used as an indicator species to assess the environmental condition of benthic communities in coastal marine environments. Recently, high-throughput sequencing technology has been proven to be a useful method for analyzing expressed sequence tags (ESTs) in non-model species. Thus, we have obtained extensive cDNA information by the pyrosequencing method, to utilize the polychaete species as a test organism for sediment quality monitoring studies. From the total RNA of P. nuntia, cDNA was reversely synthesized and randomly sequenced using a GS-FLX sequencer. In the assembly stage 1, 40,379 transcripts (13,666 contigs and 26,713 singletons) were acquired and showed 47% hitting rate compared with the GenBank non-redundant (NR) amino acid sequence database using BLASTX. After the stage-2 assembly, 21,657 transcripts were identified and showed 28% hitting rate. Finally, we obtained 6 064 unigenes that corresponded to the GenBank NR amino acid sequence database using BLASTX. Of the transcripts obtained in this species, we found a number of stress- and cell defense-related genes (e.g. heat shock protein family, antioxidant-related genes, cytochrome P450 genes) that are potentially useful for sediment monitoring at the molecular level, indicating that the pyrosequencing method is an effective approach to uncover gene families of potential biomarker genes simultaneously, and thus make transcriptomic studies possible. To confirm the usefulness of those potential biomarker genes, we analyzed the comparative profiling of P. nuntia mRNA transcripts between the samples collected from the polychaete aquaculture farm and the southern coast field of South Korea. In this paper, we summarize the expressed cDNA information of P. nuntia and discussed its potential use in environmental genomics and ecotoxicological studies for uncovering the potential molecular mechanisms of environmental stresses and chemical toxicity to the indicator species

  15. Uncovering the Role of the Methylome in Dementia and Neurodegeneration.

    PubMed

    Klein, Hans-Ulrich; De Jager, Philip L

    2016-08-01

    Our understanding of the epigenome has advanced dramatically over the past decade, particularly in terms of DNA methylation, a modification found throughout the genome. Studies of the brain and neurons have outlined an increasingly complex architecture involving not just CG dinucleotide methylation but also methylation of other dinucleotides, and modifications of methylated bases such as 5-hydroxymethylcytosine. Different modifications may play an important role in brain development, function and decline; recent descriptions of the effects of aging and neurodegenerative processes such as Alzheimer disease on methylation profiles have ushered in an era of DNA methylome-wide association studies. Rapidly improving technologies and study designs are returning robust results, and investigations of the human brain's epigenome are increasingly feasible, complementing insights gained from genetic studies. PMID:27423266

  16. Endoscopic removal of a spontaneously fractured biliary uncovered self-expandable metal stent.

    PubMed

    Kawakubo, Kazumichi; Isayama, Hiroyuki; Tsujino, Takeshi; Nakai, Yousuke; Sasahira, Naoki; Kogure, Hirofumi; Hamada, Tsuyoshi; Nagano, Rie; Miyabayashi, Kouji; Yamamoto, Keisuke; Mohri, Dai; Sasaki, Takashi; Ito, Yukiko; Yamamoto, Natsuyo; Hirano, Kenji; Tada, Minoru; Koike, Kazuhiko

    2012-05-01

    Self-expandable metal stents (SEMS) are widely used for the palliative treatment of unresectable malignant biliary obstruction. However, the long-term durability of SEMSs in biliary strictures is not clear. We describe a case of endoscopic removal of spontaneously fractured uncovered biliary SEMS. A 59-year-old woman presented to our institution with a 1-year history of recurrent cholangitis. Her medical history included a proctectomy for rectal cancer and right hemihepatectomy for liver metastasis 10 years earlier. Five years after these operations, she developed a benign hilar stricture and had an uncovered SEMS placed in another hospital. Endoscopic retrograde cholangiopancreatography demonstrated that the SEMS was torn in half and the distal part of the stent was floating in the dilated common bile duct. The papillary orifice was dilated by endoscopic papillary large balloon dilation (EPLBD) using a 15-mm wire-guided balloon catheter. Subsequently, we inserted biopsy forceps into the bile duct and grasped the distal end of the broken SEMS under fluoroscopy. We successfully removed the fragment of the SEMS from the bile duct, along with the endoscope. The patient was discharged without complications. Placement of an uncovered biliary SEMS is not the preferred treatment for benign biliary strictures. Spontaneous fracture of an uncovered biliary SEMS is an extremely rare complication. We should be aware that stent fracture can occur when placing uncovered biliary SEMSs in patients with a long life expectancy. EPLBD is very useful for retrieving the fractured fragment of SEMS. PMID:22507093

  17. Foraminiferal Mn/Ca: Uncovering its Paleoproxy Potential

    NASA Astrophysics Data System (ADS)

    de Baere, B. J.; Klinkhammer, G. P.; Mix, A. C.

    2007-12-01

    College of Oceanic and Atmospheric Sciences, Oregon State University, Ocean Admin Bldg 104, Corvallis, OR 97331, United States of America. The flow-through time-resolved analysis (FT-TRA) technique for foraminiferal proxy work allows for the quantification of pristine biogenic elemental data, such as Mn/Ca, whilst disregarding overgrowth-induced signals. We used this state-of-the-art technique to carry out a core-top survey of the Mn/Ca ratios for surface dwelling foraminifera from across the world's oceans. This study revealed an oceanographically consistent pattern featuring order of magnitude variability, exactly what one would expect from the distribution of dissolved Mn in the mixed layer. Foraminifera at southern hemisphere sites have the lowest Mn/Ca ratios (~ 0.01) while those from the northern hemisphere are distinctly higher (~ 0.2). This pattern is strikingly similar in distribution and scale to variations in the atmospheric iron flux suggesting that foraminiferal Mn/Ca has potential as a paleoproxy for terrestrial input and productivity. The dust-dominated pattern at the surface together with the unique profile of Mn in the water column makes the Mn/Ca ratio of foraminiferal calcite a powerful new paleoproxy.

  18. New incompatibilities uncovered using the Promega DNA IQ™ chemistry.

    PubMed

    Laurin, Nancy; Célestin, Florence; Clark, Meagan; Wilkinson, Della; Yamashita, Brian; Frégeau, Chantal

    2015-12-01

    Over the years, the Promega DNA IQ™ System was proven an effective technology for the production of clean DNA from a wide variety of casework specimens. The capture of DNA using the DNA IQ™ paramagnetic beads, however, was shown to be affected by a few specific chemicals that could be present on exhibits submitted to the laboratory. In this study, various blood and latent fingerprint enhancement reagents/methods, marker pens and adhesive tapes, applied at the crime scene or in the forensic laboratory on casework exhibits or used to collect biological material, were tested for their compatibility with the DNA IQ™ technology. Although no impact on DNA recovery was observed for most reagents, the MAGNA™ Jet Black fingerprint powder and three 3M Scotch(®) adhesive tapes were shown to severely or completely inhibit DNA binding onto the DNA IQ™ beads. The effect of MAGNA™ Jet Black on DNA recovery could be counteracted by separating the magnetic powder from the lysates by centrifugation or filtration, prior to DNA extraction. High quality STR profiles were obtained from samples subjected to MAGNA™ Jet Black suggesting it does not impact DNA integrity. PMID:26295931

  19. Towards uncovering the roles of switchgrass peroxidases in plant processes

    PubMed Central

    Saathoff, Aaron J.; Donze, Teresa; Palmer, Nathan A.; Bradshaw, Jeff; Heng-Moss, Tiffany; Twigg, Paul; Tobias, Christian M.; Lagrimini, Mark; Sarath, Gautam

    2013-01-01

    Herbaceous perennial plants selected as potential biofuel feedstocks had been understudied at the genomic and functional genomic levels. Recent investments, primarily by the U.S. Department of Energy, have led to the development of a number of molecular resources for bioenergy grasses, such as the partially annotated genome for switchgrass (Panicum virgatum L.), and some related diploid species. In its current version, the switchgrass genome contains 65,878 gene models arising from the A and B genomes of this tetraploid grass. The availability of these gene sequences provides a framework to exploit transcriptomic data obtained from next-generation sequencing platforms to address questions of biological importance. One such question pertains to discovery of genes and proteins important for biotic and abiotic stress responses, and how these components might affect biomass quality and stress response in plants engineered for a specific end purpose. It can be expected that production of switchgrass on marginal lands will expose plants to diverse stresses, including herbivory by insects. Class III plant peroxidases have been implicated in many developmental responses such as lignification and in the adaptive responses of plants to insect feeding. Here, we have analyzed the class III peroxidases encoded by the switchgrass genome, and have mined available transcriptomic datasets to develop a first understanding of the expression profiles of the class III peroxidases in different plant tissues. Lastly, we have identified switchgrass peroxidases that appear to be orthologs of enzymes shown to play key roles in lignification and plant defense responses to hemipterans. PMID:23802005

  20. Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity

    PubMed Central

    Alsamarah, Abdelaziz; LaCuran, Alecander E.; Oelschlaeger, Peter; Hao, Jijun; Luo, Yun

    2015-01-01

    Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. PMID:26133550

  1. Differential SAGE analysis in Arabidopsis uncovers increased transcriptome complexity in response to low temperature

    PubMed Central

    Robinson, Stephen J; Parkin, Isobel AP

    2008-01-01

    Background Abiotic stress, including low temperature, limits the productivity and geographical distribution of plants, which has led to significant interest in understanding the complex processes that allow plants to adapt to such stresses. The wide range of physiological, biochemical and molecular changes that occur in plants exposed to low temperature require a robust global approach to studying the response. We have employed Serial Analysis of Gene Expression (SAGE) to uncover changes in the transcriptome of Arabidopsis thaliana over a time course of low temperature stress. Results Five SAGE libraries were generated from A. thaliana leaf tissue collected at time points ranging from 30 minutes to one week of low temperature treatment (4°C). Over 240,000 high quality SAGE tags, corresponding to 16,629 annotated genes, provided a comprehensive survey of changes in the transcriptome in response to low temperature, from perception of the stress to acquisition of freezing tolerance. Interpretation of these data was facilitated by representing the SAGE data by gene identifier, allowing more robust statistical analysis, cross-platform comparisons and the identification of genes sharing common expression profiles. Simultaneous statistical calculations across all five libraries identified 920 low temperature responsive genes, only 24% of which overlapped with previous global expression analysis performed using microarrays, although similar functional categories were affected. Clustering of the differentially regulated genes facilitated the identification of novel loci correlated with the development of freezing tolerance. Analysis of their promoter sequences revealed subsets of genes that were independent of CBF and ABA regulation and could provide a mechanism for elucidating complementary signalling pathways. The SAGE data emphasised the complexity of the plant response, with alternate pre-mRNA processing events increasing at low temperatures and antisense transcription

  2. A Phenomenological Approach to Uncovering the Essence of Grieving Experiences of Undergraduates

    ERIC Educational Resources Information Center

    Bergene, Lisa Beth

    2013-01-01

    Past studies have suggested that during their time on campus, as many as half of all undergraduates will experience the death of a loved one (Balk, 2001; Balk, Walker, & Baker, 2010; Holland & Neimeyer, 2010). The purpose of this study was to use a phenomenological method to uncover a thick, rich description of the lived experience of…

  3. Cross-Species Network Analysis Uncovers Conserved Nitrogen-Regulated Network Modules in Rice.

    PubMed

    Obertello, Mariana; Shrivastava, Stuti; Katari, Manpreet S; Coruzzi, Gloria M

    2015-08-01

    In this study, we used a cross-species network approach to uncover nitrogen (N)-regulated network modules conserved across a model and a crop species. By translating gene network knowledge from the data-rich model Arabidopsis (Arabidopsis thaliana) to a crop, rice (Oryza sativa), we identified evolutionarily conserved N-regulatory modules as targets for translational studies to improve N use efficiency in transgenic plants. To uncover such conserved N-regulatory network modules, we first generated an N-regulatory network based solely on rice transcriptome and gene interaction data. Next, we enhanced the network knowledge in the rice N-regulatory network using transcriptome and gene interaction data from Arabidopsis and new data from Arabidopsis and rice plants exposed to the same N treatment conditions. This cross-species network analysis uncovered a set of N-regulated transcription factors (TFs) predicted to target the same genes and network modules in both species. Supernode analysis of the TFs and their targets in these conserved network modules uncovered genes directly related to N use (e.g. N assimilation) and to other shared biological processes indirectly related to N. This cross-species network approach was validated with members of two TF families in the supernode network, BASIC-LEUCINE ZIPPER TRANSCRIPTION FACTOR1-TGA and HYPERSENSITIVITY TO LOW PI-ELICITED PRIMARY ROOT SHORTENING1 (HRS1)/HRS1 Homolog family, which have recently been experimentally validated to mediate the N response in Arabidopsis. PMID:26045464

  4. Uncovering One Trilingual Child's Multi-Literacies Development across Informal and Formal Learning Contexts

    ERIC Educational Resources Information Center

    Kim, Mi Song

    2016-01-01

    Due to globalisation and rapid technological change, today's educators need to help students develop multi-literacy competencies to enable them to function successfully in our culturally and linguistically diverse (CLD) and increasingly connected global and digital society. A qualitative, longitudinal case study attempted to uncover the…

  5. Uncovering Pre-Service Teacher Beliefs about Young Children: A Photographic Elicitation Methodology

    ERIC Educational Resources Information Center

    Stockall, Nancy; Davis, Sara

    2011-01-01

    This illustrative paper provides an introduction to using mixed qualitative methods of photo-elicitation, face to face interviews and semiotic analysis to uncover pre-service students' beliefs about young children. The researchers share their experience on conducting a study using photo-elicitation and engaging pre-service teachers in a discussion…

  6. 16 CFR 1610.34 - Only uncovered or exposed parts of wearing apparel to be tested.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... procedures set forth in § 1610.6. (b) If the outer layer of plastic film or plastic-coated fabric of a...—Standard for the Flammability of Vinyl Plastic Film. If the outer layer adheres to all or a portion of one... characteristics of the film or coating, the uncovered or exposed layer shall be tested in accordance with...

  7. 16 CFR 1610.34 - Only uncovered or exposed parts of wearing apparel to be tested.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... procedures set forth in § 1610.6. (b) If the outer layer of plastic film or plastic-coated fabric of a...—Standard for the Flammability of Vinyl Plastic Film. If the outer layer adheres to all or a portion of one... characteristics of the film or coating, the uncovered or exposed layer shall be tested in accordance with...

  8. Archaeology for Kids: Uncovering the Mysteries of Our Past--25 Activities.

    ERIC Educational Resources Information Center

    Panchyk, Richard

    This book provides 25 activities giving children hands-on archeological experience, teaches how archaeologists work, and shows what they have discovered from digging up prehistoric bones between the time when dinosaurs roamed the earth to the uncovering of modern artifacts at a contemporary office building. Ancient civilizations come to life as…

  9. 76 FR 80337 - Uncovered Innerspring Units From the People's Republic of China: Rescission of Antidumping Duty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-23

    ... Republic of China: Preliminary Intent to Rescind New Shipper Review, 76 FR 47151 (August 4, 2011... Antidumping Duty New Shipper Review, 76 FR 65695 (October 24, 2011); Uncovered Innerspring Units from the... FR 73592 (November 29, 2011). Analysis of Comments Received All issues raised in the briefs...

  10. Uncovering the Motivating Factors behind Writing in English in en EFL Context

    ERIC Educational Resources Information Center

    Büyükyavuz, Oya; Çakir, Ismail

    2014-01-01

    Writing in a language, whether the target or native, is regarded as a complex activity operating on multiple cognitive levels. This study aimed to uncover the factors which motivate teacher trainees of English to write in English in an EFL context. The study also investigated the differences in the ways teacher trainees are motivated in terms of…

  11. Feminist Approaches to Triangulation: Uncovering Subjugated Knowledge and Fostering Social Change in Mixed Methods Research

    ERIC Educational Resources Information Center

    Hesse-Biber, Sharlene

    2012-01-01

    This article explores the deployment of triangulation in the service of uncovering subjugated knowledge and promoting social change for women and other oppressed groups. Feminist approaches to mixed methods praxis create a tight link between the research problem and the research design. An analysis of selected case studies of feminist praxis…

  12. Uncovering Influence through Social Network Analysis: The Role of Schools in Education for Sustainable Development

    ERIC Educational Resources Information Center

    Kolleck, Nina

    2016-01-01

    This paper examines the implementation of Education for Sustainable Development (ESD) in Germany and explores the possibilities of Social Network Analysis (SNA) for uncovering influential actors in educational policy innovation processes. From the theoretical perspective, an actor's influence is inferred from its relative position within…

  13. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Requirements for uncovered finished water storage facilities. 141.714 Section 141.714 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for Cryptosporidium Treatment...

  14. Community Mapping in Action: Uncovering Resources and Assets for Young Children and Their Families

    ERIC Educational Resources Information Center

    Ordonez-Jasis, Rosario; Myck-Wayne, Janice

    2012-01-01

    Community mapping is a promising practice that can assist early intervention/early childhood special education (EI/ECSE) professionals uncover the depth and diversity of community needs, resources, and learning opportunities, in the neighborhoods surrounding their schools. Community mapping is an inquiry-based method that situates learning in the…

  15. 76 FR 73592 - Uncovered Innerspring Units From the People's Republic of China: Second Extension of Final...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-29

    ... Rescind New Shipper Review, 76 FR 47151 (August 4, 2011) (``Preliminary Results''). \\2\\ See Uncovered... Shipper Review, 76 FR 65695 (October 24, 2011). Statutory Time Limits Section 751(a)(2)(B)(iv) of the... respondent in this new shipper review is Foshan Nanhai Jiujiang Quan Li Spring Hardware Factory (``Quan...

  16. Learning "through" Computers: Uncovering Students' Thought Processes while Solving Physics Problems

    ERIC Educational Resources Information Center

    Soong, Benson

    2008-01-01

    This paper presents a study that illustrates how the author and an in service secondary school teacher used basic synchronous computer mediated communications (CMC) technology to help them uncover students' physics preconceptions and thought processes (including their misconceptions and misunderstandings) in a real class setting. In this paper, I…

  17. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Requirements for uncovered finished water storage facilities. 141.714 Section 141.714 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for Cryptosporidium Treatment...

  18. Using Text Mining to Uncover Students' Technology-Related Problems in Live Video Streaming

    ERIC Educational Resources Information Center

    Abdous, M'hammed; He, Wu

    2011-01-01

    Because of their capacity to sift through large amounts of data, text mining and data mining are enabling higher education institutions to reveal valuable patterns in students' learning behaviours without having to resort to traditional survey methods. In an effort to uncover live video streaming (LVS) students' technology related-problems and to…

  19. Cross-Species Network Analysis Uncovers Conserved Nitrogen-Regulated Network Modules in Rice1[OPEN

    PubMed Central

    Obertello, Mariana; Shrivastava, Stuti; Katari, Manpreet S.; Coruzzi, Gloria M.

    2015-01-01

    In this study, we used a cross-species network approach to uncover nitrogen (N)-regulated network modules conserved across a model and a crop species. By translating gene network knowledge from the data-rich model Arabidopsis (Arabidopsis thaliana) to a crop, rice (Oryza sativa), we identified evolutionarily conserved N-regulatory modules as targets for translational studies to improve N use efficiency in transgenic plants. To uncover such conserved N-regulatory network modules, we first generated an N-regulatory network based solely on rice transcriptome and gene interaction data. Next, we enhanced the network knowledge in the rice N-regulatory network using transcriptome and gene interaction data from Arabidopsis and new data from Arabidopsis and rice plants exposed to the same N treatment conditions. This cross-species network analysis uncovered a set of N-regulated transcription factors (TFs) predicted to target the same genes and network modules in both species. Supernode analysis of the TFs and their targets in these conserved network modules uncovered genes directly related to N use (e.g. N assimilation) and to other shared biological processes indirectly related to N. This cross-species network approach was validated with members of two TF families in the supernode network, BASIC-LEUCINE ZIPPER TRANSCRIPTION FACTOR1-TGA and HYPERSENSITIVITY TO LOW PI-ELICITED PRIMARY ROOT SHORTENING1 (HRS1)/HRS1 Homolog family, which have recently been experimentally validated to mediate the N response in Arabidopsis. PMID:26045464

  20. Uncovering Pre-Service Music Teachers' Assumptions of Teaching, Learning, and Music

    ERIC Educational Resources Information Center

    Bernard, Rhoda

    2009-01-01

    In this study, the author collected narratives from her students in a music teacher education programme. Using narrative analysis, students' assumptions and thoughts about music teaching, music learning and music making were uncovered. Through the presentation of a case study of one student, the author demonstrates some of the ways that the…

  1. 78 FR 65711 - Uncovered Innerspring Units From China, South Africa, and Vietnam Institution of Five-Year Reviews

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ... orders on imports of uncovered innerspring units from South Africa and Vietnam (73 FR 75390 and 75391... uncovered innerspring units from China (74 FR 7661). The Commission is conducting reviews to determine... rule 201.15(b) (19 CFR 201.15(b)), 73 FR 24609 (May 5, 2008). This advice was developed in...

  2. Methods in DNA methylation profiling

    PubMed Central

    Zuo, Tao; Tycko, Benjamin; Liu, Ta-Ming; Lin, Huey-Jen L; Huang, Tim H-M

    2010-01-01

    Metastable and somatically heritable patterns of DNA methylation provide an important level of genomic regulation. In this article, we review methods for analyzing these genome-wide epigenetic patterns and offer a perspective on the ever-expanding literature, which we hope will be useful for investigators who are new to this area. The historical aspects that we cover will be helpful in interpreting this literature and we hope that our discussion of the newest analytical methods will stimulate future progress. We emphasize that no single approach can provide a complete view of the overall methylome, and that combinations of several modalities applied to the same sample set will give the clearest picture. Given the unexpected epigenomic patterns and new biological principles, as well as new disease markers, that have been uncovered in recent studies, it is likely that important discoveries will continue to be made using genome-wide DNA methylation profiling. PMID:20526417

  3. Complementary Proteomic and Biochemical Analysis of Peptidases in Lobster Gastric Juice Uncovers the Functional Role of Individual Enzymes in Food Digestion.

