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Sample records for japonicus identified large

  1. Proteome Analysis. Novel Proteins Identified at the Peribacteroid Membrane from Lotus japonicus Root Nodules1

    PubMed Central

    Wienkoop, Stefanie; Saalbach, Gerhard

    2003-01-01

    The peribacteroid membrane (PBM) forms the structural and functional interface between the legume plant and the rhizobia. The model legume Lotus japonicus was chosen to study the proteins present at the PBM by proteome analysis. PBM was purified from root nodules by an aqueous polymer two-phase system. Extracted proteins were subjected to a global trypsin digest. The peptides were separated by nanoscale liquid chromatography and analyzed by tandem mass spectrometry. Searching the nonredundant protein database and the green plant expressed sequence tag database using the tandem mass spectrometry data identified approximately 94 proteins, a number far exceeding the number of proteins reported for the PBM hitherto. In particular, a number of membrane proteins like transporters for sugars and sulfate; endomembrane-associated proteins such as GTP-binding proteins and vesicle receptors; and proteins involved in signaling, for example, receptor kinases, calmodulin, 14-3-3 proteins, and pathogen response-related proteins, including a so-called HIR protein, were detected. Several ATPases and aquaporins were present, indicating a more complex situation than previously thought. In addition, the unexpected presence of a number of proteins known to be located in other compartments was observed. Two characteristic protein complexes obtained from native gel electrophoresis of total PBM proteins were also analyzed. Together, the results identified specific proteins at the PBM involved in important physiological processes and localized proteins known from nodule-specific expressed sequence tag databases to the PBM. PMID:12644660

  2. Expression analysis of immune related genes identified from the coelomocytes of sea cucumber (Apostichopus japonicus) in response to LPS challenge.

    PubMed

    Dong, Ying; Sun, Hongjuan; Zhou, Zunchun; Yang, Aifu; Chen, Zhong; Guan, Xiaoyan; Gao, Shan; Wang, Bai; Jiang, Bei; Jiang, Jingwei

    2014-01-01

    The sea cucumber (Apostichopus japonicus) occupies a basal position during the evolution of deuterostomes and is also an important aquaculture species. In order to identify more immune effectors, transcriptome sequencing of A. japonicus coelomocytes in response to lipopolysaccharide (LPS) challenge was performed using the Illumina HiSeq™ 2000 platform. One hundred and seven differentially expressed genes were selected and divided into four functional categories including pathogen recognition (25 genes), reorganization of cytoskeleton (27 genes), inflammation (41 genes) and apoptosis (14 genes). They were analyzed to elucidate the mechanisms of host-pathogen interactions and downstream signaling transduction. Quantitative real-time polymerase chain reactions (qRT-PCRs) of 10 representative genes validated the accuracy and reliability of RNA sequencing results with the correlation coefficients from 0.88 to 0.98 and p-value <0.05. Expression analysis of immune-related genes after LPS challenge will be useful in understanding the immune response mechanisms of A. japonicus against pathogen invasion and developing strategies for resistant markers selection. PMID:25421239

  3. Expression Analysis of Immune Related Genes Identified from the Coelomocytes of Sea Cucumber (Apostichopus japonicus) in Response to LPS Challenge

    PubMed Central

    Dong, Ying; Sun, Hongjuan; Zhou, Zunchun; Yang, Aifu; Chen, Zhong; Guan, Xiaoyan; Gao, Shan; Wang, Bai; Jiang, Bei; Jiang, Jingwei

    2014-01-01

    The sea cucumber (Apostichopus japonicus) occupies a basal position during the evolution of deuterostomes and is also an important aquaculture species. In order to identify more immune effectors, transcriptome sequencing of A. japonicus coelomocytes in response to lipopolysaccharide (LPS) challenge was performed using the Illumina HiSeq™ 2000 platform. One hundred and seven differentially expressed genes were selected and divided into four functional categories including pathogen recognition (25 genes), reorganization of cytoskeleton (27 genes), inflammation (41 genes) and apoptosis (14 genes). They were analyzed to elucidate the mechanisms of host-pathogen interactions and downstream signaling transduction. Quantitative real-time polymerase chain reactions (qRT-PCRs) of 10 representative genes validated the accuracy and reliability of RNA sequencing results with the correlation coefficients from 0.88 to 0.98 and p-value <0.05. Expression analysis of immune-related genes after LPS challenge will be useful in understanding the immune response mechanisms of A. japonicus against pathogen invasion and developing strategies for resistant markers selection. PMID:25421239

  4. RNA-seq Transcriptome Analysis of Panax japonicus, and Its Comparison with Other Panax Species to Identify Potential Genes Involved in the Saponins Biosynthesis

    PubMed Central

    Rai, Amit; Yamazaki, Mami; Takahashi, Hiroki; Nakamura, Michimi; Kojoma, Mareshige; Suzuki, Hideyuki; Saito, Kazuki

    2016-01-01

    The Panax genus has been a source of natural medicine, benefitting human health over the ages, among which the Panax japonicus represents an important species. Our understanding of several key pathways and enzymes involved in the biosynthesis of ginsenosides, a pharmacologically active class of metabolites and a major chemical constituents of the rhizome extracts from the Panax species, are limited. Limited genomic information, and lack of studies on comparative transcriptomics across the Panax species have restricted our understanding of the biosynthetic mechanisms of these and many other important classes of phytochemicals. Herein, we describe Illumina based RNA sequencing analysis to characterize the transcriptome and expression profiles of genes expressed in the five tissues of P. japonicus, and its comparison with other Panax species. RNA sequencing and de novo transcriptome assembly for P. japonicus resulted in a total of 135,235 unigenes with 78,794 (58.24%) unigenes being annotated using NCBI-nr database. Transcriptome profiling, and gene ontology enrichment analysis for five tissues of P. japonicus showed that although overall processes were evenly conserved across all tissues. However, each tissue was characterized by several unique unigenes with the leaves showing the most unique unigenes among the tissues studied. A comparative analysis of the P. japonicus transcriptome assembly with publically available transcripts from other Panax species, namely, P. ginseng, P. notoginseng, and P. quinquefolius also displayed high sequence similarity across all Panax species, with P. japonicus showing highest similarity with P. ginseng. Annotation of P. japonicus transcriptome resulted in the identification of putative genes encoding all enzymes from the triterpene backbone biosynthetic pathways, and identified 24 and 48 unigenes annotated as cytochrome P450 (CYP) and glycosyltransferases (GT), respectively. These CYPs and GTs annotated unigenes were conserved across

  5. RNA-seq Transcriptome Analysis of Panax japonicus, and Its Comparison with Other Panax Species to Identify Potential Genes Involved in the Saponins Biosynthesis.

    PubMed

    Rai, Amit; Yamazaki, Mami; Takahashi, Hiroki; Nakamura, Michimi; Kojoma, Mareshige; Suzuki, Hideyuki; Saito, Kazuki

    2016-01-01

    The Panax genus has been a source of natural medicine, benefitting human health over the ages, among which the Panax japonicus represents an important species. Our understanding of several key pathways and enzymes involved in the biosynthesis of ginsenosides, a pharmacologically active class of metabolites and a major chemical constituents of the rhizome extracts from the Panax species, are limited. Limited genomic information, and lack of studies on comparative transcriptomics across the Panax species have restricted our understanding of the biosynthetic mechanisms of these and many other important classes of phytochemicals. Herein, we describe Illumina based RNA sequencing analysis to characterize the transcriptome and expression profiles of genes expressed in the five tissues of P. japonicus, and its comparison with other Panax species. RNA sequencing and de novo transcriptome assembly for P. japonicus resulted in a total of 135,235 unigenes with 78,794 (58.24%) unigenes being annotated using NCBI-nr database. Transcriptome profiling, and gene ontology enrichment analysis for five tissues of P. japonicus showed that although overall processes were evenly conserved across all tissues. However, each tissue was characterized by several unique unigenes with the leaves showing the most unique unigenes among the tissues studied. A comparative analysis of the P. japonicus transcriptome assembly with publically available transcripts from other Panax species, namely, P. ginseng, P. notoginseng, and P. quinquefolius also displayed high sequence similarity across all Panax species, with P. japonicus showing highest similarity with P. ginseng. Annotation of P. japonicus transcriptome resulted in the identification of putative genes encoding all enzymes from the triterpene backbone biosynthetic pathways, and identified 24 and 48 unigenes annotated as cytochrome P450 (CYP) and glycosyltransferases (GT), respectively. These CYPs and GTs annotated unigenes were conserved across

  6. Hyper-expansion of large DNA segments in the genome of kuruma shrimp, Marsupenaeus japonicus

    PubMed Central

    2010-01-01

    Background Higher crustaceans (class Malacostraca) represent the most species-rich and morphologically diverse group of non-insect arthropods and many of its members are commercially important. Although the crustacean DNA sequence information is growing exponentially, little is known about the genome organization of Malacostraca. Here, we constructed a bacterial artificial chromosome (BAC) library and performed BAC-end sequencing to provide genomic information for kuruma shrimp (Marsupenaeus japonicus), one of the most widely cultured species among crustaceans, and found the presence of a redundant sequence in the BAC library. We examined the BAC clone that includes the redundant sequence to further analyze its length, copy number and location in the kuruma shrimp genome. Results Mj024A04 BAC clone, which includes one redundant sequence, contained 27 putative genes and seemed to display a normal genomic DNA structure. Notably, of the putative genes, 3 genes encode homologous proteins to the inhibitor of apoptosis protein and 7 genes encode homologous proteins to white spot syndrome virus, a virulent pathogen known to affect crustaceans. Colony hybridization and PCR analysis of 381 BAC clones showed that almost half of the BAC clones maintain DNA segments whose sequences are homologous to the representative BAC clone Mj024A04. The Mj024A04 partial sequence was detected multiple times in the kuruma shrimp nuclear genome with a calculated copy number of at least 100. Microsatellites based BAC genotyping clearly showed that Mj024A04 homologous sequences were cloned from at least 48 different chromosomal loci. The absence of micro-syntenic relationships with the available genomic sequences of Daphnia and Drosophila suggests the uniqueness of these fragments in kuruma shrimp from current arthropod genome sequences. Conclusions Our results demonstrate that hyper-expansion of large DNA segments took place in the kuruma shrimp genome. Although we analyzed only a part of the

  7. Transcriptome Sequencing and Characterization for the Sea Cucumber Apostichopus japonicus (Selenka, 1867)

    PubMed Central

    Du, Huixia; Bao, Zhenmin; Hou, Rui; Wang, Shan; Su, Hailin; Yan, Jingjing; Tian, Meilin; Li, Yan; Wei, Wen; Lu, Wei; Hu, Xiaoli; Wang, Shi; Hu, Jingjie

    2012-01-01

    Background Sea cucumbers are a special group of marine invertebrates. They occupy a taxonomic position that is believed to be important for understanding the origin and evolution of deuterostomes. Some of them such as Apostichopus japonicus represent commercially important aquaculture species in Asian countries. Many efforts have been devoted to increasing the number of expressed sequence tags (ESTs) for A. japonicus, but a comprehensive characterization of its transcriptome remains lacking. Here, we performed the large-scale transcriptome profiling and characterization by pyrosequencing diverse cDNA libraries from A. japonicus. Results In total, 1,061,078 reads were obtained by 454 sequencing of eight cDNA libraries representing different developmental stages and adult tissues in A. japonicus. These reads were assembled into 29,666 isotigs, which were further clustered into 21,071 isogroups. Nearly 40% of the isogroups showed significant matches to known proteins based on sequence similarity. Gene ontology (GO) and KEGG pathway analyses recovered diverse biological functions and processes. Candidate genes that were potentially involved in aestivation were identified. Transcriptome comparison with the sea urchin Strongylocentrotus purpuratus revealed similar patterns of GO term representation. In addition, 4,882 putative orthologous genes were identified, of which 202 were not present in the non-echinoderm organisms. More than 700 simple sequence repeats (SSRs) and 54,000 single nucleotide polymorphisms (SNPs) were detected in the A. japonicus transcriptome. Conclusion Pyrosequencing was proven to be efficient in rapidly identifying a large set of genes for the sea cucumber A. japonicus. Through the large-scale transcriptome sequencing as well as public EST data integration, we performed a comprehensive characterization of the A. japonicus transcriptome and identified candidate aestivation-related genes. A large number of potential genetic markers were also

  8. Invasion Biology of Aedes japonicus japonicus (Diptera: Culicidae)

    PubMed Central

    Fonseca, Dina M.

    2014-01-01

    Aedes japonicus japonicus (Theobald) (Diptera: Culicidae) has recently expanded beyond its native range of Japan and Korea into large parts of North America and Central Europe. Population genetic studies begun immediately after the species was detected in North America revealed genetically distinct introductions that subsequently merged, likely contributing to the successful expansion. Interactions, particularly in the larval stage, with other known disease vectors give this invasive subspecies the potential to influence local disease dynamics. Its successful invasion likely does not involve superior direct competitive abilities, but it is associated with the use of diverse larval habitats and a cold tolerance that allows an expanded seasonal activity range in temperate climates. We predict a continued but slower expansion of Ae. j. japonicus in North America and a continued rapid expansion into other areas as this mosquito will eventually be considered a permanent resident of much of North America, Europe, Asia, and parts of Hawaii. PMID:24397520

  9. Establishment of Aedes japonicus japonicus and Its Colonization of Container Habitats in Michigan

    PubMed Central

    KAUFMAN, MICHAEL G.; STANUSZEK, WILLIAM W.; BROUHARD, ELIZABETH A.; KNEPPER, RANDALL G.; WALKER, EDWARD D.

    2014-01-01

    Oviposition dynamics and colonization of container habitats by the invasive species, Aedes (Finlaya) japonicus japonicus (Theobald) were examined through the use of ovistrips placed in buckets, and larval surveys of tree holes and tires at sites in central Michigan. In general, oviposition and colonization increased during the study periods, with several sites showing large increases from <10% Ae. j. japonicus initially to over 60% in the following years. Seasonally, higher proportions of Ae. j. japonicus were found in spring and fall collection periods. Ae. j. japonicus larvae co-occurred in the artificial containers with Ae. triseriatus, Ae. hendersoni, several Culex spp., and Anopheles spp. Recent surveys of tire and tree hole habitats at our study areas in mid-Michigan revealed that Ae. j. japonicus had colonized most of these habitats, but maintained relatively low populations in tree holes occupied by Ae. triseriatus. Trends seen in tires from 2008 to 2011, and from gravid trap and New Jersey light traps in 2005–2011, suggest that Ae. j. japonicus populations are stabilizing as they integrate into native Michigan mosquito communities. PMID:23270158

  10. A new focus of Aedes japonicus japonicus (Theobald, 1901) (Diptera, Culicidae) distribution in Western Germany: rapid spread or a further introduction event?

    PubMed Central

    2012-01-01

    Background The Asian bush mosquito, Aedes japonicus japonicus, a potential vector of several viruses, was first detected in Germany in 2008 on the Swiss-German border. In the following years, this invasive species apparently succeeded in establishing populations in southern Germany and in spreading northwards. In 2011, its distribution area already covered large areas of the federal state of Baden-Wurttemberg, and its northernmost German collection point was reported to be close to Stuttgart. Several independent submissions to our laboratories of Ae. j. japonicus specimens in July 2012, originating from the same area in the federal state of North Rhine-Westphalia, western Germany, prompted us to carry out an immediate surveillance in this region in the expectation of finding a further distribution focus of Ae. j. japonicus in Germany. Methods After inspecting the places of residence of the collectors of the submitted mosquito specimens, all kinds of water containers in 123 cemeteries in surrounding towns and villages were checked for mosquito developmental stages. These were collected and kept to produce adults for morphological species identification. One specimen per collection site was identified genetically by COI sequence analysis. Results Aedes j. japonicus adults and immature stages were found in 36 towns/villages that were checked (29%) over an area of approximately 2,000 km2 in southern North Rhine-Westphalia and northern Rhineland Palatinate. The species could not be demonstrated further south when monitoring towards the northernmost previous collection sites in southern Germany. It therefore remains to be elucidated whether the species has entered western Germany from the south, from Belgium in the west where it has been demonstrated to occur locally since 2002, or through a new introduction. Conclusions Aedes j. japonicus is obviously much more widely distributed in Germany than previously thought. It appears to be well adapted, to have a strong

  11. RNA-Seq analysis of immune-relevant genes in Lateolabrax japonicus during Vibrio anguillarum infection.

    PubMed

    Zhao, Chao; Fu, Mingjun; Wang, Chengyang; Jiao, Zongyao; Qiu, Lihua

    2016-05-01

    Lateolabrax japonicus is one of the main marine aquatic fish species, and is popularly cultured in East Asia due to its highly commercial value. In recent years, because of large-scale and intensive farming and seawater pollution, fish diseases keep breaking out. However, systematic study on L. japonicus immunogenetics is limited due to the deficiency of deep sequencing technologies and genome backgrounds. In this study, the widely analysis at the transcriptome level for L. japonicus that infected with Vibrio anguillarum was performed. In total, 334,388,688 high quality reads were obtained in six libraries (HK-VA, HK-PBS, LI-VA, LI-PBS, SP-VA and SP-PBS) and de novo assembled into 101,860 Unigenes with an average unigene length of 879 bp. Based on sequence similarity 30,142 unigenes (29.59%) were annotated in the public databases. Comparative analysis revealed, 1,202, 3034 and 3519 differentially expressed genes (DEGs) were identified in three comparisons (HK-PBS VS HK-VA, LI-PBS VS LI-VA and SP-PBS VS SP-VA). Enrichment and pathway analysis of the DEGs was also carried out to excavate the candidate genes related to immunity. In conclusion, this study identifies and evaluates dozen of potential immune related pathways and candidate genes, which are indispensable for padding genomic resources of L. japonicus, and would lay the foundation for further studying and illuminating the mechanism of host-pathogen interactions. PMID:26945936

  12. Identifying Communication Barriers to Learning in Large Group Accounting Instruction.

    ERIC Educational Resources Information Center

    Doran, Martha S.; Golen, Steven

    1998-01-01

    Classroom communication barriers were identified by 291 financial accounting and 372 managerial accounting students. Both groups thought the greatest problems in large group instruction were too much information given in lectures, large class size, and lack of interest in the subject matter. (SK)

  13. The complete chloroplast genome sequence of Euonymus japonicus (Celastraceae).

    PubMed

    Choi, Kyoung Su; Park, SeonJoo

    2016-09-01

    The complete chloroplast (cp) genome sequence of the Euonymus japonicus, the first sequenced of the genus Euonymus, was reported in this study. The total length was 157 637 bp, containing a pair of 26 678 bp inverted repeat region (IR), which were separated by small single copy (SSC) region and large single copy (LSC) region of 18 340 bp and 85 941 bp, respectively. This genome contains 107 unique genes, including 74 coding genes, four rRNA genes, and 29 tRNA genes. Seventeen genes contain intron of E. japonicus, of which three genes (clpP, ycf3, and rps12) include two introns. The maximum likelihood (ML) phylogenetic analysis revealed that E. japonicus was closely related to Manihot and Populus. PMID:26407184

  14. Identifying Corridors among Large Protected Areas in the United States

    PubMed Central

    Belote, R. Travis; Dietz, Matthew S.; McRae, Brad H.; Theobald, David M.; McClure, Meredith L.; Irwin, G. Hugh; McKinley, Peter S.; Gage, Josh A.; Aplet, Gregory H.

    2016-01-01

    Conservation scientists emphasize the importance of maintaining a connected network of protected areas to prevent ecosystems and populations from becoming isolated, reduce the risk of extinction, and ultimately sustain biodiversity. Keeping protected areas connected in a network is increasingly recognized as a conservation priority in the current era of rapid climate change. Models that identify suitable linkages between core areas have been used to prioritize potentially important corridors for maintaining functional connectivity. Here, we identify the most “natural” (i.e., least human-modified) corridors between large protected areas in the contiguous Unites States. We aggregated results from multiple connectivity models to develop a composite map of corridors reflecting agreement of models run under different assumptions about how human modification of land may influence connectivity. To identify which land units are most important for sustaining structural connectivity, we used the composite map of corridors to evaluate connectivity priorities in two ways: (1) among land units outside of our pool of large core protected areas and (2) among units administratively protected as Inventoried Roadless (IRAs) or Wilderness Study Areas (WSAs). Corridor values varied substantially among classes of “unprotected” non-core land units, and land units of high connectivity value and priority represent diverse ownerships and existing levels of protections. We provide a ranking of IRAs and WSAs that should be prioritized for additional protection to maintain minimal human modification. Our results provide a coarse-scale assessment of connectivity priorities for maintaining a connected network of protected areas. PMID:27104683

  15. Identifying Corridors among Large Protected Areas in the United States.

    PubMed

    Belote, R Travis; Dietz, Matthew S; McRae, Brad H; Theobald, David M; McClure, Meredith L; Irwin, G Hugh; McKinley, Peter S; Gage, Josh A; Aplet, Gregory H

    2016-01-01

    Conservation scientists emphasize the importance of maintaining a connected network of protected areas to prevent ecosystems and populations from becoming isolated, reduce the risk of extinction, and ultimately sustain biodiversity. Keeping protected areas connected in a network is increasingly recognized as a conservation priority in the current era of rapid climate change. Models that identify suitable linkages between core areas have been used to prioritize potentially important corridors for maintaining functional connectivity. Here, we identify the most "natural" (i.e., least human-modified) corridors between large protected areas in the contiguous Unites States. We aggregated results from multiple connectivity models to develop a composite map of corridors reflecting agreement of models run under different assumptions about how human modification of land may influence connectivity. To identify which land units are most important for sustaining structural connectivity, we used the composite map of corridors to evaluate connectivity priorities in two ways: (1) among land units outside of our pool of large core protected areas and (2) among units administratively protected as Inventoried Roadless (IRAs) or Wilderness Study Areas (WSAs). Corridor values varied substantially among classes of "unprotected" non-core land units, and land units of high connectivity value and priority represent diverse ownerships and existing levels of protections. We provide a ranking of IRAs and WSAs that should be prioritized for additional protection to maintain minimal human modification. Our results provide a coarse-scale assessment of connectivity priorities for maintaining a connected network of protected areas. PMID:27104683

  16. Identifying Large-Scale Brain Networks in Fragile X Syndrome

    PubMed Central

    Hall, Scott S.; Jiang, Heidi; Reiss, Allan L.; Greicius, Michael D.

    2014-01-01

    IMPORTANCE Fragile X syndrome (FXS) is an X-linked neurogenetic disorder characterized by a cognitive and behavioral phenotype resembling features of autism spectrum disorder. Until now, research has focused largely on identifying regional differences in brain structure and function between individuals with FXS and various control groups. Very little is known about the large-scale brain networks that may underlie the cognitive and behavioral symptoms of FXS. OBJECTIVE To identify large-scale, resting-state networks in FXS that differ from control individuals matched on age, IQ, and severity of behavioral and cognitive symptoms. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional, in vivo neuroimaging study conducted in an academic medical center. Participants (aged 10–23 years) included 17 males and females with FXS and 16 males and females serving as controls. MAIN OUTCOMES AND MEASURES Univariate voxel-based morphometric analyses, fractional amplitude of low-frequency fluctuations (fALFF) analysis, and group-independent component analysis with dual regression. RESULTS Patients with FXS showed decreased functional connectivity in the salience, precuneus, left executive control, language, and visuospatial networks compared with controls. Decreased fALFF in the bilateral insular, precuneus, and anterior cingulate cortices also was found in patients with FXS compared with control participants. Furthermore, fALFF in the left insular cortex was significantly positively correlated with IQ in patients with FXS. Decreased gray matter density, resting-state connectivity, and fALFF converged in the left insular cortex in patients with FXS. CONCLUSIONS AND RELEVANCE Fragile X syndrome results in widespread reductions in functional connectivity across multiple cognitive and affective brain networks. Converging structural and functional abnormalities in the left insular cortex, a region also implicated in individuals diagnosed with autism spectrum disorder, suggests that

  17. A Suite of Lotus japonicus Starch Mutants Reveals Both Conserved and Novel Features of Starch Metabolism1[W][OA

    PubMed Central

    Vriet, Cécile; Welham, Tracey; Brachmann, Andreas; Pike, Marilyn; Pike, Jodie; Perry, Jillian; Parniske, Martin; Sato, Shusei; Tabata, Satoshi; Smith, Alison M.; Wang, Trevor L.

    2010-01-01

    The metabolism of starch is of central importance for many aspects of plant growth and development. Information on leaf starch metabolism other than in Arabidopsis (Arabidopsis thaliana) is scarce. Furthermore, its importance in several agronomically important traits exemplified by legumes remains to be investigated. To address this issue, we have provided detailed information on the genes involved in starch metabolism in Lotus japonicus and have characterized a comprehensive collection of forward and TILLING (for Targeting Induced Local Lesions IN Genomes) reverse genetics mutants affecting five enzymes of starch synthesis and two enzymes of starch degradation. The mutants provide new insights into the structure-function relationships of ADP-glucose pyrophosphorylase and glucan, water dikinase1 in particular. Analyses of the mutant phenotypes indicate that the pathways of leaf starch metabolism in L. japonicus and Arabidopsis are largely conserved. However, the importance of these pathways for plant growth and development differs substantially between the two species. Whereas essentially starchless Arabidopsis plants lacking plastidial phosphoglucomutase grow slowly relative to wild-type plants, the equivalent mutant of L. japonicus grows normally even in a 12-h photoperiod. In contrast, the loss of GLUCAN, WATER DIKINASE1, required for starch degradation, has a far greater effect on plant growth and fertility in L. japonicus than in Arabidopsis. Moreover, we have also identified several mutants likely to be affected in new components or regulators of the pathways of starch metabolism. This suite of mutants provides a substantial new resource for further investigations of the partitioning of carbon and its importance for symbiotic nitrogen fixation, legume seed development, and perenniality and vegetative regrowth. PMID:20699404

  18. Large screen approaches to identify novel malaria vaccine candidates.

    PubMed

    Davies, D Huw; Duffy, Patrick; Bodmer, Jean-Luc; Felgner, Philip L; Doolan, Denise L

    2015-12-22

    Until recently, malaria vaccine development efforts have focused almost exclusively on a handful of well characterized Plasmodium falciparum antigens. Despite dedicated work by many researchers on different continents spanning more than half a century, a successful malaria vaccine remains elusive. Sequencing of the P. falciparum genome has revealed more than five thousand genes, providing the foundation for systematic approaches to discover candidate vaccine antigens. We are taking advantage of this wealth of information to discover new antigens that may be more effective vaccine targets. Herein, we describe different approaches to large-scale screening of the P. falciparum genome to identify targets of either antibody responses or T cell responses using human specimens collected in Controlled Human Malaria Infections (CHMI) or under conditions of natural exposure in the field. These genome, proteome and transcriptome based approaches offer enormous potential for the development of an efficacious malaria vaccine. PMID:26428458

  19. Identification and molecular characterization of nitric oxide synthase (NOS) gene in the intertidal copepod Tigriopus japonicus.

    PubMed

    Jeong, Chang-Bum; Kang, Hye-Min; Seo, Jung Soo; Park, Heum Gi; Rhee, Jae-Sung; Lee, Jae-Seong

    2016-02-10

    In copepods, no information has been reported on the structure or molecular characterization of the nitric oxide synthase (NOS) gene. In the intertidal copepod Tigriopus japonicus, we identified a NOS gene that is involved in immune responses of vertebrates and invertebrates. In silico analyses revealed that nitric oxide (NO) synthase domains, such as the oxygenase and reductase domains, are highly conserved in the T. japonicus NOS gene. The T. japonicus NOS gene was highly transcribed in the nauplii stages, implying that it plays a role in protecting the host during the early developmental stages. To examine the involvement of the T. japonicus NOS gene in the innate immune response, the copepods were exposed to lipopolysaccharide (LPS) and two Vibrio sp. After exposure to different concentrations of LPS and Vibrio sp., T. japonicus NOS transcription was significantly increased over time in a dose-dependent manner, and the NO/nitrite concentration increased as well. Taken together, our findings suggest that T. japonicus NOS transcription is induced in response to an immune challenge as part of the conserved innate immunity. PMID:26611530

  20. Standardized Laboratory Feeding of Larval Aedes japonicus japonicus (Diptera: Culicidae)

    PubMed Central

    Bock, Friederike; Kuch, Ulrich; Pfenninger, Markus; Müller, Ruth

    2015-01-01

    The Asian bush mosquito (Aedes japonicus japonicus, Theobald 1901) is an invasive culicid species which originates in Asia but is nowadays present in northern America and Europe. It is a competent vector for several human disease pathogens. In addition to the public health threat, this invasive species may also be an ecological threat for native container-breeding mosquitoes which share a similar larval habitat. Therefore, it is of importance to gain knowledge on ecological and eco-toxicological features of the Asian bush mosquito. However, optimal laboratory feeding conditions have not yet been established. Standardized feeding methods will be needed in assessing the impact of insecticides or competitional strength of this species. To fill this gap, we performed experiments on food quality and quantity for Ae. j. japonicus larvae. We found out that the commercial fish food TetraMin (Tetra, Melle, Germany) in a dose of 10 mg per larva is the most suitable food tested. We also suggest a protocol with a feeding sequence of seven portions for all larval stages of this species. PMID:26452522

  1. Standardized Laboratory Feeding of Larval Aedes japonicus japonicus (Diptera: Culicidae).

    PubMed

    Bock, Friederike; Kuch, Ulrich; Pfenninger, Markus; Müller, Ruth

    2015-01-01

    The Asian bush mosquito (Aedes japonicus japonicus, Theobald 1901) is an invasive culicid species which originates in Asia but is nowadays present in northern America and Europe. It is a competent vector for several human disease pathogens. In addition to the public health threat, this invasive species may also be an ecological threat for native container-breeding mosquitoes which share a similar larval habitat. Therefore, it is of importance to gain knowledge on ecological and eco-toxicological features of the Asian bush mosquito. However, optimal laboratory feeding conditions have not yet been established. Standardized feeding methods will be needed in assessing the impact of insecticides or competitional strength of this species. To fill this gap, we performed experiments on food quality and quantity for Ae. j. japonicus larvae. We found out that the commercial fish food TetraMin (Tetra, Melle, Germany) in a dose of 10 mg per larva is the most suitable food tested. We also suggest a protocol with a feeding sequence of seven portions for all larval stages of this species. PMID:26452522

  2. Large data series: Modeling the usual to identify the unusual

    SciTech Connect

    Downing, D.J.; Fedorov, V.V.; Lawkins, W.F.; Morris, M.D.; Ostrouchov, G.

    1997-04-01

    {open_quotes}Standard{close_quotes} approaches such as regression analysis, Fourier analysis, Box-Jenkins procedure, et al., which handle a data series as a whole, are not useful for very large data sets for at least two reasons. First, even with computer hardware available today, including parallel processors and storage devices, there are no effective means for manipulating and analyzing gigabyte, or larger, data files. Second, in general it can not be assumed that a very large data set is {open_quotes}stable{close_quotes} by the usual measures, like homogeneity, stationarity, and ergodicity, that standard analysis techniques require. Both reasons dictate the necessity to use {open_quotes}local{close_quotes} data analysis methods whereby the data is segmented and ordered, where order leads to a sense of {open_quotes}neighbor,{close_quotes} and then analyzed segment by segment. The idea of local data analysis is central to the study reported here.

  3. Expert systems identify fossils and manage large paleontological databases

    SciTech Connect

    Beightol, D.S. ); Conrad, M.A.

    1988-02-01

    EXPAL is a computer program permitting creation and maintenance of comprehensive databases in marine paleontology. It is designed to assist specialists and non-specialists. EXPAL includes a powerful expert system based on the morphological descriptors specific to a given group of fossils. The expert system may be used, for example, to describe and automatically identify an unknown specimen. EXPAL was first applied to Dasycladales (Calcareous green algae). Projects are under way for corresponding expert systems and databases on planktonic foraminifers and calpionellids. EXPAL runs on an IBM XT or compatible microcomputer.

  4. Identifying Recent Adaptations in Large-scale Genomic Data

    PubMed Central

    Grossman, Sharon R.; Andersen, Kristian G.; Shlyakhter, Ilya; Tabrizi, Shervin; Winnicki, Sarah; Yen, Angela; Park, Daniel J.; Griesemer, Dustin; Karlsson, Elinor K.; Wong, Sunny H.; Cabili, Moran; Adegbola, Richard A.; Bamezai, Rameshwar N. K.; Hill, Adrian V. S.; Vannberg, Fredrik O.; Rinn, John L.; Lander, Eric S.; Schaffner, Stephen F.; Sabeti, Pardis C.

    2013-01-01

    SUMMARY While several hundred regions of the human genome harbor signals of positive natural selection, few of the relevant adaptive traits and variants have been elucidated. Using full-genome sequence variation from the 1000 Genomes Project (1000G) and the Composite of Multiple Signals (CMS) test, we investigated 412 candidate signals and leveraged functional annotation, protein structure modeling, epigenetics, and association studies to identify and extensively annotate candidate causal variants. The resulting catalog provides a tractable list for experimental follow-up; it includes thirty-five high-scoring non-synonymous variants, fifty-nine variants associated with expression levels of a nearby coding gene or lincRNA, and numerous variants associated with susceptibility to infectious disease and other phenotypes. We experimentally characterized one candidate non-synonymous variant in TLR5, and show that it leads to altered NF-κB signaling in response to bacterial flagellin. PMID:23415221

  5. Changes in collagenous tissue microstructures and distributions of cathepsin L in body wall of autolytic sea cucumber (Stichopus japonicus).

    PubMed

    Liu, Yu-Xin; Zhou, Da-Yong; Ma, Dong-Dong; Liu, Yan-Fei; Li, Dong-Mei; Dong, Xiu-Ping; Tan, Ming-Qian; Du, Ming; Zhu, Bei-Wei

    2016-12-01

    The autolysis of sea cucumber (Stichopus japonicus) was induced by ultraviolet (UV) irradiation, and the changes of microstructures of collagenous tissues and distributions of cathepsin L were investigated using histological and histochemical techniques. Intact collagen fibers in fresh S. japonicus dermis were disaggregated into collagen fibrils after UV stimuli. Cathepsin L was identified inside the surface of vacuoles in the fresh S. japonicus dermis cells. After the UV stimuli, the membranes of vacuoles and cells were fused together, and cathepsin L was released from cells and diffused into tissues. The density of cathepsin L was positively correlated with the speed and degree of autolysis in different layers of body wall. Our results revealed that lysosomal cathepsin L was released from cells in response to UV stimuli, which contacts and degrades the extracellular substrates such as collagen fibers, and thus participates in the autolysis of S. japonicus. PMID:27374541

  6. Proteomic investigation of the secretome of Cellvibrio japonicus during growth on chitin.

    PubMed

    Tuveng, Tina Rise; Arntzen, Magnus Øverlie; Bengtsson, Oskar; Gardner, Jeffrey G; Vaaje-Kolstad, Gustav; Eijsink, Vincent G H

    2016-07-01

    Studies of the secretomes of microbes grown on insoluble substrates are important for the discovery of novel proteins involved in biomass conversion. However, data in literature and this study indicate that secretome samples tend to be contaminated with cytoplasmic proteins. We have examined the secretome of the Gram-negative soil bacterium Cellvibrio japonicus using a simple plate-based culturing technique that yields samples with high fractions (60-75%) of proteins that are predicted to be secreted. By combining this approach with label-free quantification using the MaxLFQ algorithm, we have mapped and quantified proteins secreted by C. japonicus during growth on α- and β-chitin. Hierarchical clustering of the detected protein quantities revealed groups of up-regulated proteins that include all five putative C. japonicus chitinases as well as a chitin-specific lytic polysaccharide monooxygenase (CjLPMO10A). A small set of secreted proteins were co-regulated with known chitin-specific enzymes, including several with unknown catalytic functions. These proteins provide interesting targets for further studies aimed at unraveling the enzymatic machineries used by C. japonicus for recalcitrant polysaccharide degradation. Studies of chitin degradation indicated that C. japonicus indeed produces an efficient chitinolytic enzyme cocktail. All MS data have been deposited in the ProteomeXchange with the dataset identifier PXD002843 (http://proteomecentral.proteomexchange.org/dataset/PXD002843). PMID:27169553

  7. In-Frame Deletions Allow Functional Characterization of Complex Cellulose Degradation Phenotypes in Cellvibrio japonicus

    PubMed Central

    Nelson, Cassandra E.

    2015-01-01

    The depolymerization of the recalcitrant polysaccharides found in lignocellulose has become an area of intense interest due to the role of this process in global carbon cycling, human gut microbiome nutritional contributions, and bioenergy production. However, underdeveloped genetic tools have hampered study of bacterial lignocellulose degradation, especially outside model organisms. In this report, we describe an in-frame deletion strategy for the Gram-negative lignocellulose-degrading bacterium Cellvibrio japonicus. This method leverages optimized growth conditions for conjugation and sacB counterselection for the generation of markerless in-frame deletions. This method produces mutants in as few as 8 days and allows for the ability to make multiple gene deletions per strain. It is also possible to remove large sections of the genome, as shown in this report with the deletion of the nine-gene (9.4-kb) gsp operon in C. japonicus. We applied this system to study the complex phenotypes of cellulose degradation in C. japonicus. Our data indicated that a Δcel5B Δcel6A double mutant is crippled for cellulose utilization, more so than by either single mutation alone. Additionally, we deleted individual genes in the two-gene cbp2ED operon and showed that both genes contribute to cellulose degradation in C. japonicus. Overall, these described techniques substantially enhance the utility of C. japonicus as a model system to study lignocellulose degradation. PMID:26116676

  8. Long Non-Coding RNAs (lncRNAs) of Sea Cucumber: Large-Scale Prediction, Expression Profiling, Non-Coding Network Construction, and lncRNA-microRNA-Gene Interaction Analysis of lncRNAs in Apostichopus japonicus and Holothuria glaberrima During LPS Challenge and Radial Organ Complex Regeneration.

    PubMed

    Mu, Chuang; Wang, Ruijia; Li, Tianqi; Li, Yuqiang; Tian, Meilin; Jiao, Wenqian; Huang, Xiaoting; Zhang, Lingling; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

    2016-08-01

    Long non-coding RNA (lncRNA) structurally resembles mRNA but cannot be translated into protein. Although the systematic identification and characterization of lncRNAs have been increasingly reported in model species, information concerning non-model species is still lacking. Here, we report the first systematic identification and characterization of lncRNAs in two sea cucumber species: (1) Apostichopus japonicus during lipopolysaccharide (LPS) challenge and in heathy tissues and (2) Holothuria glaberrima during radial organ complex regeneration, using RNA-seq datasets and bioinformatics analysis. We identified A. japonicus and H. glaberrima lncRNAs that were differentially expressed during LPS challenge and radial organ complex regeneration, respectively. Notably, the predicted lncRNA-microRNA-gene trinities revealed that, in addition to targeting protein-coding transcripts, miRNAs might also target lncRNAs, thereby participating in a potential novel layer of regulatory interactions among non-coding RNA classes in echinoderms. Furthermore, the constructed coding-non-coding network implied the potential involvement of lncRNA-gene interactions during the regulation of several important genes (e.g., Toll-like receptor 1 [TLR1] and transglutaminase-1 [TGM1]) in response to LPS challenge and radial organ complex regeneration in sea cucumbers. Overall, this pioneer systematic identification, annotation, and characterization of lncRNAs in echinoderm pave the way for similar studies and future genetic, genomic, and evolutionary research in non-model species. PMID:27392411

  9. Does Autocthonous Primary Production Influence Oviposition by Aedes japonicus japonicus (Diptera: Culicidae) in Container Habitats?

    PubMed Central

    LORENZ, AMANDA R.; WALKER, EDWARD D.; KAUFMAN, MICHAEL G.

    2014-01-01

    Aedes (Finlaya) japonicus japonicus (Theobald) (Diptera: Culicidae) is recently invasive in North America and has expanded its range rapidly since 1998. Throughout its native and expanded range, Ae. j. japonicus larvae are commonly observed in many types of natural and artificial water-filled containers that vary in organic matter content and exposure to sunlight. Larvae are most often found in containers with decaying leaf material or algae, and we postulated that the added autocthonous primary production from algae could be both an important food source for larvae and an influential oviposition attractant to adult Ae. j. japonicus. We tested this hypothesis by placing plastic containers with varied levels of shading to manipulate algal density in the field, and then monitored oviposition by natural populations of Ae. j. japonicus. Over 99% of larvae hatching from eggs laid on the walls of our containers were Ae. j. japonicus, indicating that this species is a dominant colonizer of artificial containers in the study areas. Although full shading treatments effectively reduced algal biomass (significant reduction in chlorophyll a levels), at only one of three sites did this appear to affect Ae. j. japonicus oviposition. We conclude that algae in larval habitats are not a major factor in oviposition choices of adult Ae. j. japonicus females except when in situ primary production is high enough to substantially alter overall organic matter content cues. PMID:23427654

  10. A Novel Phenolic Compound, Chloroxynil, Improves Agrobacterium-Mediated Transient Transformation in Lotus japonicus

    PubMed Central

    Kimura, Mitsuhiro; Cutler, Sean; Isobe, Sachiko

    2015-01-01

    Agrobacterium-mediated transformation is a commonly used method for plant genetic engineering. However, the limitations of Agrobacterium host-plant interactions and the complexity of plant tissue culture often make the production of transgenic plants difficult. Transformation efficiency in many legume species, including soybean and the common bean, has been reported to be quite low. To improve the transformation procedure in legumes, we screened for chemicals that increase the transformation efficiency of Lotus japonicus, a model legume species. A Chemical library was screened and chemicals that increase in transient transformation efficiency of L. japonicus accession, Miyakojima MG-20 were identified. The transient transformation efficiency was quantified by reporter activity in which an intron-containing reporter gene produces the GUS protein only when the T-DNA is expressed in the plant nuclei. We identified a phenolic compound, chloroxynil, which increased the genetic transformation of L. japonicus by Agrobacterium tumefaciens strain EHA105. Characterization of the mode of chloroxynil action indicated that it enhanced Agrobacterium-mediated transformation through the activation of the Agrobacterium vir gene expression, similar to acetosyringone, a phenolic compound known to improve Agrobacterium-mediated transformation efficiency. Transient transformation efficiency of L. japonicus with 5 μM chloroxynil was 60- and 6- fold higher than that of the control and acetosyringone treatment, respectively. In addition, transgenic L. japonicus lines were successfully generated by 5 μM chloroxynil treatment.Furthermore, we show that chloroxynil improves L. japonicus transformation by Agrobacterium strain GV3101 and rice transformation. Our results demonstrate that chloroxynil significantly improves Agrobacterium tumefaciens-mediated transformation efficiency of various agriculturally important crops. PMID:26176780

  11. Glucaric acids from Leonurus japonicus.

    PubMed

    Jiang, Jianshuang; Li, Yixiu; Feng, Ziming; Yang, Yanan; Zhang, Peicheng

    2015-12-01

    Three new glucaric acids, namely 2-feruloyl-4-syringoyl or 5-feruloyl-3-syringoyl glucaric acid (1), 2-syringoyl-4-feruloyl or 5-syringoyl-3-feruloyl glucaric acid (2), and 3-feruloyl-4-syringoyl or 4-feruloyl-3-syringoyl glucaric acid (3), were isolated from Leonurus japonicus Houtt. Their structures were elucidated by detailed spectroscopic means including UV, IR, HR-ESI-MS, 1D and 2D NMR data spectra. The bioactive assays of compounds 1-3 against hepatoprotection activity were determined. The result suggested that compound 2 exhibited a moderate hepatoprotection activity and the cell survival rate was 74% (10(-5)mol/L), using bicyclol (survival rate: 66%, 10(-5)mol/L) as a positive control. Furthermore, compounds 1-3 were evaluated cytotoxic activities in vitro using HCT-8, Bel-7402, BGC-823, A-549, and A2780 model and the results exhibited no obvious cytotoxicity activity. PMID:26526024

  12. Larval mosquito habitat utilization and community dynamics of Aedes albopictus and Aedes japonicus (Diptera: Culicidae).

    PubMed

    Bartlett-Healy, Kristen; Unlu, Isik; Obenauer, Peter; Hughes, Tony; Healy, Sean; Crepeau, Taryn; Farajollahi, Ary; Kesavaraju, Banu; Fonseca, Dina; Schoeler, George; Gaugler, Randy; Strickman, Daniel

    2012-07-01

    Aedes albopictus (Skuse) and Ae. japonicus (Theobald) are important container-inhabiting mosquitoes that transmit disease agents, outcompete native species, and continue to expand their range in the United States. Both species deposit eggs in natural and artificial containers and thrive in peridomestic environments. The goal of our study was to examine the types and characteristics of containers that are most productive for these species in the northeastern United States. In total, 306 containers were sampled in urban, suburban, and rural areas of New Jersey. Multiple biotic and abiotic factors were recorded in an attempt to identify variables associated with the productivity of each species. Based on pupal abundance and density of container types, results showed that tires, trash cans, and planter dishes were the most important containers for Ae. albopictus, while planter dishes were the most important containers for Ae. japonicus. Container color (black and gray), material (rubber), and type (tires) were correlated with species presence for Ae. albopictus and Ae. japonicus. These factors may play a role in the selection of oviposition sites by female mosquitoes or in the survival of their progeny. Differences in species composition and abundance were detected between areas classified as urban, suburban, and rural. In urban and suburban areas, Ae. albopictus was more abundant in container habitats than Ae. japonicus; however, Ae. japonicus was more abundant in rural areas, and when water temperatures were below 14 degrees C. Our results suggest many variables can influence the presence of Ae. albopictus and Ae. japonicus in container habitats in northeastern United States. PMID:22897041

  13. The complete chloroplast genome sequence of Chloranthus japonicus.

    PubMed

    Sun, Jing; Zhang, Gang; Li, Yimin; Chen, Ying; Zhang, Xiaofei; Tang, Zhishu; Wu, Haifeng

    2016-09-01

    The complete chloroplast genome of Chloranthus japonicus, an important traditional Chinese herbal medicine, was sequenced and characterized in this study. The genome size is 158,640 bp in length with 38.9% GC content. Two inverted repeats of 26,149 bp are separated by a large single-copy region (87,724 bp) and a small single-copy region (18,618 bp). The genome contains 131 individual genes, including 86 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Eighteen genes contain one or two introns. PMID:25707409

  14. Biosynthesis and hyper production of pullulan by a newly isolated strain of Aspergillus japonicus-VIT-SB1.

    PubMed

    Mishra, Bishwambhar; Suneetha, V

    2014-07-01

    The main focus of this study was to screen and characterize novel microbial strains isolated from culinary leaf samples, capable of producing high concentrations of pullulan. Hundred isolates were screened from the phylloplane of different plants. The results revealed that eight strains had the capability to produce exopolysaccharide (EPS) and only one potential strain (designated as VIT-SB1) could produce the significant amount of EPS (3.9 ± 0.02%) on the 6th day of the fermentation without optimisation. The EPS synthesized by VIT-SB1 strain was confirmed to be pullulan on the basis of the results of FT-IR, HPLC and the enzymatic (Pullulanase) analysis. More than 91% hydrolysis of pullulan by pullulanase enzyme also indicated the presence of α (1 → 6) glycosidic linkages of α (1 → 4) linked maltotriose units. This VIT-SB1 strain was identified as Aspergillus japonicus based on the nucleotide sequence of the D1/D2 domain of Large-Subunit rRNA gene. The sequence was submitted to the GenBank Nucleotide sequence database with Accession No: KC128815. This study has confirmed that pullulan production capacity of this novel strain and Aureobasidium pullulans are comparable. Hence Aspergillus japonicus-VIT-SB1 strain can be commercially exploited as a potential pullulan producing strain. PMID:24609496

  15. Transcriptome Response Mediated by Cold Stress in Lotus japonicus

    PubMed Central

    Calzadilla, Pablo I.; Maiale, Santiago J.; Ruiz, Oscar A.; Escaray, Francisco J.

    2016-01-01

    Members of the Lotus genus are important as agricultural forage sources under marginal environmental conditions given their high nutritional value and tolerance of various abiotic stresses. However, their dry matter production is drastically reduced in cooler seasons, while their response to such conditions is not well studied. This paper analyzes cold acclimation of the genus by studying Lotus japonicus over a stress period of 24 h. High-throughput RNA sequencing was used to identify and classify 1077 differentially expressed genes, of which 713 were up-regulated and 364 were down-regulated. Up-regulated genes were principally related to lipid, cell wall, phenylpropanoid, sugar, and proline regulation, while down-regulated genes affected the photosynthetic process and chloroplast development. Together, a total of 41 cold-inducible transcription factors were identified, including members of the AP2/ERF, NAC, MYB, and WRKY families; two of them were described as putative novel transcription factors. Finally, DREB1/CBFs were described with respect to their cold stress expression profiles. This is the first transcriptome profiling of the model legume L. japonicus under cold stress. Data obtained may be useful in identifying candidate genes for breeding modified species of forage legumes that more readily acclimate to low temperatures. PMID:27066029

  16. Feeding behavior and digestive physiology in sea cucumber Apostichopus japonicus.

    PubMed

    Sun, Jiamin; Zhang, Libin; Pan, Yang; Lin, Chenggang; Wang, Fang; Kan, Rentao; Yang, Hongsheng

    2015-02-01

    The feeding behavior and digestive physiology of the sea cucumber, Apostichopus japonicus are not well understood. A better understanding may provide useful information for the development of the aquaculture of this species. In this article the tentacle locomotion, feeding rhythms, ingestion rate (IR), feces production rate (FPR) and digestive enzyme activities were studied in three size groups (small, medium and large) of sea cucumber under a 12h light/12h dark cycle. Frame-by-frame video analysis revealed that all size groups had similar feeding strategies using a grasping motion to pick up sediment particles. The tentacle insertion rates of the large size group were significantly faster than those of the small and medium-sized groups (P<0.05). Feeding activities investigated by charge coupled device cameras with infrared systems indicated that all size groups of sea cucumber were nocturnal and their feeding peaks occurred at 02:00-04:00. The medium and large-sized groups also had a second feeding peak during the day. Both IR and FPR in all groups were significantly higher at night than those during the daytime (P<0.05). Additionally, the peak activities of digestive enzymes were 2-4h earlier than the peak of feeding. Taken together, these results demonstrated that the light/dark cycle was a powerful environment factor that influenced biological rhythms of A. japonicus, which had the ability to optimize the digestive processes for a forthcoming ingestion. PMID:25449414

  17. Orostachys japonicus Suppresses Osteoclast Differentiation by Inhibiting NFATc1 Expression.

    PubMed

    Shim, Ki-Shuk; Ha, Hyunil; Kim, Taesoo; Lee, Chung-Jo; Ma, Jin Yeul

    2015-01-01

    The herb Orostachys japonicus has been traditionally used to treat chronic diseases, such as hepatitis, hemorrhoids, and cancer, in Asia. In this study, we investigated the effect of Orostachys japonicus water extract (OJWE) on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone loss. We found that OJWE inhibited RANKL-induced osteoclast differentiation in a dose-dependent manner without affecting bone resorption in bone marrow-derived macrophage cells. Interestingly, OJWE significantly reduced serum levels of C-terminal telopeptide of type 1 collagen and tartrate-resistant acid phosphatase (TRAP) 5b, markers of bone resorption and osteoclast number, respectively, in an animal model of bone loss. Furthermore, OJWE suppressed the RANKL-induced up-regulation of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) expression, and activation of the p38 signaling pathway, but prevented the RANKL-mediated down-regulation of interferon regulatory factor-8 (IRF-8), which is known to be an anti-osteoclastogenic factor that represses NFATc1 expression. We also identified gallic acid and quercetin-3-O-β-D-glucoside as the OJWE components that inhibit RANKL-induced osteoclast differentiation. These results suggest that OJWE inhibits osteoclast differentiation by inhibiting RANKL-induced NFATc1 expression, which prevents osteoclast differentiation and bone loss. The present study elucidated a mechanism of action underlying the inhibitory effect of OJWE on osteoclast differentiation. Our findings suggest that O. japonicus has therapeutic potential for use in the treatment of bone diseases. PMID:26205967

  18. Legume genome evolution viewed through the Medicago truncatula and Lotus japonicus genomes

    PubMed Central

    Cannon, Steven B.; Sterck, Lieven; Rombauts, Stephane; Sato, Shusei; Cheung, Foo; Gouzy, Jérôme; Wang, Xiaohong; Mudge, Joann; Vasdewani, Jayprakash; Schiex, Thomas; Spannagl, Manuel; Monaghan, Erin; Nicholson, Christine; Humphray, Sean J.; Schoof, Heiko; Mayer, Klaus F. X.; Rogers, Jane; Quétier, Francis; Oldroyd, Giles E.; Debellé, Frédéric; Cook, Douglas R.; Retzel, Ernest F.; Roe, Bruce A.; Town, Christopher D.; Tabata, Satoshi; Van de Peer, Yves; Young, Nevin D.

    2006-01-01

    Genome sequencing of the model legumes, Medicago truncatula and Lotus japonicus, provides an opportunity for large-scale sequence-based comparison of two genomes in the same plant family. Here we report synteny comparisons between these species, including details about chromosome relationships, large-scale synteny blocks, microsynteny within blocks, and genome regions lacking clear correspondence. The Lotus and Medicago genomes share a minimum of 10 large-scale synteny blocks, each with substantial collinearity and frequently extending the length of whole chromosome arms. The proportion of genes syntenic and collinear within each synteny block is relatively homogeneous. Medicago–Lotus comparisons also indicate similar and largely homogeneous gene densities, although gene-containing regions in Mt occupy 20–30% more space than Lj counterparts, primarily because of larger numbers of Mt retrotransposons. Because the interpretation of genome comparisons is complicated by large-scale genome duplications, we describe synteny, synonymous substitutions and phylogenetic analyses to identify and date a probable whole-genome duplication event. There is no direct evidence for any recent large-scale genome duplication in either Medicago or Lotus but instead a duplication predating speciation. Phylogenetic comparisons place this duplication within the Rosid I clade, clearly after the split between legumes and Salicaceae (poplar). PMID:17003129

  19. Physiological properties of Scomber japonicus meat hydrolysate prepared by subcritical water hydrolysis.

    PubMed

    Choi, Jae-Suk; Moon, Hye Eun; Roh, Myong-Kyun; Ha, Yu-Mi; Lee, Bo-Bae; Cho, Kwang Keun; Choi, In Soon

    2016-01-01

    The health-beneficial biological activities, including antioxidant and tyrosinase inhibitory activities, of Scomber japonicus muscle protein hydrolysates prepared by subcritical water hydrolysis were investigated. After 5 min of subcritical hydrolysis at 140 degrees C, 59.76% of S. japonicus muscle protein was hydrolyzed, the highest degree of hydrolysis in all the groups were tested. According to the response surface methodology results, as the reaction temperature and reaction time became lower and shorter, the yield became higher. The highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity (90.63%) occurred in hydrolysates treated at 140 degrees C for 5 min, and the highest tyrosinase inhibitory activity (65.54%) was identified in hydrolysates treated at 200 degreesC for 15 min. Changes in the molecular weight distribution of S. japonicus muscle proteins after subcritical water hydrolysis were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Subcritical water hydrolysis is a suitable technique for obtaining S.japonicus muscle protein hydrolysates with useful biological activities, within a short time (5-15 min). PMID:26930861

  20. Multiple components are integrated to determine leaf complexity in Lotus japonicus.

    PubMed

    Wang, Zhenhua; Chen, Jianghua; Weng, Lin; Li, Xin; Cao, Xianglin; Hu, Xiaohe; Luo, Da; Yang, Jun

    2013-05-01

    Transcription factors and phytohormones have been reported to play crucial roles to regulate leaf complexity among plant species. Using the compound-leafed species Lotus japonicus, a model legume plant with five visible leaflets, we characterized four independent mutants with reduced leaf complexity, proliferating floral meristem (pfm), proliferating floral organ-2 (pfo-2), fused leaflets1 (ful1) and umbrella leaflets (uml), which were further identified as loss-of-function mutants of Arabidopsis orthologs LEAFY (LFY), UNUSUAL FLORAL ORGANS (UFO), CUP-SHAPED COTYLEDON 2 (CUC2) and PIN-FORMED 1 (PIN1), respectively. Comparing the leaf development of wild-type and mutants by a scanning electron microscopy approach, leaflet initiation and/or dissection were found to be affected in these mutants. Expression and phenotype analysis indicated that PFM/LjLFY and PFO/LjUFO determined the basipetal leaflet initiation manner in L. japonicus. Genetic analysis of ful1 and uml mutants and their double mutants revealed that the CUC2-like gene and auxin pathway also participated in leaflet dissection in L. japonicus, and their functions might influence cytokinin biogenesis directly or indirectly. Our results here suggest that multiple genes were interplayed and played conserved functions in controlling leaf complexity during compound leaf development in L. japonicus. PMID:23331609

  1. Divergent metabolic responses of Apostichopus japonicus suffered from skin ulceration syndrome and pathogen challenge.

    PubMed

    Shao, Yina; Li, Chenghua; Ou, Changrong; Zhang, Peng; Lu, Yali; Su, Xiurong; Li, Ye; Li, Taiwu

    2013-11-13

    Skin ulceration syndrome (SUS) is the main limitation in the development of Apostichopus japonicus culture industries, in which Vibrio splendidus has been well documented as one of the major pathogens. However, the intrinsic mechanisms toward pathogen challenge and disease outbreak remain largely unknown at the metabolic level. In this work, the metabolic responses were investigated in muscles of sea cucumber among natural SUS-diseased and V. splendidus-challenged samples. The pathogen did not induce obvious biological effects in A. japonicus samples after infection for the first 24 h. An enhanced energy storage (or reduced energy demand) and immune responses were observed in V. splendidus-challenged A. japonicus samples at 48 h, as marked by increased glucose and branched chain amino acids, respectively. Afterward, infection of V. splendidus induced significant increases in energy demand in A. japonicus samples at both 72 and 96 h, confirmed by decreased glucose and glycogen, and increased ATP. Surprisingly, high levels of glycogen and glucose and low levels of threonine, alanine, arginine, glutamate, glutamine, taurine and ATP were founded in natural SUS-diseased sea cucumber. Our present results provided essential metabolic information about host-pathogen interaction for sea cucumber, and informed that the metabolic biomarkers induced by V. splendidus were not usable for the prediction of SUS disease in practice. PMID:24127639

  2. Out of the bush: the Asian bush mosquito Aedes japonicus japonicus (Theobald, 1901) (Diptera, Culicidae) becomes invasive.

    PubMed

    Kampen, Helge; Werner, Doreen

    2014-01-01

    The Asian bush or rock pool mosquito Aedes japonicus japonicus is one of the most expansive culicid species of the world. Being native to East Asia, this species was detected out of its original distribution range for the first time in the early 1990s in New Zealand where it could not establish, though. In 1998, established populations were reported from the eastern US, most likely as a result of introductions several years earlier. After a massive spread the mosquito is now widely distributed in eastern North America including Canada and two US states on the western coast. In the year 2000, it was demonstrated for the first time in Europe, continental France, but could be eliminated. A population that had appeared in Belgium in 2002 was not controlled until 2012 as it did not propagate. In 2008, immature developmental stages were discovered in a large area in northern Switzerland and bordering parts of Germany. Subsequent studies in Germany showed a wide distribution and several populations of the mosquito in various federal states. Also in 2011, the species was found in southeastern Austria (Styria) and neighbouring Slovenia. In 2013, a population was detected in the Central Netherlands, specimens were collected in southern Alsace, France, and the complete northeastern part of Slovenia was found colonized, with specimens also present across borders in adjacent Croatia. Apparently, at the end of 2013 a total of six populations occurred in Europe although it is not clear whether all of them are completely isolated. Similarly, it is not known whether these populations go back to the same number of introductions. While entry ports and long-distance continental migration routes are also obscure, it is likely that the international used tyre trade is the most important mode of intercontinental transportation of the mosquito. Aedes j. japonicus does not only display an aggressive biting behaviour but is suspected to be a vector of various disease agents and to displace

  3. Out of the bush: the Asian bush mosquito Aedes japonicus japonicus (Theobald, 1901) (Diptera, Culicidae) becomes invasive

    PubMed Central

    2014-01-01

    The Asian bush or rock pool mosquito Aedes japonicus japonicus is one of the most expansive culicid species of the world. Being native to East Asia, this species was detected out of its original distribution range for the first time in the early 1990s in New Zealand where it could not establish, though. In 1998, established populations were reported from the eastern US, most likely as a result of introductions several years earlier. After a massive spread the mosquito is now widely distributed in eastern North America including Canada and two US states on the western coast. In the year 2000, it was demonstrated for the first time in Europe, continental France, but could be eliminated. A population that had appeared in Belgium in 2002 was not controlled until 2012 as it did not propagate. In 2008, immature developmental stages were discovered in a large area in northern Switzerland and bordering parts of Germany. Subsequent studies in Germany showed a wide distribution and several populations of the mosquito in various federal states. Also in 2011, the species was found in southeastern Austria (Styria) and neighbouring Slovenia. In 2013, a population was detected in the Central Netherlands, specimens were collected in southern Alsace, France, and the complete northeastern part of Slovenia was found colonized, with specimens also present across borders in adjacent Croatia. Apparently, at the end of 2013 a total of six populations occurred in Europe although it is not clear whether all of them are completely isolated. Similarly, it is not known whether these populations go back to the same number of introductions. While entry ports and long-distance continental migration routes are also obscure, it is likely that the international used tyre trade is the most important mode of intercontinental transportation of the mosquito. Aedes j. japonicus does not only display an aggressive biting behaviour but is suspected to be a vector of various disease agents and to displace

  4. Trissolcus japonicus (Ashmead) emerges in North America

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Trissolcus japonicus (Ashmead) is an Asian egg parasitoid of the brown marmorated stink bug, Halyomorpha halys (Stål). It has been under study in U.S. quarantine facilities since 2007 to evaluate its efficacy as a candidate classical biological control agent and its host specificity with regard to t...