    PubMed

    Bibo-Verdugo, Betsaida; O'Donoghue, Anthony J; Rojo-Arreola, Liliana; Craik, Charles S; García-Carreño, Fernando

    2016-04-01

    Crustaceans are a diverse group, distributed in widely variable environmental conditions for which they show an equally extensive range of biochemical adaptations. Some digestive enzymes have been studied by purification/characterization approaches. However, global analysis is crucial to understand how digestive enzymes interplay. Here, we present the first proteomic analysis of the digestive fluid from a crustacean (Homarus americanus) and identify glycosidases and peptidases as the most abundant classes of hydrolytic enzymes. The digestion pathway of complex carbohydrates was predicted by comparing the lobster enzymes to similar enzymes from other crustaceans. A novel and unbiased substrate profiling approach was used to uncover the global proteolytic specificity of gastric juice and determine the contribution of cysteine and aspartic acid peptidases. These enzymes were separated by gel electrophoresis and their individual substrate specificities uncovered from the resulting gel bands. This new technique is called zymoMSP. Each cysteine peptidase cleaves a set of unique peptide bonds and the S2 pocket determines their substrate specificity. Finally, affinity chromatography was used to enrich for a digestive cathepsin D1 to compare its substrate specificity and cold-adapted enzymatic properties to mammalian enzymes. We conclude that the H. americanus digestive peptidases may have useful therapeutic applications, due to their cold-adaptation properties and ability to hydrolyze collagen. PMID:26613762

  4. Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease

    SciTech Connect

    Bradford, Blair U.; O'Connell, Thomas M.; Han, Jun; Kosyk, Oksana; Shymonyak, Svitlana; Ross, Pamela K.; Winnike, Jason; Kono, Hiroshi; Rusyn, Ivan

    2008-10-15

    Metabolomic evaluation of urine and liver was conducted to assess the biochemical changes that occur as a result of alcohol-induced liver injury. Male C57BL/6J mice were fed an isocaloric control- or alcohol-containing liquid diet with 35% of calories from corn oil, 18% protein and 47% carbohydrate/alcohol for up to 36 days ad libitum. Alcohol treatment was initiated at 7 g/kg/day and gradually reached a final dose of 21 g/kg/day. Urine samples were collected at 22, 30 and 36 days and, in additional treatment groups, liver and serum samples were harvested at 28 days. Steatohepatitis was induced in the alcohol-fed group since a 5-fold increase in serum alanine aminotransferase activity, a 6-fold increase in liver injury score (necrosis, inflammation and steatosis) and an increase in lipid peroxidation in liver were observed. Liver and urine samples were analyzed by nuclear magnetic resonance spectroscopy and electrospray infusion/Fourier transform ion cyclotron resonance-mass spectrometry. In livers of alcohol-treated mice the following changes were noted. Hypoxia and glycolysis were activated as evidenced by elevated levels of alanine and lactate. Tyrosine, which is required for L-DOPA and dopamine as well as thyroid hormones, was elevated possibly reflecting alterations of basal metabolism by alcohol. A 4-fold increase in the prostacyclin inhibitor 7,10,13,16-docosatetraenoic acid, a molecule important for regulation of platelet formation and blood clotting, may explain why chronic drinking causes serious bleeding problems. Metabolomic analysis of the urine revealed that alcohol treatment leads to decreased excretion of taurine, a metabolite of glutathione, and an increase in lactate, n-acetylglutamine and n-acetylglycine. Changes in the latter two metabolites suggest an inhibition of the kidney enzyme aminoacylase I and may be useful as markers for alcohol consumption.

  5. Proteomic profiling of the autoimmune response to breast cancer antigens uncovers a suppressive effect of hormone therapy

    PubMed Central

    Chao, Timothy; Ladd, Jon J; Qiu, Ji; Johnson, Melissa M; Israel, Rebecca; Chin, Alice; Wang, Hong; Prentice, Ross L; Feng, Ziding; Disis, Mary L.; Hanash, Samir

    2015-01-01

    Purpose Proteomics technologies are well suited for harnessing the immune response to tumor antigens for diagnostic applications as in the case of breast cancer. We previously reported a substantial impact of hormone therapy (HT) on the proteome. Here we investigated the effect of HT on the immune response toward breast tumor antigens. Experimental design Plasmas collected 0-10 months prior to diagnosis of ER+ breast cancer from 190 post-menopausal women and 190 controls that participated in the Women's Health Initiative (WHI) Observational Study were analyzed for the effect of HT on IgG reactivity against arrayed proteins from MCF-7 or SKBR3 breast cancer cell line lysates following extensive fractionation. Results HT user cases exhibited significantly reduced autoantibody reactivity against arrayed proteins compared to cases who were not current users. An associated reduced level of IL-6 and other immune-related cytokines was observed among HT users relative to non-users. Conclusion and clinical relevance Our findings suggest occurrence of a global altered immune response to breast cancer derived proteins associated with HT. Thus a full understanding of factors that modulate the immune response is necessary to translate autoantibody panels into clinical applications. PMID:23401414

  6. Imprecision profiling.

    PubMed

    Sadler, William A

    2008-08-01

    * Imprecision profiles express precision characteristics of an assay over a range of concentration values. They can convert large quantities of potentially complex data into an easily interpreted graphical summary. * Imprecision profile estimation does not require precisely structured data. This implies that structured method evaluation data can be easily compared with, or merged with, less structured internal quality control (QC) data (or with data from any other source). * Although originally conceived for immunoassays, imprecision profiles could, in principle, be used as a summary method with any measurement system where precision varies with level of measurand. PMID:18852854

  7. Chemical Analysis: An Indispensable Means for Uncovering Severe Cases of Fraud with Cosmetics and Tattoo Inks.

    PubMed

    Hohl, Christopher; Hauri, Urs

    2016-01-01

    Three cases of fraud with commodities containing illegal stealth compounds are presented, which were uncovered by the State Laboratory Basel-City, Switzerland. All three commodities, grapefruit seed extracts, a phytocosmetical skin cream, and tattoo inks, were produced abroad, had forged declarations of ingredients and, in the case of the extracts and the cream, were marketed with far-reaching health claims. While inspections will identify suspicious products and would be able to eliminate health claims to some extent, only chemical analysis can uncover the illegal agents used and give law enforcement bodies the necessary evidence to immediately clamp down on those brands, where the stealth agent presents a serious health hazard to consumers. PMID:27198815

  8. Leadership Profiles.

    ERIC Educational Resources Information Center

    Teach, Beverly; And Others

    1994-01-01

    Presents profiles of two leaders in the field of educational media and technology: Carolyn Guss and Mendel Sherman, both retired professors from Indiana University's program in Information Systems Technology. (KRN)

  9. Pioneer Profile.

    ERIC Educational Resources Information Center

    Butcher, Channa Beth

    1987-01-01

    Profiles Herbert A. Sweet, founder and director of Acorn Farms Day Camp (Indiana) for 44 years. Includes reminiscences about the camp's program, staffing, food, World War II, affiliation with the American Camping Association, and camps/directors of today. (NEC)

  10. Integration of small RNAs, degradome and transcriptome sequencing in hyperaccumulator Sedum alfredii uncovers a complex regulatory network and provides insights into cadmium phytoremediation.

    PubMed

    Han, Xiaojiao; Yin, Hengfu; Song, Xixi; Zhang, Yunxing; Liu, Mingying; Sang, Jiang; Jiang, Jing; Li, Jihong; Zhuo, Renying

    2016-06-01

    The hyperaccumulating ecotype of Sedum alfredii Hance is a cadmium (Cd)/zinc/lead co-hyperaccumulating species of Crassulaceae. It is a promising phytoremediation candidate accumulating substantial heavy metal ions without obvious signs of poisoning. However, few studies have focused on the regulatory roles of miRNAs and their targets in the hyperaccumulating ecotype of S. alfredii. Here, we combined analyses of the transcriptomics, sRNAs and the degradome to generate a comprehensive resource focused on identifying key regulatory miRNA-target circuits under Cd stress. A total of 87 721 unigenes and 356 miRNAs were identified by deep sequencing, and 79 miRNAs were differentially expressed under Cd stress. Furthermore, 754 target genes of 194 miRNAs were validated by degradome sequencing. A gene ontology (GO) enrichment analysis of differential miRNA targets revealed that auxin, redox-related secondary metabolism and metal transport pathways responded to Cd stress. An integrated analysis uncovered 39 pairs of miRNA targets that displayed negatively correlated expression profiles. Ten miRNA-target pairs also exhibited negative correlations according to a real-time quantitative PCR analysis. Moreover, a coexpression regulatory network was constructed based on profiles of differentially expressed genes. Two hub genes, ARF4 (auxin response factor 4) and AAP3 (amino acid permease 3), which might play central roles in the regulation of Cd-responsive genes, were uncovered. These results suggest that comprehensive analyses of the transcriptomics, sRNAs and the degradome provided a useful platform for investigating Cd hyperaccumulation in S. alfredii, and may provide new insights into the genetic engineering of phytoremediation. PMID:26801211

  11. Magnetization of uncovered and V-covered ultrathin Fe(100) films on V(100)

    SciTech Connect

    Fritzsche, H.; Liu, Y.T.; Hauschild, J.; Maletta, H.

    2004-12-01

    We used polarized neutron reflectometry (PNR) to determine the absolute magnetic moment of uncovered and V-covered Fe films in the thickness range from 0.3 to 5.5 nm. The films were prepared by molecular beam epitaxy on a V(100) buffer layer grown on a MgO(100) crystal. The magnetic moment shows a linear dependence on the Fe film thickness with a reduction (compared to the Fe bulk value) of the magnetic moment equivalent to 0.1 nm bulk Fe for the V-covered films and a reduction equivalent to 0.03 nm bulk Fe for the uncovered Fe films. For the case of the V/Fe/V samples we observe a much smaller reduction of the magnetic moment than reported for experiments on Fe/V multilayers. As theoretical calculations show a strong decrease of the magnetic moment for an interface alloy we conclude that the larger reduction of the magnetization in Fe/V multilayers is due to an increase in interface roughness with increasing film thickness. For the uncovered Fe(100) films we find a much smaller reduction of the magnetic moment than in earlier in situ PNR experiments on V(110)/Fe(110) where we observed a reduction equivalent to 0.4 nm bulk Fe.

  12. Multi-frequency complex network from time series for uncovering oil-water flow structure

    PubMed Central

    Gao, Zhong-Ke; Yang, Yu-Xuan; Fang, Peng-Cheng; Jin, Ning-De; Xia, Cheng-Yi; Hu, Li-Dan

    2015-01-01

    Uncovering complex oil-water flow structure represents a challenge in diverse scientific disciplines. This challenge stimulates us to develop a new distributed conductance sensor for measuring local flow signals at different positions and then propose a novel approach based on multi-frequency complex network to uncover the flow structures from experimental multivariate measurements. In particular, based on the Fast Fourier transform, we demonstrate how to derive multi-frequency complex network from multivariate time series. We construct complex networks at different frequencies and then detect community structures. Our results indicate that the community structures faithfully represent the structural features of oil-water flow patterns. Furthermore, we investigate the network statistic at different frequencies for each derived network and find that the frequency clustering coefficient enables to uncover the evolution of flow patterns and yield deep insights into the formation of flow structures. Current results present a first step towards a network visualization of complex flow patterns from a community structure perspective. PMID:25649900

  13. Multi-frequency complex network from time series for uncovering oil-water flow structure

    NASA Astrophysics Data System (ADS)

    Gao, Zhong-Ke; Yang, Yu-Xuan; Fang, Peng-Cheng; Jin, Ning-De; Xia, Cheng-Yi; Hu, Li-Dan

    2015-02-01

    Uncovering complex oil-water flow structure represents a challenge in diverse scientific disciplines. This challenge stimulates us to develop a new distributed conductance sensor for measuring local flow signals at different positions and then propose a novel approach based on multi-frequency complex network to uncover the flow structures from experimental multivariate measurements. In particular, based on the Fast Fourier transform, we demonstrate how to derive multi-frequency complex network from multivariate time series. We construct complex networks at different frequencies and then detect community structures. Our results indicate that the community structures faithfully represent the structural features of oil-water flow patterns. Furthermore, we investigate the network statistic at different frequencies for each derived network and find that the frequency clustering coefficient enables to uncover the evolution of flow patterns and yield deep insights into the formation of flow structures. Current results present a first step towards a network visualization of complex flow patterns from a community structure perspective.

  14. Proteomic Analysis of Propiconazole Responses in Mouse Liver-Comparison of Genomic and Proteomic Profiles

    EPA Science Inventory

    We have performed for the first time a comprehensive profiling of changes in protein expression of soluble proteins in livers from mice treated with the mouse liver tumorigen, propiconazole, to uncover the pathways and networks altered by this commonly used fungicide. Utilizing t...

  15. Proteomic analysis of propiconazole responses in mouse liver: comparison of genomic and proteomic profiles

    EPA Science Inventory

    We have performed for the first time a comprehensive profiling of changes in protein expression of soluble proteins in livers from mice treated with the mouse liver tumorigen, propiconazole, to uncover the pathways and networks altered by this fungicide. Utilizing twodimensional...

  16. The defect level and ideal thermal conductivity of graphene uncovered by residual thermal reffusivity at the 0 K limit.

    PubMed

    Xie, Yangsu; Xu, Zaoli; Xu, Shen; Cheng, Zhe; Hashemi, Nastaran; Deng, Cheng; Wang, Xinwei

    2015-06-14

    Due to its intriguing thermal and electrical properties, graphene has been widely studied for potential applications in sensor and energy devices. However, the reported value for its thermal conductivity spans from dozens to thousands of W m(-1) K(-1) due to different levels of alternations and defects in graphene samples. In this work, the thermal diffusivity of suspended four-layered graphene foam (GF) is characterized from room temperature (RT) down to 17 K. For the first time, we identify the defect level in graphene by evaluating the inverse of thermal diffusivity (termed "thermal reffusivity": Θ) at the 0 K limit. By using the Debye model of Θ = Θ0 + C× e(-θ/2T) and fitting the Θ-T curve to the point of T = 0 K, we identify the defect level (Θ0) and determine the Debye temperature of graphene. Θ0 is found to be 1878 s m(-2) for the studied GF and 43-112 s m(-2) for three highly crystalline graphite materials. This uncovers a 16-43-fold higher defect level in GF than that in pyrolytic graphite. In GF, the phonon mean free path solely induced by defects and boundary scattering is determined as 166 nm. The Debye temperature of graphene is determined to be 1813 K, which is very close to the average theoretical Debye temperature (1911 K) of the three acoustic phonon modes in graphene. By subtracting the defect effect, we report the ideal thermal diffusivity and conductivity (κideal) of graphene presented in the 3D foam structure in the range of 33-299 K. Detailed physics based on chemical composition and structure analysis are given to explain the κideal-T profile by comparing with those reported for suspended graphene. PMID:25981826

  17. Profile video

    NASA Astrophysics Data System (ADS)

    Voglewede, Paul E.; Zampieron, Jeffrey

    2009-05-01

    For unattended persistent surveillance there is a need for a system which provides the following information: target classification, target quantity estimate, cargo presence and characterization, direction of travel, and action. Over highly bandwidth restricted links, such as Iridium, SATCOM or HF, the data rates of common techniques are too high, even after aggressive compression, to deliver the required intelligence in a timely, low power manner. We propose the following solution to this data rate problem: Profile Video. Profile video is a new technique which provides all of the required information in a very low data-rate package.

  18. Uncovering beam position monitor noise at the Relativistic Heavy Ion Collider

    NASA Astrophysics Data System (ADS)

    Shen, X.; Lee, S. Y.; Bai, M.

    2015-01-01

    We apply the independent component analysis (ICA) algorithm to uncover intrinsic noise in the beam position monitor (BPM) system. Numerical simulations found that ICA is efficient in the BPM noise estimation. The ICA algorithm is applied to the turn-by-turn data at the Relativistic Heavy Ion Collider. We found the distribution of the BPM noise level, which is consistent with the Johnson-Nyquist thermal noise model. The ICA analysis of turn-by-turn data can be used in neuronetwork feasibility of monitoring a storage ring parasitically.

  19. Patent profiles

    SciTech Connect

    Not Available

    1980-01-01

    This report presents profiles of US patents in the area of solar energy technology, and in the related areas of wind, geothermal and tide and wave energy. Each profile is divided into three parts. The first part identifies the area which is examined, lists the pertinent US Patent Classification(s), and graphically illustrates patent activity across a designated 10-year span. The second part tabulates the data upon which the graphs of the first part were based, provides a list of assignees for the period 1969 to 1978 both by the number of patents and alphabetically, and presents on alphabetical listing of inventors of unassigned patents. The third part updates the preceding material for the period January-October 1979. (SPH)

  20. Serial insertion of bilateral uncovered metal stents for malignant hilar obstruction using an 8 Fr biliary system: a case series of 17 consecutive patients.

    PubMed

    Hsieh, Jennifer; Thosani, Amar; Grunwald, Matthew; Nagula, Satish; Bucobo, Juan Carlos; Buscaglia, Jonathan M

    2015-10-01

    Controversy exists over the need for unilateral versus bilateral stent placement in patients with malignant obstruction at the biliary hilum. Placement of bilateral uncovered self-expanding metal stent (UCSEMS) at this location is technically challenging, and generally associated with lower rates of procedural success. Serial insertion of side-by-side UCSEMS may be especially difficult when simultaneous deployment is not possible using larger stent delivery catheters. In this single-center, retrospective case series of all patients who underwent bilateral placement of uncovered Wallflex(TM) biliary stents between July 2008 and July 2014, we evaluate the feasibility, technical success, and safety of patients undergoing serial insertion of bilateral UCSEMS using the 8 Fr Wallflex(TM) biliary system for malignant hilar obstruction. A total of 17 patients were included. Primary cholangiocarcinoma, Bismuth IV, was the most common diagnosis. Mean procedure time was 54.4 minutes. Overall procedural technical success was achieved in 17/17 patients. Stricture dilation was necessary prior to Wallflex(TM) insertion in 8/17 patients (47.1%). Transpapillary extension of two stents was performed in all patients. There were no cases of stent deployment malfunction, or inability to insert or deploy the 2(nd) stent. Nine of 17 patients (52.9%) required inpatient hospitalization following ERCP; the most common indications were abdominal pain and need for IV antibiotics. There was one case of ERCP-related cholangitis otherwise; there were no other major complications. Bilateral, serial insertion of UCSEMS using the 8 Fr Wallflex(TM) biliary system in malignant hilar obstruction is feasible with an excellent technical success profile. Using this device for side-by-side deployment of UCSEMS appears to be safe in the majority of patients. PMID:26605283

  1. Uncovering Sundanese Values by Analyzing Symbolic Meaning of Ménak Priangan Clothing (1800-1942)

    NASA Astrophysics Data System (ADS)

    Karmila, M.; Suciati; Widiaty, I.

    2016-04-01

    This study investigates symbolic meanings found in the Sunda ethnic clothing, particularly the Menak Priangan clothing. This study aims to uncover and document those symbolic meanings found in the Menak Priangan clothing as an effort to develop Sunda cultural artefacts of West Java. This study on Menak Priangan clothing applies ethnography (visual) and aesthetic methods. The visual method is utilized in order to uncover local cultural (Sunda) values found in Menak Priangan clothing visualization, including: design, model, name, and representing colours, which then directed towards local Sundanese aesthetic concepts living within the Priangan community. Furthermore, aesthetic method is used to explore role of aesthetic values in empowering visual cultural values within certain community, particularly Sunda aesthetic values. The study results show that since the 19th century, Sunda ethnic clothing was limited to Priangan Sunda only, while traditional clothing wearing by Priangan people reflects their social strata, consisting of: a. Menak Gede (Menak pangluhurna: mayor), bearing raden title, b. Menak Leutik/Santana (mayor assistant), titles: asep, mas, agus, ujang, (Nyimas for woman), c. Somah/Cacah: ordinary people/lower class. Clothing is a cultural phenomenon within certain culture reflecting such society experiences. For Menak people, clothing and its accessories have important meanings. They wear such traditional clothing and accessories as a symbol of power they have within bureaucratic structure and as a symbol of social status they bear within traditional community structure.

  2. Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms.

    PubMed

    Korpal, Manav; Feala, Jacob; Puyang, Xiaoling; Zou, Jian; Ramos, Alex H; Wu, Jeremy; Baumeister, Timm; Yu, Lihua; Warmuth, Markus; Zhu, Ping

    2015-01-01

    Although targeted therapies are initially effective, resistance inevitably emerges. Several methods, such as genetic analysis of resistant clinical specimens, have been applied to uncover these resistance mechanisms to facilitate follow-up care. Although these approaches have led to clinically relevant discoveries, difficulties in attaining the relevant patient material or in deconvoluting the genomic data collected from these specimens have severely hampered the path towards a cure. To this end, we here describe a tool for expeditious discovery that may guide improvement in first-line therapies and alternative clinical management strategies. By coupling preclinical in vitro or in vivo drug selection with next-generation sequencing, it is possible to identify genomic structural variations and/or gene expression alterations that may serve as functional drivers of resistance. This approach facilitates the spontaneous emergence of alterations, enhancing the probability that these mechanisms may be observed in the patients. In this protocol we provide guidelines to maximize the potential for uncovering single nucleotide variants that drive resistance using adherent lines. PMID:26710000

  3. Uncovering Quantitative Protein Interaction Networks for Mouse PDZ Domains using Protein Microarrays

    PubMed Central

    Stiffler, Michael A.; Grantcharova, Viara P.; Sevecka, Mark; MacBeath, Gavin

    2008-01-01

    One of the principle challenges in systems biology is to uncover the networks of protein-protein interactions that underlie most biological processes. To date, experimental efforts directed at this problem have largely produced only qualitative networks that are replete with false positives and false negatives. Here, we describe a domain-centered approach – compatible with genome-wide investigations – that enables us to measure the equilibrium dissociation constant (KD) of recombinant PDZ domains for fluorescently-labeled peptides that represent physiologically-relevant binding partners. Using a pilot set of 22 PDZ domains, 4 PDZ domain clusters, and 20 peptides, we define a gold standard dataset by determining the KD for all 520 PDZ-peptide combinations using fluorescence polarization. We then show that microarrays of PDZ domains identify interactions of moderate to high affinity (KD ≤ 10 μM) in a high-throughput format with a false positive rate of 14% and a false negative rate of 14%. By combining the throughput of protein microarrays with the fidelity of fluorescence polarization, our domain/peptide-based strategy yields a quantitative network that faithfully recapitulates 85% of previously reported interactions and uncovers new biophysical interactions, many of which occur between proteins that are co-expressed. From a broader perspective, the selectivity data produced by this effort reveal a strong concordance between protein sequence and protein function, supporting a model in which interaction networks evolve through small steps that do not involve dramatic rewiring of the network. PMID:16637659

  4. Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

    PubMed Central

    Korpal, Manav; Feala, Jacob; Puyang, Xiaoling; Zou, Jian; Ramos, Alex H.; Wu, Jeremy; Baumeister, Timm; Yu, Lihua; Warmuth, Markus; Zhu, Ping

    2015-01-01

    Although targeted therapies are initially effective, resistance inevitably emerges. Several methods, such as genetic analysis of resistant clinical specimens, have been applied to uncover these resistance mechanisms to facilitate follow-up care. Although these approaches have led to clinically relevant discoveries, difficulties in attaining the relevant patient material or in deconvoluting the genomic data collected from these specimens have severely hampered the path towards a cure. To this end, we here describe a tool for expeditious discovery that may guide improvement in first-line therapies and alternative clinical management strategies. By coupling preclinical in vitro or in vivo drug selection with next-generation sequencing, it is possible to identify genomic structural variations and/or gene expression alterations that may serve as functional drivers of resistance. This approach facilitates the spontaneous emergence of alterations, enhancing the probability that these mechanisms may be observed in the patients. In this protocol we provide guidelines to maximize the potential for uncovering single nucleotide variants that drive resistance using adherent lines. PMID:26710000

  5. MPI Profiling

    SciTech Connect

    Han, D K; Jones, T R

    2005-02-11

    The Message Passing Interface (MPI) is the de facto message-passing standard for massively parallel programs. It is often the case that application performance is a crucial factor, especially for solving grand challenge problems. While there have been many studies on the scalability of applications, there have not been many focusing on the specific types of MPI calls being made and their impact on application performance. Using a profiling tool called mpiP, a large spectrum of parallel scientific applications were surveyed and their performance results analyzed.

  6. Intraductal radiofrequency ablation of tumour ingrowth into an uncovered metal stent used for inoperable cholangiocarcinoma.

    PubMed

    Lui, K L; Li, K K

    2013-12-01

    A 91-year-old woman diagnosed to have an inoperable cholangiocarcinoma had an uncovered metal stent inserted for palliative drainage. About 1.5 years later, tumour ingrowth into the metal stent caused cholangitis. Intraductal radiofrequency ablation was applied to create local coagulative tumour necrosis and the necrotic tissue was removed via a balloon catheter. A plastic stent was inserted to empirically treat any ensuing potential bile duct injury. The patient was discharged without complication with good palliative drainage. Intraductal radiofrequency ablation is a new technique for the treatment of metal stent occlusion due to tumour ingrowths. This is the first case report of this relatively safe and feasible new technique for the treatment of tumour ingrowth into a metal stent used as palliation for malignant biliary obstruction. PMID:24310661

  7. Lipidomics Analyses Reveal Temporal and Spatial Lipid Organization and Uncover Daily Oscillations in Intracellular Organelles.

    PubMed

    Aviram, Rona; Manella, Gal; Kopelman, Naama; Neufeld-Cohen, Adi; Zwighaft, Ziv; Elimelech, Meytar; Adamovich, Yaarit; Golik, Marina; Wang, Chunyan; Han, Xianlin; Asher, Gad

    2016-05-19

    Cells have evolved mechanisms to handle incompatible processes through temporal organization by circadian clocks and by spatial compartmentalization within organelles defined by lipid bilayers. Recent advances in lipidomics have led to identification of plentiful lipid species, yet our knowledge regarding their spatiotemporal organization is lagging behind. In this study, we quantitatively characterized the nuclear and mitochondrial lipidome in mouse liver throughout the day, upon different feeding regimens, and in clock-disrupted mice. Our analyses revealed potential connections between lipid species within and between lipid classes. Remarkably, we uncovered diurnal oscillations in lipid accumulation in the nucleus and mitochondria. These oscillations exhibited opposite phases and readily responded to feeding time. Furthermore, we found that the circadian clock coordinates the phase relation between the organelles. In summary, our study provides temporal and spatial depiction of lipid organization and reveals the presence and coordination of diurnal rhythmicity in intracellular organelles. PMID:27161994

  8. Strategies and approaches in plasmidome studies-uncovering plasmid diversity disregarding of linear elements?

    PubMed

    Dib, Julián R; Wagenknecht, Martin; Farías, María E; Meinhardt, Friedhelm

    2015-01-01

    The term plasmid was originally coined for circular, extrachromosomal genetic elements. Today, plasmids are widely recognized not only as important factors facilitating genome restructuring but also as vehicles for the dissemination of beneficial characters within bacterial communities. Plasmid diversity has been uncovered by means of culture-dependent or -independent approaches, such as endogenous or exogenous plasmid isolation as well as PCR-based detection or transposon-aided capture, respectively. High-throughput-sequencing made possible to cover total plasmid populations in a given environment, i.e., the plasmidome, and allowed to address the quality and significance of self-replicating genetic elements. Since such efforts were and still are rather restricted to circular molecules, here we put equal emphasis on the linear plasmids which-despite their frequent occurrence in a large number of bacteria-are largely neglected in prevalent plasmidome conceptions. PMID:26074886

  9. Uncovering brain–heart information through advanced signal and image processing

    PubMed Central

    Toschi, Nicola; Barbieri, Riccardo

    2016-01-01

    Through their dynamical interplay, the brain and the heart ensure fundamental homeostasis and mediate a number of physiological functions as well as their disease-related aberrations. Although a vast number of ad hoc analytical and computational tools have been recently applied to the non-invasive characterization of brain and heart dynamic functioning, little attention has been devoted to combining information to unveil the interactions between these two physiological systems. This theme issue collects contributions from leading experts dealing with the development of advanced analytical and computational tools in the field of biomedical signal and image processing. It includes perspectives on recent advances in 7 T magnetic resonance imaging as well as electroencephalogram, electrocardiogram and cerebrovascular flow processing, with the specific aim of elucidating methods to uncover novel biological and physiological correlates of brain–heart physiology and physiopathology. PMID:27044995

  10. Health Detectives: Uncovering the Mysteries of Disease (LBNL Science at the Theater)

    SciTech Connect

    Bissell, Mina; Canaria, Christie; Celnicker, Susan; Karpen, Gary

    2012-04-23

    In this April 23, 2012 Science at the Theater event, Berkeley Lab scientists discuss how they uncover the mysteries of disease in unlikely places. Speakers and topics include: World-renowned cancer researcher Mina Bissell's pioneering research on the role of the cellular microenvironment in breast cancer has changed the conversation about the disease. How does DNA instability cause disease? To find out, Christie Canaria images neural networks to study disorders such as Huntington's disease. Fruit flies can tell us a lot about ourselves. Susan Celniker explores the fruit fly genome to learn how our genome works. DNA is not destiny. Gary Karpen explores how environmental factors shape genome function and disease through epigenetics.

  11. Treatment of symptomatic coral reef aorta with an uncovered stent graft.

    PubMed

    Bosanquet, D C; Wood, A; Williams, I M

    2015-10-01

    Coral reef aorta is a rare condition characterised by extreme calcific growths affecting the juxta and suprarenal aorta. It can cause symptoms due to visceral ischaemia, lower limb hypoperfusion, and distal embolisation. We present a case of a 61-year-old man with unresponsive hypertension, who was found to have an occluded right renal artery, and an extensive coral reef aorta with a marked pressure gradient across the lesion. Renal hypoperfusion secondary to aortic coral reef aorta was thought to be the cause for his hypertension. Endovascular placement of a balloon expandable uncovered stent resolved his hypertension within one month, with no adverse effects noted at subsequent follow-up. Endovascular treatment of coral reef aorta is technically possible and avoids a major vascular procedure. PMID:25394887

  12. Health Detectives: Uncovering the Mysteries of Disease (LBNL Science at the Theater)

    ScienceCinema

    Bissell, Mina; Canaria, Christie; Celnicker, Susan; Karpen, Gary

    2014-05-06

    In this April 23, 2012 Science at the Theater event, Berkeley Lab scientists discuss how they uncover the mysteries of disease in unlikely places. Speakers and topics include: World-renowned cancer researcher Mina Bissell's pioneering research on the role of the cellular microenvironment in breast cancer has changed the conversation about the disease. How does DNA instability cause disease? To find out, Christie Canaria images neural networks to study disorders such as Huntington's disease. Fruit flies can tell us a lot about ourselves. Susan Celniker explores the fruit fly genome to learn how our genome works. DNA is not destiny. Gary Karpen explores how environmental factors shape genome function and disease through epigenetics.

  13. Uncovering brain-heart information through advanced signal and image processing.

    PubMed

    Valenza, Gaetano; Toschi, Nicola; Barbieri, Riccardo

    2016-05-13

    Through their dynamical interplay, the brain and the heart ensure fundamental homeostasis and mediate a number of physiological functions as well as their disease-related aberrations. Although a vast number of ad hoc analytical and computational tools have been recently applied to the non-invasive characterization of brain and heart dynamic functioning, little attention has been devoted to combining information to unveil the interactions between these two physiological systems. This theme issue collects contributions from leading experts dealing with the development of advanced analytical and computational tools in the field of biomedical signal and image processing. It includes perspectives on recent advances in 7 T magnetic resonance imaging as well as electroencephalogram, electrocardiogram and cerebrovascular flow processing, with the specific aim of elucidating methods to uncover novel biological and physiological correlates of brain-heart physiology and physiopathology. PMID:27044995

  14. Strategies and approaches in plasmidome studies—uncovering plasmid diversity disregarding of linear elements?

    PubMed Central

    Dib, Julián R.; Wagenknecht, Martin; Farías, María E.; Meinhardt, Friedhelm

    2015-01-01

    The term plasmid was originally coined for circular, extrachromosomal genetic elements. Today, plasmids are widely recognized not only as important factors facilitating genome restructuring but also as vehicles for the dissemination of beneficial characters within bacterial communities. Plasmid diversity has been uncovered by means of culture-dependent or -independent approaches, such as endogenous or exogenous plasmid isolation as well as PCR-based detection or transposon-aided capture, respectively. High-throughput-sequencing made possible to cover total plasmid populations in a given environment, i.e., the plasmidome, and allowed to address the quality and significance of self-replicating genetic elements. Since such efforts were and still are rather restricted to circular molecules, here we put equal emphasis on the linear plasmids which—despite their frequent occurrence in a large number of bacteria—are largely neglected in prevalent plasmidome conceptions. PMID:26074886

  15. Whole-Genome Comparison Uncovers Genomic Mutations between Group B Streptococci Sampled from Infected Newborns and Their Mothers

    PubMed Central

    Almeida, Alexandre; Villain, Adrien; Joubrel, Caroline; Touak, Gérald; Sauvage, Elisabeth; Rosinski-Chupin, Isabelle

    2015-01-01

    ABSTRACT Streptococcus agalactiae (group B Streptococcus or GBS), a commensal of the human gut and genitourinary tract, is a leading cause of neonatal infections, in which vertical transmission from mother to child remains the most frequent route of contamination. Here, we investigated whether the progression of GBS from carriage to disease is associated with genomic adaptation. Whole-genome comparison of 47 GBS samples from 19 mother-child pairs uncovered 21 single nucleotide polymorphisms (SNPs) and seven insertions/deletions. Of the SNPs detected, 16 appear to have been fixed in the population sampled whereas five mutations were found to be polymorphic. In the infant strains, 14 mutations were detected, including two independently fixed variants affecting the covRS locus, which is known to encode a major regulatory system of virulence. A one-nucleotide insertion was also identified in the promoter region of the highly immunogenic surface protein Rib gene. Gene expression analysis after incubation in human blood showed that these mutations influenced the expression of virulence-associated genes. Additional identification of three mutated strains in the mothers' milk raised the possibility of the newborns also being a source of contamination for their mothers. Overall, our work showed that GBS strains in carriage and disease scenarios might undergo adaptive changes following colonization. The types and locations of the mutations found, together with the experimental results showing their phenotypic impact, suggest that those in a context of infection were positively selected during the transition of GBS from commensal to pathogen, contributing to an increased capacity to cause disease. IMPORTANCE Group B Streptococcus (GBS) is a major pathogen responsible for neonatal infections. Considering that its colonization of healthy adults is mostly asymptomatic, the mechanisms behind its switch from a commensal to an invasive state are largely unknown. In this work, we

  16. Uncovering novel 3-hydroxy-4-pyridinone metal ion complexes with potential anti-inflammatory properties.

    PubMed

    Chisté, Renan Campos; Ribeiro, Daniela; Freitas, Marisa; Leite, Andreia; Moniz, Tânia; Rangel, Maria; Fernandes, Eduarda

    2016-02-01

    Ligands of the 3-hydroxy-4-pyridinone (3,4-HPO) type, with one (Hmpp) or two methyl groups (Hdmpp), have been reported to possess biomedical, chemical and analytical applications. In this first screening study aiming to uncover new promising agents to mitigate the oxidative damage highly present in several metabolic disorders, such as diabetes mellitus, we assessed the potential of twelve 3,4-HPO metal ion complexes to modulate oxidative burst in human neutrophils. Metal ion 3,4-HPO complexes of Ni, Fe, V, Co, Cu and Zn were synthesized and tested up to 15μM. Among all the compounds, [Cu(mpp)2] and [Cu(dmpp)2] exhibited the highest scavenging capacity against superoxide radical (O2(-)) (IC50=0.36±0.07 and 0.30±0.06μM, respectively) and against hypochlorous acid (HOCl) (IC50=0.6±0.3 and 0.4±0.1μM, respectively). In the particular case of O2(-), [Fe(mpp)3] and [Fe(dmpp)3] (both at 15μM) presented 35% and 22% of inhibition, respectively, while all the other compounds were neither able to scavenge O2(-) nor stimulate its production. Regarding the scavenging capacity against hydrogen peroxide (H2O2), all the compounds showed low efficiency (from 6-39%). Finally, with exception of [VO(mpp)2] and [VO(dmpp)2], all compounds exhibited scavenging activity against HOCl (39-81%) and the most efficient compounds were Cu(II) and Zn(II) complexes. Thus, these preliminary results uncover promising new metal ion complexes, inhibitors of neutrophil's oxidative burst, with potential anti-inflammatory properties, which may be seen as an useful strategy for further studies in the treatment of a number of diseases where oxidative damage is a serious issue. PMID:26606288

  17. Uncovering New Pathogen–Host Protein–Protein Interactions by Pairwise Structure Similarity

    PubMed Central

    Cui, Tao; Li, Weihui; Liu, Lei; Huang, Qiaoyun; He, Zheng-Guo

    2016-01-01

    Pathogens usually evade and manipulate host-immune pathways through pathogen–host protein–protein interactions (PPIs) to avoid being killed by the host immune system. Therefore, uncovering pathogen–host PPIs is critical for determining the mechanisms underlying pathogen infection and survival. In this study, we developed a computational method, which we named pairwise structure similarity (PSS)-PPI, to predict pathogen–host PPIs. First, a high-quality and non-redundant structure–structure interaction (SSI) template library was constructed by exhaustively exploring heteromeric protein complex structures in the PDB database. New interactions were then predicted by searching for PSS with complex structures in the SSI template library. A quantitative score named the PSS score, which integrated structure similarity and residue–residue contact-coverage information, was used to describe the overall similarity of each predicted interaction with the corresponding SSI template. Notably, PSS-PPI yielded experimentally confirmed pathogen–host PPIs of human immunodeficiency virus type 1 (HIV-1) with performance close to that of in vitro high-throughput screening approaches. Finally, a pathogen–host PPI network of human pathogen Mycobacterium tuberculosis, the causative agent of tuberculosis, was constructed using PSS-PPI and refined using filtration steps based on cellular localization information. Analysis of the resulting network indicated that secreted proteins of the STPK, ESX-1, and PE/PPE family in M. tuberculosis targeted human proteins involved in immune response and phagocytosis. M. tuberculosis also targeted host factors known to regulate HIV replication. Taken together, our findings provide insights into the survival mechanisms of M. tuberculosis in human hosts, as well as co-infection of tuberculosis and HIV. With the rapid pace of three-dimensional protein structure discovery, the SSI template library we constructed and the PSS-PPI method we devised

  18. Activity-based protein profiling for biochemical pathway discovery in cancer

    PubMed Central

    Nomura, Daniel K.; Dix, Melissa M.; Cravatt, Benjamin F.

    2011-01-01

    Large-scale profiling methods have uncovered numerous gene and protein expression changes that correlate with tumorigenesis. However, determining the relevance of these expression changes and which biochemical pathways they affect has been hindered by our incomplete understanding of the proteome and its myriad functions and modes of regulation. Activity-based profiling platforms enable both the discovery of cancer-relevant enzymes and selective pharmacological probes to perturb and characterize these proteins in tumour cells. When integrated with other large-scale profiling methods, activity-based proteomics can provide insight into the metabolic and signalling pathways that support cancer pathogenesis and illuminate new strategies for disease diagnosis and treatment. PMID:20703252

  19. Uncovering the Links between Prospective Teachers' Personal Responsibility, Academic Optimism, Hope, and Emotions about Teaching: A Mediation Analysis

    ERIC Educational Resources Information Center

    Eren, Altay

    2014-01-01

    Prospective teachers' sense of personal responsibility has not been examined together with their academic optimism, hope, and emotions about teaching in a single study to date. However, to consider hope, academic optimism, and emotions about teaching together with personal responsibility is important to uncover the factors affecting…

  20. Combining data mining and machine learning for effective user profiling

    SciTech Connect

    Fawcett, T.; Provost, F.

    1996-12-31

    This paper describes the automatic design of methods for detecting fraudulent behavior. Much of the design is accomplished using a series of machine learning methods. In particular, we combine data mining and constructive induction with more standard machine learning techniques to design methods for detecting fraudulent usage of cellular telephones based on profiling customer behavior. Specifically, we use a rule-learning program to uncover indicators of fraudulent behavior from a large database of cellular calls. These indicators are used to create profilers, which then serve as features to a system that combines evidence from multiple profilers to generate high-confidence alarms. Experiments indicate that this automatic approach performs nearly as well as the best hand-tuned methods for detecting fraud.

  1. Molecular profiling of breast cancer: transcriptomic studies and beyond.

    PubMed

    Culhane, A C; Howlin, J

    2007-12-01

    Utilisation of 'omics' technologies, in particular gene expression profiling, has increased dramatically in recent years. In basic research, high-throughput profiling applications are increasingly used and may now even be considered standard research tools. In the clinic, there is a need for better and more accurate diagnosis, prognosis and treatment response indicators. As such, clinicians have looked to omics technologies for potential biomarkers. These prediction profiling studies have in turn attracted the attention of basic researchers eager to uncover biological mechanisms underlying clinically useful signatures. Here we highlight some of the seminal work establishing the arrival of the omics, in particular transcriptomics, in breast cancer research and discuss a sample of the most current applications. We also discuss the challenges of data analysis and integrated data analysis with emphasis on utilising the current publicly available gene expression datasets. (Part of a Multi-author Review). PMID:17957338

  2. Fundamental patterns underlying gene expression profiles: Simplicity from complexity

    PubMed Central

    Holter, Neal S.; Mitra, Madhusmita; Maritan, Amos; Cieplak, Marek; Banavar, Jayanth R.; Fedoroff, Nina V.