  5. Distribution and genetic structure of Aedes japonicus japonicus populations (Diptera: Culicidae) in Germany.

    PubMed

    Huber, Katrin; Schuldt, Kathrin; Rudolf, Martin; Marklewitz, Marco; Fonseca, Dina M; Kaufmann, Christian; Tsuda, Yoshio; Junglen, Sandra; Krüger, Andreas; Becker, Norbert; Tannich, Egbert; Becker, Stefanie C

    2014-09-01

    In recent years, the number of imported cases of arthropod-borne diseases in Europe, such as dengue fever, has increased steadily, as did the emergence and distribution of invasive insect vectors. Consequently, the risk of disease spreading into previously unaffected regions through invasive mosquitoes is also increasing. One example of an invasive mosquito is Aedes japonicus japonicus (A. j. japonicus), which spread from its original habitat in Japan to North America and Europe. This species has been shown to act as a vector for Japanese encephalitis and West Nile viruses. In Europe, A. j. japonicus has been detected in Switzerland, Belgium, Slovenia, and Germany, where it has become a resident species. Here, we describe the recent spread and genetic structure of A. j. japonicus populations in Germany. By monitoring the species in Baden-Württemberg in 2011 and 2012, we observed a considerable enlargement of the infested area from 54 municipalities in 2011 to 124 municipalities in 2012. To elucidate the colonization of Europe by A. j. japonicus, seven microsatellite loci were studied in 106 individuals sampled in Germany and Switzerland in 2012. The same markers were genotyped in 31 North American and 26 Japanese specimens. Population genetic analyses indicated that A. j. japonicus in Baden-Württemberg and North Rhine-Westphalia represented two genetically distinct populations with FST-values of 0.073-0.152, suggesting that they originated from two independent introduction events in the past. These results are of particular interest in light of vectorial variability for the transmission of viruses and other pathogens in Europe. PMID:25056941

  6. Understanding the Heat Shock Response in the Sea Cucumber Apostichopus japonicus, Using iTRAQ-Based Proteomics

    PubMed Central

    Xu, Dongxue; Sun, Lina; Liu, Shilin; Zhang, Libin; Yang, Hongsheng

    2016-01-01

    The sea cucumber Apostichopus japonicus is exploited as a commercial species owing to their high nutritive and medicinal value. Recent high summer temperatures have caused high mortality rates in A. japonicus. In this study, we applied the isobaric tag for relative and absolute quantitation (iTRAQ) technique to investigate the global protein expression profile under an acute short-term (48 h) heat stress. In total, 3432 proteins were identified, and 127 proteins showed significant heat stress responses, with 61 upregulated proteins and 66 downregulated proteins. Our results suggest that heat stress influenced the expression of proteins involved in various biological processes, such as tissue protection and detoxification, lipid and amino acid metabolism, energy production and usage, transcription and translation, cell apoptosis, and cell proliferation. These findings provide a better understanding about the response and thermo-tolerance mechanisms of A. japonicus under heat stress. PMID:26861288

  7. Understanding the Heat Shock Response in the Sea Cucumber Apostichopus japonicus, Using iTRAQ-Based Proteomics.

    PubMed

    Xu, Dongxue; Sun, Lina; Liu, Shilin; Zhang, Libin; Yang, Hongsheng

    2016-01-01

    The sea cucumber Apostichopus japonicus is exploited as a commercial species owing to their high nutritive and medicinal value. Recent high summer temperatures have caused high mortality rates in A. japonicus. In this study, we applied the isobaric tag for relative and absolute quantitation (iTRAQ) technique to investigate the global protein expression profile under an acute short-term (48 h) heat stress. In total, 3432 proteins were identified, and 127 proteins showed significant heat stress responses, with 61 upregulated proteins and 66 downregulated proteins. Our results suggest that heat stress influenced the expression of proteins involved in various biological processes, such as tissue protection and detoxification, lipid and amino acid metabolism, energy production and usage, transcription and translation, cell apoptosis, and cell proliferation. These findings provide a better understanding about the response and thermo-tolerance mechanisms of A. japonicus under heat stress. PMID:26861288

  8. Reassimilation of ammonium in Lotus japonicus.

    PubMed

    Betti, Marco; García-Calderón, Margarita; Pérez-Delgado, Carmen M; Credali, Alfredo; Pal'ove-Balang, Peter; Estivill, Guillermo; Repčák, Miroslav; Vega, José M; Galván, Francisco; Márquez, Antonio J

    2014-10-01

    This review summarizes the most recent results obtained in the analysis of two important metabolic pathways involved in the release of internal sources of ammonium in the model legume Lotus japonicus: photorespiratory metabolism and asparagine breakdown mediated by aparaginase (NSE). The use of photorespiratory mutants deficient in plastidic glutamine synthetase (GS2) enabled us to investigate the transcriptomics and metabolomic changes associated with photorespiratory ammonium accumulation in this plant. The results obtained indicate the existence of a coordinate regulation of genes involved in photorespiratory metabolism. Other types of evidence illustrate the multiple interconnections existing among the photorespiratory pathway and other processes such as intermediate metabolism, nodule function, and secondary metabolism in this plant, all of which are substantially affected in GS2-deficient mutants because of the impairment of the photorespiratory cycle. Finally, the importance of asparagine metabolism in L. japonicus is highlighted because of the fact that asparagine constitutes the vast majority of the reduced nitrogen translocated between different organs of this plant. The different types of NSE enzymes and genes which are present in L. japonicus are described. There is a particular focus on the most abundant K(+)-dependent LjNSE1 isoform and how TILLING mutants were used to demonstrate by reverse genetics the importance of this particular isoform in plant growth and seed production. PMID:24948681

  9. Genome Structure of the Legume, Lotus japonicus

    PubMed Central

    Sato, Shusei; Nakamura, Yasukazu; Kaneko, Takakazu; Asamizu, Erika; Kato, Tomohiko; Nakao, Mitsuteru; Sasamoto, Shigemi; Watanabe, Akiko; Ono, Akiko; Kawashima, Kumiko; Fujishiro, Tsunakazu; Katoh, Midori; Kohara, Mitsuyo; Kishida, Yoshie; Minami, Chiharu; Nakayama, Shinobu; Nakazaki, Naomi; Shimizu, Yoshimi; Shinpo, Sayaka; Takahashi, Chika; Wada, Tsuyuko; Yamada, Manabu; Ohmido, Nobuko; Hayashi, Makoto; Fukui, Kiichi; Baba, Tomoya; Nakamichi, Tomoko; Mori, Hirotada; Tabata, Satoshi

    2008-01-01

    The legume Lotus japonicus has been widely used as a model system to investigate the genetic background of legume-specific phenomena such as symbiotic nitrogen fixation. Here, we report structural features of the L. japonicus genome. The 315.1-Mb sequences determined in this and previous studies correspond to 67% of the genome (472 Mb), and are likely to cover 91.3% of the gene space. Linkage mapping anchored 130-Mb sequences onto the six linkage groups. A total of 10 951 complete and 19 848 partial structures of protein-encoding genes were assigned to the genome. Comparative analysis of these genes revealed the expansion of several functional domains and gene families that are characteristic of L. japonicus. Synteny analysis detected traces of whole-genome duplication and the presence of synteny blocks with other plant genomes to various degrees. This study provides the first opportunity to look into the complex and unique genetic system of legumes. PMID:18511435

  10. Characterization and expression analysis of a caspase-2 in an invertebrate echinoderm sea cumber Apostichopus japonicus.

    PubMed

    Ye, Shigen; Gao, Yang; Wang, Shengnan; Li, Qiang; Li, Ruijun; Li, Hua

    2016-01-01

    Caspase-2 is the most evolutionarily conserved member of the caspase family which mediates the programmed cell death and plays crucial roles in key cellular processes. In this study, a caspase-2 homolog was identified and functionally characterized in sea cucumber Apostichopus japonicus, which we named AjCASP. The full-length cDNA consists of 2100 bp with an ORF encoding a protein of 378 amino acids. The deduced amino acid sequence shows that AjCASP consists of a conserved CARD-CASP2 domain and a CASs domain containing two active residues, two proteolytic cleavage residues, a substrate pocket and a dimer interface as well. In addition, a p20 large subunit with a characteristic five-peptide motif (QACRG) and a p10 small subunit in C-terminal were identified in CASs domain. Above data demonstrated that AjCASP is similar to CED-3 (the caspase-2 homolog of nematode Caenorhabditis elegans), which is further confirmed by phylogenetic tree analysis. AjCASP was ubiquitously expressed in sea cucumber and the obviously higher expression level was observed in coelomocyte, respiratory tree and intestine. Real-time PCR analyses further demonstrated that AjCASP was significantly induced by LPS. Taken together, these results strongly suggest that AjCASP is a caspase-2 homolog and it may be involved in invertebrate immune response, especially in eliminating and degrading invading pathogens. PMID:26687532

  11. Fish Lice (Argulus japonicus) in Goldfish (Carassius auratus)

    PubMed Central

    Wafer, Lemnique N; Whitney, Jesse C; Jensen, V Behrana

    2015-01-01

    Fish lice (Argulus spp; family Argulidae) are branchiuran crustaceans that parasitize both marine and freshwater fishes. Argulus spp can be a major threat to fish health, because heavy infestations can cause significant morbidity and mortality. In addition, fish lice are known to be the vehicle for other fish diseases. During rounds at our facility, Argulus japonicus was collected from the caudal and anal fins of 3 goldfish (Carassius auratus).These goldfish were asymptomatic, and no additional cases were noted after manual removal of the lice. As soon as any Argulus organisms are identified, management and treatment are recommended because infections can escalate rapidly. Currently, there are no FDA-approved drugs for the control and treatment of this parasite, but several chemicals including organophosphates and diflubenzuron have been used with success. The screening and quarantine of incoming fish is the best way to avoid a facility-wide Argulus infestation. PMID:25926394

  12. Fish Lice (Argulus japonicus) in Goldfish (Carassius auratus).

    PubMed

    Wafer, Lemnique N; Whitney, Jesse C; Jensen, V Behrana

    2015-04-01

    Fish lice (Argulus spp; family Argulidae) are branchiuran crustaceans that parasitize both marine and freshwater fishes. Argulus spp can be a major threat to fish health, because heavy infestations can cause significant morbidity and mortality. In addition, fish lice are known to be the vehicle for other fish diseases. During rounds at our facility, Argulus japonicus was collected from the caudal and anal fins of 3 goldfish (Carassius auratus). These goldfish were asymptomatic, and no additional cases were noted after manual removal of the lice. As soon as any Argulus organisms are identified, management and treatment are recommended because infections can escalate rapidly. Currently, there are no FDA-approved drugs for the control and treatment of this parasite, but several chemicals including organophosphates and diflubenzuron have been used with success. The screening and quarantine of incoming fish is the best way to avoid a facility-wide Argulus infestation. PMID:25926394

  13. Inheritance of pink flower color in Styrax japonicus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most Styrax japonicus (Japanese snowbell) cultivars produce white flowers, but a few pink-flowered forms have been reported. ‘Pink Chimes’ is the most widely grown pink-flowered form and the only S. japonicus cultivar with deep pink flowers that hold their color even under hot growing conditions. ...

  14. Succession and seasonal variation in epilithic biofilms on artificial reefs in culture waters of the sea cucumber Apostichopus japonicus

    NASA Astrophysics Data System (ADS)

    Liu, Liming; Du, Rongbin; Zhang, Xiaoling; Dong, Shuanglin; Sun, Shichun

    2016-04-01

    Periphytic biofilms in aquaculture waters are thought to improve water quality, provide an additional food source, and improve the survival and growth of some reared animals. In the Asia- Pacific region, particularly in China, artificial reefs are commonly used in the commercial farming of sea cucumbers. However, few studies have examined the epilithic biofilms on the artificial reefs. To gain a better understanding of the succession of epilithic biofilms and their ecological processes in sea cucumber culture waters, two experiments were conducted in culture waters of the sea cucumber Apostichopus japonicus in Rongcheng, China, using artificial test panels. On the test panels of succession experiment, more than 67 species were identified in the biofilms. On the test panels of seasonal variation experiment, more than 46 species were recorded in the biofilms. In both experiments, communities of epilithic biofilms were dominated by diatoms, green algae and the annelid Spirorbis sp. In the initial colonization, the dominant diatoms were Cocconeis sp., Amphora spp. and Nitzschia closterium in June, which were succeeded by species of Navicula, Cocconeis and Nitzschia (July to September), and then by Licmophora abbreviata, Nitzschia closterium and Synedra spp. in the following months. A diatom bloom in the autumn and filamentous green algae burst in the summer were also observed. Ecological indices well annotated the succession and seasonal changes in epilithic communities. Multidimensional scaling (MDS) analysis found significant diff erences in diatom community composition among months and seasons. Fast growth of biofilms was observed in the summer and autumn, whereas the biomass of summer biofilms was largely made up of filamentous green algae. Present results show that the components of epilithic biofilms are mostly optimal foods of A. japonicus, suggesting that biofilms on artificial reefs may contribute important nutritional sources for sea cucumbers during their

  15. Differential gene expression in the respiratory tree of the sea cucumber Apostichopus japonicus during aestivation.

    PubMed

    Zhao, Ye; Yang, Hongsheng; Storey, Kenneth B; Chen, Muyan

    2014-12-01

    Sea cucumbers, Apostichopus japonicus, experience seasonally high water temperatures during the summer months and enter aestivation to survive. Aestivation is characterized by strong metabolic rate depression which is supported by a series of strategies including reorganizing metabolic processes, suppressing cell functions, enhancing cytoprotective mechanisms, and altered gene expression. The respiratory tree tissue of the sea cucumber is an excellent material for studying aestivation, undergoing obvious atrophy during aestivation. The present study analyzed the global gene expression profile of respiratory tree tissue of A. japonicus during aestivation by constructing and screening three libraries representing key stages of aestivation: non-aestivation (NA), deep-aestivation (DA), and arousal from aestivation (AA) using RNA-seq. A total of 1240, 1184 and 303 differentially expressed genes (DEGs) were identified following the criteria of |log2 ratio|≥1 and FDR≤0.001 in comparisons of DA vs. NA, AA vs. NA and DA vs. AA. A set of respiratory tree specific DEGs was identified the first time and, in addition, common DEGs that were responsive to aestivation in both respiratory tree and intestine were identified. Functional analysis of DEGs was further performed by GO enrichment analysis and respiratory tree specific GO terms were screened out and provide interesting hints for further studies of the molecular regulation of aestivation in A. japonicus. PMID:25038515

  16. Influence of flow velocity on motor behavior of sea cucumber Apostichopus japonicus.

    PubMed

    Pan, Yang; Zhang, Libin; Lin, Chenggang; Sun, Jiamin; Kan, Rentao; Yang, Hongsheng

    2015-05-15

    The influence of flow velocity on the motor behavior of the sea cucumber, Apostichopus japonicus was investigated in the laboratory. Cameras were used to record sea cucumber movements and behavior analysis software was used to measure the distance traveled, time spent, upstream or downstream of the start position and the speed of movements. In general, the mean velocity of A. japonicus was below 0.7mms(-1). The maximum velocity recorded for all the sea cucumbers tested was for a large individual (89.25±17.11g), at a flow rate of 4.6±0.5cms(-1). Medium sized (19.68±5.53g) and large individuals moved significantly faster than small individuals (2.65±1.24g) at the same flow rate. A. japonicus moved significantly faster when there was a moderate current (4.6±0.5cms(-1) and 14.7±0.3cms(-1)), compared with the fast flow rate (29.3±3.7cms(-1)) and when there was no flow (0cms(-1)). Sea cucumbers did not show positive rheotaxis in general, but did move in a downstream direction at faster current speeds. Large, medium and small sized individuals moved downstream at the fastest current speed tested, 29.3±3.7cms(-1). When there was no water flow, sea cucumbers tended to move in an irregular pattern. The movement patterns show that the sea cucumber, A. japonicus can move across the direction of flow, and can move both upstream and downstream along the direction of flow. PMID:25727024

  17. Ontogenesis of coelomocytes in sea cucumber (Apostichopus japonicus) studied with probes of monoclonal antibody.

    PubMed

    Li, Qiang; Qi, Rui-rong; Wang, Yi-nan; Qiao, Guo; Ye, Shi-gen; Li, Hua

    2014-12-01

    Monoclonal antibodies (MAbs) specifically against coelomocytes of Apostichopus japonicus were employed to study the ontogenesis of coelomocytes by indirect immunofluorescence assay technique (IIFAT). Different developmental stages were identified by histochemical staining method. Stages including blastula, gastrula, auricularia (small-auricular larvae, mid-auricular larvae and big-auricular larvae), doliolaria, pentactula and juvenile were examined. The positive reactions with both MAb1C2 against all the types of coelomocytes and MAb3F6 specific to spherulocytes, were observed firstly at the blastula stage of the embryos. The positive reaction with MAb1E2 against lymphoid cells was observed from the big-auricular larvae, which indicated that lymphoid cells may not be progenitor cells or stem cells for A. japonicus. An increase of fluorescence intensity for each cell may imply a possible enhancement of the innate defensive mechanism as the embryogenesis progress. PMID:25218682

  18. La Crosse Virus in Aedes japonicus japonicus mosquitoes in the Appalachian Region, United States.

    PubMed

    Harris, M Camille; Dotseth, Eric J; Jackson, Bryan T; Zink, Steven D; Marek, Paul E; Kramer, Laura D; Paulson, Sally L; Hawley, Dana M

    2015-04-01

    La Crosse virus (LACV), a leading cause of arboviral encephalitis in children in the United States, is emerging in Appalachia. For local arboviral surveillance, mosquitoes were tested. LACV RNA was detected and isolated from Aedes japonicus mosquitoes. These invasive mosquitoes may significantly affect LACV range expansion and dynamics. PMID:25811131

  19. The further spread of Aedes japonicus japonicus (Diptera, Culicidae) towards northern Germany.

    PubMed

    Werner, Doreen; Kampen, Helge

    2013-10-01

    After its first detection in 2008 in the south German federal state of Baden-Wuerttemberg, another distinct population of the invasive Asian bush mosquito Aedes japonicus japonicus was unexpectedly found in western Germany in 2012. Range expansion had already been observed for the southern German population and was anticipated for the western German one. Here, we report on a third, apparently independent and even more northerly German colonization area of Aedes j. japonicus in southern Lower Saxony and northeastern North Rhine-Westphalia, which was discovered in spring 2013. In a snapshot study, intended to determine the presence or absence of Aedes j. japonicus in an area close to Hanover, the capital of the northern German federal state of Lower Saxony, where a specimen had been collected in late 2012, central water basins of cemeteries were checked for pre-imaginal mosquito stages at the beginning of the mosquito season 2013. Almost 20% of the inspected cemeteries were found positive (25 out of 129), with many of them being located in towns and villages close to the motorways A2 and A7. Being of Far Eastern origin, the Asian bush mosquito is well adapted to moderate climates and appears to be further expanding its distribution area in Central Europe. As it is a proven laboratory vector of several mosquito-borne disease agents, its present and future distribution areas should be carefully monitored. PMID:23974325

  20. Genome-wide identification and evolutionary analysis of nucleotide-binding site-encoding resistance genes in Lotus japonicus (Fabaceae).

    PubMed

    Song, H; Wang, P F; Li, T T; Xia, H; Zhao, S Z; Hou, L; Zhao, C Z

    2015-01-01

    Nucleotide-binding site (NBS) disease resistance genes play a crucial role in plant defense responses against pathogens and insect pests. Many NBS-encoding genes have been detected in Lotus japonicus, an important forage crop in many parts of the world. However, most NBS genes identified so far in L. japonicus were only partial sequences. We identified 45 full-length NBS-encoding genes in the L. japonicus genome, and analyzed gene duplications, motifs, and the molecular phylogeny to further understand the NBS gene family. We found that gene duplication events rarely occur in L. japonicus NBS-encoding (LjNBS) genes. In addition, LjNBS genes were subjected to selection pressure, and codon usage bias was evident. We tested for purifying selection (specifically in the CC-NBS-LRR and TIR-NBS-LRR groups), and found strong purifying selection in the TIR-domain-containing sequences, indicating that the CC-NBS-LRR group is more likely to undergo expansion than the TIR-NBS-LRR group. Moreover, our results showed that both selection and mutation contributed to LjNBS codon usage bias, but mutational bias was the major influence on codon usage. PMID:26662396

  1. Male tarsi specific odorant-binding proteins in the diving beetle Cybister japonicus sharp.

    PubMed

    Song, Li-Mei; Jiang, Xiang; Wang, Xue-Min; Li, Jin-Dong; Zhu, Fang; Tu, Xiong-Bing; Zhang, Ze-Hua; Ban, Li-Ping

    2016-01-01

    Odorant binding proteins (OBPs) play critical roles in chemical communication of insects, as they recognize and transport environmental chemical signals to receptors. The diving beetle Cybister japonicus Sharp shows a remarkable sexual dimorphism. The foreleg tarsi of males are equipped with large suction cups, believed to help holding the female during underwater courtship and mating. Here, we identified two OBPs highly and specifically expressed in male tarsi, suggesting important functions of these structures in chemical communication. The first protein, CjapOBP1, exhibits the 6 conserved cysteines motif of classic OBPs, while the second, CjapOBP2, contains only four cysteines and can be assigned to the sub-class of C-minus OBPs. Both proteins were expressed in a bacterial system and the purified recombinant proteins were used to for antibodies preparation. Western Blot analysis showed that CjapOBP1 is predominantly expressed in male tarsi and could be also detected in antennae and palpi of both sexes, while CjapOBP2, besides male tarsi, is also present in testis. Ligand-binding experiments showed a good binding affinity between CjapOBP1, CjapOBP2 and citral and coniferyl aldehyde, respectively. These results support a possible function of these two OBPs in the male foreleg tarsi of diving beetles in chemical communication. PMID:27545810

  2. Male tarsi specific odorant-binding proteins in the diving beetle Cybister japonicus sharp

    PubMed Central

    Song, Li-Mei; Jiang, Xiang; Wang, Xue-Min; Li, Jin-Dong; Zhu, Fang; Tu, Xiong-Bing; Zhang, Ze-Hua; Ban, Li-Ping

    2016-01-01

    Odorant binding proteins (OBPs) play critical roles in chemical communication of insects, as they recognize and transport environmental chemical signals to receptors. The diving beetle Cybister japonicus Sharp shows a remarkable sexual dimorphism. The foreleg tarsi of males are equipped with large suction cups, believed to help holding the female during underwater courtship and mating. Here, we identified two OBPs highly and specifically expressed in male tarsi, suggesting important functions of these structures in chemical communication. The first protein, CjapOBP1, exhibits the 6 conserved cysteines motif of classic OBPs, while the second, CjapOBP2, contains only four cysteines and can be assigned to the sub-class of C-minus OBPs. Both proteins were expressed in a bacterial system and the purified recombinant proteins were used to for antibodies preparation. Western Blot analysis showed that CjapOBP1 is predominantly expressed in male tarsi and could be also detected in antennae and palpi of both sexes, while CjapOBP2, besides male tarsi, is also present in testis. Ligand-binding experiments showed a good binding affinity between CjapOBP1, CjapOBP2 and citral and coniferyl aldehyde, respectively. These results support a possible function of these two OBPs in the male foreleg tarsi of diving beetles in chemical communication. PMID:27545810

  3. Controller design and parameter identifiability studies for a large space antenna

    NASA Technical Reports Server (NTRS)

    Joshi, S. M.

    1985-01-01

    The problem of control systems synthesis and parameter identifiability are considered for a large, space-based antenna. Two methods are considered for control system synthesis, the first of which uses torque actuators and collocated attitude and rate sensors, and the second method is based on the linear-quadratic-Gaussian (LQG) control theory. The predicted performance obtained by computing variances of pointing, surface and feed misalignment errors in the presence of sensor noise indicates that the LQG-based controller yields superior results. Since controller design requires the knowledge of the system parameters, the identifiability of the structural parameters is investigated by obtaining Cramer-Rao lower bounds. The modal frequencies are found to have the best identifiability, followed by damping ratios, and mode-slopes.

  4. Identifying disease candidate genes via large-scale gene network analysis.

    PubMed

    Kim, Haseong; Park, Taesung; Gelenbe, Erol

    2014-01-01

    Gene Regulatory Networks (GRN) provide systematic views of complex living systems, offering reliable and large-scale GRNs to identify disease candidate genes. A reverse engineering technique, Bayesian Model Averaging-based Networks (BMAnet), which ensembles all appropriate linear models to tackle uncertainty in model selection that integrates heterogeneous biological data sets is introduced. Using network evaluation metrics, we compare the networks that are thus identified. The metric 'Random walk with restart (Rwr)' is utilised to search for disease genes. In a simulation our method shows better performance than elastic-net and Gaussian graphical models, but topological quantities vary among the three methods. Using real-data, brain tumour gene expression samples consisting of non-tumour, grade III and grade IV are analysed to estimate networks with a total of 4422 genes. Based on these networks, 169 brain tumour-related candidate genes were identified and some were found to relate to 'wound', 'apoptosis', and 'cell death' processes. PMID:25796737

  5. Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD

    PubMed Central

    Morais, Sara; Bastos-Ferreira, Rita; Sequeiros, Jorge

    2016-01-01

    Objectives: To identify the genomic mechanisms that result in PARK2 large gene deletions. Methods: We conducted mutation screening using PCR amplification of PARK2-coding regions and exon-intron boundaries, followed by sequencing to evaluate a large series of 244 unrelated Portuguese patients with symptoms of Parkinson disease. For the detection of large gene rearrangements, we performed multiplex ligation-dependent probe amplification, followed by long-range PCR and sequencing to map deletion breakpoints. Results: We identified biallelic pathogenic parkin mutations in 40 of the 244 patients. There were 18 different mutations, some of them novel. This study included mapping of 17 deletion breakpoints showing that nonhomologous end joining is the most common mechanism responsible for these gene rearrangements. None of these deletion breakpoints were previously described, and only one was present in 2 unrelated families, indicating that most of the deletions result from independent events. Conclusions: The c.155delA mutation is highly prevalent in the Portuguese population (62.5% of the cases). Large deletions were present in 42.5% of the patients. We present the largest study on the molecular mechanisms that mediate PARK2 deletions in a homogeneous population. PMID:27182553

  6. Apoptosis induction is involved in UVA-induced autolysis in sea cucumber Stichopus japonicus.

    PubMed

    Qi, Hang; Fu, Hui; Dong, Xiufang; Feng, Dingding; Li, Nan; Wen, Chengrong; Nakamura, Yoshimasa; Zhu, Beiwei

    2016-05-01

    Autolysis easily happens to sea cucumber (Stichopus japonicus, S. japonicus) for external stimulus like UV exposure causing heavy economic losses. Therefore, it is meaningful to reveal the mechanism of S. japonicas autolysis. In the present study, to examine the involvement of apoptosis induction in UVA-induced autolysis of S. japonicas, we investigated the biochemical events including the DNA fragmentation, caspase-3 activation, mitogen-activated protein kinases (MAPKs) phosphorylation and free radical formation. Substantial morphological changes such as intestine vomiting and dermatolysis were observed in S. japonicus during the incubation after 1-h UVA irradiation (10W/m(2)). The degradation of the structural proteins and enhancement of cathepsin L activity were also detected, suggesting the profound impact of proteolysis caused by the UVA irradiation even for 1h. Furthermore, the DNA fragmentation and specific activity of caspase-3 was increased up to 12h after UVA irradiation. The levels of phosphorylated p38 mitogen activated protein kinase (MAPK) and phosphorylated c-Jun.-N-terminal kinase (JNK) were significantly increased by the UVA irradiation for 1h. An electron spin resonance (ESR) analysis revealed that UVA enhanced the free radical formation in S. japonicas, even through we could not identify the attributed species. These results suggest that UVA-induced autolysis in S. japonicas at least partially involves the oxidative stress-sensitive apoptosis induction pathway. These data present a novel insight into the mechanisms of sea cucumber autolysis induced by external stress. PMID:26971278

  7. Postembryonic development of the mushroom bodies in the ant, Camponotus japonicus.

    PubMed

    Ishii, Yuri; Kubota, Kanae; Hara, Kenji

    2005-07-01

    Mushroom bodies (MB) are insect brain centers involved in learning and other complex behaviors and they are particularly large in ants. We describe the larval and pupal development of the MB in the carpenter ant, Camponotus japonicus. Based on morphological cues, we characterized the stages of preimaginal development of worker ants. We then describe morphological changes and neurogenesis underlying the MB development. Kenyon cells are produced in a proliferation cluster formed by symmetrical division of MB neuroblasts. While the duration of larval instars shows great individual variation, MB neuroblasts increase in number in each successive larval instar. The number of neuroblasts increases further during prepupal stages and peaks during early pupal stages. It decreases rapidly, and then neurogenesis generally ceases during the mid pupal stage (P4). In contrast to the larval period, the MB development of individuals is highly synchronized with physical time throughout metamorphosis. We show that carpenter ants (C. japonicus) have approximately half as many MB neuroblasts than are found in the honey bee Apis mellifera. Mature MBs of carpenter ants and honey bees reportedly comprise almost the same number of neurons. We therefore suggest that the MB neuroblasts in C. japonicus divide more often in order to produce a final number of MB neurons similar to that of honey bees. PMID:16082163

  8. Leonuketal, a Spiroketal Diterpenoid from Leonurus japonicus.

    PubMed

    Xiong, Liang; Zhou, Qin-Mei; Zou, Yike; Chen, Ming-Hua; Guo, Li; Hu, Guan-Ying; Liu, Zhao-Hua; Peng, Cheng

    2015-12-18

    An architecturally complex spiroketal diterpenoid, leonuketal (1), was isolated from the aerial parts of the plant Leonurus japonicus. This compound possessed an unprecedented tetracyclic skeleton that comprised a bridged spiroketal moiety fused with a ketal-γ-lactone unit. The structure and absolute configuration were determined by spectroscopic analyses, a modified Mosher's method, and ECD (electronic circular dichroism) calculations. Leonuketal (1) showed significant vasorelaxant activity against KCl-induced contraction of rat aorta, with the EC50 value of 2.32 μM. PMID:26634796

  9. Identification of potential markers and sensitive tissues for low or high salinity stress in an intertidal mud crab (Macrophthalmus japonicus).

    PubMed

    Nikapitiya, Chamilani; Kim, Won-Seok; Park, Kiyun; Kwak, Ihn-Sil

    2014-12-01

    Macrophthalmus japonicus is an intertidal mud crab is an ecologically important species in Korea, can tolerate a wide range of natural and anthropogenic stressors. Environmental changes especially salinity cause physiological stress to the marine habitats. Differential gene transcription of M. japonicus tissues provided information about tissue specific responses against salinity. Five potential genes were identified and their transcription levels were determined quantitatively comparison to seawater (SW: 31 ± 1 psu) in M. japonicus gills and hepatopancreas after exposed them to different salinities. Ecdysteroid receptor (Mj-EcR), trypsin (Mj-Tryp), arginine kinase (Mj-AK), lipopolysaccharide and β-1,3-glucan binding protein (Mj-LGBP) and peroxinectin (Mj-Prx) in hepatopancreas up-regulated against different salinities. In contrast, the gills, Mj-EcR, Mj-Tryp and Mj-AK showed late up-regulated responses to 40 psu compared to SW. All genes except Mj-LGBP showed up regulation in the gills as time dependent manner. These genes can be considered as potential markers to assess responses in salinity changes. This study suggests hepatopancreas is a suitable tissue for transcriptional, biochemical and physiological responses analysis on M. japonicus in low and high salinity stress. PMID:25240977

  10. Lotus japonicus flowers are defended by a cyanogenic β-glucosidase with highly restricted expression to essential reproductive organs.