    2000-01-01

    Analysis of previously published sets of DNA microarray gene expression data by singular value decomposition has uncovered underlying patterns or “characteristic modes” in their temporal profiles. These patterns contribute unequally to the structure of the expression profiles. Moreover, the essential features of a given set of expression profiles are captured using just a small number of characteristic modes. This leads to the striking conclusion that the transcriptional response of a genome is orchestrated in a few fundamental patterns of gene expression change. These patterns are both simple and robust, dominating the alterations in expression of genes throughout the genome. Moreover, the characteristic modes of gene expression change in response to environmental perturbations are similar in such distant organisms as yeast and human cells. This analysis reveals simple regularities in the seemingly complex transcriptional transitions of diverse cells to new states, and these provide insights into the operation of the underlying genetic networks. PMID:10890920

  3. Application of Synthetic Peptide Arrays To Uncover Cyclic Di-GMP Binding Motifs

    PubMed Central

    Düvel, Juliane; Bense, Sarina; Möller, Stefan; Bertinetti, Daniela; Schwede, Frank; Morr, Michael; Eckweiler, Denitsa; Genieser, Hans-Gottfried; Jänsch, Lothar; Herberg, Friedrich W.; Frank, Ronald

    2015-01-01

    ABSTRACT High levels of the universal bacterial second messenger cyclic di-GMP (c-di-GMP) promote the establishment of surface-attached growth in many bacteria. Not only can c-di-GMP bind to nucleic acids and directly control gene expression, but it also binds to a diverse array of proteins of specialized functions and orchestrates their activity. Since its development in the early 1990s, the synthetic peptide array technique has become a powerful tool for high-throughput approaches and was successfully applied to investigate the binding specificity of protein-ligand interactions. In this study, we used peptide arrays to uncover the c-di-GMP binding site of a Pseudomonas aeruginosa protein (PA3740) that was isolated in a chemical proteomics approach. PA3740 was shown to bind c-di-GMP with a high affinity, and peptide arrays uncovered LKKALKKQTNLR to be a putative c-di-GMP binding motif. Most interestingly, different from the previously identified c-di-GMP binding motif of the PilZ domain (RXXXR) or the I site of diguanylate cyclases (RXXD), two leucine residues and a glutamine residue and not the charged amino acids provided the key residues of the binding sequence. Those three amino acids are highly conserved across PA3740 homologs, and their singular exchange to alanine reduced c-di-GMP binding within the full-length protein. IMPORTANCE In many bacterial pathogens the universal bacterial second messenger c-di-GMP governs the switch from the planktonic, motile mode of growth to the sessile, biofilm mode of growth. Bacteria adapt their intracellular c-di-GMP levels to a variety of environmental challenges. Several classes of c-di-GMP binding proteins have been structurally characterized, and diverse c-di-GMP binding domains have been identified. Nevertheless, for several c-di-GMP receptors, the binding motif remains to be determined. Here we show that the use of a synthetic peptide array allowed the identification of a c-di-GMP binding motif of a putative c

  4. Uncovering Molecular Relaxation Processes with Nonlinear Spectroscopies in the Deep UV

    NASA Astrophysics Data System (ADS)

    West, Brantley Andrew

    Conical intersections mediate internal conversion dynamics that compete with even the fastest nuclear motions in molecular systems. Traditional kinetic models do not apply in this regime of commensurate electronic and nuclear motion because the surroundings do not maintain equilibrium throughout the relaxation process. This dissertation focuses on uncovering the physics associated with vibronic interactions at conical intersections. Of particular interest are coherent nuclear motions driven by steep excited state potential energy gradients. Technical advances have only recently made these dynamics accessible in many systems including DNA nucleobases and cyclic polyene molecules. Optical analogues of multidimensional NMR spectroscopies have recently yielded transformative insight in relaxation processes ranging from energy transfer in photosynthesis to bond making and breaking in liquids. Prior to the start of this research, such experiments had only been conducted at infrared and visible wavelengths. Applications in the ultraviolet were motivated by studies of numerous biological systems (e.g., DNA, proteins), but had been challenged by technical issues. The work presented in this dissertation combines pulse generation techniques developed in the optical physics community with spectroscopic techniques largely pioneered by physical chemists to implement two-dimensional ultraviolet spectroscopy (2DUV). This technique is applied at the shortest wavelengths and with the best signal-to-noise ratios reported to date. Sub-picosecond excited state deactivation processes provide photo stability to the DNA double helix. Vibrational energy transfer from the solute to surrounding solvent enables relaxation of the highly non-equilibrium ground state produced by fast internal conversion. In this dissertation, nonlinear spectroscopies carried out at cryogenic temperatures are used to uncover the particular nuclear modes in the solvent that primarily accept vibrational energy from

  5. Uncovering the pKa dependent fluorescence quenching of carbon dots induced by chlorophenols

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Wang, Yu; Guan, Yafeng; Feng, Liang

    2015-03-01

    Fluorescence quenching induced by targets is always an alluring strategy to elucidate the possible photoluminescence origin of carbon dots. In this study, a new kind of N, S co-doped carbon dots (NSCDs) was synthesized and the fluorescence of NSCDs was surprisingly found to be quenched by chlorophenols (CPs) in a pKa dependent mode. Detailed investigation of this behavior demonstrated that phenolate was the responsible species and N and/or S dopants in NSCDs failed to play a role in the fluorescence quenching. Further evidence uncovered that the quenching was a static one, where a non-fluorescent intermediate was formed between electron-deficient C&z.dbd;O on the CDs surface and the electron-rich phenolic oxygen anion of chlorophenolate via nucleophilic addition. Moreover, one of the main photoluminescence origins of this kind of CDs was derived, namely surface emissive sites mostly attributed to carbonyl groups.Fluorescence quenching induced by targets is always an alluring strategy to elucidate the possible photoluminescence origin of carbon dots. In this study, a new kind of N, S co-doped carbon dots (NSCDs) was synthesized and the fluorescence of NSCDs was surprisingly found to be quenched by chlorophenols (CPs) in a pKa dependent mode. Detailed investigation of this behavior demonstrated that phenolate was the responsible species and N and/or S dopants in NSCDs failed to play a role in the fluorescence quenching. Further evidence uncovered that the quenching was a static one, where a non-fluorescent intermediate was formed between electron-deficient C&z.dbd;O on the CDs surface and the electron-rich phenolic oxygen anion of chlorophenolate via nucleophilic addition. Moreover, one of the main photoluminescence origins of this kind of CDs was derived, namely surface emissive sites mostly attributed to carbonyl groups. Electronic supplementary information (ESI) available: Texts, figures and tables giving partial experimental procedures, detailed characterizations

  6. Advanced interferometric profile measurements through refractive media

    SciTech Connect

    Koev, Stephan T.; Ghodssi, Reza

    2008-09-15

    Optical profilers are valuable tools for the characterization of microelectromechanical systems (MEMSs). They use phase sifting interferometry (PSI) or vertical scanning interferometry to measure the topography of microscale structures with nanometer resolution. However, for many emerging MEMS applications, the sample needs to be imaged while placed in a liquid or in a package with a glass window. The increased refractive index of the transparent medium degrades the interference image contrast and prevents any measurement of the sample. We report on the modification of a Veeco NT1100 optical profiler to enable PSI measurements through refractive media. This approach can be applied to any other optical profiler with PSI capability. The modification consists in replacing the original illumination source with a custom-built narrow linewidth source, which increases the coherence length of the light and the contrast of the interference image. We present measurements taken with the modified configuration on samples covered with 3 mm water or 500 {mu}m glass, and we compare them to measurements of uncovered samples. We show that the measurement precision is only slightly reduced by the water and glass, and that it is still sufficiently high for typical MEMS applications. The described method can be readily used for measuring through other types and thicknesses of refractive materials.

  7. Characterizing inactive ribosomes in translational profiling.

    PubMed

    Liu, Botao; Qian, Shu-Bing

    2016-01-01

    The broad impact of translational regulation has emerged explosively in the last few years in part due to the technological advance in genome-wide interrogation of gene expression. During mRNA translation, the majority of actively translating ribosomes exist as polysomes in cells with multiple ribosomes loaded on a single transcript. The importance of the monosome, however, has been less appreciated in translational profiling analysis. Here we report that the monosome fraction isolated by sucrose sedimentation contains a large quantity of inactive ribosomes that do not engage on mRNAs to direct translation. We found that the elongation factor eEF2, but not eEF1A, stably resides in these non-translating ribosomes. This unique feature permits direct evaluation of ribosome status under various stress conditions and in the presence of translation inhibitors. Ribosome profiling reveals that the monosome has a similar but not identical pattern of ribosome footprints compared to the polysome. We show that the association of free ribosomal subunits minimally contributes to ribosome occupancy outside of the coding region. Our results not only offer a quantitative method to monitor ribosome availability, but also uncover additional layers of ribosome status needed to be considered in translational profiling analysis. PMID:27335722

  8. Uncovering cryptic species diversity of a termite community in a West African savanna.

    PubMed

    Hausberger, Barbara; Kimpel, Dorothea; van Neer, Abbo; Korb, Judith

    2011-12-01

    To uncover the termite species diversity of a natural African savanna ecosystem, we combined morphological analyses and sequencing of three gene fragments (cytochrome oxidase I, cytochrome oxidase II and 28SrDNA, total length about 2450 bp) to infer putative species from phylogenetic trees. We identified 18 putative species clusters with high support values and which we retrieved consistently. Samples from two genera (Ancistrotermes and Microcerotermes) were excluded from the mitochondrial phylogenetic analyses as they might represent nuclear mitochondrial sequences (NUMTs). In total, our data suggest a species richness of at least 20 species, all but one belonging to the Termitidae (higher termites), and among them the fungus-growing Macrotermitinae were most prevalent with at least nine putative species. Within the fungus-growers the most species-rich genus was Microtermes and its four putative species were all cryptic species. Their abundance in the samples suggests that they play an important ecological role which is completely unstudied also due to the lack of reliable identification means. Our study shows that morphological traits are unreliable means of species identification for several termite taxa. Yet reliable and consistent identification is necessary for studying the functional role of termites in ecosystem and global processes. PMID:21896335

  9. Uncovering the role of hypoxia inducible factor-1α in skin carcinogenesis.

    PubMed

    Nys, Kris; Maes, Hannelore; Dudek, Aleksandra Maria; Agostinis, Patrizia

    2011-08-01

    The hypoxia inducible factor-1α (HIF-1α) is a pleiotropic transcription factor typically activated in response to low oxygen tension as well as other stress factors in normoxic conditions. Upon activation HIF-1α mediates the transcriptional activation of target genes involved in a variety of processes comprising stress adaptation, metabolism, growth and invasion, but also apoptotic cell death. The molecular mechanisms, signaling pathways and downstream targets evoked by the activation of HIF-1α in epidermal cells are becoming increasingly understood and underscore the participation of HIF-1α in crucial processes including malignant transformation and cancer progression. Recent studies have implicated HIF-1α as an integral part of the multifaceted signal transduction initiated by the exposure of keratinocytes to ultraviolet radiation B (UVB), which represents the most ubiquitous hazard for human skin and the principal risk factor for skin cancer. HIF-1α activation by UVB exposure contributes to either repair or the removal of UVB-damaged keratinocytes by inducing apoptosis, thus revealing a tumor suppressor role for HIF-1α in these cells. On the other hand, the constitutive expression of HIF-1α evoked by the mild hypoxic state of the skin has been implicated as a positive factor in the transformation of normal melanocytes into malignant melanoma, one of the most aggressive types of human cancers. Here we review the uncovered and complex role of HIF-1α in skin carcinogenesis. PMID:21338656

  10. Genome-wide analysis uncovers novel recurrent alterations in primary central nervous system lymphomas

    PubMed Central

    Braggio, Esteban; Van Wier, Scott; Ojha, Juhi; McPhail, Ellen; Asmann, Yan W.; Egan, Jan; da Silva, Jackline Ayres; Schiff, David; Lopes, M Beatriz; Decker, Paul A; Valdez, Riccardo; Tibes, Raoul; Eckloff, Bruce; Witzig, Thomas E.; Stewart, A Keith; Fonseca, Rafael; O’Neill, Brian Patrick

    2015-01-01

    Purpose Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma confined to the CNS. Whether there is a PCNSL-specific genomic signature and, if so, how it differs from systemic diffuse large B-cell lymphoma (DLBCL) is uncertain. Experimental design We performed a comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL patients. Testing comprised array-comparative genomic hybridization and whole exome sequencing. Results Biallelic inactivation of TOX and PRKCD were recurrently found in PCNSL but not in systemic DLBCL, suggesting a specific role in PCNSL pathogenesis. Additionally, we found a high prevalence of MYD88 mutations (79%) and CDKN2A biallelic loss (60%). Several genes recurrently affected in PCNSL were common with systemic DLBCL, including loss of TNFAIP3, PRDM1, GNA13, TMEM30A, TBL1XR1, B2M, CD58, activating mutations of CD79B, CARD11 and translocations IgH-BCL6. Overall, BCR/TLR/NF-κB pathways were altered in >90% of PNCSL, highlighting its value for targeted therapeutic approaches. Furthermore, integrated analysis showed enrichment of pathways associated with immune response, proliferation, apoptosis, and lymphocyte differentiation. Conclusions In summary, genome-wide analysis uncovered novel recurrent alterations, including TOX and PRKCD, helping to differentiate PCNSL from systemic DLBCL and related lymphomas. PMID:25991819

  11. Percutaneous treatment of malignant jaundice due to extrahepatic cholangiocarcinoma: covered Viabil stent versus uncovered Wallstents.

    PubMed

    Krokidis, Miltiadis; Fanelli, Fabrizio; Orgera, Gianluigi; Bezzi, Mario; Passariello, Roberto; Hatzidakis, Adam

    2010-02-01

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement. PMID:19495871

  12. Systematic Triple Mutant Analysis Uncovers Functional Connectivity Between Pathways Involved in Chromosome Regulation

    PubMed Central

    Haber, James E.; Braberg, Hannes; Wu, Qiuqin; Alexander, Richard; Haase, Julian; Ryan, Colm; Lipkin-Moore, Zach; Franks-Skiba, Kathleen E.; Johnson, Tasha; Shales, Michael; Lenstra, Tineke L.; Holstege, Frank C. P.; Johnson, Jeffrey R.; Bloom, Kerry; Krogan, Nevan J.

    2013-01-01

    Genetic interactions reveal the functional relationships between pairs of genes. In this study, we describe a method for the systematic generation and quantitation of triple mutants, termed Triple Mutant Analysis (TMA). We have used this approach to interrogate partially redundant pairs of genes in S. cerevisiae, including ASF1 and CAC1, two histone chaperones. After subjecting asf1Δ cac1Δ to TMA, we found that the Swi/Snf Rdh54 protein, compensates for the absence of Asf1 and Cac1. Rdh54 more strongly associates with the chromatin apparatus and the pericentromeric region in the double mutant. Moreover, Asf1 is responsible for the synthetic lethality observed in cac1Δ strains lacking the HIRA-like proteins. A similar TMA was carried out after deleting both CLB5 and CLB6, cyclins that regulate DNA replication, revealing a strong functional connection to chromosome segregation. This approach can reveal functional redundancies that cannot be uncovered using traditional double mutant analyses. PMID:23746449

  13. Cryptic no more: soil macrofossils uncover Pleistocene forest microrefugia within a periglacial desert.

    PubMed

    de Lafontaine, Guillaume; Amasifuen Guerra, Carlos Alberto; Ducousso, Alexis; Petit, Rémy J

    2014-11-01

    Despite their critical importance for understanding the local effects of global climate change on biodiversity, glacial microrefugia are not well studied because they are difficult to detect by using classical palaeoecological or population genetics approaches. We used soil macrofossil charcoal analysis to uncover the presence of cryptic glacial refugia for European beech (Fagus sylvatica) and other tree species in the Landes de Gascogne (southwestern France). Using botanical identification and direct radiocarbon dating (140 (14) C-dates) of macrofossil charcoal extracted from mineral soils, we reconstructed the glacial and postglacial history of all extant beech stands in the region (n = 11). Soil charcoal macrofossils were found in all sites, allowing the identification of up to at least 14 distinct fire events per site. There was direct evidence of the presence of beech during the last glacial period at three sites. Beech was detected during Heinrich stadial-1, one of the coldest and driest intervals of the last glacial period in Western Europe. Together with previous results on the genetic structure of the species in the region, these findings suggest that beech persisted in situ in several microrefugia through full glacial and interglacial periods up to the present day. PMID:25312611

  14. Plant Phenotyping using Probabilistic Topic Models: Uncovering the Hyperspectral Language of Plants.

    PubMed

    Wahabzada, Mirwaes; Mahlein, Anne-Katrin; Bauckhage, Christian; Steiner, Ulrike; Oerke, Erich-Christian; Kersting, Kristian

    2016-01-01

    Modern phenotyping and plant disease detection methods, based on optical sensors and information technology, provide promising approaches to plant research and precision farming. In particular, hyperspectral imaging have been found to reveal physiological and structural characteristics in plants and to allow for tracking physiological dynamics due to environmental effects. In this work, we present an approach to plant phenotyping that integrates non-invasive sensors, computer vision, as well as data mining techniques and allows for monitoring how plants respond to stress. To uncover latent hyperspectral characteristics of diseased plants reliably and in an easy-to-understand way, we "wordify" the hyperspectral images, i.e., we turn the images into a corpus of text documents. Then, we apply probabilistic topic models, a well-established natural language processing technique that identifies content and topics of documents. Based on recent regularized topic models, we demonstrate that one can track automatically the development of three foliar diseases of barley. We also present a visualization of the topics that provides plant scientists an intuitive tool for hyperspectral imaging. In short, our analysis and visualization of characteristic topics found during symptom development and disease progress reveal the hyperspectral language of plant diseases. PMID:26957018

  15. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    DOE PAGESBeta

    Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

    2016-04-18

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method frommore » being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.« less

  16. Uncovering stem-cell heterogeneity in the microniche with label-free microfluidics

    NASA Astrophysics Data System (ADS)

    Sohn, Lydia L.

    2013-03-01

    Better suited for large number of cells from bulk tissue, traditional cell-screening techniques, such as fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS), cannot easily screen stem or progenitor cells from minute populations found in their physiological niches. Furthermore, they rely upon irreversible antibody binding, potentially altering cell properties, including gene expression and regenerative capacity. We have developed a label-free, single-cell analysis microfluidic platform capable of quantifying cell-surface marker expression of functional organ stem cells directly isolated from their micro-anatomical niche. With this platform, we have screened single quiescent muscle stem (satellite) cells derived from single myofibers, and we have uncovered an important heterogeneity in the surface-marker expression of these cells. By sorting the screened cells with our microfluidic device, we have determined what this heterogeneity means in terms of muscle stem-cell functionality. For instance, we show that the levels of beta1-integrin can predict the differentiation capacity of quiescent satellite cells, and in contrast to recent literature, that some CXCR4 + cells are not myogenic. Our results provide the first direct demonstration of a microniche-specific variation in gene expression in stem cells of the same lineage. Overall, our label-free, single-cell analysis and cell-sorting platform could be extended to other systems involving rare-cell subsets. This work was funded by the W. M. Keck Foundation, NIH, and California Institute of Regenerative Medicine

  17. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging.

    PubMed

    Rose, P B; Erickson, A S; Mayer, M; Nattress, J; Jovanovic, I

    2016-01-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as "searching for a needle in a haystack" because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material's areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications. PMID:27087555

  18. Online tools for uncovering data quality issues in satellite-based global precipitation products

    NASA Astrophysics Data System (ADS)

    Liu, Z.; Heo, G.

    2015-12-01

    Accurate and timely available global precipitation products are important to many applications such as flood forecasting, hydrological modeling, vector-borne disease research, crop yield estimates, etc. However, data quality issues such as biases and uncertainties are common in satellite-based precipitation products and it is important to understand these issues in applications. In recent years, algorithms using multi-satellites and multi-sensors for satellite-based precipitation estimates have become popular, such as the TRMM (Tropical Rainfall Measuring Mission) Multi-satellite Precipitation Analysis (TMPA) and the latest Integrated Multi-satellitE Retrievals for GPM (IMERG). Studies show that data quality issues for multi-satellite and multi-sensor products can vary with space and time and can be difficult to summarize. Online tools can provide customized results for a given area of interest, allowing customized investigation or comparison on several precipitation products. Because downloading data and software is not required, online tools can facilitate precipitation product evaluation and comparison. In this presentation, we will present online tools to uncover data quality issues in satellite-based global precipitation products. Examples will be presented as well.

  19. Uncovering novel mobile genetic elements and their dynamics through an extra-chromosomal sequencing approach.

    PubMed

    Deutsch, Douglas R; Utter, Bryan; Fischetti, Vincent A

    2016-01-01

    Staphylococcus aureus is a major clinically important pathogen with well-studied phage contributions to its virulence potential. In this commentary, we describe our method to enrich and sequence stealth extra-chromosomal DNA elements in the bacterial cell, allowing the identification of novel extra-chromosomal prophages in S. aureus clinical strains. Extra-chromosomal sequencing is a useful and broadly applicable tool to study bacterial genomics, giving a temporal glance at the extra-chromosomal compartment of the cell and allowing researchers to uncover lower-copy plasmidial elements (e.g., prophages) as well as gain a greater understanding of mobile genetic elements that shuffle on and off the chromosome. Here, we describe how episomal and plasmidial DNA elements can have profound downstream effects on the host cell and surrounding bacterial population, and discuss specific examples of their importance in Gram-positive bacteria. We also offer potential avenues of future research where extra-chromosomal sequencing may play a key role in our understanding of the complete virulence potential of infectious bacteria. PMID:27581613

  20. Microarray data mining: A novel optimization-based approach to uncover biologically coherent structures

    PubMed Central

    Tan, Meng P; Smith, Erin N; Broach, James R; Floudas, Christodoulos A

    2008-01-01

    Background DNA microarray technology allows for the measurement of genome-wide expression patterns. Within the resultant mass of data lies the problem of analyzing and presenting information on this genomic scale, and a first step towards the rapid and comprehensive interpretation of this data is gene clustering with respect to the expression patterns. Classifying genes into clusters can lead to interesting biological insights. In this study, we describe an iterative clustering approach to uncover biologically coherent structures from DNA microarray data based on a novel clustering algorithm EP_GOS_Clust. Results We apply our proposed iterative algorithm to three sets of experimental DNA microarray data from experiments with the yeast Saccharomyces cerevisiae and show that the proposed iterative approach improves biological coherence. Comparison with other clustering techniques suggests that our iterative algorithm provides superior performance with regard to biological coherence. An important consequence of our approach is that an increasing proportion of genes find membership in clusters of high biological coherence and that the average cluster specificity improves. Conclusion The results from these clustering experiments provide a robust basis for extracting motifs and trans-acting factors that determine particular patterns of expression. In addition, the biological coherence of the clusters is iteratively assessed independently of the clustering. Thus, this method will not be severely impacted by functional annotations that are missing, inaccurate, or sparse. PMID:18538024

  1. Plant Phenotyping using Probabilistic Topic Models: Uncovering the Hyperspectral Language of Plants

    PubMed Central

    Wahabzada, Mirwaes; Mahlein, Anne-Katrin; Bauckhage, Christian; Steiner, Ulrike; Oerke, Erich-Christian; Kersting, Kristian

    2016-01-01

    Modern phenotyping and plant disease detection methods, based on optical sensors and information technology, provide promising approaches to plant research and precision farming. In particular, hyperspectral imaging have been found to reveal physiological and structural characteristics in plants and to allow for tracking physiological dynamics due to environmental effects. In this work, we present an approach to plant phenotyping that integrates non-invasive sensors, computer vision, as well as data mining techniques and allows for monitoring how plants respond to stress. To uncover latent hyperspectral characteristics of diseased plants reliably and in an easy-to-understand way, we “wordify” the hyperspectral images, i.e., we turn the images into a corpus of text documents. Then, we apply probabilistic topic models, a well-established natural language processing technique that identifies content and topics of documents. Based on recent regularized topic models, we demonstrate that one can track automatically the development of three foliar diseases of barley. We also present a visualization of the topics that provides plant scientists an intuitive tool for hyperspectral imaging. In short, our analysis and visualization of characteristic topics found during symptom development and disease progress reveal the hyperspectral language of plant diseases. PMID:26957018