    PubMed

    Lai, Daniela; Pičmanová, Martina; Abou Hachem, Maher; Motawia, Mohammed Saddik; Olsen, Carl Erik; Møller, Birger Lindberg; Rook, Fred; Takos, Adam M

    2015-09-01

    Flowers and leaves of Lotus japonicus contain α-, β-, and γ-hydroxynitrile glucoside (HNG) defense compounds, which are bioactivated by β-glucosidase enzymes (BGDs). The α-HNGs are referred to as cyanogenic glucosides because their hydrolysis upon tissue disruption leads to release of toxic hydrogen cyanide gas, which can deter herbivore feeding. BGD2 and BGD4 are HNG metabolizing BGD enzymes expressed in leaves. Only BGD2 is able to hydrolyse the α-HNGs. Loss of function mutants of BGD2 are acyanogenic in leaves but fully retain cyanogenesis in flowers pointing to the existence of an alternative cyanogenic BGD in flowers. This enzyme, named BGD3, is identified and characterized in this study. Whereas all floral tissues contain α-HNGs, only those tissues in which BGD3 is expressed, the keel and the enclosed reproductive organs, are cyanogenic. Biochemical analysis, active site architecture molecular modelling, and the observation that L. japonicus accessions lacking cyanogenic flowers contain a non-functional BGD3 gene, all support the key role of BGD3 in floral cyanogenesis. The nectar of L. japonicus flowers was also found to contain HNGs and additionally their diglycosides. The observed specialisation in HNG based defence in L. japonicus flowers is discussed in the context of balancing the attraction of pollinators with the protection of reproductive structures against herbivores. PMID:26249044

  11. An interaction screen identifies headcase as a regulator of large-scale pruning

    PubMed Central

    Loncle, Nicolas; Williams, Darren W

    2012-01-01

    Large-scale pruning, the removal of long neuronal processes, is deployed widely within the developing nervous system and is essential for proper circuit formation. In Drosophila the dendrites of the class IV dendritic arborization sensory neuron ddaC undergo large-scale pruning by local degeneration controlled by the steroid hormone ecdysone. The molecular mechanisms that control such events are largely unknown. To identify new molecules that orchestrate this developmental degeneration we performed a genetic interaction screen. Our approach combines the strength of Drosophila forward genetics with detailed in vivo imaging of ddaC neurons. This screen allowed us to identify headcase (hdc) as a new gene involved in dendrite pruning. hdc is evolutionarily conserved, but the protein’s function is unknown. Here we show that hdc is expressed just prior to metamorphosis in sensory neurons that undergo remodeling. hdc is required in a cell autonomous manner to control dendrite severing, the first phase of pruning. Our epistasis experiments with known regulators of dendrite pruning reveal hdc as a founding member of a new pathway downstream of ecdysone signaling. PMID:23197702

  12. Inter-point procrustes: identifying regional and large differences in 3D anatomical shapes.

    PubMed

    Lekadir, Karim; Frangi, Alejandro F; Yang, Guang-Zhong

    2012-01-01

    This paper presents a new approach for the robust alignment and interpretation of 3D anatomical structures with large and localized shape differences. In such situations, existing techniques based on the well-known Procrustes analysis can be significantly affected due to the introduced non-Gaussian distribution of the residuals. In the proposed technique, influential points that induce large dissimilarities are identified and displaced with the aim to obtain an intermediate template with an improved distribution of the residuals. The key element of the algorithm is the use of pose invariant shape variables to robustly guide both the influential point detection and displacement steps. The intermediate template is then used as the basis for the estimation of the final pose parameters between the source and destination shapes, enabling to effectively highlight the regional differences of interest. The validation using synthetic and real datasets of different morphologies demonstrates robustness up-to 50% regional differences and potential for shape classification. PMID:23286119

  13. Elimination of Radio-Frequency Noise by Identifying and Diverting Large RF Ground Currents

    SciTech Connect

    Perkins, R. J.; Bellan, P. M.

    2011-12-23

    The problem of electromagnetic interference in scientific instruments is compounded for high-power plasma experiments by the large currents and voltages as well as by the broad bandwidths of the instruments. Ground loops are known to allow stray magnetic fields to drive large ground currents that can induce spurious signals and damage electronics. Furthermore, even when a ground loop is broken, capacitive coupling can still permit the flow of radio-frequency current, resulting in high-frequency spurious signals that can overwhelm the desired signal. We present the effects of RF ground loops on the output of vacuum photodiodes used in the Caltech Solar Loop Experiment and demonstrate the elimination of the spurious signals by diverting the ground currents away from the most vulnerable point of the signal line. Techniques for identifying the RF ground loops are also discussed. These techniques should be valuable in many high-power systems where interference from spurious coupling is an issue.

  14. A method for identifying EMI critical circuits during development of a large C3

    NASA Astrophysics Data System (ADS)

    Barr, Douglas H.

    The circuit analysis methods and process Boeing Aerospace used on a large, ground-based military command, control, and communications (C3) system are described. This analysis was designed to help identify electromagnetic interference (EMI) critical circuits. The methodology used the MIL-E-6051 equipment criticality categories as the basis for defining critical circuits, relational database technology to help sort through and account for all of the approximately 5000 system signal cables, and Macintosh Plus personal computers to predict critical circuits based on safety margin analysis. The EMI circuit analysis process systematically examined all system circuits to identify which ones were likely to be EMI critical. The process used two separate, sequential safety margin analyses to identify critical circuits (conservative safety margin analysis, and detailed safety margin analysis). These analyses used field-to-wire and wire-to-wire coupling models using both worst-case and detailed circuit parameters (physical and electrical) to predict circuit safety margins. This process identified the predicted critical circuits that could then be verified by test.

  15. HUGE: a database for human large proteins identified in the Kazusa cDNA sequencing project.

    PubMed

    Kikuno, R; Nagase, T; Suyama, M; Waki, M; Hirosawa, M; Ohara, O

    2000-01-01

    HUGE is a database for human large proteins newly identified in the Kazusa cDNA project, the aim of which is to predict the primary structure of proteins from the sequences of human large cDNAs (>4 kb). In particular, cDNA clones capable of coding for large proteins (>50 kDa) are the current targets of the project. HUGE contains >1100 cDNA sequences and detailed information obtained through analysis of the sequences of cDNAs and the predicted proteins. Besides an increase in the number of cDNA entries, the amount of experimental data for expression profiling has been largely increased and data on chromosomal locations have been newly added. All of the protein-coding regions were examined by GeneMark analysis, and the results of a motif/domain search of each predicted protein sequence against the Pfam database have been newly added. HUGE is available through the WWW at http://www.kazusa.or.jp/huge PMID:10592264

  16. Diagnostic accuracy of clinical examination features for identifying large rotator cuff tears in primary health care

    PubMed Central

    Cadogan, Angela; McNair, Peter; Laslett, Mark; Hing, Wayne; Taylor, Stephen

    2013-01-01

    Objectives: Rotator cuff tears are a common and disabling complaint. The early diagnosis of medium and large size rotator cuff tears can enhance the prognosis of the patient. The aim of this study was to identify clinical features with the strongest ability to accurately predict the presence of a medium, large or multitendon (MLM) rotator cuff tear in a primary care cohort. Methods: Participants were consecutively recruited from primary health care practices (n = 203). All participants underwent a standardized history and physical examination, followed by a standardized X-ray series and diagnostic ultrasound scan. Clinical features associated with the presence of a MLM rotator cuff tear were identified (P<0.200), a logistic multiple regression model was derived for identifying a MLM rotator cuff tear and thereafter diagnostic accuracy was calculated. Results: A MLM rotator cuff tear was identified in 24 participants (11.8%). Constant pain and a painful arc in abduction were the strongest predictors of a MLM tear (adjusted odds ratio 3.04 and 13.97 respectively). Combinations of ten history and physical examination variables demonstrated highest levels of sensitivity when five or fewer were positive [100%, 95% confidence interval (CI): 0.86–1.00; negative likelihood ratio: 0.00, 95% CI: 0.00–0.28], and highest specificity when eight or more were positive (0.91, 95% CI: 0.86–0.95; positive likelihood ratio 4.66, 95% CI: 2.34–8.74). Discussion: Combinations of patient history and physical examination findings were able to accurately detect the presence of a MLM rotator cuff tear. These findings may aid the primary care clinician in more efficient and accurate identification of rotator cuff tears that may require further investigation or orthopedic consultation. PMID:24421626

  17. Large-Scale RNA Interference Screening in Mammalian Cells Identifies Novel Regulators of Mutant Huntingtin Aggregation

    PubMed Central

    Tosaki, Asako; Bauer, Peter O.; Wada, Koji; Kurosawa, Masaru; Shimogori, Tomomi; Hattori, Nobutaka; Nukina, Nobuyuki

    2014-01-01

    In polyglutamine (polyQ) diseases including Huntington's disease (HD), mutant proteins containing expanded polyQ stretch form aggregates in neurons. Genetic or RNAi screenings in yeast, C. elegans or Drosophila have identified multiple genes modifying polyQ aggregation, a few of which are confirmed effective in mammals. However, the overall molecular mechanism underlying polyQ protein aggregation in mammalian cells still remains obscure. We here perform RNAi screening in mouse neuro2a cells to identify mammalian modifiers for aggregation of mutant huntingtin, a causative protein of HD. By systematic cell transfection and automated cell image analysis, we screen ∼12000 shRNA clones and identify 111 shRNAs that either suppress or enhance mutant huntingtin aggregation, without altering its gene expression. Classification of the shRNA-targets suggests that genes with various cellular functions such as gene transcription and protein phosphorylation are involved in modifying the aggregation. Subsequent analysis suggests that, in addition to the aggregation-modifiers sensitive to proteasome inhibition, some of them, such as a transcription factor Tcf20, and kinases Csnk1d and Pik3c2a, are insensitive to it. As for Tcf20, which contains polyQ stretches at N-terminus, its binding to mutant huntingtin aggregates is observed in neuro2a cells and in HD model mouse neurons. Notably, except Pik3c2a, the rest of the modifiers identified here are novel. Thus, our first large-scale RNAi screening in mammalian system identifies previously undescribed genetic players that regulate mutant huntingtin aggregation by several, possibly mammalian-specific mechanisms. PMID:24705917

  18. Large-scale RNA interference screening in mammalian cells identifies novel regulators of mutant huntingtin aggregation.

    PubMed

    Yamanaka, Tomoyuki; Wong, Hon Kit; Tosaki, Asako; Bauer, Peter O; Wada, Koji; Kurosawa, Masaru; Shimogori, Tomomi; Hattori, Nobutaka; Nukina, Nobuyuki

    2014-01-01

    In polyglutamine (polyQ) diseases including Huntington's disease (HD), mutant proteins containing expanded polyQ stretch form aggregates in neurons. Genetic or RNAi screenings in yeast, C. elegans or Drosophila have identified multiple genes modifying polyQ aggregation, a few of which are confirmed effective in mammals. However, the overall molecular mechanism underlying polyQ protein aggregation in mammalian cells still remains obscure. We here perform RNAi screening in mouse neuro2a cells to identify mammalian modifiers for aggregation of mutant huntingtin, a causative protein of HD. By systematic cell transfection and automated cell image analysis, we screen ∼ 12000 shRNA clones and identify 111 shRNAs that either suppress or enhance mutant huntingtin aggregation, without altering its gene expression. Classification of the shRNA-targets suggests that genes with various cellular functions such as gene transcription and protein phosphorylation are involved in modifying the aggregation. Subsequent analysis suggests that, in addition to the aggregation-modifiers sensitive to proteasome inhibition, some of them, such as a transcription factor Tcf20, and kinases Csnk1d and Pik3c2a, are insensitive to it. As for Tcf20, which contains polyQ stretches at N-terminus, its binding to mutant huntingtin aggregates is observed in neuro2a cells and in HD model mouse neurons. Notably, except Pik3c2a, the rest of the modifiers identified here are novel. Thus, our first large-scale RNAi screening in mammalian system identifies previously undescribed genetic players that regulate mutant huntingtin aggregation by several, possibly mammalian-specific mechanisms. PMID:24705917

  19. Polysaccharide degradation systems of the saprophytic bacterium Cellvibrio japonicus.

    PubMed

    Gardner, Jeffrey G

    2016-07-01

    Study of recalcitrant polysaccharide degradation by bacterial systems is critical for understanding biological processes such as global carbon cycling, nutritional contributions of the human gut microbiome, and the production of renewable fuels and chemicals. One bacterium that has a robust ability to degrade polysaccharides is the Gram-negative saprophyte Cellvibrio japonicus. A bacterium with a circuitous history, C. japonicus underwent several taxonomy changes from an initially described Pseudomonas sp. Most of the enzymes described in the pre-genomics era have also been renamed. This review aims to consolidate the biochemical, structural, and genetic data published on C. japonicus and its remarkable ability to degrade cellulose, xylan, and pectin substrates. Initially, C. japonicus carbohydrate-active enzymes were studied biochemically and structurally for their novel polysaccharide binding and degradation characteristics, while more recent systems biology approaches have begun to unravel the complex regulation required for lignocellulose degradation in an environmental context. Also included is a discussion for the future of C. japonicus as a model system, with emphasis on current areas unexplored in terms of polysaccharide degradation and emerging directions for C. japonicus in both environmental and biotechnological applications. PMID:27263016

  20. Polysaccharide degradation systems of the saprophytic bacterium Cellvibrio japonicus

    DOE PAGESBeta

    Gardner, Jeffrey G.

    2016-06-04

    Study of recalcitrant polysaccharide degradation by bacterial systems is critical for understanding biological processes such as global carbon cycling, nutritional contributions of the human gut microbiome, and the production of renewable fuels and chemicals. One bacterium that has a robust ability to degrade polysaccharides is the Gram-negative saprophyte Cellvibrio japonicus. A bacterium with a circuitous history, C. japonicus underwent several taxonomy changes from an initially described Pseudomonas sp. Most of the enzymes described in the pre-genomics era have also been renamed. Furthermore, this review aims to consolidate the biochemical, structural, and genetic data published on C. japonicus and its remarkablemore » ability to degrade cellulose, xylan, and pectin substrates. Initially, C. japonicus carbohydrate-active enzymes were studied biochemically and structurally for their novel polysaccharide binding and degradation characteristics, while more recent systems biology approaches have begun to unravel the complex regulation required for lignocellulose degradation in an environmental context. Also included is a discussion for the future of C. japonicus as a model system, with emphasis on current areas unexplored in terms of polysaccharide degradation and emerging directions for C. japonicus in both environmental and biotechnological applications.« less

  1. Using DNA barcoding and phylogenetics to identify Antarctic invertebrate larvae: Lessons from a large scale study.

    PubMed

    Heimeier, Dorothea; Lavery, Shane; Sewell, Mary A

    2010-01-01

    Ecological studies of the diversity and distribution of marine planktonic larvae are increasingly depending on molecular methods for accurate taxonomic identification. The greater coverage of reference marine species on genetic databases such as GenBank and BoLD (Barcoding of Life Data Systems; www.boldystems.org); together with the decreasing costs for DNA sequencing have made large scale larval identification studies using molecular methods more feasible. Here, we present the development and implementation of a practical molecular approach to identify over 2000 individual marine invertebrate larvae that were collected in the Ross Sea, Antarctica, during the austral summer over five years (2002-2007) as part of the LGP (Latitudinal Gradient Project). Larvae for molecular ID were morphologically identified to belong to the Phyla Mollusca, Echinodermata, Nemertea and Annelida (Class Polychaeta), but also included unidentified early developmental stages which could not be assigned a specific taxon (e.g., eggs, blastulae). The use of a 100μm mesh plankton net makes this one of the first larval identification studies to simultaneously consider both embryos and larvae. Molecular identification methods included amplification of up to three molecular loci for each specimen, a pre-identification step using BLAST with GenBank, phylogenetic reconstructions and cross-validation of assigned Molecular Operational Taxonomic Units (MOTUs). This combined approach of morphological and molecular methods assigned about 700 individuals to 53 MOTUs, which were identified to the lowest possible taxonomic level. During the course of this long-term study we identified several procedural difficulties, including issues with the collection of larvae, locus amplification, contamination, assignment and validation of MOTUs. The practical guidelines that we describe here should greatly assist other researchers to conduct reliable molecular identification studies of larvae in the future. PMID

  2. Using Soluble Reactive Phosphorus and Ammonia to Identify Point Source Discharge from Large Livestock Facilities

    NASA Astrophysics Data System (ADS)

    Borrello, M. C.; Scribner, M.; Chessin, K.

    2013-12-01

    A growing body of research draws attention to the negative environmental impacts on surface water from large livestock facilities. These impacts are mostly in the form of excessive nutrient loading resulting in significantly decreased oxygen levels. Over-application of animal waste on fields as well as direct discharge into surface water from facilities themselves has been identified as the main contributor to the development of hypoxic zones in Lake Erie, Chesapeake Bay and the Gulf of Mexico. Some regulators claim enforcement of water quality laws is problematic because of the nature and pervasiveness of non-point source impacts. Any direct discharge by a facility is a violation of permits governed by the Clean Water Act, unless the facility has special dispensation for discharge. Previous research by the principal author and others has shown runoff and underdrain transport are the main mechanisms by which nutrients enter surface water. This study utilized previous work to determine if the effects of non-point source discharge can be distinguished from direct (point-source) discharge using simple nutrient analysis and dissolved oxygen (DO) parameters. Nutrient and DO parameters were measured from three sites: 1. A stream adjacent to a field receiving manure, upstream of a large livestock facility with a history of direct discharge, 2. The same stream downstream of the facility and 3. A stream in an area relatively unimpacted by large-scale agriculture (control site). Results show that calculating a simple Pearson correlation coefficient (r) of soluble reactive phosphorus (SRP) and ammonia over time as well as temperature and DO, distinguishes non-point source from point source discharge into surface water. The r value for SRP and ammonia for the upstream site was 0.01 while the r value for the downstream site was 0.92. The control site had an r value of 0.20. Likewise, r values were calculated on temperature and DO for each site. High negative correlations

  3. Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

    PubMed

    Asselbergs, Folkert W; Guo, Yiran; van Iperen, Erik P A; Sivapalaratnam, Suthesh; Tragante, Vinicius; Lanktree, Matthew B; Lange, Leslie A; Almoguera, Berta; Appelman, Yolande E; Barnard, John; Baumert, Jens; Beitelshees, Amber L; Bhangale, Tushar R; Chen, Yii-Der Ida; Gaunt, Tom R; Gong, Yan; Hopewell, Jemma C; Johnson, Toby; Kleber, Marcus E; Langaee, Taimour Y; Li, Mingyao; Li, Yun R; Liu, Kiang; McDonough, Caitrin W; Meijs, Matthijs F L; Middelberg, Rita P S; Musunuru, Kiran; Nelson, Christopher P; O'Connell, Jeffery R; Padmanabhan, Sandosh; Pankow, James S; Pankratz, Nathan; Rafelt, Suzanne; Rajagopalan, Ramakrishnan; Romaine, Simon P R; Schork, Nicholas J; Shaffer, Jonathan; Shen, Haiqing; Smith, Erin N; Tischfield, Sam E; van der Most, Peter J; van Vliet-Ostaptchouk, Jana V; Verweij, Niek; Volcik, Kelly A; Zhang, Li; Bailey, Kent R; Bailey, Kristian M; Bauer, Florianne; Boer, Jolanda M A; Braund, Peter S; Burt, Amber; Burton, Paul R; Buxbaum, Sarah G; Chen, Wei; Cooper-Dehoff, Rhonda M; Cupples, L Adrienne; deJong, Jonas S; Delles, Christian; Duggan, David; Fornage, Myriam; Furlong, Clement E; Glazer, Nicole; Gums, John G; Hastie, Claire; Holmes, Michael V; Illig, Thomas; Kirkland, Susan A; Kivimaki, Mika; Klein, Ronald; Klein, Barbara E; Kooperberg, Charles; Kottke-Marchant, Kandice; Kumari, Meena; LaCroix, Andrea Z; Mallela, Laya; Murugesan, Gurunathan; Ordovas, Jose; Ouwehand, Willem H; Post, Wendy S; Saxena, Richa; Scharnagl, Hubert; Schreiner, Pamela J; Shah, Tina; Shields, Denis C; Shimbo, Daichi; Srinivasan, Sathanur R; Stolk, Ronald P; Swerdlow, Daniel I; Taylor, Herman A; Topol, Eric J; Toskala, Elina; van Pelt, Joost L; van Setten, Jessica; Yusuf, Salim; Whittaker, John C; Zwinderman, A H; Anand, Sonia S; Balmforth, Anthony J; Berenson, Gerald S; Bezzina, Connie R; Boehm, Bernhard O; Boerwinkle, Eric; Casas, Juan P; Caulfield, Mark J; Clarke, Robert; Connell, John M; Cruickshanks, Karen J; Davidson, Karina W; Day, Ian N M; de Bakker, Paul I W; Doevendans, Pieter A; Dominiczak, Anna F; Hall, Alistair S; Hartman, Catharina A; Hengstenberg, Christian; Hillege, Hans L; Hofker, Marten H; Humphries, Steve E; Jarvik, Gail P; Johnson, Julie A; Kaess, Bernhard M; Kathiresan, Sekar; Koenig, Wolfgang; Lawlor, Debbie A; März, Winfried; Melander, Olle; Mitchell, Braxton D; Montgomery, Grant W; Munroe, Patricia B; Murray, Sarah S; Newhouse, Stephen J; Onland-Moret, N Charlotte; Poulter, Neil; Psaty, Bruce; Redline, Susan; Rich, Stephen S; Rotter, Jerome I; Schunkert, Heribert; Sever, Peter; Shuldiner, Alan R; Silverstein, Roy L; Stanton, Alice; Thorand, Barbara; Trip, Mieke D; Tsai, Michael Y; van der Harst, Pim; van der Schoot, Ellen; van der Schouw, Yvonne T; Verschuren, W M Monique; Watkins, Hugh; Wilde, Arthur A M; Wolffenbuttel, Bruce H R; Whitfield, John B; Hovingh, G Kees; Ballantyne, Christie M; Wijmenga, Cisca; Reilly, Muredach P; Martin, Nicholas G; Wilson, James G; Rader, Daniel J; Samani, Nilesh J; Reiner, Alex P; Hegele, Robert A; Kastelein, John J P; Hingorani, Aroon D; Talmud, Philippa J; Hakonarson, Hakon; Elbers, Clara C; Keating, Brendan J; Drenos, Fotios

    2012-11-01

    Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids. PMID:23063622

  4. Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

    PubMed Central

    Asselbergs, Folkert W.; Guo, Yiran; van Iperen, Erik P.A.; Sivapalaratnam, Suthesh; Tragante, Vinicius; Lanktree, Matthew B.; Lange, Leslie A.; Almoguera, Berta; Appelman, Yolande E.; Barnard, John; Baumert, Jens; Beitelshees, Amber L.; Bhangale, Tushar R.; Chen, Yii-Der Ida; Gaunt, Tom R.; Gong, Yan; Hopewell, Jemma C.; Johnson, Toby; Kleber, Marcus E.; Langaee, Taimour Y.; Li, Mingyao; Li, Yun R.; Liu, Kiang; McDonough, Caitrin W.; Meijs, Matthijs F.L.; Middelberg, Rita P.S.; Musunuru, Kiran; Nelson, Christopher P.; O’Connell, Jeffery R.; Padmanabhan, Sandosh; Pankow, James S.; Pankratz, Nathan; Rafelt, Suzanne; Rajagopalan, Ramakrishnan; Romaine, Simon P.R.; Schork, Nicholas J.; Shaffer, Jonathan; Shen, Haiqing; Smith, Erin N.; Tischfield, Sam E.; van der Most, Peter J.; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Volcik, Kelly A.; Zhang, Li; Bailey, Kent R.; Bailey, Kristian M.; Bauer, Florianne; Boer, Jolanda M.A.; Braund, Peter S.; Burt, Amber; Burton, Paul R.; Buxbaum, Sarah G.; Chen, Wei; Cooper-DeHoff, Rhonda M.; Cupples, L. Adrienne; deJong, Jonas S.; Delles, Christian; Duggan, David; Fornage, Myriam; Furlong, Clement E.; Glazer, Nicole; Gums, John G.; Hastie, Claire; Holmes, Michael V.; Illig, Thomas; Kirkland, Susan A.; Kivimaki, Mika; Klein, Ronald; Klein, Barbara E.; Kooperberg, Charles; Kottke-Marchant, Kandice; Kumari, Meena; LaCroix, Andrea Z.; Mallela, Laya; Murugesan, Gurunathan; Ordovas, Jose; Ouwehand, Willem H.; Post, Wendy S.; Saxena, Richa; Scharnagl, Hubert; Schreiner, Pamela J.; Shah, Tina; Shields, Denis C.; Shimbo, Daichi; Srinivasan, Sathanur R.; Stolk, Ronald P.; Swerdlow, Daniel I.; Taylor, Herman A.; Topol, Eric J.; Toskala, Elina; van Pelt, Joost L.; van Setten, Jessica; Yusuf, Salim; Whittaker, John C.; Zwinderman, A.H.; Anand, Sonia S.; Balmforth, Anthony J.; Berenson, Gerald S.; Bezzina, Connie R.; Boehm, Bernhard O.; Boerwinkle, Eric; Casas, Juan P.; Caulfield, Mark J.; Clarke, Robert; Connell, John M.; Cruickshanks, Karen J.; Davidson, Karina W.; Day, Ian N.M.; de Bakker, Paul I.W.; Doevendans, Pieter A.; Dominiczak, Anna F.; Hall, Alistair S.; Hartman, Catharina A.; Hengstenberg, Christian; Hillege, Hans L.; Hofker, Marten H.; Humphries, Steve E.; Jarvik, Gail P.; Johnson, Julie A.; Kaess, Bernhard M.; Kathiresan, Sekar; Koenig, Wolfgang; Lawlor, Debbie A.; März, Winfried; Melander, Olle; Mitchell, Braxton D.; Montgomery, Grant W.; Munroe, Patricia B.; Murray, Sarah S.; Newhouse, Stephen J.; Onland-Moret, N. Charlotte; Poulter, Neil; Psaty, Bruce; Redline, Susan; Rich, Stephen S.; Rotter, Jerome I.; Schunkert, Heribert; Sever, Peter; Shuldiner, Alan R.; Silverstein, Roy L.; Stanton, Alice; Thorand, Barbara; Trip, Mieke D.; Tsai, Michael Y.; van der Harst, Pim; van der Schoot, Ellen; van der Schouw, Yvonne T.; Verschuren, W.M. Monique; Watkins, Hugh; Wilde, Arthur A.M.; Wolffenbuttel, Bruce H.R.; Whitfield, John B.; Hovingh, G. Kees; Ballantyne, Christie M.; Wijmenga, Cisca; Reilly, Muredach P.; Martin, Nicholas G.; Wilson, James G.; Rader, Daniel J.; Samani, Nilesh J.; Reiner, Alex P.; Hegele, Robert A.; Kastelein, John J.P.; Hingorani, Aroon D.; Talmud, Philippa J.; Hakonarson, Hakon; Elbers, Clara C.; Keating, Brendan J.; Drenos, Fotios

    2012-01-01

    Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids. PMID:23063622

  5. Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations

    SciTech Connect

    Kleijnen, J.P.C.; Helton, J.C.

    1999-04-01

    The robustness of procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses is investigated. These procedures are based on attempts to detect increasingly complex patterns in the scatterplots under consideration and involve the identification of (1) linear relationships with correlation coefficients, (2) monotonic relationships with rank correlation coefficients, (3) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (4) trends in variability as defined by variances and interquartile ranges, and (5) deviations from randomness as defined by the chi-square statistic. The following two topics related to the robustness of these procedures are considered for a sequence of example analyses with a large model for two-phase fluid flow: the presence of Type I and Type II errors, and the stability of results obtained with independent Latin hypercube samples. Observations from analysis include: (1) Type I errors are unavoidable, (2) Type II errors can occur when inappropriate analysis procedures are used, (3) physical explanations should always be sought for why statistical procedures identify variables as being important, and (4) the identification of important variables tends to be stable for independent Latin hypercube samples.

  6. Identifying localized changes in large systems: Change-point detection for biomolecular simulations

    PubMed Central

    Fan, Zhou; Dror, Ron O.; Mildorf, Thomas J.; Piana, Stefano; Shaw, David E.

    2015-01-01

    Research on change-point detection, the classical problem of detecting abrupt changes in sequential data, has focused predominantly on datasets with a single observable. A growing number of time series datasets, however, involve many observables, often with the property that a given change typically affects only a few of the observables. We introduce a general statistical method that, given many noisy observables, detects points in time at which various subsets of the observables exhibit simultaneous changes in data distribution and explicitly identifies those subsets. Our work is motivated by the problem of identifying the nature and timing of biologically interesting conformational changes that occur during atomic-level simulations of biomolecules such as proteins. This problem has proved challenging both because each such conformational change might involve only a small region of the molecule and because these changes are often subtle relative to the ever-present background of faster structural fluctuations. We show that our method is effective in detecting biologically interesting conformational changes in molecular dynamics simulations of both folded and unfolded proteins, even in cases where these changes are difficult to detect using alternative techniques. This method may also facilitate the detection of change points in other types of sequential data involving large numbers of observables—a problem likely to become increasingly important as such data continue to proliferate in a variety of application domains. PMID:26025225

  7. A large scale European database to identify dominant drivers of flood seasonality

    NASA Astrophysics Data System (ADS)

    Hall, Julia; Parajka, Juraj; Perdigão, Rui A. P.; Viglione, Alberto; Blöschl, Günter

    2014-05-01

    The study of the seasonality of various hydrological processes and their spatial properties has recently attracted renewed interest, especially in connection with floods, low flows and water resources management and studies on the climatic influence on hydrological processes. Hydrological data across Europe from various sources is combined into a large database with over 7000 stations. The database is a result of existing datasets of European coverage amended by a collaborative effort as part of a joint European flood research agreement based on the exchange of data, models, staff and expertise. With the help of this database, maximum annual floods and the dominant processes influencing observed flood seasonality in Europe are analysed. The seasonality analysis is based on directional statistics, which represent an effective method for defining similarity measures on the basis of the temporal consistency of hydrological extreme events within a year. Spatial variability and distinct patterns of mean flood seasonality are found in many catchments across a large range of different climatic and physiographic conditions. The role of driving processes of flood generation and their interconnections is investigated within a linear and non-linear statistical framework to disentangle signatures of different mechanisms and process interactions at play. For instance, the results show that signatures of atmospheric and land-related driving processes can be identified such as the effect of topography (e.g. the Alps or the Carpathians), and their individual and combined role on flood seasonality is discussed.

  8. Large-scale gene-centric analysis identifies novel variants for coronary artery disease.

    PubMed

    2011-09-01

    Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p<10(-33); LPA:p<10(-19); 1p13.3:p<10(-17)) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p<5×10(-7)). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ∼4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and

  9. microRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma

    PubMed Central

    Liu, Cuiling; Iqbal, Javeed; Teruya-Feldstein, Julie; Shen, Yulei; Dabrowska, Magdalena Julia; Dybkaer, Karen; Lim, Megan S.; Piva, Roberto; Barreca, Antonella; Pellegrino, Elisa; Spaccarotella, Elisa; Lachel, Cynthia M.; Kucuk, Can; Jiang, Chun-Sun; Hu, Xiaozhou; Bhagavathi, Sharathkumar; Greiner, Timothy C.; Weisenburger, Dennis D.; Aoun, Patricia; Perkins, Sherrie L.; McKeithan, Timothy W.; Inghirami, Giorgio

    2013-01-01

    Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[+]) ALCLs, 25 ALK-negative (ALK[−]) ALCLs, 9 angioimmunoblastic T-cell lymphomas, 11 peripheral T-cell lymphomas not otherwise specified (PTCLNOS), and normal T cells, and demonstrated that ALCLs express many of the miRNAs that are highly expressed in normal T cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(+) ALCL and ALK(–) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR-512-3p, miR-886-5p, miR-886-3p, miR-708, miR-135b; 2 downregulated: miR-146a, miR-155) significantly associated with ALK(+) ALCL cases. In addition, we derived an 11-miRNA signature (4 upregulated: miR-210, miR-197, miR-191, miR-512-3p; 7 downregulated: miR-451, miR-146a, miR-22, miR-455-3p, miR-455-5p, miR-143, miR-494) that differentiates ALK(–) ALCL from other PTCLs. Our in vitro studies identified a set of 32 miRNAs associated with ALK expression. Of these, the miR-17∼92 cluster and its paralogues were also highly expressed in ALK(+) ALCL and may represent important downstream effectors of the ALK oncogenic pathway. PMID:23801630

  10. Large-Scale Functional Networks Identified from Resting-State EEG Using Spatial ICA

    PubMed Central

    2016-01-01

    Several methods have been applied to EEG or MEG signals to detect functional networks. In recent works using MEG/EEG and fMRI data, temporal ICA analysis has been used to extract spatial maps of resting-state networks with or without an atlas-based parcellation of the cortex. Since the links between the fMRI signal and the electromagnetic signals are not fully established, and to avoid any bias, we examined whether EEG alone was able to derive the spatial distribution and temporal characteristics of functional networks. To do so, we propose a two-step original method: 1) An individual multi-frequency data analysis including EEG-based source localisation and spatial independent component analysis, which allowed us to characterize the resting-state networks. 2) A group-level analysis involving a hierarchical clustering procedure to identify reproducible large-scale networks across the population. Compared with large-scale resting-state networks obtained with fMRI, the proposed EEG-based analysis revealed smaller independent networks thanks to the high temporal resolution of EEG, hence hierarchical organization of networks. The comparison showed a substantial overlap between EEG and fMRI networks in motor, premotor, sensory, frontal, and parietal areas. However, there were mismatches between EEG-based and fMRI-based networks in temporal areas, presumably resulting from a poor sensitivity of fMRI in these regions or artefacts in the EEG signals. The proposed method opens the way for studying the high temporal dynamics of networks at the source level thanks to the high temporal resolution of EEG. It would then become possible to study detailed measures of the dynamics of connectivity. PMID:26785116

  11. Identifying Influential Nodes in Large-Scale Directed Networks: The Role of Clustering

    PubMed Central

    Chen, Duan-Bing; Gao, Hui; Lü, Linyuan; Zhou, Tao

    2013-01-01

    Identifying influential nodes in very large-scale directed networks is a big challenge relevant to disparate applications, such as accelerating information propagation, controlling rumors and diseases, designing search engines, and understanding hierarchical organization of social and biological networks. Known methods range from node centralities, such as degree, closeness and betweenness, to diffusion-based processes, like PageRank and LeaderRank. Some of these methods already take into account the influences of a node’s neighbors but do not directly make use of the interactions among it’s neighbors. Local clustering is known to have negative impacts on the information spreading. We further show empirically that it also plays a negative role in generating local connections. Inspired by these facts, we propose a local ranking algorithm named ClusterRank, which takes into account not only the number of neighbors and the neighbors’ influences, but also the clustering coefficient. Subject to the susceptible-infected-recovered (SIR) spreading model with constant infectivity, experimental results on two directed networks, a social network extracted from delicious.com and a large-scale short-message communication network, demonstrate that the ClusterRank outperforms some benchmark algorithms such as PageRank and LeaderRank. Furthermore, ClusterRank can also be applied to undirected networks where the superiority of ClusterRank is significant compared with degree centrality and k-core decomposition. In addition, ClusterRank, only making use of local information, is much more efficient than global methods: It takes only 191 seconds for a network with about nodes, more than 15 times faster than PageRank. PMID:24204833

  12. Genomic islands of divergence in hybridizing Heliconius butterflies identified by large-scale targeted sequencing

    PubMed Central

    Nadeau, Nicola J.; Whibley, Annabel; Jones, Robert T.; Davey, John W.; Dasmahapatra, Kanchon K.; Baxter, Simon W.; Quail, Michael A.; Joron, Mathieu; ffrench-Constant, Richard H.; Blaxter, Mark L.; Mallet, James; Jiggins, Chris D.