  2. Uncovering major genomic features of essential genes in Bacteria and a methanogenic Archaea.

    PubMed

    Grazziotin, Ana Laura; Vidal, Newton M; Venancio, Thiago M

    2015-09-01

    Identification of essential genes is critical to understanding the physiology of a species, proposing novel drug targets and uncovering minimal gene sets required for life. Although essential gene sets of several organisms have been determined using large-scale mutagenesis techniques, systematic studies addressing their conservation, genomic context and functions remain scant. Here we integrate 17 essential gene sets from genome-wide in vitro screenings and three gene collections required for growth in vivo, encompassing 15 Bacteria and one Archaea. We refine and generalize important theories proposed using Escherichia coli. Essential genes are typically monogenic and more conserved than nonessential genes. Genes required in vivo are less conserved than those essential in vitro, suggesting that more divergent strategies are deployed when the organism is stressed by the host immune system and unstable nutrient availability. We identified essential analogous pathways that would probably be missed by orthology-based essentiality prediction strategies. For example, Streptococcus sanguinis carries horizontally transferred isoprenoid biosynthesis genes that are widespread in Archaea. Genes specifically essential in Mycobacterium tuberculosis and Burkholderia pseudomallei are reported as potential drug targets. Moreover, essential genes are not only preferentially located in operons, but also occupy the first position therein, supporting the influence of their regulatory regions in driving transcription of whole operons. Finally, these important genomic features are shared between Bacteria and at least one Archaea, suggesting that high order properties of gene essentiality and genome architecture were probably present in the last universal common ancestor or evolved independently in the prokaryotic domains. PMID:26084810

  3. Uncovering system-specific stress signatures in primate teeth with multimodal imaging

    PubMed Central

    Austin, Christine; Smith, Tanya M.; Farahani, Ramin M. Z.; Hinde, Katie; Carter, Elizabeth A.; Lee, Joonsup; Lay, Peter A.; Kennedy, Brendan J.; Sarrafpour, Babak; Wright, Rosalind J.; Wright, Robert O.; Arora, Manish

    2016-01-01

    Early life stress can disrupt development and negatively impact long-term health trajectories. Reconstructing histories of early life exposure to external stressors is hampered by the absence of retrospective time-specific biomarkers. Defects in tooth enamel have been used to reconstruct stress but the methods used are subjective and do not identify the specific biological systems impacted by external stressors. Here we show that external physical and social stressors impart biochemical signatures in primate teeth that can be retrieved to objectively reconstruct the timing of early life developmental disruptions. Using teeth from captive macaques, we uncovered elemental imprints specific to disruptions of skeletal growth, including major disruptions in body weight trajectory and moderate to severe illnesses. Discrete increases in heat shock protein-70 expression in dentine coincided with elemental signatures, confirming that elemental signals were associated with activation of stress-related pathways. To overcome limitations of conventional light-microscopic analysis, we used high resolution Raman microspectral imaging to identify structural and compositional alterations in enamel and dentine that coincided with elemental signatures and with detailed medical and behavioural data. Integrating these objective biochemical markers with temporal mapping of teeth enables the retrospective study of early life developmental disruptions and their ensuing health sequelae. PMID:26727334

  4. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    NASA Astrophysics Data System (ADS)

    Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

    2016-04-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.

  5. Uncovering the connectivity of coral reef systems via Lagrangian Coherent Structures

    NASA Astrophysics Data System (ADS)

    Leclair, Matthieu; Lowe, Ryan; Zang, Zhenlin; Ivey, Gregory; Peacock, Thomas

    2015-04-01

    There has been a staggering decline in the health of coral reef ecosystems worldwide over the past century, driven by anthropogenic influences, natural processes, and overall climate change. The future of coral reefs depends largely on their ability to recover from catastrophic events, which in turn crucially relies on the ability of reef larval populations to supply and restore damaged reefs. Improving quantitative predictions of reef larval transport and connectivity has thus emerged as a high priority research area in coral reef science. Ocean circulation models are being increasingly utilized in conjunction with particle tracking methods to provide spatially explicit predictions of larval transport within reef systems. The current major drawback of this approach is that it does not elucidate the underlying yet dynamic flow structures that drive reef connectivity. Recently, however, novel Lagrangian-based analysis approaches have been developed to identify the hidden coherent structures that govern material transport in spatiotemporally complex flow fields. Here we apply these methods to investigate the connectivity within a complex coral reef system, using the UNESCO World Heritage Ningaloo Reef in Australia as a case study. Our study demonstrates how this new approach identifies the dominant flow structures present on the reef, thereby uncovering connectivity and advocating a new practical framework for investigating and understanding how ocean processes shape the ecological transport in and around coral reefs. The technique can prove particularly valuable in supporting the design of Marine Protected Areas that are intended to safeguard the future of coral reefs and other ocean ecosystems.

  6. Using comparative genomics to uncover new kinds of protein-based metabolic organelles in bacteria

    PubMed Central

    Jorda, Julien; Lopez, David; Wheatley, Nicole M; Yeates, Todd O

    2013-01-01

    Bacterial microcompartment (MCP) organelles are cytosolic, polyhedral structures consisting of a thin protein shell and a series of encapsulated, sequentially acting enzymes. To date, different microcompartments carrying out three distinct types of metabolic processes have been characterized experimentally in various bacteria. In the present work, we use comparative genomics to explore the existence of yet uncharacterized microcompartments encapsulating a broader set of metabolic pathways. A clustering approach was used to group together enzymes that show a strong tendency to be encoded in chromosomal proximity to each other while also being near genes for microcompartment shell proteins. The results uncover new types of putative microcompartments, including one that appears to encapsulate B12-independent, glycyl radical-based degradation of 1,2-propanediol, and another potentially involved in amino alcohol metabolism in mycobacteria. Preliminary experiments show that an unusual shell protein encoded within the glycyl radical-based microcompartment binds an iron-sulfur cluster, hinting at complex mechanisms in this uncharacterized system. In addition, an examination of the computed microcompartment clusters suggests the existence of specific functional variations within certain types of MCPs, including the alpha carboxysome and the glycyl radical-based microcompartment. The findings lead to a deeper understanding of bacterial microcompartments and the pathways they sequester. PMID:23188745

  7. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma

    PubMed Central

    Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data. PMID:27610367

  8. Phylogenetic Analyses Uncover a Novel Clade of Transferrin in Nonmammalian Vertebrates

    PubMed Central

    Mohd-Adnan, Adura; Gabaldón, Toni

    2013-01-01

    Transferrin is a protein super-family involved in iron transport, a central process in cellular homeostasis. Throughout the evolution of vertebrates, transferrin members have diversified into distinct subfamilies including serotransferrin, ovotransferrin, lactoferrin, melanotransferrin, the inhibitor of carbonic anhydrase, pacifastin, and the major yolk protein in sea urchin. Previous phylogenetic analyses have established the branching order of the diverse transferrin subfamilies but were mostly focused on the transferrin repertoire present in mammals. Here, we conduct a comprehensive phylogenetic analysis of transferrin protein sequences in sequenced vertebrates, placing a special focus on the less-studied nonmammalian vertebrates. Our analyses uncover a novel transferrin clade present across fish, sauropsid, and amphibian genomes but strikingly absent from mammals. Our reconstructed scenario implies that this novel class emerged through a duplication event at the vertebrate ancestor, and that it was subsequently lost in the lineage leading to mammals. We detect footprints of accelerated evolution following the duplication event, which suggest positive selection and early functional divergence of this novel clade. Interestingly, the loss of this novel class of transferrin in mammals coincided with the divergence by duplication of lactoferrin and serotransferrin in this lineage. Altogether, our results provide novel insights on the evolution of iron-binding proteins in the various vertebrate groups. PMID:23258311

  9. Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs

    PubMed Central

    Pehrsson, Erica C.; Forsberg, Kevin J.; Gibson, Molly K.; Ahmadi, Sara; Dantas, Gautam

    2013-01-01

    Rates of infection with antibiotic-resistant bacteria have increased precipitously over the past several decades, with far-reaching healthcare and societal costs. Recent evidence has established a link between antibiotic resistance genes in human pathogens and those found in non-pathogenic, commensal, and environmental organisms, prompting deeper investigation of natural and human-associated reservoirs of antibiotic resistance. Functional metagenomic selections, in which shotgun-cloned DNA fragments are selected for their ability to confer survival to an indicator host, have been increasingly applied to the characterization of many antibiotic resistance reservoirs. These experiments have demonstrated that antibiotic resistance genes are highly diverse and widely distributed, many times bearing little to no similarity to known sequences. Through unbiased selections for survival to antibiotic exposure, functional metagenomics can improve annotations by reducing the discovery of false-positive resistance and by allowing for the identification of previously unrecognizable resistance genes. In this review, we summarize the novel resistance functions uncovered using functional metagenomic investigations of natural and human-impacted resistance reservoirs. Examples of novel antibiotic resistance genes include those highly divergent from known sequences, those for which sequence is entirely unable to predict resistance function, bifunctional resistance genes, and those with unconventional, atypical resistance mechanisms. Overcoming antibiotic resistance in the clinic will require a better understanding of existing resistance reservoirs and the dissemination networks that govern horizontal gene exchange, informing best practices to limit the spread of resistance-conferring genes to human pathogens. PMID:23760651

  10. UNCOVERING THE ORIGINS OF SPIRAL STRUCTURE BY MEASURING RADIAL VARIATION IN PATTERN SPEEDS

    SciTech Connect

    Meidt, Sharon E.; Rand, Richard J.; Merrifield, Michael R.

    2009-09-01

    Current theories of spiral and bar structure predict a variety of pattern speed behaviors, calling for detailed, direct measurement of the radial variation of pattern speeds. Our recently developed Radial Tremaine-Weinberg (TWR) method allows this goal to be achieved for the first time. Here, we present TWR spiral pattern speed estimates for M101, IC 342, NGC 3938, and NGC 3344 in order to investigate whether spiral structure is steady or winding, whether spirals are described by multiple pattern speeds, and the relation between bar and spiral speeds. Where possible, we interpret our pattern speeds estimates according to the resonance radii associated with each (established with the disk angular rotation), and compare these to previous determinations. By analyzing the high-quality H I and CO data cubes available for these galaxies, we show that it is possible to determine directly multiple pattern speeds within these systems, and hence identify the characteristic signatures of the processes that drive the spiral structure. Even this small sample of galaxies reveals a surprisingly complex taxonomy, with the first direct evidence for the presence of resonant coupling of multiple patterns found in some systems, and the measurement of a simple single-pattern speed in others. Overall, this study demonstrates that we are now in a position to uncover more of the apparently complex physics that lies behind spiral structure.

  11. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

    PubMed

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  12. Uncovering a new role for peroxidase enzymes as drivers of angiogenesis.

    PubMed

    Panagopoulos, Vasilios; Zinonos, Irene; Leach, Damien A; Hay, Shelley J; Liapis, Vasilios; Zysk, Aneta; Ingman, Wendy V; DeNichilo, Mark O; Evdokiou, Andreas

    2015-11-01

    Peroxidases are heme-containing enzymes released by activated immune cells at sites of inflammation. To-date their functional role in human health has mainly been limited to providing a mechanism for oxidative defence against invading bacteria and other pathogenic microorganisms. Our laboratory has recently identified a new functional role for peroxidase enzymes in stimulating fibroblast migration and collagen biosynthesis, offering a new insight into the causative association between inflammation and the pro-fibrogenic events that mediate tissue repair and regeneration. Peroxidases are found at elevated levels within and near blood vessels however, their direct involvement in angiogenesis has never been reported. Here we report for the first time that myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are readily internalised by human umbilical vein endothelial cells (HUVEC) where they promote cellular proliferation, migration, invasion, and stimulate angiogenesis both in vitro and in vivo. These pro-angiogenic effects were attenuated using the specific peroxidase inhibitor 4-ABAH, indicating the enzyme's catalytic activity is essential in mediating this response. Mechanistically, we provide evidence that MPO and EPO regulate endothelial FAK, Akt, p38 MAPK, ERK1/2 phosphorylation and stabilisation of HIF-2α, culminating in transcriptional regulation of key angiogenesis pathways. These findings uncover for the first time an important and previously unsuspected role for peroxidases as drivers of angiogenesis, and suggest that peroxidase inhibitors may have therapeutic potential for the treatment of angiogenesis related diseases driven by inflammation. PMID:26386352

  13. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    PubMed Central

    Kilpeläinen, Tuomas O.; Carli, Jayne F. Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H.; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Greco M, Fabiola Del; Pasko, Dorota; Renström, Frida; Willems, Sara M.; Mahajan, Anubha; Rose, Lynda M.; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E.; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S.; Ju Sung, Yun; Ramos, Yolande F.; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M.; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J. N.; Crosslin, David R.; Dale, Caroline E.; Dastani, Zari; Day, Felix R.; Deelen, Joris; Delgado, Graciela E.; Demirkan, Ayse; Finucane, Francis M.; Ford, Ian; Garcia, Melissa E.; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E.; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A.; Hunter, David J.; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S.; Jørgensen, Marit E.; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A.; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P.; Myers, Richard H.; Männistö, Satu; Nalls, Mike A.; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rathmann, Wolfgang; Rice, Treva K.; Brent Richards, J; Ridker, Paul M.; Sattar, Naveed; Savage, David B.; Söderberg, Stefan; Timpson, Nicholas J.; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R.; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I. A.; Sarzynski, Mark A.; Rao, D. C.; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G.; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G.; Heliövaara, Markku; Knekt, Paul B.; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K.; Viikari, Jorma S.; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T.; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P.; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W.; van Duijn, Cornelia M.; Harris, Tamara B.; Bouchard, Claude; Allison, Matthew A.; Chasman, Daniel I.; Ohlsson, Claes; Lind, Lars; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.; Ferrucci, Luigi; Frayling, Timothy M.; Pramstaller, Peter P.; Borecki, Ingrid B.; Waterworth, Dawn M.; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B.; Eline Slagboom, P; Grallert, Harald; Spector, Tim D.; Jukema, J.W.; Klein, Robert J.; Schadt, Erik E; Franks, Paul W.; Lindgren, Cecilia M.; Leibel, Rudolph L.; Loos, Ruth J. F.

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10−8) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  14. Effectiveness of WISE colour-based selection techniques to uncover obscured AGN

    NASA Astrophysics Data System (ADS)

    Mateos, S.

    2014-07-01

    We present a highly reliable and efficient mid-infrared colour-based selection technique for luminous active galactic nuclei (AGN) using the Wide-field Infrared Survey Explorer (WISE) survey. Our technique is designed to identify objects with red mid-infrared power-law spectral energy distributions. We studied the dependency of our mid-infrared selection on the AGN intrinsic luminosity and the effectiveness of our technique to uncover obscured AGN missed in X-ray surveys. To do so we used two samples of luminous AGN independently selected in hard X-ray and optical surveys. We used the largest catalogue of 887 [OIII] λ5007-selected type 2 quasars (QSO2s) at z<~0.83 in the literature from the Sloan Digital Sky Survey (SDSS), and the 258 hard (>4.5 keV) X-ray-selected AGN from the Bright Ultrahard XMM-Newton Survey (BUXS). The effectiveness of our mid-infrared selection technique increases with the AGN luminosity. At high luminosities and at least up to z~1 our technique is very effective at identifying both Compton-thin and Compton-thick AGN.

  15. Percutaneous Treatment of Malignant Jaundice Due to Extrahepatic Cholangiocarcinoma: Covered Viabil Stent Versus Uncovered Wallstents

    SciTech Connect

    Krokidis, Miltiadis; Fanelli, Fabrizio; Orgera, Gianluigi; Bezzi, Mario; Passariello, Roberto; Hatzidakis, Adam

    2010-02-15

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement.

  16. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma.

    PubMed

    Zhang, Xindong; Gao, Lin; Liu, Zhi-Ping; Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data. PMID:27610367

  17. Uncovering DELLA-Independent Gibberellin Responses by Characterizing New Tomato procera Mutants

    PubMed Central

    Livne, Sivan; Lor, Vai S.; Nir, Ido; Eliaz, Natanella; Aharoni, Asaph; Olszewski, Neil E.; Eshed, Yuval; Weiss, David

    2015-01-01

    Gibberellin (GA) regulates plant development primarily by triggering the degradation/deactivation of the DELLA proteins. However, it remains unclear whether all GA responses are regulated by DELLAs. Tomato (Solanum lycopersicum) has a single DELLA gene named PROCERA (PRO), and its recessive pro allele exhibits constitutive GA activity but retains responsiveness to external GA. In the loss-of-function mutant proΔGRAS, all examined GA developmental responses were considerably enhanced relative to pro and a defect in seed desiccation tolerance was uncovered. As pro, but not proΔGRAS, elongation was promoted by GA treatment, pro may retain residual DELLA activity. In agreement with homeostatic feedback regulation of the GA biosynthetic pathway, we found that GA20oxidase1 expression was suppressed in proΔGRAS and was not affected by exogenous GA3. In contrast, expression of GA2oxidase4 was not affected by the elevated GA signaling in proΔGRAS but was strongly induced by exogenous GA3. Since a similar response was found in Arabidopsis thaliana plants with impaired activity of all five DELLA genes, we suggest that homeostatic GA responses are regulated by both DELLA-dependent and -independent pathways. Transcriptome analysis of GA-treated proΔGRAS leaves suggests that 5% of all GA-regulated genes in tomato are DELLA independent. PMID:26036254

  18. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    PubMed Central

    Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

    2016-01-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications. PMID:27087555

  19. Perturbations in small molecule synthesis uncovers an iron-responsive secondary metabolite network in Aspergillus fumigatus

    PubMed Central

    Wiemann, Philipp; Lechner, Beatrix E.; Baccile, Joshua A.; Velk, Thomas A.; Yin, Wen-Bing; Bok, Jin Woo; Pakala, Suman; Losada, Liliana; Nierman, William C.; Schroeder, Frank C.; Haas, Hubertus; Keller, Nancy P.

    2014-01-01

    Iron plays a critical role in survival and virulence of the opportunistic pathogen Aspergillus fumigatus. Two transcription factors, the GATA-factor SreA and the bZip-factor HapX oppositely monitor iron homeostasis with HapX activating iron acquisition pathways (e.g., siderophores) and shutting down iron consumptive pathways (and SreA) during iron starvation conditions whereas SreA negatively regulates HapX and corresponding pathways during iron sufficiency. Recently the non-ribosomal peptide, hexadehydroastechrome (HAS; a tryptophan-derived iron (III)-complex), has been found important in A. fumigatus virulence. We found that HAS overproduction caused an iron starvation phenotype, from alteration of siderophore pools to regulation of iron homeostasis gene expression including sreA. Moreover, we uncovered an iron dependent secondary metabolism network where both SreA and HapX oppositely regulate multiple other secondary metabolites including HAS. This circuitry links iron-acquisition and consumption pathways with secondary metabolism—thus placing HAS as part of a metabolic feedback circuitry designed to balance iron pools in the fungus and presenting iron availability as one environmental trigger of secondary metabolism. PMID:25386169

  20. Uncovering secrets behind low-resistance planing craft hull forms through optimization

    NASA Astrophysics Data System (ADS)

    Mohamad Ayob, Ahmad F.; Ray, Tapabrata; Smith, Warren F.

    2011-11-01

    There has always been significant interest within the naval architectural research community to identify ship hull forms with low resistance. While numerous design optimization frameworks have been proposed over the years to support the activity, very little attention has been paid towards the process of gaining an understanding of 'what makes a good ship design superior?'. Furthermore, there have been limited attempts to identify computationally cheap indicators that can be used to distinguish between good and poor designs. A recent technique named discovery of innovative design principles, which is aimed at understanding the relationship between the design variables, is incorporated in this work. In this article, optimal high-speed planing craft hull forms with minimum calm-water resistance are identified through the use of three state-of-the-art optimization algorithms. Collections of such designs are then used to uncover insights into the underlying relationships between the variables. The importance of such relationships is further analysed to identify computationally cheap performance indicators that can be used in lieu of detailed calm-water resistance calculations. Such indicators are useful at the concept and preliminary design stages, where one needs to sieve efficiently through a number of candidate designs to identify the better ones for further analysis.