    2012-01-01

    Heliconius butterflies represent a recent radiation of species, in which wing pattern divergence has been implicated in speciation. Several loci that control wing pattern phenotypes have been mapped and two were identified through sequencing. These same gene regions play a role in adaptation across the whole Heliconius radiation. Previous studies of population genetic patterns at these regions have sequenced small amplicons. Here, we use targeted next-generation sequence capture to survey patterns of divergence across these entire regions in divergent geographical races and species of Heliconius. This technique was successful both within and between species for obtaining high coverage of almost all coding regions and sufficient coverage of non-coding regions to perform population genetic analyses. We find major peaks of elevated population differentiation between races across hybrid zones, which indicate regions under strong divergent selection. These ‘islands’ of divergence appear to be more extensive between closely related species, but there is less clear evidence for such islands between more distantly related species at two further points along the ‘speciation continuum’. We also sequence fosmid clones across these regions in different Heliconius melpomene races. We find no major structural rearrangements but many relatively large (greater than 1 kb) insertion/deletion events (including gain/loss of transposable elements) that are variable between races. PMID:22201164

  13. Field evaluation of baited traps for surveillance of Aedes japonicus japonicus in Switzerland.

    PubMed

    Balestrino, F; Schaffner, F; Forgia, D L; Paslaru, A I; Torgerson, P R; Mathis, A; Veronesi, E

    2016-03-01

    The efficacy of Centers for Disease Control (CDC) miniature light traps and ovitraps was tested in the outskirts of the city of Zurich in Switzerland for their use in the surveillance of Aedes (Hulecoeteomyia) japonicus japonicus (Theobald) (Diptera: Culicidae), the invasive Asian bush mosquito. Sets of single CDC traps were run overnight (n = 18) in three different environments (forest, suburban and urban) in 3 × 3 Latin square experimental designs. Traps were baited with: (a) carbon dioxide (CO2 ); (b) CO2 plus light, or (c) CO2 plus lure blend [Combi FRC 3003 (iGu® )]. At the same locations, mosquito eggs were collected weekly using standard ovitraps baited with different infusions (oak, hay or tap water) and equipped with different oviposition substrates (a block of extruded polystyrene, a germination paper strip or a wooden stick). Data were analysed using Poisson and negative binomial general linear models. The use of light (P < 0.001) or lure (P < 0.001) significantly increased the attractiveness of CDC traps baited with CO2 . Oak and hay infusions did not increase the attractiveness of ovitraps compared with standing tap water (P > 0.05), and extruded polystyrene blocks were preferred as an oviposition substrate over wooden sticks (P < 0.05) and seed germination paper (P < 0.05). Carbon dioxide-baited CDC miniature light traps complemented with light or iGu® lure and ovitraps containing standing tap water and polystyrene oviposition blocks can be considered as efficient and simple tools for use in Ae. j. japonicus surveillance programmes. PMID:26685872

  14. Identifying Space Use at Foraging Arena Scale within the Home Ranges of Large Herbivores.

    PubMed

    Owen-Smith, Norman; Martin, Jodie

    2015-01-01

    An intermediate spatiotemporal scale of food procurement by large herbivores is evident within annual or seasonal home ranges. It takes the form of settlement periods spanning several days or weeks during which foraging activity is confined to spatially discrete foraging arenas, separated by roaming interludes. Extended by areas occupied for other activities, these foraging arenas contribute towards generating the home range structure. We delineated and compared the foraging arenas exploited by two African large herbivores, sable antelope (a ruminant) and plains zebra (a non-ruminant), using GPS-derived movement data. We developed a novel approach to specifically delineate foraging arenas based on local change points in distance relative to adjoining clusters of locations, and compared its output with modifications of two published methods developed for home range estimation and residence time estimation respectively. We compared how these herbivore species responded to seasonal variation in food resources and how they differed in their spatial patterns of resource utilization. Sable antelope herds tended to concentrate their space use locally, while zebra herds moved more opportunistically over a wider set of foraging arenas. The amalgamated extent of the foraging arenas exploited by sable herds amounted to 12-30 km2, compared with 22-100 km2 for the zebra herds. Half-day displacement distances differed between settlement periods and roaming interludes, and zebra herds generally shifted further over 12h than sable herds. Foraging arenas of sable herds tended to be smaller than those of zebra, and were occupied for period twice as long, and hence exploited more intensively in days spent per unit area than the foraging arenas of zebra. For sable both the intensity of utilization of foraging arenas and proportion of days spent in foraging arenas relative to roaming interludes declined as food resources diminished seasonally, while zebra showed no seasonal variation

  15. Identifying Space Use at Foraging Arena Scale within the Home Ranges of Large Herbivores

    PubMed Central

    Owen-Smith, Norman; Martin, Jodie

    2015-01-01

    An intermediate spatiotemporal scale of food procurement by large herbivores is evident within annual or seasonal home ranges. It takes the form of settlement periods spanning several days or weeks during which foraging activity is confined to spatially discrete foraging arenas, separated by roaming interludes. Extended by areas occupied for other activities, these foraging arenas contribute towards generating the home range structure. We delineated and compared the foraging arenas exploited by two African large herbivores, sable antelope (a ruminant) and plains zebra (a non-ruminant), using GPS-derived movement data. We developed a novel approach to specifically delineate foraging arenas based on local change points in distance relative to adjoining clusters of locations, and compared its output with modifications of two published methods developed for home range estimation and residence time estimation respectively. We compared how these herbivore species responded to seasonal variation in food resources and how they differed in their spatial patterns of resource utilization. Sable antelope herds tended to concentrate their space use locally, while zebra herds moved more opportunistically over a wider set of foraging arenas. The amalgamated extent of the foraging arenas exploited by sable herds amounted to 12-30 km2, compared with 22-100 km2 for the zebra herds. Half-day displacement distances differed between settlement periods and roaming interludes, and zebra herds generally shifted further over 12h than sable herds. Foraging arenas of sable herds tended to be smaller than those of zebra, and were occupied for period twice as long, and hence exploited more intensively in days spent per unit area than the foraging arenas of zebra. For sable both the intensity of utilization of foraging arenas and proportion of days spent in foraging arenas relative to roaming interludes declined as food resources diminished seasonally, while zebra showed no seasonal variation

  16. The invasive mosquito Aedes japonicus in Central Europe.

    PubMed

    Schaffner, F; Kaufmann, C; Hegglin, D; Mathis, A

    2009-12-01

    Complaints about a biting pest led to the recognition of invasive Aedes (Finlaya) japonicus japonicus (Theobald) (Diptera: Culicidae) in Central Europe. Larval collections from cemetery vases revealed a colonized area of approximately 1400 km(2) in northern Switzerland spreading into bordering Germany, suggesting that the mosquito has been established in this region for several years. Within this range, larvae of Ae. japonicus were recovered from more containers than the most common resident culicid species Culex pipiens. Possible introduction sites (used tyre yards and international airports) revealed few or no larvae, and the mode of introduction remains unclear. Given the vector potential of this species for arboviruses, implementation of surveillance and control measures should be considered. PMID:19941611

  17. Expression of the CLE-RS3 gene suppresses root nodulation in Lotus japonicus.

    PubMed

    Nishida, Hanna; Handa, Yoshihiro; Tanaka, Sachiko; Suzaki, Takuya; Kawaguchi, Masayoshi

    2016-09-01

    Cell-to-cell communication, principally mediated by short- or long-range mobile signals, is involved in many plant developmental processes. In root nodule symbiosis, a mutual relationship between leguminous plants and nitrogen-fixing rhizobia, the mechanism for the autoregulation of nodulation (AON) plays a key role in preventing the production of an excess number of nodules. AON is based on long-distance cell-to-cell communication between roots and shoots. In Lotus japonicus, two CLAVATA3/ESR-related (CLE) peptides, encoded by CLE-ROOT SIGNAL 1 (CLE-RS1) and -RS2, act as putative root-derived signals that transmit signals inhibiting further nodule development through interaction with a shoot-acting receptor-like kinase HYPERNODULATION ABERRANT ROOT FORMATION 1 (HAR1). Here, an in silico search and subsequent expression analyses enabled us to identify two new L. japonicus CLE genes that are potentially involved in nodulation, designated as CLE-RS3 and LjCLE40. Time-course expression patterns showed that CLE-RS1/2/3 and LjCLE40 expression is induced during nodulation with different activation patterns. Furthermore, constitutive expression of CLE-RS3 significantly suppressed nodule formation in a HAR1-dependent manner. TOO MUCH LOVE, a root-acting regulator of AON, is also required for the CLE-RS3 action. These results suggest that CLE-RS3 is a new component of AON in L. japonicus that may act as a potential root-derived signal through interaction with HAR1. Because CLE-RS2, CLE-RS3 and LjCLE40 are located in tandem in the genome and their expression is induced not only by rhizobial infection but also by nitrate, these genes may have duplicated from a common gene. PMID:27294965

  18. Defense Responses in Two Ecotypes of Lotus japonicus against Non-Pathogenic Pseudomonas syringae

    PubMed Central

    Bordenave, Cesar D.; Escaray, Francisco J.; Menendez, Ana B.; Serna, Eva; Carrasco, Pedro; Ruiz, Oscar A.; Gárriz, Andrés

    2013-01-01

    Lotus japonicus is a model legume broadly used to study many important processes as nitrogen fixing nodule formation and adaptation to salt stress. However, no studies on the defense responses occurring in this species against invading microorganisms have been carried out at the present. Understanding how this model plant protects itself against pathogens will certainly help to develop more tolerant cultivars in economically important Lotus species as well as in other legumes. In order to uncover the most important defense mechanisms activated upon bacterial attack, we explored in this work the main responses occurring in the phenotypically contrasting ecotypes MG-20 and Gifu B-129 of L. japonicus after inoculation with Pseudomonas syringae DC3000 pv. tomato. Our analysis demonstrated that this bacterial strain is unable to cause disease in these accessions, even though the defense mechanisms triggered in these ecotypes might differ. Thus, disease tolerance in MG-20 was characterized by bacterial multiplication, chlorosis and desiccation at the infiltrated tissues. In turn, Gifu B-129 plants did not show any symptom at all and were completely successful in restricting bacterial growth. We performed a microarray based analysis of these responses and determined the regulation of several genes that could play important roles in plant defense. Interestingly, we were also able to identify a set of defense genes with a relative high expression in Gifu B-129 plants under non-stress conditions, what could explain its higher tolerance. The participation of these genes in plant defense is discussed. Our results position the L. japonicus-P. syringae interaction as a interesting model to study defense mechanisms in legume species. PMID:24349460

  19. Two evolved supernova remnants with newly identified Fe-rich cores in the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Kavanagh, P. J.; Sasaki, M.; Bozzetto, L. M.; Points, S. D.; Crawford, E. J.; Dickel, J.; Filipović, M. D.; Haberl, F.; Maggi, P.; Whelan, E. T.

    2016-02-01

    Aims: We present a multi-wavelength analysis of the evolved supernova remnants MCSNR J0506-7025 and MCSNR J0527-7104 in the Large Magellanic Cloud. Methods: We used observational data from XMM-Newton, the Australian Telescope Compact Array, and the Magellanic Cloud Emission Line Survey to study their broad-band emission and used Spitzer and H i data to gain a picture of the environment into which the remnants are expanding. We performed a multi-wavelength morphological study and detailed radio and X-ray spectral analyses to determine their physical characteristics. Results: Both remnants were found to have bright X-ray cores, dominated by Fe L-shell emission, which is consistent with reverse shock-heated ejecta with determined Fe masses in agreement with Type Ia explosion yields. A soft X-ray shell, which is consistent with swept-up interstellar medium, was observed in MCSNR J0506-7025, suggestive of a remnant in the Sedov phase. Using the spectral fit results and the Sedov self-similar solution, we estimated the age of MCSNR J0506-7025 to be ~16-28 kyr, with an initial explosion energy of (0.07-0.84) × 1051 erg. A soft shell was absent in MCSNR J0527-7104, with only ejecta emission visible in an extremely elongated morphology that extends beyond the optical shell. We suggest that the blast wave has broken out into a low density cavity, allowing the shock heated ejecta to escape. We find that the radio spectral index of MCSNR J0506-7025 is consistent with the standard -0.5 for supernova remnants. Radio polarisation at 6 cm indicates a higher degree of polarisation along the western front and at the eastern knot with a mean fractional polarisation across the remnant of P ≅ (20 ± 6)%. Conclusions: The detection of Fe-rich ejecta in the remnants suggests that both resulted from Type Ia explosions. The newly identified Fe-rich cores in MCSNR J0506-7025 and MCSNR J0527-7104 make them members of the expanding class of evolved Fe-rich remnants in the Magellanic Clouds

  20. Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease

    PubMed Central

    Ganna, Andrea; Salihovic, Samira; Sundström, Johan; Broeckling, Corey D.; Hedman, Åsa K.; Magnusson, Patrik K. E.; Pedersen, Nancy L.; Larsson, Anders; Siegbahn, Agneta; Zilmer, Mihkel; Prenni, Jessica; Ärnlöv, Johan; Lind, Lars; Fall, Tove; Ingelsson, Erik

    2014-01-01

    Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10−7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development. PMID:25502724

  1. Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease.

    PubMed

    Ganna, Andrea; Salihovic, Samira; Sundström, Johan; Broeckling, Corey D; Hedman, Asa K; Magnusson, Patrik K E; Pedersen, Nancy L; Larsson, Anders; Siegbahn, Agneta; Zilmer, Mihkel; Prenni, Jessica; Arnlöv, Johan; Lind, Lars; Fall, Tove; Ingelsson, Erik

    2014-12-01

    Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development. PMID:25502724

  2. A new identified complication of intracystic hemorrhage in a large pineal gland cyst.

    PubMed

    Mehrzad, Raman; Mishra, Suprav; Feinstein, Alexander; Ho, Michael G

    2014-01-01

    Pineal gland cysts are typically asymptomatic, benign cysts most commonly found incidentally in adults. In rare cases, a large pineal gland cyst can be complicated by intracystic hemorrhage, which could then manifest with neurological symptoms. We report a new complication of intracystic hemorrhage in a large pineal gland cyst in a 40-year-old man with new onset seizures. PMID:24746445

  3. Modeling Retention at a Large Public University: Can At-Risk Students Be Identified Early Enough to Treat?

    ERIC Educational Resources Information Center

    Singell, Larry D.; Waddell, Glen R.

    2010-01-01

    We examine the extent to which readily available data at a large public university can be used to a priori identify at-risk students who may benefit from targeted retention efforts. Although it is possible to identify such students, there remains an inevitable tradeoff in any resource allocation between not treating the students who are likely to…

  4. Individual variation in growth in sea cucumber Apostichopus japonicus (Selenck) housed individually

    NASA Astrophysics Data System (ADS)

    Liang, Miao; Dong, Shuanglin; Gao, Qinfeng; Wang, Fang; Tian, Xiangli

    2010-09-01

    The exceptionally large individual growth variation has been previously recognized in several sea cucumber cohorts. However, there is a lack of information regarding the mechanism of such individual differences. In this study, the sea cucumber Apostichopus japonicus (Selenka) was reared individually in order to eliminate possible effects of social interaction, stocking density, etc. The results showed that there were substantial differences in growth among the sea cucumber individuals during the 100-day experiment. The special growth rate of the sea cucumber individuals differed by up to three folds (from 0.40% to 1.01%), and the coefficient of variation in body weight increased from 12.04% to 40.51%. The final wet body weight, food intake and food conversion efficiency for each sea cucumber were generally positively correlated with their initial wet body weight ( P<0.05). Energy budget of the animals showed that the food energy spent on respiration was much greater (about four folds) but energy deposited for growth was much less for (initially) smaller than for larger A. japonicus. The present result implies that there are obvious genetic differences among the sea cucumber individuals, largely accounting for the individual growth variation of the cohort sea cucumber. These results will provide some basic data for promoting selective breeding and farming of the sea cucumber.

  5. Construction of a Lotus japonicus late nodulin expressed sequence tag library and identification of novel nodule-specific genes.

    PubMed Central

    Szczyglowski, K; Hamburger, D; Kapranov, P; de Bruijn, F J

    1997-01-01

    A range of novel expressed sequence tags (ESTs) associated with late developmental events during nodule organogenesis in the legume Lotus japonicus were identified using mRNA differential display; 110 differentially displayed polymerase chain reaction products were cloned and analyzed. Of 88 unique cDNAs obtained, 22 shared significant homology to DNA/protein sequences in the respective databases. This group comprises, among others, a nodule-specific homolog of protein phosphatase 2C, a peptide transporter protein, and a nodule-specific form of cytochrome P450. RNA gel-blot analysis of 16 differentially displayed ESTs confirmed their nodule-specific expression pattern. The kinetics of mRNA accumulation of the majority of the ESTs analyzed were found to resemble the expression pattern observed for the L. japonicus leghemoglobin gene. These results indicate that the newly isolated molecular markers correspond to genes induced during late developmental stages of L. japonicus nodule organogenesis and provide important, novel tools for the study of nodulation. PMID:9276951

  6. Overexpression of the Starch Phosphorylase-Like Gene (PHO3) in Lotus japonicus has a Profound Effect on the Growth of Plants and Reduction of Transitory Starch Accumulation

    PubMed Central

    Qin, Shanshan; Tang, Yuehui; Chen, Yaping; Wu, Pingzhi; Li, Meiru; Wu, Guojiang; Jiang, Huawu

    2016-01-01

    Two isoforms of starch phosphorylase (PHO; EC 2.4.1.1), plastidic PHO1 and cytosolic PHO2, have been found in all plants studied to date. Another starch phosphorylase-like gene, PHO3, which is an ortholog of Chlamydomonas PHOB, has been detected in some plant lineages. In this study, we identified three PHO isoform (LjPHO) genes in the Lotus japonicus genome. Expression of the LjPHO3 gene was observed in all tissues tested in L. japonicus, and the LjPHO3 protein was located in the chloroplast. Overexpression of LjPHO3 in L. japonicus resulted in a drastic decline in starch granule sizes and starch content in leaves. The LjPHO3 overexpression transgenic seedlings were smaller, and showed decreased pollen fertility and seed set rate. Our results suggest that LjPHO3 may participate in transitory starch metabolism in L. japonicus leaves, but its catalytic properties remain to be studied.

  7. A Lotus japonicus Cochaperone Protein Interacts With the Ubiquitin-Like Domain Protein CIP73 and Plays a Negative Regulatory Role in Nodulation.

    PubMed

    Kang, Heng; Xiao, Aifang; Huang, Xiaoqin; Gao, Xioumei; Yu, Haixiang; He, Xingxing; Zhu, Hui; Hong, Zonglie; Zhang, Zhongming

    2015-05-01

    The calcium/calmodulin-dependent protein kinase CCaMK forms a complex with its phosphorylation target CIP73 (CCaMK-interacting protein of 73 kDa). In this work, a homolog of the animal HSC/HSP70 interacting protein (HIP) was identified as an interacting partner of CIP73 in Lotus japonicus. L. japonicus HIP contains all functional domains characteristic of animal HIP proteins. The C-terminal STI1-like domain of L. japonicus HIP was found to be necessary and sufficient for interaction with CIP73. The interaction between CIP73 and HIP occurred in both the nuclei and cytoplasm in Nicotiana benthamiana leaf cells. The interactions between CIP73 and HIP and between CIP73 and CCaMK could take place simultaneously in the same nuclei. HIP transcripts were detected in all plant tissues tested. As nodule primordia developed into young nodules, the expression of HIP was down-regulated and the HIP transcript level became very low in mature nodules. More nodules were formed in transgenic hairy roots of L. japonicus expressing HIP RNA interference at 16 days postinoculation as compared with the control hairy roots expressing the empty vector. It appears that HIP may play a role as a negative regulator for nodulation. PMID:25761207

  8. Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholest...

  9. New soybean variants in oil composition identified by large scale mutagenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To identify loci involved in the determination of fatty acid content in mature soybean seeds, we subject 3400 seed samples to fatty acid profiling by gas chromatography. In the mutagenized population, a wide range of variation in the content of each of the five major fatty acids was observed. 74 mu...

  10. First occurrence of Ochlerotatus japonicus in the state of Washington.

    PubMed

    Roppo, Monica R; Lilja, Jack L; Maloney, Francis A; Sames, William J

    2004-03-01

    This is a report on the 1st occurrence of Ochlerotatus japonicus in the state of Washington. In August through November 2001, immature stages were found near the King County communities of Carnation (2 sites), Black Diamond, Kent, and Issaquah and were reared to the adult stage for identification and preservation. PMID:15088708

  11. MATURITY AND TEMPERATURE AFFECTS THE GERMINATION OF STYRAX JAPONICUS SEEDS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of seed maturity, warm (18oC) or cold (5.5oC) temperature, and gibberellic acid (GA3) on seed germination of Styrax japonicus Sieb. et. Zucc was investigated. Seed maturity and morphological changes were observed using magnetic resonance (MR) imaging (MRI). Fruits harvested on July 22,...

  12. Novel, highly expressed late nodulin gene (LjNOD16) from Lotus japonicus

    SciTech Connect

    Kapranov, P.; Bruijn, F.J. de; Szczyglowski, K.

    1997-04-01

    We have isolated a Lotus japonicus cDNA corresponding to a highly abundant, late nodule-specific RNA species that encodes a polypeptide with a predicted molecular mass of 15.6 kD. The protein and its corresponding gene were designated NIj16 and LjNOD16, respectively. LjNOD16 was found to be expressed only in the infected cells of L. japonicus nodules. Related DNA sequences could be identified in the genomes of both Glycine max and Medicago sativa. In the latter, a homologous mRNA species was detected in the nodules. Unlike LiNOD16, its alfalfa homologs appear to represent low-abundance mRNA species. However, the proteins corresponding to the LjNOD16 and its alfalfa homolog could be detected at similar levels in nodules but not in roots of both legume species. The predicted amino acid sequence analysis of nodulin NIj16 revealed the presence of a long {alpha}-helical region and a positively charged C terminus. The former domain has a very high propensity to form a coiled-coil type structure, indicating that nodulin NIj16 may interact with an as-yet-unidentified protein target(s) in the nodule-infected cells. Homology searches revealed no significant similarities to any known sequences in the databases, with the exception of two related, anonymous Arabidopsis expressed sequence tags.

  13. Proteomic identification of differentially expressed proteins in sea cucumber Apostichopus japonicus coelomocytes after Vibrio splendidus infection.

    PubMed

    Zhang, Peng; Li, Chenghua; Li, Ye; Zhang, Pengjuan; Shao, Yina; Jin, Chunhua; Li, Taiwu

    2014-06-01

    Skin ulceration syndrome (SUS) was the main limitation in the development of Apostichopus japonicus culture industries. To better understand how Vibrio splendidus modulates SUS outbreak, the immune response of A. japonicus coelomocytes after the pathogen challenge were investigated through comparative proteomics approach, and differentially expressed proteins were screened and characterized in the present study. A total of 40 protein spots representing 30 entries were identified at 24, 72 and 96 h post-infection. Of these proteins, 32 were up-regulated and 8 were down-regulated in the V. splendidus challenged samples compared to those of control. These differentially expressed proteins were mainly classified into four categories by GO analysis, in which approximate 33% of proteins showed to be related to immunity response. The mRNA expression levels of 6 differentially expressed proteins were further validated by qRT-PCR. Similar protein-mRNA-level expression patterns were detected in genes of phospholipase (spot 4), G protein (spot 20), annexin (spot 30) and filamin (spot 31). Whilst the levels of ficolin (spot 12) and calumenin (spot 14) transcripts were not corresponded with those of their translation products. These data provide a new insight to understand the molecular immune mechanism of sea cucumber responsive towards pathogen infection. PMID:24468075

  14. Chemical constituents and antioxidant activities of waste liquid extract from Apostichopus japonicus Selenka processing

    NASA Astrophysics Data System (ADS)

    Li, Chaofeng; Li, Xiancui; Li, Hong; Guo, Shuju; Zhu, Xiaobin

    2013-07-01

    Apos tichopus japonicus Selenka is an ideal tonic food that is used traditionally in many Asian countries, and it contains many bioactive substances, such as antioxidant, antimicrobial, and anticancer materials. To convert waste liquid generated during production into a useful resource, extract from waste liquid was isolated by column chromatography and studied by the pyrogallol autoxidation and 1,10-phenanthroline-Fe2+ oxidation methods. Results show that the extract scavenged about 91% of the superoxide anion radical at a concentration of 1.4 mg/mL and 24% of the hydroxyl radical at 3.3 mg/mL. Four compounds were isolated and identified from the extract: 2,4-dihydroxy-5-methyl-1,3-azine; 2,4-dihydroxy-1,3-diazine; 3-O-[β-D-quinovopranosyl-(1→2)-4-O-sodium sulfate-β-D-xylopranosyl]-holosta-9(11)-ene-3β,12α,17α-triol; and 24-ethyl-5α-cholesta-7-ene-3β-O-β-D-xylopyranoside. All of these compounds are known in A. japonicus, and were found in the waste liquid for the first time.

  15. A novel crustin from Marsupenaeus japonicus promotes hemocyte phagocytosis.

    PubMed

    Liu, Ning; Lan, Jiang-Feng; Sun, Jie-Jie; Jia, Wen-Ming; Zhao, Xiao-Fan; Wang, Jin-Xing

    2015-04-01

    Crustins are cationic cysteine-rich antimicrobial peptides (AMPs) that contain multiple domains (glycine-rich, cysteine-rich, or proline-rich) at the N-terminus and whey acidic protein (WAP) domains at the C-terminus. Crustins have multiple functions, including protease inhibition and antimicrobial activity. Other functions of crustins need to be clarified. In this study, a novel crustin with a cysteine-rich region, and a single WAP domain, belonging to type I crustins, was identified in Marsupenaeus japonicus and designated as MjCru I-1. MjCru I-1 was expressed in various tissues. The expression of MjCru I-1 was upregulated in the hemocytes of shrimp challenged with bacteria. MjCru I-1 could bind to bacteria by binding to the cell wall molecules of the bacteria, such as lipopolysaccharide (LPS), peptidoglycan (PGN), and lipoteichoic acid (LTA). The synthesized WAP domain of MjCru I-1 but not synthesized Cys-rich domain has antibacterial and agglutinative activities. Scanning electron microscope assay showed that the bacterial cells treated with sMjCru I-1 appeared to be disrupted and cracked compared with those of the control samples. The knockdown of MjCru I-1 could reduce bacterial clearance and injection of MjCru I-1 could significantly increase the survival rate of shrimp infected with Vibrio anguillarum and Staphylococcus aureus compared with those of the control samples. Further study discovered that MjCru I-1 could increase the hemocyte phagocytosis against V. anguillarum and S. aureus. These results suggest that MjCru I-1 has dual functions, bactericidal and phagocytosis promoting activities, in the antibacterial immunity of shrimp. PMID:25479014

  16. Evolution of crop production under a pseudo-space environment using model plants, Lotus japonicus

    NASA Astrophysics Data System (ADS)

    Tomita-Yokotani, Kaori; Motohashi, Kyohei; Omi, Naomi; Sato, Seigo; Aoki, Toshio; Hashimoto, Hirofumi; Yamashita, Masamichi

    Habitation in outer space is one of our challenges. We have been studying space agriculture and/or spacecraft agriculture to provide food and oxygen for the habitation area in the space environment. However, careful investigation should be made concerning the results of exotic environmental effects on the endogenous production of biologically active substances in indi-vidual cultivated plants in a space environment. We have already reported that the production of functional substances in cultivated plants as crops are affected by gravity. The amounts of the main physiological substances in these plants grown under terrestrial control were different from that grown in a pseudo-microgravity. These results suggested that the nutrition would be changed in the plants/crops grown in the space environment when human beings eat in space. This estimation required us to investigate each of the useful components produced by each plant grown in the space environment. These estimations involved several study fields, includ-ing nutrition, plant physiology, etc. On the other hand, the analysis of model plant genomes has recently been remarkably advanced. Lotus japonicus, a leguminous plant, is also one of the model plant. The leguminosae is a large family in the plant vegetable kingdom and almost the entire genome sequence of Lotus japonicus has been determined. Nitrogen fixation would be possible even in a space environment. We are trying to determine the best conditions and evolution for crop production using the model plants.