  1. Structural phylogenomics uncovers the early and concurrent origins of cysteine biosynthesis and iron-sulfur proteins.

    PubMed

    Zhang, Hong-Yu; Qin, Tao; Jiang, Ying-Ying; Caetano-Anollés, Gustavo

    2012-01-01

    Cysteine (Cys) has unique chemical properties of catalysis, metal chelation, and protein stabilization. While Cys biosynthesis is assumed to be very ancient, the actual time of origin of these metabolic pathways remains unknown. Here, we use the molecular clocks of protein folds and fold superfamilies to time the origin of Cys biosynthesis. We find that the tRNA-dependent biosynthetic pathway appeared ~3.5 billion years ago while the tRNA-independent counterpart emerged ~500 million years later. A deep analysis of the origins of Cys biosynthesis in the context of emerging biochemistry uncovers some intriguing features of the planetary environment of early Earth. Results suggest that iron-sulfur (Fe-S) proteins that use cysteinyl sulfur to bind iron atoms were not the first to arise in evolution. Instead, their origin coincides with the appearance of the first Cys biosynthetic pathway. It is therefore likely that Cys did not play an important role in the make up of primordial protein molecules and that Fe-S clusters were not part of active sites at the beginning of biological history. PMID:22731683

  2. Covered Stents versus Uncovered Stents for Unresectable Malignant Biliary Strictures: A Meta-Analysis

    PubMed Central

    Chen, Ming-Yu; Lin, Jia-Wei; Zhu, He-Pan; Zhang, Bin; Jiang, Guang-Yi; Yan, Pei-Jian; Cai, Xiu-Jun

    2016-01-01

    Aim. To summarize the covered or uncovered SEMS for treatment of unresectable malignant distal biliary obstruction, comparing the stent patency, patient survival, and incidence of adverse events between the two SEMSs. Methods. The meta-analysis search was performed independently by two of the authors, using MEDLINE, EMBASE, OVID, and Cochrane databases on all studies between 2010 and 2015. Pooled effect was calculated using either the fixed or the random effects model. Results. Statistics shows that there is no difference between SEMSs in the hazard ratio for patient survival (HR 1.04; 95% CI, 0.92–1.17; P = 0.55) and stent patency (HR 0.87, 95% CI: 0.58 to 1.30, P = 0.5). However, incidence of adverse events (OR: 0.74, 95% CI: 0.57 to 0.97, P = 0.03) showed significant different results in the covered SEMS, with dysfunctions events (OR: 0.75, 95% CI: 0.56 to 1.00, P = 0.05) playing a more important role than complications (OR: 0.87, 95% CI: 0.58 to 1.30, P = 0.50). Conclusions. Covered SEMS group had lower incidence of adverse events. There is no significant difference in dysfunctions, but covered SEMS trends to be better, with no difference in stent patency, patient survival, and complications. PMID:27051667

  3. Profiling and Racial Profiling: An Interactive Exercise

    ERIC Educational Resources Information Center

    Semple, Philip

    2013-01-01

    Racial Profiling has been recognized as a serious problem that affects many segments of our society and is especially notable in law enforcement. Governments and police services have pronounced that racial profiling is not acceptable and will not be tolerated. They have gone to great lengths in trying to eradicate racial profiling through…

  4. Syphilis Profiles, 2012

    MedlinePlus

    ... STD on Facebook Data & Statistics Sexually Transmitted Diseases Syphilis Profiles, 2012 Recommend on Facebook Tweet Share Compartir ... Profiles The following profiles provide an overview of syphilis morbidity in each of the 50 states, the ...

  5. COMPENDEX Profiling Guide.

    ERIC Educational Resources Information Center

    Standera, Oldrich

    This manual provides instructions for completing the COMPENDEX (Computerized Engineering Index) Profile Submission Form used to prepare Current Information Selection (CIS) profiles. An annotated bibliography lists nine items useful in searching for proper profile words. (AB)

  6. RNA-Seq Uncovers SNPs and Alternative Splicing Events in Asian Lotus (Nelumbo nucifera).

    PubMed

    Yang, Mei; Xu, Liming; Liu, Yanling; Yang, Pingfang

    2015-01-01

    RNA-Seq is an efficient way to comprehensively identify single nucleotide polymorphisms (SNPs) and alternative splicing (AS) events from the expressed genes. In this study, we conducted transcriptome sequencing of four Asian lotus (Nelumbo nucifera) cultivars using Illumina HiSeq2000 platform to identify SNPs and AS events in lotus. A total of 505 million pair-end RNA-Seq reads were generated from four cultivars, of which 86% were mapped to the lotus reference genome. Using the four sets of data together, a total of 357,689 putative SNPs were identified with an average density of one SNP per 2.2 kb. These SNPs were located in 1,253 scaffolds and 15,016 expressed genes. A/G and C/T were the two major types of SNPs in the Asian lotus transcriptome. In parallel, a total of 177,540 AS events were detected in the four cultivars and were distributed in 64% of the expressed genes of lotus. The predominant type of AS events was alternative 5' first exon, which accounted for 41.2% of all the observed AS events, and exon skipping only accounted for 4.3% of all AS. Gene Ontology analysis was conducted to analyze the function of the genes containing SNPs and AS events. Validation of selected SNPs and AS events revealed that 74% of SNPs and 80% of AS events were reliable, which indicates that RNA-Seq is an efficient approach to uncover gene-associated SNPs and AS events. A large number of SNPs and AS events identified in our study will facilitate further genetic and functional genomics research in lotus. PMID:25928215

  7. The proteome and phosphoproteome of maize pollen uncovers fertility candidate proteins.

    PubMed

    Chao, Qing; Gao, Zhi-Fang; Wang, Yue-Feng; Li, Zhe; Huang, Xia-He; Wang, Ying-Chun; Mei, Ying-Chang; Zhao, Biligen-Gaowa; Li, Liang; Jiang, Yu-Bo; Wang, Bai-Chen

    2016-06-01

    Maize is unique since it is both monoecious and diclinous (separate male and female flowers on the same plant). We investigated the proteome and phosphoproteome of maize pollen containing modified proteins and here we provide a comprehensive pollen proteome and phosphoproteome which contain 100,990 peptides from 6750 proteins and 5292 phosphorylated sites corresponding to 2257 maize phosphoproteins, respectively. Interestingly, among the total 27 overrepresented phosphosite motifs we identified here, 11 were novel motifs, which suggested different modification mechanisms in plants compared to those of animals. Enrichment analysis of pollen phosphoproteins showed that pathways including DNA synthesis/chromatin structure, regulation of RNA transcription, protein modification, cell organization, signal transduction, cell cycle, vesicle transport, transport of ions and metabolisms, which were involved in pollen development, the following germination and pollen tube growth, were regulated by phosphorylation. In this study, we also found 430 kinases and 105 phosphatases in the maize pollen phosphoproteome, among which calcium dependent protein kinases (CDPKs), leucine rich repeat kinase, SNF1 related protein kinases and MAPK family proteins were heavily enriched and further analyzed. From our research, we also uncovered hundreds of male sterility-associated proteins and phosphoproteins that might influence maize productivity and serve as targets for hybrid maize seed production. At last, a putative complex signaling pathway involving CDPKs, MAPKs, ubiquitin ligases and multiple fertility proteins was constructed. Overall, our data provides new insight for further investigation of protein phosphorylation status in mature maize pollen and construction of maize male sterile mutants in the future. PMID:26969016

  8. Step selection techniques uncover the environmental predictors of space use patterns in flocks of Amazonian birds

    PubMed Central

    Potts, Jonathan R; Mokross, Karl; Stouffer, Philip C; Lewis, Mark A

    2014-01-01

    Understanding the behavioral decisions behind animal movement and space use patterns is a key challenge for behavioral ecology. Tools to quantify these patterns from movement and animal–habitat interactions are vital for transforming ecology into a predictive science. This is particularly important in environments undergoing rapid anthropogenic changes, such as the Amazon rainforest, where animals face novel landscapes. Insectivorous bird flocks are key elements of avian biodiversity in the Amazonian ecosystem. Therefore, disentangling and quantifying the drivers behind their movement and space use patterns is of great importance for Amazonian conservation. We use a step selection function (SSF) approach to uncover environmental drivers behind movement choices. This is used to construct a mechanistic model, from which we derive predicted utilization distributions (home ranges) of flocks. We show that movement decisions are significantly influenced by canopy height and topography, but depletion and renewal of resources do not appear to affect movement significantly. We quantify the magnitude of these effects and demonstrate that they are helpful for understanding various heterogeneous aspects of space use. We compare our results to recent analytic derivations of space use, demonstrating that the analytic approximation is only accurate when assuming that there is no persistence in the animals' movement. Our model can be translated into other environments or hypothetical scenarios, such as those given by proposed future anthropogenic actions, to make predictions of spatial patterns in bird flocks. Furthermore, our approach is quite general, so could potentially be used to understand the drivers of movement and spatial patterns for a wide variety of animal communities. PMID:25558353

  9. Uncovering multiple populations with washington photometry. I. The globular cluster NGC 1851

    SciTech Connect

    Cummings, Jeffrey D.; Geisler, D.; Villanova, S.; Carraro, G.

    2014-08-01

    The analysis of multiple populations (MPs) in globular clusters (GCs) has become a forefront area of research in astronomy. Multiple red giant branches (RGBs), subgiant branches (SGBs), and even main sequences (MSs) have now been observed photometrically in many GCs, while broad abundance distributions of certain elements have been detected spectroscopically in most, if not all, GCs. UV photometry has been crucial in discovering and analyzing these MPs, but the Johnson U and the Stromgren and Sloan u filters that have generally been used are relatively inefficient and very sensitive to reddening and atmospheric extinction. In contrast, the Washington C filter is much broader and redder than these competing UV filters, making it far more efficient at detecting MPs and much less sensitive to reddening and extinction. Here, we investigate the use of the Washington system to uncover MPs using only a 1 m telescope. Our analysis of the well-studied GC NGC 1851 finds that the C filter is both very efficient and effective at detecting its previously discovered MPs in the RGB and SGB. Remarkably, we have also detected an intrinsically broad MS best characterized by two distinct but heavily overlapping populations that cannot be explained by binaries, field stars, or photometric errors. The MS distribution is in very good agreement with that seen on the RGB, with ∼30% of the stars belonging to the second population. There is also evidence for two sequences in the red horizontal branch, but this appears to be unrelated to the MPs in this cluster. Neither of these latter phenomena have been observed previously in this cluster. The redder MS stars are also more centrally concentrated than the blue MS. This is the first time MPs in an MS have been discovered from the ground, and using only a 1 m telescope. The Washington system thus proves to be a very powerful tool for investigating MPs, and holds particular promise for extragalactic objects where photons are limited.

  10. Analysis of retrotransposon structural diversity uncovers properties and propensities in angiosperm genome evolution

    PubMed Central

    Vitte, Clémentine; Bennetzen, Jeffrey L.

    2006-01-01

    Analysis of LTR retrotransposon structures in five diploid angiosperm genomes uncovered very different relative levels of different types of genomic diversity. All species exhibited recent LTR retrotransposon mobility and also high rates of DNA removal by unequal homologous recombination and illegitimate recombination. The larger plant genomes contained many LTR retrotransposon families with >10,000 copies per haploid genome, whereas the smaller genomes contained few or no LTR retrotransposon families with >1,000 copies, suggesting that this differential potential for retroelement amplification is a primary factor in angiosperm genome size variation. The average ratios of transition to transversion mutations (Ts/Tv) in diverging LTRs were >1.5 for each species studied, suggesting that these elements are mostly 5-methylated at cytosines in an epigenetically silenced state. However, the diploid wheat Triticum monococcum and barley have unusually low Ts/Tv values (respectively, 1.9 and 1.6) compared with maize (3.9), medicago (3.6), and lotus (2.5), suggesting that this silencing is less complete in the two Triticeae. Such characteristics as the ratios of point mutations to indels (insertions and deletions) and the relative efficiencies of DNA removal by unequal homologous recombination compared with illegitimate recombination were highly variable between species. These latter variations did not correlate with genome size or phylogenetic relatedness, indicating that they frequently change during the evolutionary descent of plant lineages. In sum, the results indicate that the different sizes, contents, and structures of angiosperm genomes are outcomes of the same suite of mechanistic processes, but acting with different relative efficiencies in different plant lineages. PMID:17101966

  11. Uncovering paradoxes from physicians' experiences of patient-centered ward-round.

    PubMed

    Bååthe, Fredrik; Ahlborg, Gunnar; Edgren, Lars; Lagström, Annica; Nilsson, Kerstin

    2016-05-01

    Purpose The purpose of this paper is to uncover paradoxes emerging from physicians' experiences of a patient-centered and team-based ward round, in an internal medicine department. Design/methodology/approach Abductive reasoning relates empirical material to complex responsive processes theory in a dialectical process to further understandings. Findings This paper found the response from physicians, to a patient-centered and team-based ward round, related to whether the new demands challenged or confirmed individual physician's professional identity. Two empirically divergent perspectives on enacting the role of physician during ward round emerged: We-perspective and I-perspective, based on where the physician's professional identity was centered. Physicians with more of a We-perspective experienced challenges with the new round, while physicians with more of an I-perspective experienced alignment with their professional identity and embraced the new round. When identity is challenged, anxiety is aroused, and if anxiety is not catered to, then resistance is likely to follow and changes are likely to be hampered. Practical implications For change processes affecting physicians' professional identity, it is important for managers and change leaders to acknowledge paradox and find a balance between new knowledge that needs to be learnt and who the physician is becoming in this new procedure. Originality/value This paper provides increased understanding about how physicians' professional identity is interacting with a patient-centered ward round. It adds to the knowledge about developing health care in line with recent societal requests and with sustainable physician engagement. PMID:27198705

  12. RNA shotgun metagenomic sequencing of northern California (USA) mosquitoes uncovers viruses, bacteria, and fungi

    PubMed Central

    Chandler, James Angus; Liu, Rachel M.; Bennett, Shannon N.

    2015-01-01

    Mosquitoes, most often recognized for the microbial agents of disease they may carry, harbor diverse microbial communities that include viruses, bacteria, and fungi, collectively called the microbiota. The composition of the microbiota can directly and indirectly affect disease transmission through microbial interactions that could be revealed by its characterization in natural populations of mosquitoes. Furthermore, the use of shotgun metagenomic sequencing (SMS) approaches could allow the discovery of unknown members of the microbiota. In this study, we use RNA SMS to characterize the microbiota of seven individual mosquitoes (species include Culex pipiens, Culiseta incidens, and Ochlerotatus sierrensis) collected from a variety of habitats in California, USA. Sequencing was performed on the Illumina HiSeq platform and the resulting sequences were quality-checked and assembled into contigs using the A5 pipeline. Sequences related to single stranded RNA viruses of the Bunyaviridae and Rhabdoviridae were uncovered, along with an unclassified genus of double-stranded RNA viruses. Phylogenetic analysis finds that in all three cases, the closest relatives of the identified viral sequences are other mosquito-associated viruses, suggesting widespread host-group specificity among disparate viral taxa. Interestingly, we identified a Narnavirus of fungi, also reported elsewhere in mosquitoes, that potentially demonstrates a nested host-parasite association between virus, fungi, and mosquito. Sequences related to 8 bacterial families and 13 fungal families were found across the seven samples. Bacillus and Escherichia/Shigella were identified in all samples and Wolbachia was identified in all Cx. pipiens samples, while no single fungal genus was found in more than two samples. This study exemplifies the utility of RNA SMS in the characterization of the natural microbiota of mosquitoes and, in particular, the value of identifying all microbes associated with a specific host

  13. Decomposition of brain diffusion imaging data uncovers latent schizophrenias with distinct patterns of white matter anisotropy.

    PubMed

    Arnedo, Javier; Mamah, Daniel; Baranger, David A; Harms, Michael P; Barch, Deanna M; Svrakic, Dragan M; de Erausquin, Gabriel A; Cloninger, C Robert; Zwir, Igor

    2015-10-15

    Fractional anisotropy (FA) analysis of diffusion tensor-images (DTI) has yielded inconsistent abnormalities in schizophrenia (SZ). Inconsistencies may arise from averaging heterogeneous groups of patients. Here we investigate whether SZ is a heterogeneous group of disorders distinguished by distinct patterns of FA reductions. We developed a Generalized Factorization Method (GFM) to identify biclusters (i.e., subsets of subjects associated with a subset of particular characteristics, such as low FA in specific regions). GFM appropriately assembles a collection of unsupervised techniques with Non-negative Matrix Factorization to generate biclusters, rather than averaging across all subjects and all their characteristics. DTI tract-based spatial statistics images, which output is the locally maximal FA projected onto the group white matter skeleton, were analyzed in 47 SZ and 36 healthy subjects, identifying 8 biclusters. The mean FA of the voxels of each bicluster was significantly different from those of other SZ subjects or 36 healthy controls. The eight biclusters were organized into four more general patterns of low FA in specific regions: 1) genu of corpus callosum (GCC), 2) fornix (FX)+external capsule (EC), 3) splenium of CC (SCC)+retrolenticular limb (RLIC)+posterior limb (PLIC) of the internal capsule, and 4) anterior limb of the internal capsule. These patterns were significantly associated with particular clinical features: Pattern 1 (GCC) with bizarre behavior, pattern 2 (FX+EC) with prominent delusions, and pattern 3 (SCC+RLIC+PLIC) with negative symptoms including disorganized speech. The uncovered patterns suggest that SZ is a heterogeneous group of disorders that can be distinguished by different patterns of FA reductions associated with distinct clinical features. PMID:26151103

  14. Step selection techniques uncover the environmental predictors of space use patterns in flocks of Amazonian birds.

    PubMed

    Potts, Jonathan R; Mokross, Karl; Stouffer, Philip C; Lewis, Mark A

    2014-12-01

    Understanding the behavioral decisions behind animal movement and space use patterns is a key challenge for behavioral ecology. Tools to quantify these patterns from movement and animal-habitat interactions are vital for transforming ecology into a predictive science. This is particularly important in environments undergoing rapid anthropogenic changes, such as the Amazon rainforest, where animals face novel landscapes. Insectivorous bird flocks are key elements of avian biodiversity in the Amazonian ecosystem. Therefore, disentangling and quantifying the drivers behind their movement and space use patterns is of great importance for Amazonian conservation. We use a step selection function (SSF) approach to uncover environmental drivers behind movement choices. This is used to construct a mechanistic model, from which we derive predicted utilization distributions (home ranges) of flocks. We show that movement decisions are significantly influenced by canopy height and topography, but depletion and renewal of resources do not appear to affect movement significantly. We quantify the magnitude of these effects and demonstrate that they are helpful for understanding various heterogeneous aspects of space use. We compare our results to recent analytic derivations of space use, demonstrating that the analytic approximation is only accurate when assuming that there is no persistence in the animals' movement. Our model can be translated into other environments or hypothetical scenarios, such as those given by proposed future anthropogenic actions, to make predictions of spatial patterns in bird flocks. Furthermore, our approach is quite general, so could potentially be used to understand the drivers of movement and spatial patterns for a wide variety of animal communities. PMID:25558353

  15. Sub-footprint analysis to uncover tree height variation using ICESat/GLAS

    NASA Astrophysics Data System (ADS)

    Tian, Jinyan; Wang, Le; Li, Xiaojuan

    2015-03-01

    Detailed forest height data are an indispensable prerequisite for many forestry and earth science applications. Existing research of using Geoscience Laser Altimeter System (GLAS) data mainly focuses on deriving average or maximum tree heights within a GLAS footprint, i.e. an ellipse with a diameter of 65 m. However, in most forests, it is likely that the tree heights within such ellipse are heterogeneous. Therefore, it is desired to uncover detailed tree height variation within a GLAS footprint. To the best of our knowledge, no such methods have been reported as of now. In this study, we aim to characterize tree heights' variation within a GLAS footprint as different layers, each of which corresponds to trees with similar heights. As such, we developed a new method that embraces two steps: first, a refined Levenberg-Marquardt (LM) algorithm is proposed to decompose raw GLAS waveform into multiple Gaussian signals, within which it is hypothesized that each vegetation signal corresponds to a particular tree height layer. Second, for each layer, three parameters were first defined: Canopy Top Height (CTH), Crown Length (CL), and Cover Proportion (CP). Then we extracted the three parameters from each Gaussian signal through a defined model. In order to test our developed method, we set up a study site in Ejina, China where the dominant specie is Populus euphratica. Both simulated and field tree height data were adopted. With regard to the simulation data, results presented a very high agreement for the three predefined parameters between our results and simulation data. When our methods were applied to the field data, the respective R2 become 0.78 (CTH), CL (R2 = 0.76), CP (R2 = 0.74). Overall, our studies revealed that large footprint GLAS waveform data have the potentials for obtaining detailed forest height variation.

  16. Uncovering protein interaction in abstracts and text using a novel linear model and word proximity networks

    PubMed Central

    Abi-Haidar, Alaa; Kaur, Jasleen; Maguitman, Ana; Radivojac, Predrag; Rechtsteiner, Andreas; Verspoor, Karin; Wang, Zhiping; Rocha, Luis M

    2008-01-01

    Background: We participated in three of the protein-protein interaction subtasks of the Second BioCreative Challenge: classification of abstracts relevant for protein-protein interaction (interaction article subtask [IAS]), discovery of protein pairs (interaction pair subtask [IPS]), and identification of text passages characterizing protein interaction (interaction sentences subtask [ISS]) in full-text documents. We approached the abstract classification task with a novel, lightweight linear model inspired by spam detection techniques, as well as an uncertainty-based integration scheme. We also used a support vector machine and singular value decomposition on the same features for comparison purposes. Our approach to the full-text subtasks (protein pair and passage identification) includes a feature expansion method based on word proximity networks. Results: Our approach to the abstract classification task (IAS) was among the top submissions for this task in terms of measures of performance used in the challenge evaluation (accuracy, F-score, and area under the receiver operating characteristic curve). We also report on a web tool that we produced using our approach: the Protein Interaction Abstract Relevance Evaluator (PIARE). Our approach to the full-text tasks resulted in one of the highest recall rates as well as mean reciprocal rank of correct passages. Conclusion: Our approach to abstract classification shows that a simple linear model, using relatively few features, can generalize and uncover the conceptual nature of protein-protein interactions from the bibliome. Because the novel approach is based on a rather lightweight linear model, it can easily be ported and applied to similar problems. In full-text problems, the expansion of word features with word proximity networks is shown to be useful, although the need for some improvements is discussed. PMID:18834489

  17. Destroyed documents: uncovering the science that Imperial Tobacco Canada sought to conceal

    PubMed Central

    Hammond, David; Chaiton, Michael; Lee, Alex; Collishaw, Neil

    2009-01-01

    Background In 1992, British American Tobacco had its Canadian affiliate, Imperial Tobacco Canada, destroy internal research documents that could expose the company to liability or embarrassment. Sixty of these destroyed documents were subsequently uncovered in British American Tobacco’s files. Methods Legal counsel for Imperial Tobacco Canada provided a list of 60 destroyed documents to British American Tobacco. Information in this list was used to search for copies of the documents in British American Tobacco files released through court disclosure. We reviewed and summarized this information. Results Imperial Tobacco destroyed documents that included evidence from scientific reviews prepared by British American Tobacco’s researchers, as well as 47 original research studies, 35 of which examined the biological activity and carcinogenicity of tobacco smoke. The documents also describe British American Tobacco research on cigarette modifications and toxic emissions, including the ways in which consumers adapted their smoking behaviour in response to these modifications. The documents also depict a comprehensive research program on the pharmacology of nicotine and the central role of nicotine in smoking behaviour. British American Tobacco scientists noted that “… the present scale of the tobacco industry is largely dependent on the intensity and nature of the pharmacological action of nicotine,” and that “... should nicotine become less attractive to smokers, the future of the tobacco industry would become less secure.” Interpretation The scientific evidence contained in the documents destroyed by Imperial Tobacco demonstrates that British American Tobacco had collected evidence that cigarette smoke was carcinogenic and addictive. The evidence that Imperial Tobacco sought to destroy had important implications for government regulation of tobacco. PMID:19828670

  18. Multivariate weighted recurrence network inference for uncovering oil-water transitional flow behavior in a vertical pipe

    NASA Astrophysics Data System (ADS)

    Gao, Zhong-Ke; Yang, Yu-Xuan; Cai, Qing; Zhang, Shan-Shan; Jin, Ning-De

    2016-06-01

    Exploring the dynamical behaviors of high water cut and low velocity oil-water flows remains a contemporary and challenging problem of significant importance. This challenge stimulates us to design a high-speed cycle motivation conductance sensor to capture spatial local flow information. We systematically carry out experiments and acquire the multi-channel measurements from different oil-water flow patterns. Then we develop a novel multivariate weighted recurrence network for uncovering the flow behaviors from multi-channel measurements. In particular, we exploit graph energy and weighted clustering coefficient in combination with multivariate time-frequency analysis to characterize the derived complex networks. The results indicate that the network measures are very sensitive to the flow transitions and allow uncovering local dynamical behaviors associated with water cut and flow velocity. These properties render our method particularly useful for quantitatively characterizing dynamical behaviors governing the transition and evolution of different oil-water flow patterns.

  19. Multivariate weighted recurrence network inference for uncovering oil-water transitional flow behavior in a vertical pipe.

    PubMed

    Gao, Zhong-Ke; Yang, Yu-Xuan; Cai, Qing; Zhang, Shan-Shan; Jin, Ning-De

    2016-06-01

    Exploring the dynamical behaviors of high water cut and low velocity oil-water flows remains a contemporary and challenging problem of significant importance. This challenge stimulates us to design a high-speed cycle motivation conductance sensor to capture spatial local flow information. We systematically carry out experiments and acquire the multi-channel measurements from different oil-water flow patterns. Then we develop a novel multivariate weighted recurrence network for uncovering the flow behaviors from multi-channel measurements. In particular, we exploit graph energy and weighted clustering coefficient in combination with multivariate time-frequency analysis to characterize the derived complex networks. The results indicate that the network measures are very sensitive to the flow transitions and allow uncovering local dynamical behaviors associated with water cut and flow velocity. These properties render our method particularly useful for quantitatively characterizing dynamical behaviors governing the transition and evolution of different oil-water flow patterns. PMID:27368782

  20. Optical coherence tomography derived cut-off value of uncovered stent struts to predict adverse clinical outcomes after drug-eluting stent implantation.

    PubMed

    Won, Hoyoun; Shin, Dong-Ho; Kim, Byeong-Keuk; Mintz, Gary S; Kim, Jung-Sun; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

    2013-08-01

    Although the presence of uncovered struts may be associated with occurrence of stent thrombosis, the impact of uncovered struts detected routinely by optical coherence tomography (OCT) on subsequent long-term clinical outcomes remains unclear. The objective of this study was to determine the cut-off value of uncovered struts that predicted adverse clinical outcomes after drug eluting stent (DES) implantation. Major safety events (MSEs, a composite occurrence of cardiovascular death, myocardial infarction, and stent thrombosis) were evaluated in 489 DES-treated patients (535 lesions) during the median 851 days after follow-up OCT. MSEs occurred in six patients (four definite stent thrombosis and two sudden cardiac death). The best cut-off value of percentage of uncovered struts for predicting MSE was 5.9 % using the maximal χ(2) method: area under the receiver-operating characteristic curve = 0.779, 95 % confidence interval (CI) = 0.648-0.910, p = 0.019, a sensitivity of 83.3 % and a specificity of 70.3 %. Independent predictors for MSE were post-intervention minimal lumen diameter (odds ratio 0.019, 95 % CI = 0.001-0.513, p = 0.018) and percentage of uncovered struts ≥5.9 % (odds ratio 19.781, 95 % CI = 2.071-188.968, p = 0.010). A greater percentage of uncovered struts (the cut-off value of ≥5.9 % uncovered struts) might be significantly associated with occurrence of MSE after DES implantation. PMID:23615849

  1. Self-Efficacy Beliefs and Mental Time Travel Ability: Uncovering a Hidden Relationship in Educational Settings

    ERIC Educational Resources Information Center

    Eren, Altay

    2009-01-01

    The aim of this study was threefold: first, it was to explore the profiles of student teachers' mental time travel ability; second, it was to examine the relationship between student teachers' mental time travel ability and self-efficacy beliefs; and third, it was to investigate the role of self-efficacy beliefs in relationship between the past…

  2. Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes

    PubMed Central

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

    2012-01-01

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

  3. Panoramic view of a superfamily of phosphatases through substrate profiling.

    PubMed

    Huang, Hua; Pandya, Chetanya; Liu, Chunliang; Al-Obaidi, Nawar F; Wang, Min; Zheng, Li; Toews Keating, Sarah; Aono, Miyuki; Love, James D; Evans, Brandon; Seidel, Ronald D; Hillerich, Brandan S; Garforth, Scott J; Almo, Steven C; Mariano, Patrick S; Dunaway-Mariano, Debra; Allen, Karen N; Farelli, Jeremiah D

    2015-04-21

    Large-scale activity profiling of enzyme superfamilies provides information about cellular functions as well as the intrinsic binding capabilities of conserved folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase superfamily (HADSF) was revealed by screening a customized substrate library against >200 enzymes from representative prokaryotic species, enabling inferred annotation of ∼35% of the HADSF. An extremely high level of substrate ambiguity was revealed, with the majority of HADSF enzymes using more than five substrates. Substrate profiling allowed assignment of function to previously unannotated enzymes with known structure, uncovered potential new pathways, and identified iso-functional orthologs from evolutionarily distant taxonomic groups. Intriguingly, the HADSF subfamily having the least structural elaboration of the Rossmann fold catalytic domain was the most specific, consistent with the concept that domain insertions drive the evolution of new functions and that the broad specificity observed in HADSF may be a relic of this process. PMID:25848029

  4. Panoramic view of a superfamily of phosphatases through substrate profiling

    PubMed Central

    Huang, Hua; Pandya, Chetanya; Liu, Chunliang; Al-Obaidi, Nawar F.; Wang, Min; Zheng, Li; Toews Keating, Sarah; Aono, Miyuki; Love, James D.; Evans, Brandon; Seidel, Ronald D.; Hillerich, Brandan S.; Garforth, Scott J.; Almo, Steven C.; Mariano, Patrick S.; Dunaway-Mariano, Debra; Allen, Karen N.; Farelli, Jeremiah D.

    2015-01-01

    Large-scale activity profiling of enzyme superfamilies provides information about cellular functions as well as the intrinsic binding capabilities of conserved folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase superfamily (HADSF) was revealed by screening a customized substrate library against >200 enzymes from representative prokaryotic species, enabling inferred annotation of ∼35% of the HADSF. An extremely high level of substrate ambiguity was revealed, with the majority of HADSF enzymes using more than five substrates. Substrate profiling allowed assignment of function to previously unannotated enzymes with known structure, uncovered potential new pathways, and identified iso-functional orthologs from evolutionarily distant taxonomic groups. Intriguingly, the HADSF subfamily having the least structural elaboration of the Rossmann fold catalytic domain was the most specific, consistent with the concept that domain insertions drive the evolution of new functions and that the broad specificity observed in HADSF may be a relic of this process. PMID:25848029

  5. Single-Cell Analysis Uncovers Extensive Biological Noise in Poliovirus Replication

    PubMed Central

    Schulte, Michael B.

    2014-01-01

    ABSTRACT Viral infections often begin with a very small number of initiating particles. Accordingly, the outcome of an infection is likely to be affected by variability in the initial molecular interactions between virus and host. In this study, we investigated the range of outcomes upon infection of single cells. We isolated individual cells infected with poliovirus at low or high multiplicities of infection (MOI) and measured viral genomic replication and infectious viral progeny in each cell. We first determined that at 7 h postinfection, the ratio of positive to negative strands in individual cells varies from 5:1 to more than 190:1, with and average of 20:1, suggesting a significant variability in RNA synthesis. We further found that while virus genome production is higher in cells infected at a high multiplicity, the production of infectious particles is largely independent of the number of viruses infecting each cell. Strikingly, by correlating RNA and particle production within individual infections, we uncovered a significant contribution of stochastic noise to the outcome of infection. At low MOI, stochastic influences appear as kinetic effects which are most critical at the initial steps in infection. At high MOI, stochastic influences appear to dictate the virus's ability to harness cellular resources. We conclude that biological noise is a critical determinant of the overall productivity of viral infections. The distinct nature of stochasticity in the outcome of infection by low and high numbers of viral particles may have important implications for our understanding of the determinants of successful viral infections. IMPORTANCE By correlating genome and particle production in single-cell infections, we elucidated sources of noise in viral infections. When a cell was infected by only a single infectious particle, variation in the kinetics of the initial steps of replication contributed significantly to the overall productivity of the infection

  6. No Place to Hide: Missing Primitive Stars Outside Milky Way Uncovered

    NASA Astrophysics Data System (ADS)

    2010-02-01

    After years of successful concealment, the most primitive stars outside our Milky Way galaxy have finally been unmasked. New observations using ESO's Very Large Telescope have been used to solve an important astrophysical puzzle concerning the oldest stars in our galactic neighbourhood - which is crucial for our understanding of the earliest stars in the Universe. "We have, in effect, found a flaw in the forensic methods used until now," says Else Starkenburg, lead author of the paper reporting the study. "Our improved approach allows us to uncover the primitive stars hidden among all the other, more common stars." Primitive stars are thought to have formed from material forged shortly after the Big Bang, 13.7 billion years ago. They typically have less than one thousandth the amount of chemical elements heavier than hydrogen and helium found in the Sun and are called "extremely metal-poor stars" [1]. They belong to one of the first generations of stars in the nearby Universe. Such stars are extremely rare and mainly observed in the Milky Way. Cosmologists think that larger galaxies like the Milky Way formed from the merger of smaller galaxies. Our Milky Way's population of extremely metal-poor or "primitive" stars should already have been present in the dwarf galaxies from which it formed, and similar populations should be present in other dwarf galaxies. "So far, evidence for them has been scarce," says co-author Giuseppina Battaglia. "Large surveys conducted in the last few years kept showing that the most ancient populations of stars in the Milky Way and dwarf galaxies did not match, which was not at all expected from cosmological models." Element abundances are measured from spectra, which provide the chemical fingerprints of stars [2]. The Dwarf galaxies Abundances and Radial-velocities Team [3] used the FLAMES instrument on ESO's Very Large Telescope to measure the spectra of over 2000 individual giant stars in four of our galactic neighbours, the Fornax

  7. Primary School Teachers’ Assessment Profiles in Mathematics Education

    PubMed Central

    Veldhuis, Michiel; van den Heuvel-Panhuizen, Marja

    2014-01-01

    The aim of this study was to contribute to knowledge about classroom assessment by identifying profiles of teachers’ assessment of their students’ understanding of mathematics. For carrying out this study we used data of a nationwide teacher survey (N = 960) in the Netherlands. The data were collected by an online questionnaire. Through exploratory factor analyses the underlying structure of what is measured by this questionnaire was uncovered as consisting of five factors: Goal centeredness of assessment, Authentic nature of assessment, Perceived usefulness of assessment, Diversity of assessment problem format, and Allocated importance of assessing skills and knowledge. By using a latent class analysis four different assessment profiles of teachers were identified: Enthusiastic assessors, Mainstream assessors, Non-enthusiastic assessors, and Alternative assessors. The findings suggest that teachers with particular assessment profiles have qualitatively different assessment practices. The paper concludes with discussing theoretical implications of these assessment profiles and indications these profiles can offer both for designing material for professional development in classroom assessment and for evaluating changes in teachers’ classroom assessment practice. PMID:24466255

  8. Uncovering new thermal and mechanical behavior at the nanoscale using coherent extreme ultraviolet light

    NASA Astrophysics Data System (ADS)

    Hoogeboom-Pot, Kathleen Marie

    Tremendous recent progress in nanofabrication capabilities has made high-quality single-atomic layers and nanostructures with dimensions well below 50 nm commonplace, enabling unprecedented access to materials at the nanoscale. However, tools and techniques capable of characterizing the properties and function of nanosystems are still quite limited, leaving much of the fundamental physics that dominates material behavior in the deep nano-regime still unknown. Further understanding gained by studying nanoscale materials is critical both to fundamental science and to continued technological development. This thesis applies coherent extreme ultraviolet (EUV) light from tabletop high harmonic generation to study nanoscale systems on their intrinsic length and time scales (nanometers and femtoseconds, and above), specifically following thermal transport and acoustic dynamics. These studies have shown where and how nanostructured material properties can be quite different from their bulk counterparts. This has in turn allowed us to develop new theoretical descriptions to guide further work. By observing heat dissipation from the smallest nanostructure heat sources measured to date (at 20 nm in lateral size), this work uncovers a previously unobserved and unpredicted nanoscale thermal transport regime where both size and spacing of heat sources play a role in determining the heat dissipation effciency. Surprisingly, this shows that nanoscale heat sources can cool more quickly when spaced close together than when far apart. This discovery is significant to the engineering of thermal management in nanoscale systems and devices while also revealing new insight into the fundamental nature of thermal transport. Furthermore, we harness this new regime to demonstrate the first experimental measurement of the differential contributions of phonons with different mean free paths to thermal conductivity, down to mean free paths as short as 14 nm for the first time. The same

  9. DNA profiles from fingermarks.

    PubMed

    Templeton, Jennifer E L; Linacre, Adrian

    2014-11-01

    Criminal investigations would be considerably improved if DNA profiles could be routinely generated from single fingermarks. Here we report a direct DNA profiling method that was able to generate interpretable profiles from 71% of 170 fingermarks. The data are based on fingermarks from all 5 digits of 34 individuals. DNA was obtained from the fingermarks using a swab moistened with Triton-X, and the fibers were added directly to one of two commercial DNA profiling kits. All profiles were obtained without increasing the number of amplification cycles; therefore, our method is ideally suited for adoption by the forensic science community. We indicate the use of the technique in a criminal case in which a DNA profile was generated from a fingermark on tape that was wrapped around a drug seizure. Our direct DNA profiling approach is rapid and able to generate profiles from touched items when current forensic practices have little chance of success. PMID:25391915

  10. Uncovering microRNA-mediated response to SO2 stress in Arabidopsis thaliana by deep sequencing.

    PubMed

    Li, Lihong; Xue, Meizhao; Yi, Huilan

    2016-10-01

    Sulfur dioxide (SO2) is a major air pollutant and has significant impacts on plants. MicroRNAs (miRNAs) are a class of gene expression regulators that play important roles in response to environmental stresses. In this study, deep sequencing was used for genome-wide identification of miRNAs and their expression profiles in response to SO2 stress in Arabidopsis thaliana shoots. A total of 27 conserved miRNAs and 5 novel miRNAs were found to be differentially expressed under SO2 stress. qRT-PCR analysis showed mostly negative correlation between miRNA accumulation and target gene mRNA abundance, suggesting regulatory roles of these miRNAs during SO2 exposure. The target genes of SO2-responsive miRNAs encode transcription factors and proteins that regulate auxin signaling and stress response, and the miRNAs-mediated suppression of these genes could improve plant resistance to SO2 stress. Promoter sequence analysis of genes encoding SO2-responsive miRNAs showed that stress-responsive and phytohormone-related cis-regulatory elements occurred frequently, providing additional evidence of the involvement of miRNAs in adaption to SO2 stress. This study represents a comprehensive expression profiling of SO2-responsive miRNAs in Arabidopsis and broads our perspective on the ubiquitous regulatory roles of miRNAs under stress conditions. PMID:27232729

  11. Profiles in Action.

    ERIC Educational Resources Information Center

    Mortimore, Jo, Ed.

    This publication traces developments in the use of profiles produced over the last two years and attempts to face some difficult and controversial issues raised repeatedly in any consideration of profiling. The introduction addresses assessment issues. Section 2 discusses the technical issues surrounding profiles, or records of achievement, and…

  12. Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker

    PubMed Central

    Rachidi, Saleh M.; Qin, Tingting; Sun, Shaoli; Zheng, W. Jim; Li, Zihai

    2013-01-01

    Background Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. Methods and Findings Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. Conclusion This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications. PMID:23536776

  13. Integrative comparative analyses of transcript and metabolite profiles from pepper and tomato ripening and development stages uncovers species-specific patterns of network regulatory behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Integrative comparative analyses of transcript and metabolite levels from climacteric and nonclimacteric fruits can be employed to unravel the similarities and differences of the underlying regulatory processes. To this end, we conducted combined gas chromatography-mass spectrometry, and heterologou...

  14. Genome-wide profiling of Hfq-binding RNAs uncovers extensive post-transcriptional rewiring of major stress response and symbiotic regulons in Sinorhizobium meliloti

    PubMed Central

    Torres-Quesada, Omar; Reinkensmeier, Jan; Schlüter, Jan-Philip; Robledo, Marta; Peregrina, Alexandra; Giegerich, Robert; Toro, Nicolás; Becker, Anke; Jiménez-Zurdo, Jose I

    2014-01-01

    The RNA chaperone Hfq is a global post-transcriptional regulator in bacteria. Here, we used RNAseq to analyze RNA populations from the legume symbiont Sinorhizobium meliloti that were co-immunoprecipitated (CoIP-RNA) with a FLAG-tagged Hfq in five growth/stress conditions. Hfq-bound transcripts (1315) were largely identified in stressed bacteria and derived from small RNAs (sRNAs), both trans-encoded (6.4%) and antisense (asRNAs; 6.3%), and mRNAs (86%). Pull-down with Hfq recovered a small proportion of annotated S. meliloti sRNAs (14% of trans-sRNAs and 2% of asRNAs) suggesting a discrete impact of this protein in sRNA pathways. Nonetheless, Hfq selectively stabilized CoIP-enriched sRNAs, anticipating that these interactions are functionally significant. Transcription of 26 Hfq-bound sRNAs was predicted to occur from promoters recognized by the major stress σ factors σE2 or σH1/2. Recovery rates of sRNAs in each of the CoIP–RNA libraries suggest a large impact of Hfq-assisted riboregulation in S. meliloti osmoadaptation. Hfq directly targeted 18% of the predicted S. meliloti mRNAs, which encode functionally diverse proteins involved in transport and metabolism, σE2-dependent stress responses, quorum sensing, flagella biosynthesis, ribosome, and membrane assembly or symbiotic nitrogen fixation. Canonical targeting of the 5′ regions of two of the ABC transporter mRNAs by the homologous Hfq-binding AbcR1 and AbcR2 sRNAs leading to inhibition of protein synthesis was confirmed in vivo. We therefore provide a comprehensive resource for the systems-level deciphering of hitherto unexplored S. meliloti stress and symbiotic post-transcriptional regulons and the identification of Hfq-dependent sRNA–mRNA regulatory pairs. PMID:24786641

  15. Genome-wide profiling of Hfq-binding RNAs uncovers extensive post-transcriptional rewiring of major stress response and symbiotic regulons in Sinorhizobium meliloti.