  17. Transcriptome Profiling of Lotus japonicus Roots During Arbuscular Mycorrhiza Development and Comparison with that of Nodulation

    PubMed Central

    Deguchi, Yuichi; Banba, Mari; Shimoda, Yoshikazu; Chechetka, Svetlana A.; Suzuri, Ryota; Okusako, Yasuhiro; Ooki, Yasuhiro; Toyokura, Koichi; Suzuki, Akihiro; Uchiumi, Toshiki; Higashi, Shiro; Abe, Mikiko; Kouchi, Hiroshi; Izui, Katsura; Hata, Shingo

    2007-01-01

    Abstract To better understand the molecular responses of plants to arbuscular mycorrhizal (AM) fungi, we analyzed the differential gene expression patterns of Lotus japonicus, a model legume, with the aid of a large-scale cDNA macroarray. Experiments were carried out considering the effects of contaminating microorganisms in the soil inoculants. When the colonization by AM fungi, i.e. Glomus mosseae and Gigaspora margarita, was well established, four cysteine protease genes were induced. In situ hybridization revealed that these cysteine protease genes were specifically expressed in arbuscule-containing inner cortical cells of AM roots. On the other hand, phenylpropanoid biosynthesis-related genes for phenylalanine ammonia-lyase (PAL), chalcone synthase, etc. were repressed in the later stage, although they were moderately up-regulated on the initial association with the AM fungus. Real-time RT–PCR experiments supported the array experiments. To further confirm the characteristic expression, a PAL promoter was fused with a reporter gene and introduced into L. japonicus, and then the transformants were grown with a commercial inoculum of G. mosseae. The reporter activity was augmented throughout the roots due to the presence of contaminating microorganisms in the inoculum. Interestingly, G. mosseae only colonized where the reporter activity was low. Comparison of the transcriptome profiles of AM roots and nitrogen-fixing root nodules formed with Mesorhizobium loti indicated that the PAL genes and other phenylpropanoid biosynthesis-related genes were similarly repressed in the two organs. PMID:17634281

  18. Differences in MITF gene expression and histology between albino and normal sea cucumbers ( Apostichopus japonicus Selenka)

    NASA Astrophysics Data System (ADS)

    Zhao, Heling; Yang, Hongsheng; Zhao, Huan; Liu, Shilin; Wang, Tianming

    2012-01-01

    Albino Apostichopus japonicus occur both in the wild and in captivity. The offspring of albino A. japonicus also suffer from albinism. The formation of melanin in the melanocytes is dependant on microphthalmia-associated transcription factor (MITF). To investigate the role of MITF in controlling albinism, we cloned the full-length MITF cDNA from A. japonicus and compared MITF mRNA expression in albino and normal A. japonicus. In addition, we used light and electron microscopy to compare histological samples of normal and albino A. japonicus. The body wall of albino adults was characterized by significantly lower levels of MITF expression and lower numbers of epidermal melanocytes, which also contained less melanin. In albino juvenile offspring, MITF expression levels were significantly lower 32 d after fertilization and there were fewer, and less developed, epidermal melanocytes. Thus, we conclude that albino A. japonicus have fewer melanocytes and a reduced ability to synthesize melanin, likely because of lower expression of MITF.

  19. Large Dog Relinquishment to Two Municipal Facilities in New York City and Washington, D.C.: Identifying Targets for Intervention

    PubMed Central

    Weiss, Emily; Slater, Margaret; Garrison, Laurie; Drain, Natasha; Dolan, Emily; Scarlett, Janet M.; Zawistowski, Stephen L.

    2014-01-01

    Simple Summary While the overall trend in euthanasia has been decreasing nationally, large dogs are at a higher risk of euthanasia than other-sized dogs in most animal shelters in the United States. We hypothesized that one way to increase the lives saved with regard to large dogs in shelters is to keep them home in the first place when possible. Our research is the first to collect data in New York City and Washington, D.C., identifying the process leading to the owner relinquishment of large dogs. We found that targets for interventions to decrease large dog relinquishment are likely different in each community. Abstract While the overall trend in euthanasia has been decreasing nationally, large dogs are at a higher risk of euthanasia than other sized dogs in most animal shelters in the United States. We hypothesized one way to increase the lives saved with respect to these large dogs is to keep them home when possible. In order to develop solutions to decrease relinquishment, a survey was developed to learn more about the reasons owners relinquish large dogs. The survey was administered to owners relinquishing their dogs at two large municipal facilities, one in New York City and one in Washington, D.C. There were 157 responses between the two facilities. We found both significant similarities and differences between respondents and their dogs from the two cities. We identified opportunities to potentially support future relinquishers and found that targets for interventions are likely different in each community. PMID:26480315

  20. Large-Scale Analysis of Kinase Signaling in Yeast Pseudohyphal Development Identifies Regulation of Ribonucleoprotein Granules.

    PubMed

    Shively, Christian A; Kweon, Hye Kyong; Norman, Kaitlyn L; Mellacheruvu, Dattatreya; Xu, Tao; Sheidy, Daniel T; Dobry, Craig J; Sabath, Ivan; Cosky, Eric E P; Tran, Elizabeth J; Nesvizhskii, Alexey; Andrews, Philip C; Kumar, Anuj

    2015-10-01

    Yeast pseudohyphal filamentation is a stress-responsive growth transition relevant to processes required for virulence in pathogenic fungi. Pseudohyphal growth is controlled through a regulatory network encompassing conserved MAPK (Ste20p, Ste11p, Ste7p, Kss1p, and Fus3p), protein kinase A (Tpk2p), Elm1p, and Snf1p kinase pathways; however, the scope of these pathways is not fully understood. Here, we implemented quantitative phosphoproteomics to identify each of these signaling networks, generating a kinase-dead mutant in filamentous S. cerevisiae and surveying for differential phosphorylation. By this approach, we identified 439 phosphoproteins dependent upon pseudohyphal growth kinases. We report novel phosphorylation sites in 543 peptides, including phosphorylated residues in Ras2p and Flo8p required for wild-type filamentous growth. Phosphoproteins in these kinase signaling networks were enriched for ribonucleoprotein (RNP) granule components, and we observe co-localization of Kss1p, Fus3p, Ste20p, and Tpk2p with the RNP component Igo1p. These kinases localize in puncta with GFP-visualized mRNA, and KSS1 is required for wild-type levels of mRNA localization in RNPs. Kss1p pathway activity is reduced in lsm1Δ/Δ and pat1Δ/Δ strains, and these genes encoding P-body proteins are epistatic to STE7. The P-body protein Dhh1p is also required for hyphal development in Candida albicans. Collectively, this study presents a wealth of data identifying the yeast phosphoproteome in pseudohyphal growth and regulatory interrelationships between pseudohyphal growth kinases and RNPs. PMID:26447709

  1. Large-Scale Analysis of Kinase Signaling in Yeast Pseudohyphal Development Identifies Regulation of Ribonucleoprotein Granules

    PubMed Central

    Mellacheruvu, Dattatreya; Xu, Tao; Sheidy, Daniel T.; Dobry, Craig J.; Sabath, Ivan; Cosky, Eric E. P.; Tran, Elizabeth J.; Nesvizhskii, Alexey; Andrews, Philip C.; Kumar, Anuj

    2015-01-01

    Yeast pseudohyphal filamentation is a stress-responsive growth transition relevant to processes required for virulence in pathogenic fungi. Pseudohyphal growth is controlled through a regulatory network encompassing conserved MAPK (Ste20p, Ste11p, Ste7p, Kss1p, and Fus3p), protein kinase A (Tpk2p), Elm1p, and Snf1p kinase pathways; however, the scope of these pathways is not fully understood. Here, we implemented quantitative phosphoproteomics to identify each of these signaling networks, generating a kinase-dead mutant in filamentous S. cerevisiae and surveying for differential phosphorylation. By this approach, we identified 439 phosphoproteins dependent upon pseudohyphal growth kinases. We report novel phosphorylation sites in 543 peptides, including phosphorylated residues in Ras2p and Flo8p required for wild-type filamentous growth. Phosphoproteins in these kinase signaling networks were enriched for ribonucleoprotein (RNP) granule components, and we observe co-localization of Kss1p, Fus3p, Ste20p, and Tpk2p with the RNP component Igo1p. These kinases localize in puncta with GFP-visualized mRNA, and KSS1 is required for wild-type levels of mRNA localization in RNPs. Kss1p pathway activity is reduced in lsm1Δ/Δ and pat1Δ/Δ strains, and these genes encoding P-body proteins are epistatic to STE7. The P-body protein Dhh1p is also required for hyphal development in Candida albicans. Collectively, this study presents a wealth of data identifying the yeast phosphoproteome in pseudohyphal growth and regulatory interrelationships between pseudohyphal growth kinases and RNPs. PMID:26447709

  2. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    PubMed Central

    Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Morris, Andrew P; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Langenberg, Claudia; Hofmann, Oliver M; Dupuis, Josée; Qi, Lu; Segrè, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noisël P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Couper, David J; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Perry, John R B; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L; Morris, Andrew D; Palmer, Colin N A; Pramstaller, Peter P; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J; Watanabe, Richard M; Abecasis, Gonçalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Hu, Frank B; Meigs, James B; Pankow, James S; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Inês; Florez, Jose C; Frayling, Timothy M; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I

    2011-01-01

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combinedP < 5 × 10−8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits. PMID:20581827

  3. Large-scale genotyping identifies 41 new loci associated with breast cancer risk

    PubMed Central

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L; Schmidt, Marjanka K; Chang-Claude, Jenny; Bojesen, Stig E; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Silva, Isabel dos Santos; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L; Southey, Melissa C; Makalic, Enes; Schmidt, Daniel F; Uitterlinden, Andre G; Hofman, Albert; Hunter, David J; Chanock, Stephen J; Vincent, Daniel; Bacot, François; Tessier, Daniel C; Canisius, Sander; Wessels, Lodewyk F A; Haiman, Christopher A; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; Van’t Veer, Laura J; van der Schoot, C Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M Rosario; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Bui, Quang M; Stone, Jennifer; Dite, Gillian S; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline; van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Kristensen, Vessela N; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J; Signorello, Lisa B; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D P; Chenevix-Trench, Georgia; Dunning, Alison M; Benitez, Javier; Easton, Douglas F

    2013-01-01

    Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ~9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10−8). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility. PMID:23535729

  4. Large-scale genotyping identifies 41 new loci associated with breast cancer risk.

    PubMed

    Michailidou, Kyriaki; Hall, Per; Gonzalez-Neira, Anna; Ghoussaini, Maya; Dennis, Joe; Milne, Roger L; Schmidt, Marjanka K; Chang-Claude, Jenny; Bojesen, Stig E; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Lee, Andrew; Turnbull, Clare; Rahman, Nazneen; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; Dos Santos Silva, Isabel; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel; van der Luijt, Rob B; Hein, Rebecca; Dahmen, Norbert; Beckman, Lars; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Hopper, John L; Southey, Melissa C; Makalic, Enes; Schmidt, Daniel F; Uitterlinden, Andre G; Hofman, Albert; Hunter, David J; Chanock, Stephen J; Vincent, Daniel; Bacot, François; Tessier, Daniel C; Canisius, Sander; Wessels, Lodewyk F A; Haiman, Christopher A; Shah, Mitul; Luben, Robert; Brown, Judith; Luccarini, Craig; Schoof, Nils; Humphreys, Keith; Li, Jingmei; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Stevens, Kristen N; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Johnson, Nichola; Aitken, Zoe; Aaltonen, Kirsimari; Heikkinen, Tuomas; Broeks, Annegien; Veer, Laura J Van't; van der Schoot, C Ellen; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Menegaux, Florence; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Zamora, M Pilar; Perez, Jose Ignacio Arias; Pita, Guillermo; Alonso, M Rosario; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W R; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Lindblom, Annika; Margolin, Sara; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Bui, Quang M; Stone, Jennifer; Dite, Gillian S; Apicella, Carmel; Tsimiklis, Helen; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bonanni, Bernardo; Devilee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline; van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Bogdanova, Natalia V; Antonenkova, Natalia N; Dörk, Thilo; Kristensen, Vessela N; Anton-Culver, Hoda; Slager, Susan; Toland, Amanda E; Edge, Stephen; Fostira, Florentia; Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Sueta, Aiko; Wu, Anna H; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Teo, Soo Hwang; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Sng, Jen-Hwei; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Ding, Shian-Ling; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Blot, William J; Signorello, Lisa B; Cai, Qiuyin; Zheng, Wei; Deming-Halverson, Sandra; Shrubsole, Martha; Long, Jirong; Simard, Jacques; Garcia-Closas, Montse; Pharoah, Paul D P; Chenevix-Trench, Georgia; Dunning, Alison M; Benitez, Javier; Easton, Douglas F

    2013-04-01

    Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility. PMID:23535729

  5. Large-scale association analysis identifies new risk loci for coronary artery disease

    PubMed Central

    2013-01-01

    Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways. PMID:23202125

  6. Identifying the Root Causes of Wait States in Large-Scale Parallel Applications

    DOE PAGESBeta

    Böhme, David; Geimer, Markus; Arnold, Lukas; Voigtlaender, Felix; Wolf, Felix

    2016-07-20

    Driven by growing application requirements and accelerated by current trends in microprocessor design, the number of processor cores on modern supercomputers is increasing from generation to generation. However, load or communication imbalance prevents many codes from taking advantage of the available parallelism, as delays of single processes may spread wait states across the entire machine. Moreover, when employing complex point-to-point communication patterns, wait states may propagate along far-reaching cause-effect chains that are hard to track manually and that complicate an assessment of the actual costs of an imbalance. Building on earlier work by Meira Jr. et al., we present amore » scalable approach that identifies program wait states and attributes their costs in terms of resource waste to their original cause. Ultimately, by replaying event traces in parallel both forward and backward, we can identify the processes and call paths responsible for the most severe imbalances even for runs with hundreds of thousands of processes.« less

  7. Large-scale association analysis identifies new risk loci for coronary artery disease.

    PubMed

    Deloukas, Panos; Kanoni, Stavroula; Willenborg, Christina; Farrall, Martin; Assimes, Themistocles L; Thompson, John R; Ingelsson, Erik; Saleheen, Danish; Erdmann, Jeanette; Goldstein, Benjamin A; Stirrups, Kathleen; König, Inke R; Cazier, Jean-Baptiste; Johansson, Asa; Hall, Alistair S; Lee, Jong-Young; Willer, Cristen J; Chambers, John C; Esko, Tõnu; Folkersen, Lasse; Goel, Anuj; Grundberg, Elin; Havulinna, Aki S; Ho, Weang K; Hopewell, Jemma C; Eriksson, Niclas; Kleber, Marcus E; Kristiansson, Kati; Lundmark, Per; Lyytikäinen, Leo-Pekka; Rafelt, Suzanne; Shungin, Dmitry; Strawbridge, Rona J; Thorleifsson, Gudmar; Tikkanen, Emmi; Van Zuydam, Natalie; Voight, Benjamin F; Waite, Lindsay L; Zhang, Weihua; Ziegler, Andreas; Absher, Devin; Altshuler, David; Balmforth, Anthony J; Barroso, Inês; Braund, Peter S; Burgdorf, Christof; Claudi-Boehm, Simone; Cox, David; Dimitriou, Maria; Do, Ron; Doney, Alex S F; El Mokhtari, NourEddine; Eriksson, Per; Fischer, Krista; Fontanillas, Pierre; Franco-Cereceda, Anders; Gigante, Bruna; Groop, Leif; Gustafsson, Stefan; Hager, Jörg; Hallmans, Göran; Han, Bok-Ghee; Hunt, Sarah E; Kang, Hyun M; Illig, Thomas; Kessler, Thorsten; Knowles, Joshua W; Kolovou, Genovefa; Kuusisto, Johanna; Langenberg, Claudia; Langford, Cordelia; Leander, Karin; Lokki, Marja-Liisa; Lundmark, Anders; McCarthy, Mark I; Meisinger, Christa; Melander, Olle; Mihailov, Evelin; Maouche, Seraya; Morris, Andrew D; Müller-Nurasyid, Martina; Nikus, Kjell; Peden, John F; Rayner, N William; Rasheed, Asif; Rosinger, Silke; Rubin, Diana; Rumpf, Moritz P; Schäfer, Arne; Sivananthan, Mohan; Song, Ci; Stewart, Alexandre F R; Tan, Sian-Tsung; Thorgeirsson, Gudmundur; van der Schoot, C Ellen; Wagner, Peter J; Wells, George A; Wild, Philipp S; Yang, Tsun-Po; Amouyel, Philippe; Arveiler, Dominique; Basart, Hanneke; Boehnke, Michael; Boerwinkle, Eric; Brambilla, Paolo; Cambien, Francois; Cupples, Adrienne L; de Faire, Ulf; Dehghan, Abbas; Diemert, Patrick; Epstein, Stephen E; Evans, Alun; Ferrario, Marco M; Ferrières, Jean; Gauguier, Dominique; Go, Alan S; Goodall, Alison H; Gudnason, Villi; Hazen, Stanley L; Holm, Hilma; Iribarren, Carlos; Jang, Yangsoo; Kähönen, Mika; Kee, Frank; Kim, Hyo-Soo; Klopp, Norman; Koenig, Wolfgang; Kratzer, Wolfgang; Kuulasmaa, Kari; Laakso, Markku; Laaksonen, Reijo; Lee, Ji-Young; Lind, Lars; Ouwehand, Willem H; Parish, Sarah; Park, Jeong E; Pedersen, Nancy L; Peters, Annette; Quertermous, Thomas; Rader, Daniel J; Salomaa, Veikko; Schadt, Eric; Shah, Svati H; Sinisalo, Juha; Stark, Klaus; Stefansson, Kari; Trégouët, David-Alexandre; Virtamo, Jarmo; Wallentin, Lars; Wareham, Nicholas; Zimmermann, Martina E; Nieminen, Markku S; Hengstenberg, Christian; Sandhu, Manjinder S; Pastinen, Tomi; Syvänen, Ann-Christine; Hovingh, G Kees; Dedoussis, George; Franks, Paul W; Lehtimäki, Terho; Metspalu, Andres; Zalloua, Pierre A; Siegbahn, Agneta; Schreiber, Stefan; Ripatti, Samuli; Blankenberg, Stefan S; Perola, Markus; Clarke, Robert; Boehm, Bernhard O; O'Donnell, Christopher; Reilly, Muredach P; März, Winfried; Collins, Rory; Kathiresan, Sekar; Hamsten, Anders; Kooner, Jaspal S; Thorsteinsdottir, Unnur; Danesh, John; Palmer, Colin N A; Roberts, Robert; Watkins, Hugh; Schunkert, Heribert; Samani, Nilesh J

    2013-01-01

    Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways. PMID:23202125

  8. Spider Transcriptomes Identify Ancient Large-Scale Gene Duplication Event Potentially Important in Silk Gland Evolution.

    PubMed

    Clarke, Thomas H; Garb, Jessica E; Hayashi, Cheryl Y; Arensburger, Peter; Ayoub, Nadia A

    2015-07-01

    The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are thought to be required for generating evolutionary novelty. Such an event has been proposed for spiders, but not tested. We de novo assembled transcriptomes from three cobweb weaving spider species. Based on phylogenetic analyses of gene families with representatives from each of the three species, we found numerous duplication events indicative of a whole genome or segmental duplication. We estimated the age of the gene duplications relative to several speciation events within spiders and arachnids and found that the duplications likely occurred after the divergence of scorpions (order Scorpionida) and spiders (order Araneae), but before the divergence of the spider suborders Mygalomorphae and Araneomorphae, near the evolutionary origin of spider silk glands. Transcripts that are expressed exclusively or primarily within black widow silk glands are more likely to have a paralog descended from the ancient duplication event and have elevated amino acid replacement rates compared with other transcripts. Thus, an ancient large-scale gene duplication event within the spider lineage was likely an important source of molecular novelty during the evolution of silk gland-specific expression. This duplication event may have provided genetic material for subsequent silk gland diversification in the true spiders (Araneomorphae). PMID:26058392

  9. Spider Transcriptomes Identify Ancient Large-Scale Gene Duplication Event Potentially Important in Silk Gland Evolution

    PubMed Central

    Clarke, Thomas H.; Garb, Jessica E.; Hayashi, Cheryl Y.; Arensburger, Peter; Ayoub, Nadia A.

    2015-01-01

    The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are thought to be required for generating evolutionary novelty. Such an event has been proposed for spiders, but not tested. We de novo assembled transcriptomes from three cobweb weaving spider species. Based on phylogenetic analyses of gene families with representatives from each of the three species, we found numerous duplication events indicative of a whole genome or segmental duplication. We estimated the age of the gene duplications relative to several speciation events within spiders and arachnids and found that the duplications likely occurred after the divergence of scorpions (order Scorpionida) and spiders (order Araneae), but before the divergence of the spider suborders Mygalomorphae and Araneomorphae, near the evolutionary origin of spider silk glands. Transcripts that are expressed exclusively or primarily within black widow silk glands are more likely to have a paralog descended from the ancient duplication event and have elevated amino acid replacement rates compared with other transcripts. Thus, an ancient large-scale gene duplication event within the spider lineage was likely an important source of molecular novelty during the evolution of silk gland-specific expression. This duplication event may have provided genetic material for subsequent silk gland diversification in the true spiders (Araneomorphae). PMID:26058392

  10. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.

    PubMed

    van Os, Jim; Rutten, Bart P; Myin-Germeys, Inez; Delespaul, Philippe; Viechtbauer, Wolfgang; van Zelst, Catherine; Bruggeman, Richard; Reininghaus, Ulrich; Morgan, Craig; Murray, Robin M; Di Forti, Marta; McGuire, Philip; Valmaggia, Lucia R; Kempton, Matthew J; Gayer-Anderson, Charlotte; Hubbard, Kathryn; Beards, Stephanie; Stilo, Simona A; Onyejiaka, Adanna; Bourque, Francois; Modinos, Gemma; Tognin, Stefania; Calem, Maria; O'Donovan, Michael C; Owen, Michael J; Holmans, Peter; Williams, Nigel; Craddock, Nicholas; Richards, Alexander; Humphreys, Isla; Meyer-Lindenberg, Andreas; Leweke, F Markus; Tost, Heike; Akdeniz, Ceren; Rohleder, Cathrin; Bumb, J Malte; Schwarz, Emanuel; Alptekin, Köksal; Üçok, Alp; Saka, Meram Can; Atbaşoğlu, E Cem; Gülöksüz, Sinan; Gumus-Akay, Guvem; Cihan, Burçin; Karadağ, Hasan; Soygür, Haldan; Cankurtaran, Eylem Şahin; Ulusoy, Semra; Akdede, Berna; Binbay, Tolga; Ayer, Ahmet; Noyan, Handan; Karadayı, Gülşah; Akturan, Elçin; Ulaş, Halis; Arango, Celso; Parellada, Mara; Bernardo, Miguel; Sanjuán, Julio; Bobes, Julio; Arrojo, Manuel; Santos, Jose Luis; Cuadrado, Pedro; Rodríguez Solano, José Juan; Carracedo, Angel; García Bernardo, Enrique; Roldán, Laura; López, Gonzalo; Cabrera, Bibiana; Cruz, Sabrina; Díaz Mesa, Eva Ma; Pouso, María; Jiménez, Estela; Sánchez, Teresa; Rapado, Marta; González, Emiliano; Martínez, Covadonga; Sánchez, Emilio; Olmeda, Ma Soledad; de Haan, Lieuwe; Velthorst, Eva; van der Gaag, Mark; Selten, Jean-Paul; van Dam, Daniella; van der Ven, Elsje; van der Meer, Floor; Messchaert, Elles; Kraan, Tamar; Burger, Nadine; Leboyer, Marion; Szoke, Andrei; Schürhoff, Franck; Llorca, Pierre-Michel; Jamain, Stéphane; Tortelli, Andrea; Frijda, Flora; Vilain, Jeanne; Galliot, Anne-Marie; Baudin, Grégoire; Ferchiou, Aziz; Richard, Jean-Romain; Bulzacka, Ewa; Charpeaud, Thomas; Tronche, Anne-Marie; De Hert, Marc; van Winkel, Ruud; Decoster, Jeroen; Derom, Catherine; Thiery, Evert; Stefanis, Nikos C; Sachs, Gabriele; Aschauer, Harald; Lasser, Iris; Winklbaur, Bernadette; Schlögelhofer, Monika; Riecher-Rössler, Anita; Borgwardt, Stefan; Walter, Anna; Harrisberger, Fabienne; Smieskova, Renata; Rapp, Charlotte; Ittig, Sarah; Soguel-dit-Piquard, Fabienne; Studerus, Erich; Klosterkötter, Joachim; Ruhrmann, Stephan; Paruch, Julia; Julkowski, Dominika; Hilboll, Desiree; Sham, Pak C; Cherny, Stacey S; Chen, Eric Y H; Campbell, Desmond D; Li, Miaoxin; Romeo-Casabona, Carlos María; Emaldi Cirión, Aitziber; Urruela Mora, Asier; Jones, Peter; Kirkbride, James; Cannon, Mary; Rujescu, Dan; Tarricone, Ilaria; Berardi, Domenico; Bonora, Elena; Seri, Marco; Marcacci, Thomas; Chiri, Luigi; Chierzi, Federico; Storbini, Viviana; Braca, Mauro; Minenna, Maria Gabriella; Donegani, Ivonne; Fioritti, Angelo; La Barbera, Daniele; La Cascia, Caterina Erika; Mulè, Alice; Sideli, Lucia; Sartorio, Rachele; Ferraro, Laura; Tripoli, Giada; Seminerio, Fabio; Marinaro, Anna Maria; McGorry, Patrick; Nelson, Barnaby; Amminger, G Paul; Pantelis, Christos; Menezes, Paulo R; Del-Ben, Cristina M; Gallo Tenan, Silvia H; Shuhama, Rosana; Ruggeri, Mirella; Tosato, Sarah; Lasalvia, Antonio; Bonetto, Chiara; Ira, Elisa; Nordentoft, Merete; Krebs, Marie-Odile; Barrantes-Vidal, Neus; Cristóbal, Paula; Kwapil, Thomas R; Brietzke, Elisa; Bressan, Rodrigo A; Gadelha, Ary; Maric, Nadja P; Andric, Sanja; Mihaljevic, Marina; Mirjanic, Tijana

    2014-07-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. PMID:24860087

  11. Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations

    PubMed Central

    2014-01-01

    Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi–center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. PMID:24860087

  12. Use of laser microdissection for the construction of Humulus japonicus Siebold et Zuccarini, 1846 (Cannabaceae) sex chromosome-specific DNA library and cytogenetics analysis

    PubMed Central

    Yakovin, Nickolay A.; Divashuk, Mikhail G.; Razumova, Olga V.; Soloviev, Alexander A.; Karlov, Gennady I.

    2014-01-01

    Abstract Dioecy is relatively rare among plant species, and distinguishable sex chromosomes have been reported in few dioecious species. The multiple sex chromosome system (XX/XY1Y2) of Humulus japonicus Siebold et Zuccarini, 1846 differs from that of other members of the family Cannabaceae, in which the XX/XY chromosome system is present. Sex chromosomes of Humulus japonicus were isolated from meiotic chromosome spreads of males by laser microdissection with the P.A.L.M. MicroLaser system. The chromosomal DNA was directly amplified by degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR). Fast fluorescence in situ hybridization (FAST-FISH) using a labeled, chromosome-specific DOP-PCR product as a probe showed preferential hybridization to sex chromosomes. In addition, the DOP-PCR product was used to construct a short-insert, Humulus japonicus sex chromosomes-specific DNA library. The randomly sequenced clones showed that about 12% of them have significant homology to Humulus lupulus and 88% to Cannabis sativa Linnaeus, 1753 sequences from GenBank database. Forty-four percent of the sequences show homology to plant retroelements. It was concluded that laser microdissection is a useful tool for isolating the DNA of sex chromosomes of Humulus japonicus and for the construction of chromosome-specific DNA libraries for the study of the structure and evolution of sex chromosomes. The results provide the potential for identifying unique or sex chromosome-specific sequence elements in Humulus japonicus and could aid in the identification of sex chromosome-specific repeat and coding regions through chromosome isolation and genome complexity reduction. PMID:25610546

  13. Temperature-sensitive mutants identify crucial structural regions of simian virus 40 large T antigen.

    PubMed Central

    Loeber, G; Tevethia, M J; Schwedes, J F; Tegtmeyer, P

    1989-01-01

    We have completed the cloning and sequencing of all known temperature-sensitive, amino acid substitution mutants of simian virus 40 large T antigen (tsA mutants). Surprisingly, many of the mutants isolated from distinct viral strains by different laboratories are identical. Thus, 17 independently isolated mutants represent only eight distinct genotypes. This remarkable clustering of tsA mutations in a few "hot spots" in the amino acid sequence of T antigen and the temperature-sensitive phenotypes of the mutations strongly suggest that these amino acids play crucial roles in organizing the structure of one or more functional domains. Most of the mutations are located in highly conserved regions of T antigen that correlate with DNA binding, protein-protein interactions, or ATP binding. With the exception of one mutant with a lesion in the putative ATP-binding region, all the mutants are temperature sensitive for DNA replication. PMID:2778883

  14. Unexpected patterns of admixture in German populations of Aedes japonicus japonicus (Diptera: Culicidae) underscore the importance of human intervention.

    PubMed

    Zielke, Dorothee E; Werner, Doreen; Schaffner, Francis; Kampen, Helge; Fonseca, Dina M

    2014-01-01

    The mosquito Aedes japonicus japonicus, originally restricted to temperate East Asia, is now widespread in North America and more recently has become established in Europe. To ascertain the putative number of separate introductions to Europe and examine patterns of expansion we analyzed the genetic makeup of Ae. j. japonicus populations from five cemeteries in North Rhine-Westphalia and Rhineland-Palatinate, two western German federal states, as well as of specimens from populations in Belgium, Switzerland, and Austria/Slovenia. To do so, we genotyped individual specimens at seven pre-existing polymorphic microsatellite loci and sequenced part of the nad4 mitochondrial locus. We found evidence of two different genotypic signatures associated with different nad4 mitochondrial haplotypes, indicating at least two genetically differentiated populations of Ae. j. japonicus in Europe (i.e. two distinct genotypes). Belgian, Swiss, and Austrian/Slovenian populations all share the same genotypic signature although they have become differentiated since isolation. Contrary to expectations, the German Ae. j. japonicus are not closely related to those in Belgium which are geographically nearest but are also highly inbred. German populations have a unique genotype but also evidence of mixing between the two genotypes. Also unexpectedly, the populations closest to the center of the German infestation had the highest levels of admixture indicating that separate introductions did not expand and merge but instead their expansion was driven by punctuated human-mediated transport. Critically, the resulting admixed populations have higher genetic diversity and appear invasive as indicated by their increased abundance and recent spread across western Germany. PMID:24992470

  15. Unexpected Patterns of Admixture in German Populations of Aedes japonicus japonicus (Diptera: Culicidae) Underscore the Importance of Human Intervention

    PubMed Central

    Zielke, Dorothee E.; Werner, Doreen; Schaffner, Francis; Kampen, Helge; Fonseca, Dina M.