    PubMed

    Torres-Quesada, Omar; Reinkensmeier, Jan; Schlüter, Jan-Philip; Robledo, Marta; Peregrina, Alexandra; Giegerich, Robert; Toro, Nicolás; Becker, Anke; Jiménez-Zurdo, Jose I

    2014-01-01

    The RNA chaperone Hfq is a global post-transcriptional regulator in bacteria. Here, we used RNAseq to analyze RNA populations from the legume symbiont Sinorhizobium meliloti that were co-immunoprecipitated (CoIP-RNA) with a FLAG-tagged Hfq in five growth/stress conditions. Hfq-bound transcripts (1315) were largely identified in stressed bacteria and derived from small RNAs (sRNAs), both trans-encoded (6.4%) and antisense (asRNAs; 6.3%), and mRNAs (86%). Pull-down with Hfq recovered a small proportion of annotated S. meliloti sRNAs (14% of trans-sRNAs and 2% of asRNAs) suggesting a discrete impact of this protein in sRNA pathways. Nonetheless, Hfq selectively stabilized CoIP-enriched sRNAs, anticipating that these interactions are functionally significant. Transcription of 26 Hfq-bound sRNAs was predicted to occur from promoters recognized by the major stress σ factors σ(E2) or σ(H1/2). Recovery rates of sRNAs in each of the CoIP-RNA libraries suggest a large impact of Hfq-assisted riboregulation in S. meliloti osmoadaptation. Hfq directly targeted 18% of the predicted S. meliloti mRNAs, which encode functionally diverse proteins involved in transport and metabolism, σ(E2)-dependent stress responses, quorum sensing, flagella biosynthesis, ribosome, and membrane assembly or symbiotic nitrogen fixation. Canonical targeting of the 5' regions of two of the ABC transporter mRNAs by the homologous Hfq-binding AbcR1 and AbcR2 sRNAs leading to inhibition of protein synthesis was confirmed in vivo. We therefore provide a comprehensive resource for the systems-level deciphering of hitherto unexplored S. meliloti stress and symbiotic post-transcriptional regulons and the identification of Hfq-dependent sRNA-mRNA regulatory pairs. PMID:24786641

  16. Genome-Wide Transcriptional Profiling and Metabolic Analysis Uncover Multiple Molecular Responses of the Grass Species Lolium perenne Under Low-Intensity Xenobiotic Stress

    PubMed Central

    Serra, Anne-Antonella; Couée, Ivan; Heijnen, David; Michon-Coudouel, Sophie; Sulmon, Cécile; Gouesbet, Gwenola

    2015-01-01

    Lolium perenne, which is a major component of pastures, lawns, and grass strips, can be exposed to xenobiotic stresses due to diffuse and residual contaminations of soil. L. perenne was recently shown to undergo metabolic adjustments in response to sub-toxic levels of xenobiotics. To gain insight in such chemical stress responses, a de novo transcriptome analysis was carried out on leaves from plants subjected at the root level to low levels of xenobiotics, glyphosate, tebuconazole, and a combination of the two, leading to no adverse physiological effect. Chemical treatments influenced significantly the relative proportions of functional categories and of transcripts related to carbohydrate processes, to signaling, to protein-kinase cascades, such as Serine/Threonine-protein kinases, to transcriptional regulations, to responses to abiotic or biotic stimuli and to responses to phytohormones. Transcriptomics-based expressions of genes encoding different types of SNF1 (sucrose non-fermenting 1)-related kinases involved in sugar and stress signaling or encoding key metabolic enzymes were in line with specific qRT-PCR analysis or with the important metabolic and regulatory changes revealed by metabolomic analysis. The effects of pesticide treatments on metabolites and gene expression strongly suggest that pesticides at low levels, as single molecule or as mixture, affect cell signaling and functioning even in the absence of major physiological impact. This global analysis of L. perenne therefore highlighted the interactions between molecular regulation of responses to xenobiotics, and also carbohydrate dynamics, energy dysfunction, phytohormones and calcium signaling. PMID:26734031

  17. Genome-Wide Expression Profiling of Anoxia/Reoxygenation in Rat Cardiomyocytes Uncovers the Role of MitoKATP in Energy Homeostasis

    PubMed Central

    Cao, Song; Liu, Yun; Sun, Wenting; Zhao, Li; Zhang, Lin; Liu, Xinkui; Yu, Tian

    2015-01-01

    Mitochondrial ATP-sensitive potassium channel (mitoKATP) is a common end effector of many protective stimuli in myocardial ischemia-reperfusion injury (MIRI). However, the specific molecular mechanism underlying its myocardial protective effect is not well elucidated. We characterized an anoxia/reoxygenation (A/R) model using freshly isolated adult rat cardiomyocytes. MitoKATP status was interfered with its specific opener diazoxide (DZ) or blocker 5-hydroxydecanote (5-HD). Digital gene expression (DGE) and bioinformatic analysis were deployed. Three energy metabolism related genes (MT-ND6, Idh2, and Acadl) were upregulated when mitoKATP opened. In addition, as many as 20 differentially expressed genes (DEGs) were significantly enriched in five energy homeostasis correlated pathways (PPAR, TCA cycle, fatty acid metabolism, and peroxisome). These findings indicated that mitoKATP opening in MIRI resulted in energy mobilization, which was confirmed by measuring ATP content in cardiomyocytes. These causal outcomes could be a molecular mechanism of myocardial protection of mitoKATP and suggested that the mitoKATP opening plays a physiologic role in triggering cardiomyocytes' energy homeostasis during MIRI. Strategies of modulating energy expenditure during myocardial ischemia-reperfusion may be promising approaches to reduce MIRI. PMID:26171116

  18. Uncovering the mechanism behind quasi-periodic oscillations in black holes

    NASA Astrophysics Data System (ADS)

    Ingram, Adam

    2012-10-01

    We propose a triggered 200ks XMM-Newton observation of a high inclination black hole binary in the hard intermediate state. This will allow us to constrain a characteristic shift in the iron line profile between the rising and falling phases of the quasi-periodic oscillations (QPOs) observed in these objects. Such a property is a necessary and sufficient condition of a QPO driven by precession in the inner regions of the accretion flow and is predicted by our model which invokes the relativistic effect of frame dragging. The model predicts the QPO phase dependence of the iron line to be stronger for high inclination sources displaying intermediate hardness ratios, leaving the hard intermediate state as the ideal configuration. We will trigger the observation from Swift monitoring throughout the outburst.

  19. An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours.

    PubMed

    Mestdagh, P; Fredlund, E; Pattyn, F; Rihani, A; Van Maerken, T; Vermeulen, J; Kumps, C; Menten, B; De Preter, K; Schramm, A; Schulte, J; Noguera, R; Schleiermacher, G; Janoueix-Lerosey, I; Laureys, G; Powel, R; Nittner, D; Marine, J-C; Ringnér, M; Speleman, F; Vandesompele, J

    2010-06-17

    Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma. Genome-wide expression profiling revealed correlations between specific T-UCR expression levels and important clinicogenetic parameters such as MYCN amplification status. A functional genomics approach based on the integration of multi-level transcriptome data was adapted to gain insights into T-UCR functions. Assignments of T-UCRs to cellular processes such as TP53 response, differentiation and proliferation were verified using various cellular model systems. For the first time, our results define a T-UCR expression landscape in neuroblastoma and suggest widespread T-UCR involvement in diverse cellular processes that are deregulated in the process of tumourigenesis. PMID:20383195

  20. Uncovering a Dual Regulatory Role for Caspases During Endoplasmic Reticulum Stress-induced Cell Death

    PubMed Central

    Anania, Veronica G.; Yu, Kebing; Gnad, Florian; Pferdehirt, Rebecca R.; Li, Han; Ma, Taylur P.; Jeon, Diana; Fortelny, Nikolaus; Forrest, William; Ashkenazi, Avi; Overall, Christopher M.; Lill, Jennie R.

    2016-01-01

    Many diseases are associated with endoplasmic reticulum (ER) stress, which results from an accumulation of misfolded proteins. This triggers an adaptive response called the “unfolded protein response” (UPR), and prolonged exposure to ER stress leads to cell death. Caspases are reported to play a critical role in ER stress-induced cell death but the underlying mechanisms by which they exert their effect continue to remain elusive. To understand the role caspases play during ER stress, a systems level approach integrating analysis of the transcriptome, proteome, and proteolytic substrate profile was employed. This quantitative analysis revealed transcriptional profiles for most human genes, provided information on protein abundance for 4476 proteins, and identified 445 caspase substrates. Based on these data sets many caspase substrates were shown to be downregulated at the protein level during ER stress suggesting caspase activity inhibits their cellular function. Additionally, RNA sequencing revealed a role for caspases in regulation of ER stress-induced transcriptional pathways and gene set enrichment analysis showed expression of multiple gene targets of essential transcription factors to be upregulated during ER stress upon inhibition of caspases. Furthermore, these transcription factors were degraded in a caspase-dependent manner during ER stress. These results indicate that caspases play a dual role in regulating the cellular response to ER stress through both post-translational and transcriptional regulatory mechanisms. Moreover, this study provides unique insight into progression of the unfolded protein response into cell death, which may help identify therapeutic strategies to treat ER stress-related diseases. PMID:27125827

  1. Uncovering MicroRNA Regulatory Hubs that Modulate Plasma Cell Differentiation

    PubMed Central

    Tsai, Dong-Yan; Hung, Kuo-Hsuan; Lin, I-Ying; Su, Shin-Tang; Wu, Shih-Ying; Chung, Cheng-Han; Wang, Tong-Cheng; Li, Wen-Hsiung; Shih, Arthur Chun-Chieh; Lin, Kuo-I

    2015-01-01

    Using genome-wide approaches, we studied the microRNA (miRNA) expression profile during human plasma cell (PC) differentiation induced by stimulation of human blood B cells with T follicular helper cell–dependent signals. Combining the profiles of differentially expressed genes in PC differentiation with gene ontology (GO) analysis revealed that a significant group of genes involved in the transcription factor (TF) activity was preferentially changed. We thus focused on studying the effects of differentially expressed miRNAs on several key TFs in PC differentiation. Cohorts of differentially expressed miRNAs cooperating as miRNA hubs were predicted and validated to modulate key TFs, including a down-regulated miRNA hub containing miR-101-3p, -125b-5p, and -223-3p contributing to induction of PRDM1 as well as an up-regulated miRNA hub containing miR-34a-5p, -148a-3p, and -183-5p suppressing BCL6, BACH2, and FOXP1. Induced expression of NF-κB and PRDM1 during PC differentiation controlled the expression of up- and down-regulated miRNA hubs, respectively. Co-expression of miR-101-3p, -125b-5p, and -223-3p in stimulated B cells showed synergistic effects on inhibition of PC formation, which can be rescued by re-introduction of PRDM1. Together, we catalogue the complex roadmap of miRNAs and their functional interplay in collaboratively directing PC differentiation. PMID:26655851

  2. Contribution of the Nurses’ Health Studies to Uncovering Risk Factors for Type 2 Diabetes: Diet, Lifestyle, Biomarkers, and Genetics

    PubMed Central

    Ley, Sylvia H.; Ardisson Korat, Andres V.; Sun, Qi; Tobias, Deirdre K.; Zhang, Cuilin; Qi, Lu; Willett, Walter C.; Manson, JoAnn E.

    2016-01-01

    Objectives. To review the contribution of the Nurses’ Health Study (NHS) and the NHS II to addressing hypotheses regarding risk factors for type 2 diabetes. Methods. We carried out a narrative review of 1976 to 2016 NHS and NHS II publications. Results. The NHS and NHS II have uncovered important roles in type 2 diabetes for individual nutrients, foods, dietary patterns, and physical activity independent of excess body weight. Up to 90% of type 2 diabetes cases are potentially preventable if individuals follow a healthy diet and lifestyle. The NHS investigations have also identified novel biomarkers for diabetes, including adipokines, inflammatory cytokines, nutrition metabolites, and environmental pollutants, offering new insights into the pathophysiology of the disease. Global collaborative efforts have uncovered many common genetic variants associated with type 2 diabetes and improved our understanding of gene–environment interactions. Continued efforts to identify epigenetic, metagenomic, and metabolomic risk factors for type 2 diabetes have the potential to reveal new pathways and improve prediction and prevention. Conclusions. Over the past several decades, the NHS and NHS II have made major contributions to public health recommendations and strategies designed to reduce the global burden of diabetes. PMID:27459454

  3. A distinctive avian assemblage (Aves: Passeriformes) in Western Darién, Panama is uncovered through a disease surveillance program.

    PubMed

    Miller, Matthew J

    2014-06-01

    Basic knowledge about the distribution of flora and fauna is lacking for most tropical areas. Improving our knowledge of the tropical biota will help address contemporary global problems, including emerging tropical diseases. Less appreciated is the role that applied studies can have in improving our understanding of basic biological patterns and processes in the tropics. Here, I describe a novel avifauna assemblage uncovered in Western Darién province in the Republic of Panama that was uncovered during a vector-borne disease surveillance program. I compared the passerine bird species composition at 16 sites using records from recent ornithological expeditions sponsored by the Smithsonian Tropical Research Institute in Central and Eastern Panama. Based on the results of a Mantel test, geographic distance did not correlate with pairwise distinctiveness of sites. instead, based on an index of distinctiveness modified from the Chao-Jaccard index, most sites were more or less similarly distinctive, with one site, Aruza Abajo, significantly more distinctive than the rest. I found that the distinctiveness of this site was due not only to the presence of several rare and range-restricted taxa, but also to the absence of taxa that are common elsewhere. This finding provides more evidence of high species composition turnover (beta-diversity) in the Panamanian biota, which appears to be driven by a combination of soil and climate differences over narrow distances. PMID:25102652

  4. Realizing full coverage of perovskite film on substrate surface during solution processing: Characterization and elimination of uncovered surface

    NASA Astrophysics Data System (ADS)

    Li, Yan; He, Xue-Long; Ding, Bin; Gao, Li-Li; Yang, Guan-Jun; Li, Cheng-Xin; Li, Chang-Jiu

    2016-07-01

    The full coverage of the perovskite film on the substrate surface is of significant importance for the high performance perovskite solar cells. In order to obtain full coverage perovskite films by one-step deposition method, the microstructures of both uncovered areas and covered areas of the CH3NH3PbI3 film are comparatively investigated. Results show that the uncovered area indeed has an ultra-thin layer of CH3NH3PbI3 film which is too thin to cover the rough surface morphology of the substrate, and the localized solute accumulation due to long crystal growth time is responsible for the non-full coverage of the perovskite film. Then by decreasing the crystal growth time, the localized solute accumulation is eliminated gradually and subsequently a full coverage of perovskite film on substrate surface is realized. As a result, the perovskite solar cells show a conversion efficiency of ∼13% with the uniform and full coverage perovskite film.

  5. Synergy of entry inhibitors with direct-acting antivirals uncovers novel combinations for prevention and treatment of hepatitis C

    PubMed Central

    Xiao, Fei; Fofana, Isabel; Thumann, Christine; Mailly, Laurent; Alles, Roxane; Robinet, Eric; Meyer, Nicolas; Schaeffer, Mickaël; Habersetzer, François; Doffoël, Michel; Leyssen, Pieter; Neyts, Johan; Zeisel, Mirjam B; Baumert, Thomas F

    2015-01-01

    Objective Although direct-acting antiviral agents (DAAs) have markedly improved the outcome of treatment in chronic HCV infection, there continues to be an unmet medical need for improved therapies in difficult-to-treat patients as well as liver graft infection. Viral entry is a promising target for antiviral therapy. Design Aiming to explore the role of entry inhibitors for future clinical development, we investigated the antiviral efficacy and toxicity of entry inhibitors in combination with DAAs or other host-targeting agents (HTAs). Screening a large series of combinations of entry inhibitors with DAAs or other HTAs, we uncovered novel combinations of antivirals for prevention and treatment of HCV infection. Results Combinations of DAAs or HTAs and entry inhibitors including CD81-, scavenger receptor class B type I (SR-BI)- or claudin-1 (CLDN1)-specific antibodies or small-molecule inhibitors erlotinib and dasatinib were characterised by a marked and synergistic inhibition of HCV infection over a broad range of concentrations with undetectable toxicity in experimental designs for prevention and treatment both in cell culture models and in human liver-chimeric uPA/SCID mice. Conclusions Our results provide a rationale for the development of antiviral strategies combining entry inhibitors with DAAs or HTAs by taking advantage of synergy. The uncovered combinations provide perspectives for efficient strategies to prevent liver graft infection and novel interferon-free regimens. PMID:24848265

  6. Quantitative Proteomics Uncovers Novel Factors Involved in Developmental Differentiation of Trypanosoma brucei

    PubMed Central

    Dejung, Mario; Subota, Ines; Bucerius, Ferdinand; Dindar, Gülcin; Freiwald, Anja; Engstler, Markus; Boshart, Michael; Butter, Falk; Janzen, Christian J.

    2016-01-01

    Developmental differentiation is a universal biological process that allows cells to adapt to different environments to perform specific functions. African trypanosomes progress through a tightly regulated life cycle in order to survive in different host environments when they shuttle between an insect vector and a vertebrate host. Transcriptomics has been useful to gain insight into RNA changes during stage transitions; however, RNA levels are only a moderate proxy for protein abundance in trypanosomes. We quantified 4270 protein groups during stage differentiation from the mammalian-infective to the insect form and provide classification for their expression profiles during development. Our label-free quantitative proteomics study revealed previously unknown components of the differentiation machinery that are involved in essential biological processes such as signaling, posttranslational protein modifications, trafficking and nuclear transport. Furthermore, guided by our proteomic survey, we identified the cause of the previously observed differentiation impairment in the histone methyltransferase DOT1B knock-out strain as it is required for accurate karyokinesis in the first cell division during differentiation. This epigenetic regulator is likely involved in essential chromatin restructuring during developmental differentiation, which might also be important for differentiation in higher eukaryotic cells. Our proteome dataset will serve as a resource for detailed investigations of cell differentiation to shed more light on the molecular mechanisms of this process in trypanosomes and other eukaryotes. PMID:26910529

  7. Transcriptome sequencing uncovers a three–long noncoding RNA signature in predicting breast cancer survival

    PubMed Central

    Guo, Wenna; Wang, Qiang; Zhan, Yueping; Chen, Xijia; Yu, Qi; Zhang, Jiawei; Wang, Yi; Xu, Xin-jian; Zhu, Liucun

    2016-01-01

    Long noncoding RNAs (lncRNAs) play a crucial role in tumorigenesis. The aim of this study is to identify lncRNA signature that can predict breast cancer patient survival. RNA expression data from 1064 patients were downloaded from The Cancer Genome Atlas project. Cox regression, Kaplan–Meier, and receiver operating characteristic (ROC) analyses were performed to construct a model for predicting the overall survival (OS) of patients and evaluate it. A model consisting of three lncRNA genes (CAT104, LINC01234, and STXBP5-AS1) was identified. The Kaplan–Meier analysis and ROC curves proved that the model could predict the prognostic survival with good sensitivity and specificity in both the validation set (AUC = 0.752, 95% confidence intervals (CI): 0.651–0.854) and the microarray dataset (AUC = 0.714, 95%CI: 0.615–0.814). Further study showed the three-lncRNA signature was not only pervasive in different breast cancer stages, subtypes and age groups, but also provides more accurate prognostic information than some widely known biomarkers. The results suggested that RNA-seq transcriptome profiling provides that the three-lncRNA signature is an independent prognostic biomarker, and have clinical significance. In addition, lncRNA, miRNA, and mRNA interaction network indicated lncRNAs may intervene in breast cancer pathogenesis by binding to miR-190b, acting as competing endogenous RNAs. PMID:27338266

  8. RNA sequencing uncovers antisense RNAs and novel small RNAs in Streptococcus pyogenes

    PubMed Central

    Le Rhun, Anaïs; Beer, Yan Yan; Reimegård, Johan; Chylinski, Krzysztof; Charpentier, Emmanuelle

    2016-01-01

    ABSTRACT Streptococcus pyogenes is a human pathogen responsible for a wide spectrum of diseases ranging from mild to life-threatening infections. During the infectious process, the temporal and spatial expression of pathogenicity factors is tightly controlled by a complex network of protein and RNA regulators acting in response to various environmental signals. Here, we focus on the class of small RNA regulators (sRNAs) and present the first complete analysis of sRNA sequencing data in S. pyogenes. In the SF370 clinical isolate (M1 serotype), we identified 197 and 428 putative regulatory RNAs by visual inspection and bioinformatics screening of the sequencing data, respectively. Only 35 from the 197 candidates identified by visual screening were assigned a predicted function (T-boxes, ribosomal protein leaders, characterized riboswitches or sRNAs), indicating how little is known about sRNA regulation in S. pyogenes. By comparing our list of predicted sRNAs with previous S. pyogenes sRNA screens using bioinformatics or microarrays, 92 novel sRNAs were revealed, including antisense RNAs that are for the first time shown to be expressed in this pathogen. We experimentally validated the expression of 30 novel sRNAs and antisense RNAs. We show that the expression profile of 9 sRNAs including 2 predicted regulatory elements is affected by the endoribonucleases RNase III and/or RNase Y, highlighting the critical role of these enzymes in sRNA regulation. PMID:26580233

  9. RNA sequencing uncovers antisense RNAs and novel small RNAs in Streptococcus pyogenes.

    PubMed

    Le Rhun, Anaïs; Beer, Yan Yan; Reimegård, Johan; Chylinski, Krzysztof; Charpentier, Emmanuelle

    2016-02-01

    Streptococcus pyogenes is a human pathogen responsible for a wide spectrum of diseases ranging from mild to life-threatening infections. During the infectious process, the temporal and spatial expression of pathogenicity factors is tightly controlled by a complex network of protein and RNA regulators acting in response to various environmental signals. Here, we focus on the class of small RNA regulators (sRNAs) and present the first complete analysis of sRNA sequencing data in S. pyogenes. In the SF370 clinical isolate (M1 serotype), we identified 197 and 428 putative regulatory RNAs by visual inspection and bioinformatics screening of the sequencing data, respectively. Only 35 from the 197 candidates identified by visual screening were assigned a predicted function (T-boxes, ribosomal protein leaders, characterized riboswitches or sRNAs), indicating how little is known about sRNA regulation in S. pyogenes. By comparing our list of predicted sRNAs with previous S. pyogenes sRNA screens using bioinformatics or microarrays, 92 novel sRNAs were revealed, including antisense RNAs that are for the first time shown to be expressed in this pathogen. We experimentally validated the expression of 30 novel sRNAs and antisense RNAs. We show that the expression profile of 9 sRNAs including 2 predicted regulatory elements is affected by the endoribonucleases RNase III and/or RNase Y, highlighting the critical role of these enzymes in sRNA regulation. PMID:26580233

  10. Uncovering the genetic basis for early isogamete differentiation: a case study of Ectocarpus siliculosus

    PubMed Central

    2013-01-01

    Background The phenomenon of sexual reproduction characterizes nearly all eukaryotes, with anisogamy being the most prevalent form of gamete discrimination. Since dimorphic gametes most likely descend from equal-sized specialized germ cells, identifying the genetic bases of the early functional diversification in isogametes can provide better understanding of the evolution of sexual dimorphism. However, despite the potential importance to the evolutionary biology field, no comprehensive survey of the transcriptome profiling in isomorphic gametes has been reported hitherto. Results Gamete differentiation on the genomic level was investigated using Ectocarpus siliculosus, a model organism for brown algal lineage which displays an isogamous sexual reproduction cycle. Transcriptome libraries of male and female gametes were generated using Next Generation Sequencing technology (SOLiD) and analyzed to identify differentially regulated genes and pathways with potential roles in fertilization and gamete specialization. Gamete transcriptomes showed a high level of complexity with a large portion of gender specific gene expression. Our results indicate that over 4,000 of expressed genes are differentially regulated between male and female, including sequences related to cell movement, carbohydrate and lipid metabolism, signaling, transport and RNA processing. Conclusions This first comprehensive transcriptomic study of protist isogametes describes considerable adaptation to distinct sexual roles, suggesting that functional anisogamy precedes morphological differentiation. Several sex-biased genes and pathways with a putative role in reproduction were identified, providing the basis for more detailed investigations of the mechanisms underlying evolution of mating types and sexual dimorphism. PMID:24359479