    2014-01-01

    The mosquito Aedes japonicus japonicus, originally restricted to temperate East Asia, is now widespread in North America and more recently has become established in Europe. To ascertain the putative number of separate introductions to Europe and examine patterns of expansion we analyzed the genetic makeup of Ae. j. japonicus populations from five cemeteries in North Rhine-Westphalia and Rhineland-Palatinate, two western German federal states, as well as of specimens from populations in Belgium, Switzerland, and Austria/Slovenia. To do so, we genotyped individual specimens at seven pre-existing polymorphic microsatellite loci and sequenced part of the nad4 mitochondrial locus. We found evidence of two different genotypic signatures associated with different nad4 mitochondrial haplotypes, indicating at least two genetically differentiated populations of Ae. j. japonicus in Europe (i.e. two distinct genotypes). Belgian, Swiss, and Austrian/Slovenian populations all share the same genotypic signature although they have become differentiated since isolation. Contrary to expectations, the German Ae. j. japonicus are not closely related to those in Belgium which are geographically nearest but are also highly inbred. German populations have a unique genotype but also evidence of mixing between the two genotypes. Also unexpectedly, the populations closest to the center of the German infestation had the highest levels of admixture indicating that separate introductions did not expand and merge but instead their expansion was driven by punctuated human-mediated transport. Critically, the resulting admixed populations have higher genetic diversity and appear invasive as indicated by their increased abundance and recent spread across western Germany. PMID:24992470

  16. The complete mitochondrial genome sequence of Squalidus japonicus coreanus (Teleostei, Cypriniformes, Cyprinidae).

    PubMed

    Eon Park, Chang; Park, Gun-Seok; Kwak, Yunyoung; Kim, Min-Chul; Kim, Kgu-Hwan; Park, Hee Cheon; Shin, Jae-Ho

    2016-09-01

    The short-barbel gudgeon Squalidus japonicus coreanus (Teleostei, Cypriniformes, Cyprinidae) is a subspecies of S. japonicus, and is endemic to Korea. The complete mitochondrial genome sequence consisted of 16 597 base pairs (bp) encoding 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and two non-coding regions. The overall base composition of S. japonicus coreanus was G + C: 47.4% and A + T: 52.6%, apparently with a slight AT bias. Phylogenetic analysis showed that S. japonicus coreanus was closely related to Pungtungia herzi. PMID:26329666

  17. Large genetic screens for gynogenesis and androgenesis haploid inducers in Arabidopsis thaliana failed to identify mutants

    PubMed Central

    Portemer, Virginie; Renne, Charlotte; Guillebaux, Alexia; Mercier, Raphael

    2015-01-01

    Gynogenesis is a process in which the embryo genome originates exclusively from female origin, following embryogenesis stimulation by a male gamete. In contrast, androgenesis is the development of embryos that contain only the male nuclear genetic background. Both phenomena are of great interest in plant breeding as haploidization is an efficient tool to reduce the length of breeding schemes to create varieties. Although few inducer lines have been described, the genetic control of these phenomena is poorly understood. We developed genetic screens to identify mutations that would induce gynogenesis or androgenesis in Arabidopsis thaliana. The ability of mutant pollen to induce either gynogenesis or androgenesis was tested by crossing mutagenized plants as males. Seedlings from these crosses were screened with recessive phenotypic markers, one genetically controlled by the female genome and another by the male genome. Positive and negative controls confirmed the unambiguous detection of both gynogenesis and androgenesis events. This strategy was applied to 1,666 EMS-mutagenised lines and 47 distant Arabidopsis strains. While an internal control suggested that the mutagenesis reached saturation, no gynogenesis or androgenesis inducer was found. However, spontaneous gynogenesis was observed at a frequency of 1/10,800. Altogether, these results suggest that no simple EMS-induced mutation in the male genome is able to induce gynogenesis or androgenesis in Arabidopsis. PMID:25814999

  18. Large-scale association analyses identifies 13 new susceptibility loci for coronary artery disease

    PubMed Central

    Schunkert, Heribert; König, Inke R.; Kathiresan, Sekar; Reilly, Muredach P.; Assimes, Themistocles L.; Holm, Hilma; Preuss, Michael; Stewart, Alexandre F. R.; Barbalic, Maja; Gieger, Christian; Absher, Devin; Aherrahrou, Zouhair; Allayee, Hooman; Altshuler, David; Anand, Sonia S.; Andersen, Karl; Anderson, Jeffrey L.; Ardissino, Diego; Ball, Stephen G.; Balmforth, Anthony J.; Barnes, Timothy A.; Becker, Diane M.; Becker, Lewis C.; Berger, Klaus; Bis, Joshua C.; Boekholdt, S. Matthijs; Boerwinkle, Eric; Braund, Peter S.; Brown, Morris J.; Burnett, Mary Susan; Buysschaert, Ian; Carlquist, Cardiogenics, John F.; Chen, Li; Cichon, Sven; Codd, Veryan; Davies, Robert W.; Dedoussis, George; Dehghan, Abbas; Demissie, Serkalem; Devaney, Joseph M.; Do, Ron; Doering, Angela; Eifert, Sandra; El Mokhtari, Nour Eddine; Ellis, Stephen G.; Elosua, Roberto; Engert, James C.; Epstein, Stephen E.; Faire, Ulf de; Fischer, Marcus; Folsom, Aaron R.; Freyer, Jennifer; Gigante, Bruna; Girelli, Domenico; Gretarsdottir, Solveig; Gudnason, Vilmundur; Gulcher, Jeffrey R.; Halperin, Eran; Hammond, Naomi; Hazen, Stanley L.; Hofman, Albert; Horne, Benjamin D.; Illig, Thomas; Iribarren, Carlos; Jones, Gregory T.; Jukema, J.Wouter; Kaiser, Michael A.; Kaplan, Lee M.; Kastelein, John J.P.; Khaw, Kay-Tee; Knowles, Joshua W.; Kolovou, Genovefa; Kong, Augustine; Laaksonen, Reijo; Lambrechts, Diether; Leander, Karin; Lettre, Guillaume; Li, Mingyao; Lieb, Wolfgang; Linsel-Nitschke, Patrick; Loley, Christina; Lotery, Andrew J.; Mannucci, Pier M.; Maouche, Seraya; Martinelli, Nicola; McKeown, Pascal P.; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Merlini, Pier Angelica; Mooser, Vincent; Morgan, Thomas; Mühleisen, Thomas W.; Muhlestein, Joseph B.; Münzel, Thomas; Musunuru, Kiran; Nahrstaedt, Janja; Nelson, Christopher P.; Nöthen, Markus M.; Olivieri, Oliviero; Patel, Riyaz S.; Patterson, Chris C.; Peters, Annette; Peyvandi, Flora; Qu, Liming; Quyyumi, Arshed A.; Rader, Daniel J.; Rallidis, Loukianos S.; Rice, Catherine; Rosendaal, Frits R.; Rubin, Diana; Salomaa, Veikko; Sampietro, M. Lourdes; Sandhu, Manj S.; Schadt, Eric; Schäfer, Arne; Schillert, Arne; Schreiber, Stefan; Schrezenmeir, Jürgen; Schwartz, Stephen M.; Siscovick, David S.; Sivananthan, Mohan; Sivapalaratnam, Suthesh; Smith, Albert; Smith, Tamara B.; Snoep, Jaapjan D.; Soranzo, Nicole; Spertus, John A.; Stark, Klaus; Stirrups, Kathy; Stoll, Monika; Tang, W. H. Wilson; Tennstedt, Stephanie; Thorgeirsson, Gudmundur; Thorleifsson, Gudmar; Tomaszewski, Maciej; Uitterlinden, Andre G.; van Rij, Andre M.; Voight, Benjamin F.; Wareham, Nick J.; Wells, George A.; Wichmann, H.-Erich; Wild, Philipp S.; Willenborg, Christina; Witteman, Jaqueline C. M.; Wright, Benjamin J.; Ye, Shu; Zeller, Tanja; Ziegler, Andreas; Cambien, Francois; Goodall, Alison H.; Cupples, L. Adrienne; Quertermous, Thomas; März, Winfried; Hengstenberg, Christian; Blankenberg, Stefan; Ouwehand, Willem H.; Hall, Alistair S.; Deloukas, Panos; Thompson, John R.; Stefansson, Kari; Roberts, Robert; Thorsteinsdottir, Unnur; O’Donnell, Christopher J.; McPherson, Ruth; Erdmann, Jeanette; Samani, Nilesh J.

    2011-01-01

    We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 cases and 64,762 controls of European descent, followed by genotyping of top association signals in 60,738 additional individuals. This genomic analysis identified 13 novel loci harboring one or more SNPs that were associated with CAD at P<5×10−8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 novel loci displayed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6 to 17 percent increase in the risk of CAD per allele. Notably, only three of the novel loci displayed significant association with traditional CAD risk factors, while the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the novel CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits. PMID:21378990

  19. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.

    PubMed

    Schunkert, Heribert; König, Inke R; Kathiresan, Sekar; Reilly, Muredach P; Assimes, Themistocles L; Holm, Hilma; Preuss, Michael; Stewart, Alexandre F R; Barbalic, Maja; Gieger, Christian; Absher, Devin; Aherrahrou, Zouhair; Allayee, Hooman; Altshuler, David; Anand, Sonia S; Andersen, Karl; Anderson, Jeffrey L; Ardissino, Diego; Ball, Stephen G; Balmforth, Anthony J; Barnes, Timothy A; Becker, Diane M; Becker, Lewis C; Berger, Klaus; Bis, Joshua C; Boekholdt, S Matthijs; Boerwinkle, Eric; Braund, Peter S; Brown, Morris J; Burnett, Mary Susan; Buysschaert, Ian; Carlquist, John F; Chen, Li; Cichon, Sven; Codd, Veryan; Davies, Robert W; Dedoussis, George; Dehghan, Abbas; Demissie, Serkalem; Devaney, Joseph M; Diemert, Patrick; Do, Ron; Doering, Angela; Eifert, Sandra; Mokhtari, Nour Eddine El; Ellis, Stephen G; Elosua, Roberto; Engert, James C; Epstein, Stephen E; de Faire, Ulf; Fischer, Marcus; Folsom, Aaron R; Freyer, Jennifer; Gigante, Bruna; Girelli, Domenico; Gretarsdottir, Solveig; Gudnason, Vilmundur; Gulcher, Jeffrey R; Halperin, Eran; Hammond, Naomi; Hazen, Stanley L; Hofman, Albert; Horne, Benjamin D; Illig, Thomas; Iribarren, Carlos; Jones, Gregory T; Jukema, J Wouter; Kaiser, Michael A; Kaplan, Lee M; Kastelein, John J P; Khaw, Kay-Tee; Knowles, Joshua W; Kolovou, Genovefa; Kong, Augustine; Laaksonen, Reijo; Lambrechts, Diether; Leander, Karin; Lettre, Guillaume; Li, Mingyao; Lieb, Wolfgang; Loley, Christina; Lotery, Andrew J; Mannucci, Pier M; Maouche, Seraya; Martinelli, Nicola; McKeown, Pascal P; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Merlini, Pier Angelica; Mooser, Vincent; Morgan, Thomas; Mühleisen, Thomas W; Muhlestein, Joseph B; Münzel, Thomas; Musunuru, Kiran; Nahrstaedt, Janja; Nelson, Christopher P; Nöthen, Markus M; Olivieri, Oliviero; Patel, Riyaz S; Patterson, Chris C; Peters, Annette; Peyvandi, Flora; Qu, Liming; Quyyumi, Arshed A; Rader, Daniel J; Rallidis, Loukianos S; Rice, Catherine; Rosendaal, Frits R; Rubin, Diana; Salomaa, Veikko; Sampietro, M Lourdes; Sandhu, Manj S; Schadt, Eric; Schäfer, Arne; Schillert, Arne; Schreiber, Stefan; Schrezenmeir, Jürgen; Schwartz, Stephen M; Siscovick, David S; Sivananthan, Mohan; Sivapalaratnam, Suthesh; Smith, Albert; Smith, Tamara B; Snoep, Jaapjan D; Soranzo, Nicole; Spertus, John A; Stark, Klaus; Stirrups, Kathy; Stoll, Monika; Tang, W H Wilson; Tennstedt, Stephanie; Thorgeirsson, Gudmundur; Thorleifsson, Gudmar; Tomaszewski, Maciej; Uitterlinden, Andre G; van Rij, Andre M; Voight, Benjamin F; Wareham, Nick J; Wells, George A; Wichmann, H-Erich; Wild, Philipp S; Willenborg, Christina; Witteman, Jaqueline C M; Wright, Benjamin J; Ye, Shu; Zeller, Tanja; Ziegler, Andreas; Cambien, Francois; Goodall, Alison H; Cupples, L Adrienne; Quertermous, Thomas; März, Winfried; Hengstenberg, Christian; Blankenberg, Stefan; Ouwehand, Willem H; Hall, Alistair S; Deloukas, Panos; Thompson, John R; Stefansson, Kari; Roberts, Robert; Thorsteinsdottir, Unnur; O'Donnell, Christopher J; McPherson, Ruth; Erdmann, Jeanette; Samani, Nilesh J

    2011-04-01

    We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10⁻⁸ and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits. PMID:21378990

  20. Prospective large-scale field study generates predictive model identifying major contributors to colony losses.

    PubMed

    Kielmanowicz, Merav Gleit; Inberg, Alex; Lerner, Inbar Maayan; Golani, Yael; Brown, Nicholas; Turner, Catherine Louise; Hayes, Gerald J R; Ballam, Joan M

    2015-04-01

    Over the last decade, unusually high losses of colonies have been reported by beekeepers across the USA. Multiple factors such as Varroa destructor, bee viruses, Nosema ceranae, weather, beekeeping practices, nutrition, and pesticides have been shown to contribute to colony losses. Here we describe a large-scale controlled trial, in which different bee pathogens, bee population, and weather conditions across winter were monitored at three locations across the USA. In order to minimize influence of various known contributing factors and their interaction, the hives in the study were not treated with antibiotics or miticides. Additionally, the hives were kept at one location and were not exposed to potential stress factors associated with migration. Our results show that a linear association between load of viruses (DWV or IAPV) in Varroa and bees is present at high Varroa infestation levels (>3 mites per 100 bees). The collection of comprehensive data allowed us to draw a predictive model of colony losses and to show that Varroa destructor, along with bee viruses, mainly DWV replication, contributes to approximately 70% of colony losses. This correlation further supports the claim that insufficient control of the virus-vectoring Varroa mite would result in increased hive loss. The predictive model also indicates that a single factor may not be sufficient to trigger colony losses, whereas a combination of stressors appears to impact hive health. PMID:25875764

  1. Prospective Large-Scale Field Study Generates Predictive Model Identifying Major Contributors to Colony Losses

    PubMed Central

    Kielmanowicz, Merav Gleit; Inberg, Alex; Lerner, Inbar Maayan; Golani, Yael; Brown, Nicholas; Turner, Catherine Louise; Hayes, Gerald J. R.; Ballam, Joan M.

    2015-01-01

    Over the last decade, unusually high losses of colonies have been reported by beekeepers across the USA. Multiple factors such as Varroa destructor, bee viruses, Nosema ceranae, weather, beekeeping practices, nutrition, and pesticides have been shown to contribute to colony losses. Here we describe a large-scale controlled trial, in which different bee pathogens, bee population, and weather conditions across winter were monitored at three locations across the USA. In order to minimize influence of various known contributing factors and their interaction, the hives in the study were not treated with antibiotics or miticides. Additionally, the hives were kept at one location and were not exposed to potential stress factors associated with migration. Our results show that a linear association between load of viruses (DWV or IAPV) in Varroa and bees is present at high Varroa infestation levels (>3 mites per 100 bees). The collection of comprehensive data allowed us to draw a predictive model of colony losses and to show that Varroa destructor, along with bee viruses, mainly DWV replication, contributes to approximately 70% of colony losses. This correlation further supports the claim that insufficient control of the virus-vectoring Varroa mite would result in increased hive loss. The predictive model also indicates that a single factor may not be sufficient to trigger colony losses, whereas a combination of stressors appears to impact hive health. PMID:25875764

  2. Pharmacoproteomics identifies combinatorial therapy targets for diffuse large B cell lymphoma

    PubMed Central

    Goldstein, Rebecca L.; Yang, Shao Ning; Taldone, Tony; Chang, Betty; Gerecitano, John; Elenitoba-Johnson, Kojo; Shaknovich, Rita; Tam, Wayne; Leonard, John P.; Chiosis, Gabriela; Cerchietti, Leandro; Melnick, Ari

    2015-01-01

    Rationally designed combinations of targeted therapies for refractory cancers, such as activated B cell–like diffuse large B cell lymphoma (ABC DLBCL), are likely required to achieve potent, durable responses. Here, we used a pharmacoproteomics approach to map the interactome of a tumor-enriched isoform of HSP90 (teHSP90). Specifically, we chemically precipitated teHSP90-client complexes from DLBCL cell lines with the small molecule PU-H71 and found that components of the proximal B cell receptor (BCR) signalosome were enriched within teHSP90 complexes. Functional assays revealed that teHSP90 facilitates BCR signaling dynamics by enabling phosphorylation of key BCR signalosome components, including the kinases SYK and BTK. Consequently, treatment of BCR-dependent ABC DLBCL cells with PU-H71 attenuated BCR signaling, calcium flux, and NF-κB signaling, ultimately leading to growth arrest. Combined exposure of ABC DLBCL cell lines to PU-H71 and ibrutinib, a BCR pathway inhibitor, more potently suppressed BCR signaling than either drug alone. Correspondingly, PU-H71 combined with ibrutinib induced synergistic killing of lymphoma cell lines, primary human lymphoma specimens ex vivo, and lymphoma xenografts in vivo, without notable toxicity. Together, our results demonstrate that a pharmacoproteome-driven rational combination therapy has potential to provide more potent BCR-directed therapy for ABC DLCBL patients. PMID:26529251

  3. Identifying Microlenses In Large, Non-uniformly Sampled Surveys: The Case Of PTF

    NASA Astrophysics Data System (ADS)

    Price-Whelan, Adrian M.; Agúeros, M.; Fournier, A.; Ofek, E.; Street, R.

    2012-05-01

    Many current photometric, time-domain surveys are driven by specific goals, such as supernova searches, transiting exoplanet discoveries, or stellar variability studies, which set the cadence with which individual fields get re-imaged. In the case of the Palomar Transient Factory (PTF), several such sub-surveys are being conducted in parallel, leading to an extremely non-uniform sampling gradient over the survey footprint of nearly 20,000 deg^2: while the typical 7.26 deg^2 PTF field has been imaged 15 times, 1000 deg^2 of the survey has been observed more than 150 times. We use the existing PTF data to study the trade-off between a large survey footprint and irregular sampling when searching for microlensing events, and to examine the probability that such events can be recovered in these data. We conduct Monte Carlo simulations to evaluate our detection efficiency in a hypothetical survey field as a function of both the baseline and number of observations. We also apply variability statistics to systematically differentiate between periodic, transient, and flat light curves. Preliminary results suggest that both recovery and discovery of microlensing events are possible with a careful consideration of photometric systematics. This work can help inform predictions about the observability of microlensing signals in future wide-field time-domain surveys such as that of LSST.

  4. A Large-Scale Behavioral Screen to Identify Neurons Controlling Motor Programs in the Drosophila Brain

    PubMed Central

    Flood, Thomas F.; Gorczyca, Michael; White, Benjamin H.; Ito, Kei; Yoshihara, Motojiro

    2013-01-01

    Drosophila is increasingly used for understanding the neural basis of behavior through genetically targeted manipulation of specific neurons. The primary approach in this regard has relied on the suppression of neuronal activity. Here, we report the results of a novel approach to find and characterize neural circuits by expressing neuronal activators to stimulate subsets of neurons to induce behavior. Classical electrophysiological studies demonstrated that stimulation of command neurons could activate neural circuits to trigger fixed action patterns. Our method was designed to find such command neurons for diverse behaviors by screening flies in which random subsets of brain cells were activated. We took advantage of the large collection of Gal4 lines from the NP project and crossed 835 Gal4 strains with relatively limited Gal4 expression in the brain to flies carrying a UAS transgene encoding TRPM8, a cold-sensitive ion channel. Low temperatures opened the TRPM8 channel in Gal4-expressing cells, leading to their excitation, and in many cases induced overt behavioral changes in adult flies. Paralysis was reproducibly observed in the progeny of crosses with 84 lines, whereas more specific behaviors were induced with 24 other lines. Stimulation performed using the heat-activated channel, TrpA1, resulted in clearer and more robust behaviors, including flight, feeding, and egg-laying. Through follow-up studies starting from this screen, we expect to find key components of the neural circuits underlying specific behaviors, thus providing a new avenue for their functional analysis. PMID:23934998

  5. Effect of intestinal autochthonous probiotics isolated from the gut of sea cucumber (Apostichopus japonicus) on immune response and growth of A. japonicus.

    PubMed

    Chi, Cheng; Liu, Jia-Yan; Fei, Shi-Zhou; Zhang, Chao; Chang, Ya-Qing; Liu, Xiao-Lin; Wang, Gao-Xue

    2014-06-01

    The study isolated 224 bacteria from the intestine of Apostichopus japonicus, then selected and identified three of the bacteria (HS1, HS7, and HS10) which demonstrated amylase, lipase, and protease production capacity as candidate probiotics for sea cucumbers. The three potential probiotics showed no pathogenicity both in hemolytic assays on sheep blood agar plates and after immersing sea cucumbers in a suspension of the bacteria. To reveal the effects of these three potential probiotics on the innate immunity of sea cucumbers, total coelomocyte counts, respiratory burst activity, superoxide dismutase activity, lysozyme activity, acid phosphatase activity, and phagocytic activity by coelomocytes were examined after feeding with four different diets for up to 28 days. Also the specific growth rate and survival rate were investigated after a 60-day feeding trial. Sea cucumbers were fed with 4 diets: one control, three diets supplemented with 1 × 10(9) cell g(-1) of HS1, HS7, and HS10 for 28-60 days. Results showed that sea cucumbers fed diets containing HS1, HS7, and HS10 had led to an enhanced cellular and humoral immune response, notably higher total coelomocytes counts, respiratory burst activity, lysozyme activity, acid phosphatase activity, and phagocytic activity, as recorded during the four weeks of probiotics administration. On the other hand, the survival rate among dietary treatments ranged from 90.71 to 97.97% with significant improvement (P < 0.05) compared to that of the control; and the growth rate observed in the sea cucumbers fed HS1 and HS7 showed sharp increases after 60 days feeding. The present study confirmed the potential beneficial effects of Pseudoalteromonas elyakovii HS1, Shewanella japonica HS7, and Vibrio tasmaniensis HS10 as dietary probiotics in A. japonicus. PMID:24727198

  6. A large-scale genetic screen in Arabidopsis to identify genes involved in pollen exine production.

    PubMed

    Dobritsa, Anna A; Geanconteri, Aliza; Shrestha, Jay; Carlson, Ann; Kooyers, Nicholas; Coerper, Daniel; Urbanczyk-Wochniak, Ewa; Bench, Bennie J; Sumner, Lloyd W; Swanson, Robert; Preuss, Daphne

    2011-10-01

    Exine, the outer plant pollen wall, has elaborate species-specific patterns, provides a protective barrier for male gametophytes, and serves as a mediator of strong and species-specific pollen-stigma adhesion. Exine is made of sporopollenin, a material remarkable for its strength, elasticity, and chemical durability. The chemical nature of sporopollenin, as well as the developmental mechanisms that govern its assembly into diverse patterns in different species, are poorly understood. Here, we describe a simple yet effective genetic screen in Arabidopsis (Arabidopsis thaliana) that was undertaken to advance our understanding of sporopollenin synthesis and exine assembly. This screen led to the recovery of mutants with a variety of defects in exine structure, including multiple mutants with novel phenotypes. Fifty-six mutants were selected for further characterization and are reported here. In 14 cases, we have mapped defects to specific genes, including four with previously demonstrated or suggested roles in exine development (MALE STERILITY2, CYP703A2, ANTHER-SPECIFIC PROTEIN6, TETRAKETIDE α-PYRONE REDUCTASE/DIHYDROFLAVONOL-4-REDUCTASE-LIKE1), and a number of genes that have not been implicated in exine production prior to this screen (among them, fatty acid ω-hydroxylase CYP704B1, putative glycosyl transferases At1g27600 and At1g33430, 4-coumarate-coenzyme A ligase 4CL3, polygalacturonase QUARTET3, novel gene At5g58100, and nucleotide-sugar transporter At5g65000). Our study illustrates that morphological screens of pollen can be extremely fruitful in identifying previously unknown exine genes and lays the foundation for biochemical, developmental, and evolutionary studies of exine production. PMID:21849515

  7. High-resolution sulfur isotopes in ice cores identify large stratospheric volcanic eruptions

    NASA Astrophysics Data System (ADS)

    Burke, Andrea; Sigl, Michael; Adkins, Jess; Paris, Guillaume; McConnell, Joe

    2016-04-01

    The record of the volcanic forcing of climate over the past 2500 years is reconstructed primarily from sulfate concentrations in ice cores. Of particular interest are stratospheric eruptions, as these afford sulfate aerosols the longest residence time and largest dispersion in the atmosphere, and thus the greatest impact on radiative forcing. Identification of stratospheric eruptions currently relies on the successful matching of the same volcanic sulphate peak in ice cores from both the Northern and Southern hemispheres (a "bipolar event"). These are interpreted to reflect the global distribution of sulfur aerosols by the stratospheric winds. Despite its recent success, this method relies on precise and accurate dating of ice cores, in order to distinguish between a true 'bipolar event' and two separate eruptions that occurred in close temporal succession. Sulfur isotopes can been used to distinguish between these two scenarios since stratospheric sulfur aerosols are exposed to UV radiation which imparts a mass independent fractionation (Baroni et al., 2007). Mass independent fractionation of sulfate in ice cores thus offers a novel method of fingerprinting stratospheric eruptions, and thus refining the historic record of explosive volcanism and its forcing of climate. Here we present new high-resolution (sub-annual) sulfur isotope data from the Tunu Ice core in Greenland over seven eruptions. Sulfur isotopes were measured by MC-ICP-MS, which substantially reduces sample size requirements and allows high temporal resolution from a single ice core. We demonstrate the efficacy of the method on recent, well-known eruptions (including Pinatubo and Katmai/Novarupta), and then apply it to unidentified sulfate peaks, allowing us to identify new stratospheric eruptions. Baroni, M., Thiemens, M. H., Delmas, R. J., & Savarino, J. (2007). Mass-independent sulfur isotopic compositions in stratospheric volcanic eruptions. Science, 315(5808), 84-87. http://doi.org/10

  8. Identifying the locations of future eruptions within large calderas: Campi Flegrei, Southern Italy.

    NASA Astrophysics Data System (ADS)

    Charlton, Danielle; Kilburn, Christopher; Sobradelo, Rosa; Edwards, Stephen

    2016-04-01

    Large calderas, with surface areas of 100 km2 or more, are among the most populated active volcanoes on Earth. New vents commonly open at locations across the caldera floor. An important goal for hazard mitigation, therefore, is to develop reliable methods for evaluating the most likely location for a future eruption. A preferred approach is to analyse statistically the distributions of previous vents. Using the Campi Flegrei caldera as a test case, we here examine the sensitivity of results to starting assumptions, notably the choice of data set for defining preferred vent locations. Situated immediately west of Naples, in southern Italy, Campi Flegrei poses a direct threat to more than 300,000 people. It has been in episodic unrest since the late 1950s. The unrest is the first since the last eruption in Campi Flegrei in 1538 and suggests that the caldera may have re-entered a state with an increased probability of an eruption. Since the most recent episode of caldera collapse 15.5 ka BP, at least 60 intra-caldera eruptions have occurred across the 150 km2 that make up the modern onshore area of Campi Flegrei. The eruptions have been concentrated within three epochs: 15.5-9.5 ka BP (Epoch 1, c. 27 eruptions), 8.6-8.2 ka BP (Epoch 2; c. 6 eruptions) and 4.8-3.8 ka BP (Epoch 3; c. 27 eruptions). Recent statistical studies of future vent locations have assumed that (1) only data from Epoch 3 are relevant to modern Campi Flegrei, and (2) repeated eruptions from the same vent can be incorporated, whether they are independent events or belong to a connected sequence of activity. We have relaxed these assumptions to investigate data from all epochs and to distinguish between independent and related eruptions from the same vent. Quadrat and nearest-neighbour statistics show that eruptions from Epochs 1 and 2 were distributed within an annulus 3-5 km around modern Pozzuoli, but that, in agreement with previous studies, eruptions occurred preferentially NE-ENE of Pozzuoli

  9. Petasites japonicus Stimulates the Proliferation of Mouse Spermatogonial Stem Cells.

    PubMed

    Kang, Hye-Ryun; Lee, Yong-An; Kim, Yong-Hee; Lee, Dong Gu; Kim, Bang-Jin; Kim, Ki-Jung; Kim, Byung-Gak; Oh, Myeong-Geun; Han, Chan Kyu; Lee, Sanghyun; Ryu, Buom-Yong

    2015-01-01

    Oriental natural plants have been used as medical herbs for the treatment of various diseases for over 2,000 years. In this study, we evaluated the effect of several natural plants on the preservation of male fertility by assessing the ability of plant extracts to stimulate spermatogonial stem cell (SSC) proliferation by using a serum-free culture method. In vitro assays showed that Petasites japonicus extracts, especially the butanol fraction, have a significant effect on germ cells proliferation including SSCs. The activity of SSCs cultured in the presence of the Petasites japonicus butanol fraction was confirmed by normal colony formation and spermatogenesis following germ cell transplantation of the treated SSCs. Our findings could lead to the discovery of novel factors that activate SSCs and could be useful for the development of technologies for the prevention of male infertility. PMID:26207817

  10. The complete mitochondrial genome sequence of Heteromycteris japonicus (Pleuronectiformes: Soleidae).

    PubMed

    Shi, Wei; Jiang, Jin-Xia; Miao, Xian-Guang; Kong, Xiao-Yu

    2014-08-01

    The bamboo sole Heteromycteris japonicus (Pleuronectiformes: Soleidae) is characterized by both eyes on the right side of the body and a rostral hook. In this article, the complete mitochondrial genome sequence of this sole was first determined. The total length is 17,111 bp, including 13 protein-coding genes, 22 tRNA genes and 2 rRNA genes (12 S and 16 S), as well as a putative control region and a putative L-strand replication origin (OL). Gene contents, locations and arrangements are identical to those of typical bony fishes. Overall base composition of the mitogenome is 29.2%, 27.5%, 16.3% and 27.1% for A, C, G and T, with a high A + T content (56.3%). The determination of H. japonicus mitogenome sequence could contribute to understanding the systematic evolution of the genus Heteromycteris and further phylogenetic study on Soleidae and Pleuronectiformes. PMID:23808925

  11. Petasites japonicus Stimulates the Proliferation of Mouse Spermatogonial Stem Cells

    PubMed Central

    Kim, Yong-Hee; Lee, Dong Gu; Kim, Bang-Jin; Kim, Ki-Jung; Kim, Byung-Gak; Oh, Myeong-Geun; Han, Chan Kyu; Lee, Sanghyun; Ryu, Buom-Yong

    2015-01-01

    Oriental natural plants have been used as medical herbs for the treatment of various diseases for over 2,000 years. In this study, we evaluated the effect of several natural plants on the preservation of male fertility by assessing the ability of plant extracts to stimulate spermatogonial stem cell (SSC) proliferation by using a serum-free culture method. In vitro assays showed that Petasites japonicus extracts, especially the butanol fraction, have a significant effect on germ cells proliferation including SSCs. The activity of SSCs cultured in the presence of the Petasites japonicus butanol fraction was confirmed by normal colony formation and spermatogenesis following germ cell transplantation of the treated SSCs. Our findings could lead to the discovery of novel factors that activate SSCs and could be useful for the development of technologies for the prevention of male infertility. PMID:26207817

  12. Postembryonic development of the bone-eating worm Osedax japonicus

    NASA Astrophysics Data System (ADS)

    Miyamoto, Norio; Yamamoto, Tomoko; Yusa, Yoichi; Fujiwara, Yoshihiro

    2013-03-01

    Bone-eating worms of the genus Osedax exclusively inhabit sunken vertebrate bones on the seafloor. The unique lifestyle and morphology of Osedax spp. have received much scientific attention, but the whole process of their development has not been observed. We herein report the postembryonic development and settlement of Osedax japonicus Fujikura et al. (Zool Sci 23:733-740, 2006). Fertilised eggs were spawned into the mucus of a female, and the larvae swam out from the mucus at the trochophore stage. Larvae survived for 10 days under laboratory conditions. The larvae settled on bones, elongated their bodies and crawled around on the bones. Then they secreted mucus to create a tube and the palps started to develop. The palps of O. japonicus arose from the prostomium, whereas the anterior appendages of other siboglinids arose from the peristomium. The recruitment of dwarf males was induced by rearing larvae with adult females. Females started to spawn eggs 6 weeks after settlement.

  13. [Reactivating factor of Luteococcus japonicus subsp. casei: isolation and characterization].

    PubMed

    Vorob'eva, L I; Rogozhin, E A; Khodzhaev, E Iu; Nikolaev, I V; Turova, T P

    2015-01-01

    It has been shown that a producer strain of reactivating factor (RF) is identical to a typical strain of Luteococcus japonicus DSM 10546 from the Propionibacteriaceae family according to the physiological and biochemical properties and the sequencing of 16S rRNA fragments. A number of phenotypical differences from the model strain allowed the producer strain to be considered a subspecies of Luteococcus japonicus, and it was named Luteococcus japonicus subsp. casei. At cultivation of the producer, RF is secreted into the medium and plays the role of a signaling molecule. RF antioxidant activities towards various organic radicals may be a possible mechanism of its protective and reactivating effects. Metabolites secreted by the L. casei producer strain into the culture medium were separated by a combination of liquid chromatographies. Four components possessing biological activities were found. The most active one was studied by MALDI-TOF mass spectrometry, which revealed that it is a polypeptide. Primary identification of some amino acid residues was performed. Sugar residues were found in the structure. PMID:25842902

  14. RNA-seq dependent transcriptional analysis unveils gene expression profile in the intestine of sea cucumber Apostichopus japonicus during aestivation.

    PubMed

    Zhao, Ye; Yang, Hongsheng; Storey, Kenneth B; Chen, Muyan

    2014-06-01

    The seasonal marine, the sea cucumber Apostichopus japonicus (Selenka, 1867), cycles annually between periods of torpor when water temperature is above about 25°C in summer and active life when temperature is below about 18°C. This species is a good candidate model organism for studies of environmentally-induced aestivation in marine invertebrates. Previous studies have examined various aspects of aestivation of A. japonicus, however, knowledge of the molecular regulation underpinning these events is still fragmentary. In the present study, we constructed a global gene expression profile of the intestine tissue of A. japonicus using RNA-seq to identify transcriptional responses associated with transitions between different states: non-aestivation (NA), deep-aestivation (DA), and arousal from aestivation (AA). The analysis identified 1245 differentially expressed genes (DEGs) between DA vs. NA states, 1338 DEGs between AA vs. DA, and 1321 DEGs between AA vs. NA using the criteria |Log2Ratio|≥1 and FDR≤0.001. Of these, 25 of the most significant DEGs were verified by real-time PCR, showing trends in expression patterns that were almost in full concordance between the two techniques. GO analysis revealed that for DA vs. NA, 24 metabolic associated processes were highly enriched (corrected p value<0.05) whereas for AA vs. NA, 12 transport and metabolism associated processes were significantly enriched (corrected p value<0.05). Pathways associated with aestivation were also mined, and indicated that most DEGs were enriched in metabolic and signal transduction pathways in the deep aestivation stage. Two up pathways were significantly enriched at the arousal stage (ribosome and metabolism of xenobiotics by cytochrome P450 pathway). A set of key DEGs was identified that may play vital roles in aestivation; these involved metabolism, detoxification and tissue protection, and energy-expensive processes. Our work presents an overview of dynamic gene expression in torpor

  15. Evaluation of body weight of sea cucumber Apostichopus japonicus by computer vision

    NASA Astrophysics Data System (ADS)

    Liu, Hui; Xu, Qiang; Liu, Shilin; Zhang, Libin; Yang, Hongsheng

    2015-01-01

    A postichopus japonicus (Holothuroidea, Echinodermata) is an ecological and economic species in East Asia. Conventional biometric monitoring method includes diving for samples and weighing above water, with highly variable in weight measurement due to variation in the quantity of water in the respiratory tree and intestinal content of this species. Recently, video survey method has been applied widely in biometric detection on underwater benthos. However, because of the high flexibility of A. japonicus body, video survey method of monitoring is less used in sea cucumber. In this study, we designed a model to evaluate the wet weight of A. japonicus, using machine vision technology combined with a support vector machine (SVM) that can be used in field surveys on the A. japonicus population. Continuous dorsal images of free-moving A. japonicus individuals in seawater were captured, which also allows for the development of images of the core body edge as well as thorn segmentation. Parameters that include body length, body breadth, perimeter and area, were extracted from the core body edge images and used in SVM regression, to predict the weight of A. japonicus and for comparison with a power model. Results indicate that the use of SVM for predicting the weight of 33 A. japonicus individuals is accurate ( R 2=0.99) and compatible with the power model ( R 2 =0.96). The image-based analysis and size-weight regression models in this study may be useful in body weight evaluation of A. japonicus in lab and field study.

  16. Ontogeny of swimming speed, schooling behaviour and jellyfish avoidance by Japanese anchovy Engraulis japonicus.

    PubMed

    Masuda, R

    2011-05-01

    The ontogeny of swimming speed, schooling behaviour and jellyfish avoidance was studied in hatchery-reared Japanese anchovy Engraulis japonicus to compare its life-history strategy with two other common pelagic fishes, jack mackerel Trachurus japonicus and chub mackerel Scomber japonicus. Cruise swimming speed of E. japonicus increased allometrically from 1·4 to 3·9 standard length (L(S) ) per s (L(S) s(-1) ) from early larval to metamorphosing stage. Burst swimming speed also increased from 6·1 to 28 L(S) s(-1) in these stages. Cruise speed was inferior to that of S. japonicus, as was burst speed to that of T. japonicus. Engraulis japonicus larvae were highly vulnerable to predation by moon jellyfish Aurelia aurita and were readily eaten until they reached 23 mm L(S) , but not at 26 mm L(S) . Schooling behaviour (indicated by parallel swimming) started at c. 17 mm L(S) . Average distance to the nearest neighbour was shorter than values reported in other pelagic fishes. The relatively low predator avoidance capability of E. japonicus may be compensated for by their transparent and thus less conspicuous body, in addition to their early maturation and high fecundity. PMID:21539545

  17. Automated NMR Fragment Based Screening Identified a Novel Interface Blocker to the LARG/RhoA Complex

    PubMed Central

    Gao, Jia; Ma, Rongsheng; Wang, Wei; Wang, Na; Sasaki, Ryan; Snyderman, David; Wu, Jihui; Ruan, Ke

    2014-01-01

    The small GTPase cycles between the inactive GDP form and the activated GTP form, catalyzed by the upstream guanine exchange factors. The modulation of such process by small molecules has been proven to be a fruitful route for therapeutic intervention to prevent the over-activation of the small GTPase. The fragment based approach emerging in the past decade has demonstrated its paramount potential in the discovery of inhibitors targeting such novel and challenging protein-protein interactions. The details regarding the procedure of NMR fragment screening from scratch have been rarely disclosed comprehensively, thus restricts its wider applications. To achieve a consistent screening applicable to a number of targets, we developed a highly automated protocol to cover every aspect of NMR fragment screening as possible, including the construction of small but diverse libray, determination of the aqueous solubility by NMR, grouping compounds with mutual dispersity to a cocktail, and the automated processing and visualization of the ligand based screening spectra. We exemplified our streamlined screening in RhoA alone and the complex of the small GTPase RhoA and its upstream guanine exchange factor LARG. Two hits were confirmed from the primary screening in cocktail and secondary screening over individual hits for LARG/RhoA complex, while one of them was also identified from the screening for RhoA alone. HSQC titration of the two hits over RhoA and LARG alone, respectively, identified one compound binding to RhoA.GDP at a 0.11 mM affinity, and perturbed the residues at the switch II region of RhoA. This hit blocked the formation of the LARG/RhoA complex, validated by the native gel electrophoresis, and the titration of RhoA to 15N labeled LARG in the absence and presence the compound, respectively. It therefore provides us a starting point toward a more potent inhibitor to RhoA activation catalyzed by LARG. PMID:24505392

  18. Individual Apostichopus japonicus fecal microbiome reveals a link with polyhydroxybutyrate producers in host growth gaps

    PubMed Central

    Yamazaki, Yohei; Meirelles, Pedro Milet; Mino, Sayaka; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Thompson, Fabiano L.; Sakai, Yuichi; Sawabe, Toko; Sawabe, Tomoo

    2016-01-01

    Gut microbiome shapes various aspects of a host’s physiology, but these functions in aquatic animal hosts have yet to be fully investigated. The sea cucumber Apostichopus japonicus Selenka is one such example. The large growth gap in their body size has delayed the development of intensive aquaculture, nevertheless the species is in urgent need of conservation. To understand possible contributions of the gut microbiome to its host’s growth, individual fecal microbiome comparisons were performed. High-throughput 16S rRNA sequencing revealed significantly different microbiota in larger and smaller individuals; Rhodobacterales in particular was the most significantly abundant bacterial group in the larger specimens. Further shotgun metagenome of representative samples revealed a significant abundance of microbiome retaining polyhydroxybutyrate (PHB) metabolism genes in the largest individual. The PHB metabolism reads were potentially derived from Rhodobacterales. These results imply a possible link between microbial PHB producers and potential growth promotion in Deuterostomia marine invertebrates. PMID:26905381

  19. Individual Apostichopus japonicus fecal microbiome reveals a link with polyhydroxybutyrate producers in host growth gaps.

    PubMed

    Yamazaki, Yohei; Meirelles, Pedro Milet; Mino, Sayaka; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Thompson, Fabiano L; Sakai, Yuichi; Sawabe, Toko; Sawabe, Tomoo

    2016-01-01

    Gut microbiome shapes various aspects of a host's physiology, but these functions in aquatic animal hosts have yet to be fully investigated. The sea cucumber Apostichopus japonicus Selenka is one such example. The large growth gap in their body size has delayed the development of intensive aquaculture, nevertheless the species is in urgent need of conservation. To understand possible contributions of the gut microbiome to its host's growth, individual fecal microbiome comparisons were performed. High-throughput 16S rRNA sequencing revealed significantly different microbiota in larger and smaller individuals; Rhodobacterales in particular was the most significantly abundant bacterial group in the larger specimens. Further shotgun metagenome of representative samples revealed a significant abundance of microbiome retaining polyhydroxybutyrate (PHB) metabolism genes in the largest individual. The PHB metabolism reads were potentially derived from Rhodobacterales. These results imply a possible link between microbial PHB producers and potential growth promotion in Deuterostomia marine invertebrates. PMID:26905381

  20. Genome-wide mining, characterization, and development of microsatellite markers in Marsupenaeus japonicus by genome survey sequencing

    NASA Astrophysics Data System (ADS)

    Lu, Xia; Luan, Sheng; Kong, Jie; Hu, Longyang; Mao, Yong; Zhong, Shengping

    2015-12-01

    The kuruma prawn, Marsupenaeus japonicus, is one of the most cultivated and consumed species of shrimp. However, very few molecular genetic/genomic resources are publically available for it. Thus, the characterization and distribution of simple sequence repeats (SSRs) remains ambiguous and the use of SSR markers in genomic studies and marker-assisted selection is limited. The goal of this study is to characterize and develop genome-wide SSR markers in M. japonicus by genome survey sequencing for application in comparative genomics and breeding. A total of 326 945 perfect SSRs were identifi ed, among which dinucleotide repeats were the most frequent class (44.08%), followed by mononucleotides (29.67%), trinucleotides (18.96%), tetranucleotides (5.66%), hexanucleotides (1.07%), and pentanucleotides (0.56%). In total, 151 541 SSR loci primers were successfully designed. A subset of 30 SSR primer pairs were synthesized and tested in 42 individuals from a wild population, of which 27 loci (90.0%) were successfully amplifi ed with specifi c products and 24 (80.0%) were polymorphic. For the amplifi ed polymorphic loci, the alleles ranged from 5 to 17 (with an average of 9.63), and the average PIC value was 0.796. A total of 58 256 SSR-containing sequences had signifi cant Gene Ontology annotation; these are good functional molecular marker candidates for association studies and comparative genomic analysis. The newly identifi ed SSRs signifi cantly contribute to the M. japonicus genomic resources and will facilitate a number of genetic and genomic studies, including high density linkage mapping, genome-wide association analysis, marker-aided selection, comparative genomics analysis, population genetics, and evolution.

  1. Understanding mechanism of sea cucumber Apostichopus japonicus aestivation: Insights from TMT-based proteomic study.

    PubMed

    Chen, Muyan; Li, Xingke; Zhu, Aijun; Storey, Kenneth B; Sun, Lina; Gao, Tianxiang; Wang, Tianming

    2016-09-01

    Marine invertebrate aestivation is a unique strategy for summer survival in response to hot marine conditions. The sea cucumber, Apostichopus japonicus, is an excellent model marine invertebrate for studies of environmentally-induced aestivation. In the present study, we used a tandem mass tag (TMT)-coupled LC-MS/MS approach to identify and quantify the global proteome expression profile over the aestivation-arousal cycle of A. japonicus. A total of 3920 proteins were identified from the intestine of sea cucumber. Among them, 630 proteins showed significant differential expression when comparing three conditions of sea cucumbers: non-aestivating (active), deep-aestivation (at least 15days of continuous aestivation), and arousal after aestivation (renewed moving and feeding). Sea cucumbers in deep aestivation showed substantial differentially expressed proteins (143 up-regulated and 267 down-regulated proteins compared with non-aestivating controls). These differentially expressed proteins suggested that protein and phospholipid probably are major fuel sources during hypometabolism and a general attenuation of carbohydrate metabolism was observed during deep aestivation. Differentially expressed proteins also provided the first global picture of a shift in protein synthesis, protein folding, DNA binding, apoptosis, cellular transport and signaling, and cytoskeletal proteins during deep aestivation in sea cucumbers. A comparison of arousal from aestivation with deep aestivation, revealed a general reversal of the changes that occurred in aestivation for most proteins. Western blot detection further validated the significant up-regulation of HSP70 and down-regulation of methyltransferase-like protein 7A-like in deep-aestivation. Our results suggest that there is substantial post-transcriptional regulation of proteins during the aestivation-arousal cycle in sea cucumbers. PMID:27376927

  2. Heterologous Overexpression and Characterization of a Flavoprotein-Cytochrome c Complex Fructose Dehydrogenase of Gluconobacter japonicus NBRC3260

    PubMed Central

    Kawai, Shota; Goda-Tsutsumi, Maiko; Kano, Kenji; Matsushita, Kazunobu

    2013-01-01

    A heterotrimeric flavoprotein-cytochrome c complex fructose dehydrogenase (FDH) of Gluconobacter japonicus NBRC3260 catalyzes the oxidation of d-fructose to produce 5-keto-d-fructose and is used for diagnosis and basic research purposes as a direct electron transfer-type bioelectrocatalysis. The fdhSCL genes encoding the FDH complex of G. japonicus NBRC3260 were isolated by a PCR-based gene amplification method with degenerate primers designed from the amino-terminal amino acid sequence of the large subunit and sequenced. Three open reading frames for fdhSCL encoding the small, cytochrome c, and large subunits, respectively, were found and were presumably in a polycistronic transcriptional unit. Heterologous overexpression of fdhSCL was conducted using a broad-host-range plasmid vector, pBBR1MCS-4, carrying a DNA fragment containing the putative promoter region of the membrane-bound alcohol dehydrogenase gene of Gluconobacter oxydans and a G. oxydans strain as the expression host. We also constructed derivatives modified in the translational initiation codon to ATG from TTG, designated TTGFDH and ATGFDH. Membranes of the cells producing recombinant TTGFDH and ATGFDH showed approximately 20 times and 100 times higher specific activity than those of G. japonicus NBRC3260, respectively. The cells producing only FdhS and FdhL had no fructose-oxidizing activity, but showed significantly high d-fructose:ferricyanide oxidoreductase activity in the soluble fraction of cell extracts, whereas the cells producing the FDH complex showed activity in the membrane fraction. It is reasonable to conclude that the cytochrome c subunit is responsible not only for membrane anchoring but also for ubiquinone reduction. PMID:23275508

  3. Reconstruction of Oomycete Genome Evolution Identifies Differences in Evolutionary Trajectories Leading to Present-Day Large Gene Families

    PubMed Central

    Seidl, Michael F.; Van den Ackerveken, Guido; Govers, Francine; Snel, Berend

    2012-01-01

    The taxonomic class of oomycetes contains numerous pathogens of plants and animals but is related to nonpathogenic diatoms and brown algae. Oomycetes have flexible genomes comprising large gene families that play roles in pathogenicity. The evolutionary processes that shaped the gene content have not yet been studied by applying systematic tree reconciliation of the phylome of these species. We analyzed evolutionary dynamics of ten Stramenopiles. Gene gains, duplications, and losses were inferred by tree reconciliation of 18,459 gene trees constituting the phylome with a highly supported species phylogeny. We reconstructed a strikingly large last common ancestor of the Stramenopiles that contained ∼10,000 genes. Throughout evolution, the genomes of pathogenic oomycetes have constantly gained and lost genes, though gene gains through duplications outnumber the losses. The branch leading to the plant pathogenic Phytophthora genus was identified as a major transition point characterized by increased frequency of duplication events that has likely driven the speciation within this genus. Large gene families encoding different classes of enzymes associated with pathogenicity such as glycoside hydrolases are formed by complex and distinct patterns of duplications and losses leading to their expansion in extant oomycetes. This study unveils the large-scale evolutionary dynamics that shaped the genomes of pathogenic oomycetes. By the application of phylogenetic based analyses methods, it provides additional insights that shed light on the complex history of oomycete genome evolution and the emergence of large gene families characteristic for this important class of pathogens. PMID:22230142

  4. Large-Scale Chemical Similarity Networks for Target Profiling of Compounds Identified in Cell-Based Chemical Screens

    PubMed Central

    Lo, Yu-Chen; Senese, Silvia; Li, Chien-Ming; Hu, Qiyang; Huang, Yong; Damoiseaux, Robert; Torres, Jorge Z.

    2015-01-01

    Target identification is one of the most critical steps following cell-based phenotypic chemical screens aimed at identifying compounds with potential uses in cell biology and for developing novel disease therapies. Current in silico target identification methods, including chemical similarity database searches, are limited to single or sequential ligand analysis that have limited capabilities for accurate deconvolution of a large number of compounds with diverse chemical structures. Here, we present CSNAP (Chemical Similarity Network Analysis Pulldown), a new computational target identification method that utilizes chemical similarity networks for large-scale chemotype (consensus chemical pattern) recognition and drug target profiling. Our benchmark study showed that CSNAP can achieve an overall higher accuracy (>80%) of target prediction with respect to representative chemotypes in large (>200) compound sets, in comparison to the SEA approach (60–70%). Additionally, CSNAP is capable of integrating with biological knowledge-based databases (Uniprot, GO) and high-throughput biology platforms (proteomic, genetic, etc) for system-wise drug target validation. To demonstrate the utility of the CSNAP approach, we combined CSNAP's target prediction with experimental ligand evaluation to identify the major mitotic targets of hit compounds from a cell-based chemical screen and we highlight novel compounds targeting microtubules, an important cancer therapeutic target. The CSNAP method is freely available and can be accessed from the CSNAP web server (http://services.mbi.ucla.edu/CSNAP/). PMID:25826798

  5. Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations, 2. Robustness of Techniques

    SciTech Connect

    Helton, J.C.; Kleijnen, J.P.C.

    1999-03-24

    Procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses are described and illustrated. These procedures attempt to detect increasingly complex patterns in scatterplots and involve the identification of (i) linear relationships with correlation coefficients, (ii) monotonic relationships with rank correlation coefficients, (iii) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (iv) trends in variability as defined by variances and interquartile ranges, and (v) deviations from randomness as defined by the chi-square statistic. A sequence of example analyses with a large model for two-phase fluid flow illustrates how the individual procedures can differ in the variables that they identify as having effects on particular model outcomes. The example analyses indicate that the use of a sequence of procedures is a good analysis strategy and provides some assurance that an important effect is not overlooked.

  6. Use of large-scale expression cloning screens in the Xenopus laevis tadpole to identify gene function.

    PubMed

    Grammer, T C; Liu, K J; Mariani, F V; Harland, R M

    2000-12-15

    We have conducted an expression cloning screen of approximately 50, 000 cDNAs from a tadpole stage Xenopus laevis cDNA library to functionally identify genes affecting a wide range of cellular and developmental processes. Fifty-seven cDNAs were isolated for their ability to alter gross tadpole morphology or the expression patterns of tissue-specific markers. Thirty-seven of the cDNAs have not been previously described for Xenopus, and 15 of these show little or no similarity to sequences in the NCBI database. The screen and the identified genes are presented in this paper to demonstrate the power, ease, speed, and flexibility of expression cloning in the X. laevis embryo. Future screens such as this one can be done on a larger scale and will complement the sequence-based screens and genome-sequencing projects which are producing a large body of novel genes without ascribed functions. PMID:11112324

  7. Quantitative high-throughput screening: A titration-based approach that efficiently identifies biological activities in large chemical libraries

    PubMed Central

    Inglese, James; Auld, Douglas S.; Jadhav, Ajit; Johnson, Ronald L.; Simeonov, Anton; Yasgar, Adam; Zheng, Wei; Austin, Christopher P.

    2006-01-01

    High-throughput screening (HTS) of chemical compounds to identify modulators of molecular targets is a mainstay of pharmaceutical development. Increasingly, HTS is being used to identify chemical probes of gene, pathway, and cell functions, with the ultimate goal of comprehensively delineating relationships between chemical structures and biological activities. Achieving this goal will require methodologies that efficiently generate pharmacological data from the primary screen and reliably profile the range of biological activities associated with large chemical libraries. Traditional HTS, which tests compounds at a single concentration, is not suited to this task, because HTS is burdened by frequent false positives and false negatives and requires extensive follow-up testing. We have developed a paradigm, quantitative HTS (qHTS), tested with the enzyme pyruvate kinase, to generate concentration–response curves for >60,000 compounds in a single experiment. We show that this method is precise, refractory to variations in sample preparation, and identifies compounds with a wide range of activities. Concentration–response curves were classified to rapidly identify pyruvate kinase activators and inhibitors with a variety of potencies and efficacies and elucidate structure–activity relationships directly from the primary screen. Comparison of qHTS with traditional single-concentration HTS revealed a high prevalence of false negatives in the single-point screen. This study demonstrates the feasibility of qHTS for accurately profiling every compound in large chemical libraries (>105 compounds). qHTS produces rich data sets that can be immediately mined for reliable biological activities, thereby providing a platform for chemical genomics and accelerating the identification of leads for drug discovery. PMID:16864780

  8. A Novel Locus Harbouring a Functional CD164 Nonsense Mutation Identified in a Large Danish Family with Nonsyndromic Hearing Impairment

    PubMed Central

    Nielsen, Morten S.; Corydon, Thomas J.; Demontis, Ditte; Starnawska, Anna; Hedemand, Anne; Buniello, Annalisa; Niola, Francesco; Overgaard, Michael T.; Leal, Suzanne M.; Ahmad, Wasim; Wikman, Friedrik P.; Petersen, Kirsten B.; Crüger, Dorthe G.; Oostrik, Jaap; Kremer, Hannie; Tommerup, Niels; Frödin, Morten; Steel, Karen P.; Tranebjærg, Lisbeth; Børglum, Anders D.

    2015-01-01

    Nonsyndromic hearing impairment (NSHI) is a highly heterogeneous condition with more than eighty known causative genes. However, in the clinical setting, a large number of NSHI families have unexplained etiology, suggesting that there are many more genes to be identified. In this study we used SNP-based linkage analysis and follow up microsatellite markers to identify a novel locus (DFNA66) on chromosome 6q15-21 (LOD 5.1) in a large Danish family with dominantly inherited NSHI. By locus specific capture and next-generation sequencing, we identified a c.574C>T heterozygous nonsense mutation (p.R192*) in CD164. This gene encodes a 197 amino acid transmembrane sialomucin (known as endolyn, MUC-24 or CD164), which is widely expressed and involved in cell adhesion and migration. The mutation segregated with the phenotype and was absent in 1200 Danish control individuals and in databases with whole-genome and exome sequence data. The predicted effect of the mutation was a truncation of the last six C-terminal residues of the cytoplasmic tail of CD164, including a highly conserved canonical sorting motif (YXXФ). In whole blood from an affected individual, we found by RT-PCR both the wild-type and the mutated transcript suggesting that the mutant transcript escapes nonsense mediated decay. Functional studies in HEK cells demonstrated that the truncated protein was almost completely retained on the plasma cell membrane in contrast to the wild-type protein, which targeted primarily to the endo-lysosomal compartments, implicating failed endocytosis as a possible disease mechanism. In the mouse ear, we found CD164 expressed in the inner and outer hair cells of the organ of Corti, as well as in other locations in the cochlear duct. In conclusion, we have identified a new DFNA locus located on chromosome 6q15-21 and implicated CD164 as a novel gene for hearing impairment. PMID:26197441

  9. A Novel Locus Harbouring a Functional CD164 Nonsense Mutation Identified in a Large Danish Family with Nonsyndromic Hearing Impairment.

    PubMed

    Nyegaard, Mette; Rendtorff, Nanna D; Nielsen, Morten S; Corydon, Thomas J; Demontis, Ditte; Starnawska, Anna; Hedemand, Anne; Buniello, Annalisa; Niola, Francesco; Overgaard, Michael T; Leal, Suzanne M; Ahmad, Wasim; Wikman, Friedrik P; Petersen, Kirsten B; Crüger, Dorthe G; Oostrik, Jaap; Kremer, Hannie; Tommerup, Niels; Frödin, Morten; Steel, Karen P; Tranebjærg, Lisbeth; Børglum, Anders D

    2015-07-01

    Nonsyndromic hearing impairment (NSHI) is a highly heterogeneous condition with more than eighty known causative genes. However, in the clinical setting, a large number of NSHI families have unexplained etiology, suggesting that there are many more genes to be identified. In this study we used SNP-based linkage analysis and follow up microsatellite markers to identify a novel locus (DFNA66) on chromosome 6q15-21 (LOD 5.1) in a large Danish family with dominantly inherited NSHI. By locus specific capture and next-generation sequencing, we identified a c.574C>T heterozygous nonsense mutation (p.R192*) in CD164. This gene encodes a 197 amino acid transmembrane sialomucin (known as endolyn, MUC-24 or CD164), which is widely expressed and involved in cell adhesion and migration. The mutation segregated with the phenotype and was absent in 1200 Danish control individuals and in databases with whole-genome and exome sequence data. The predicted effect of the mutation was a truncation of the last six C-terminal residues of the cytoplasmic tail of CD164, including a highly conserved canonical sorting motif (YXXФ). In whole blood from an affected individual, we found by RT-PCR both the wild-type and the mutated transcript suggesting that the mutant transcript escapes nonsense mediated decay. Functional studies in HEK cells demonstrated that the truncated protein was almost completely retained on the plasma cell membrane in contrast to the wild-type protein, which targeted primarily to the endo-lysosomal compartments, implicating failed endocytosis as a possible disease mechanism. In the mouse ear, we found CD164 expressed in the inner and outer hair cells of the organ of Corti, as well as in other locations in the cochlear duct. In conclusion, we have identified a new DFNA locus located on chromosome 6q15-21 and implicated CD164 as a novel gene for hearing impairment. PMID:26197441

  10. The cloning and characterization of the enolase2 gene of Gekko japonicus and its polyclonal antibody preparation.

    PubMed

    Li, Jing; Wu, Ronghua; Chen, Haijiao; Zhou, Youlang; Li, Yan; Wang, Yongjun; Liu, Yan; Liu, Mei

    2013-01-01

    The enolase2 gene is usually expressed in mature neurons and also named neuron specific enolase (NSE). In the present study, we first obtained the NSE gene cDNA sequence by using the RACE method based on the expressed sequence tag (EST) fragment from the cDNA library of Gekko japonicus and identified one transcript of about 2.2 kb in central nervous system of Gekko japonicus by Northern blotting. The open reading frame of NSE is 1305 bp, which encodes a 435 amino-acid protein. We further investigated the multi-tissue expression pattern of NSE by RT-PCR and found that the expression of NSE mRNA was very high in brain, spinal cord and low in heart, while it was not detectable in other tissues. The real-time quantitative PCR was used to investigate the time-dependent change in the expression of the NSE mRNA level after gecko spinal cord transection and found it significantly increased at one day, reaching its highest level three days post-injury and then decreasing at the seventh day of the experiment. The recombinant plasmid of pET-32a-NSE was constructed and induced to express His fused NSE protein. The purified NSE protein was used to immunize rabbits to generate polyclonal antisera. The titer of the antiserum was more than 1:65536 determined by ELISA. Western blotting showed that the prepared antibody could specifically recognize the recombinant and endogenous NSE protein. The result of immunohistochemistry revealed that positive signals were present in neurons of the brain and the spinal cord. This study provided the tools of cDNA and polyclonal antibody for studying NSE function in Gekko japonicus. PMID:23615470

  11. Expression analysis of microRNAs related to the skin ulceration syndrome of sea cucumber Apostichopus japonicus.

    PubMed

    Sun, Hongjuan; Zhou, Zunchun; Dong, Ying; Yang, Aifu; Jiang, Jingwei; Chen, Zhong; Guan, Xiaoyan; Wang, Bai; Gao, Shan; Jiang, Bei

    2016-02-01

    MicroRNAs (miRNAs) are small non-coding RNAs that are involved in many biological processes. To investigate the miRNAs related to skin ulceration syndrome (SUS) of Apostichopus japonicus, small RNA libraries of body wall, intestine, respiratory tree and coelomocytes from healthy and diseased A. japonicus were sequenced on Illumina Hiseq 2000 platform. A total of 247 conserved and 10 novel miRNAs were identified across all libraries. After pair-wise comparisons, 215 miRNAs in body wall, 36 in intestine, 2 in respiratory tree and 38 in coelomocytes showed significant expression differences. Further analyses were conducted on some tissue-specific differentially expressed miRNAs: miR-8 and miR-486-5p in body wall, miR-200-3p, let-7-5p and miR-125 in intestine, miR-278a-3p and bantam in respiratory, miR-10a and miR-184 in coelomocytes. Notably, these miRNAs in some species were reported to function in various physiological or pathological processes associated with immune regulations. Using stem-loop quantitative real time PCR, six representative miRNAs in four tissues were selected to validate the sequencing results. The Pearson's correlation coefficient (R) of the six miRNAs ranged from 0.777 to 0.948, which confirmed the consistency and accuracy between these two approaches. This study provides comprehensive expression and regulation patterns of functional miRNAs in different tissues and gives insights into the tissue-specific immune response mechanisms in SUS-infected A. japonicus. PMID:26723265

  12. Molecular cloning and characterization of four caspases members in Apostichopus japonicus.

    PubMed

    Shao, Yina; Li, Chenghua; Zhang, Weiwei; Duan, Xuemei; Li, Ye; Jin, Chunhua; Xiong, Jinbo; Qiu, Qiongfen

    2016-08-01

    The caspase family representing aspartate-specific cysteine proteases have been demonstrated to possess key roles in apoptosis and immune response. We previously demonstrated that LPS challenged Apostichopus japonicus coelomocyte could significantly induced apoptosis in vitro. However, apoptosis related molecules were scarcely investigated in this economic species. In the present work, we cloned and characterized four members caspase family from A. japonicus (designated as Ajcaspase-2, Ajcaspase-3, Ajcaspase-6, and Ajcaspase-8, respectively) by RACE. Multiple sequence alignment and structural analysis revealed that all Ajcaspases contained the conservative CASC domain at C terminal, in which some unique features for each Ajcaspase made them different from each other. These specific domains together with phylogenetic analysis supported that all these four identified proteins belonged to novel members of apoptotic signaling pathway in sea cucumber. Tissue distribution analysis revealed that four Ajcaspase genes were constitutively expressed in all examined tissues. The expression of Ajcaspase-2 was tightly correlated with that of Ajcaspase-8 in each detected tissues. Ajcaspase-3 and Ajcaspase-6 transcripts were both highly expressed in immune tissue of coelomocytes. Furthermore, the Vibrio splendidus challenged sea cucumber coelomocytes could significantly up-regulate the mRNA expressions of four genes. The expression levels of Ajcaspase-2 and Ajcaspase-8 were relative earlier than those of Ajcaspase-6 and Ajcaspase-3, respectively, which could be inferred that Ajcapase-2 might directly modulate Ajcaspase-6, and Ajcaspase-8 initiate the expression of Ajcaspase-3. The induce expressions differed among each Ajcaspase depending upon their roles such as initiator or effector caspase. All our results demonstrated that four Ajcaspases present diversified functions in apoptotic cascade signaling pathway of sea cucumber under immune response. PMID:27245866

  13. Molecular characterization of muscle-parasitizing didymozoid from a chub mackerel, Scomber japonicus.

    PubMed

    Abe, Niichiro; Okamoto, Mitsuru

    2015-09-01

    Didymozoids found in the muscles of marine fish are almost always damaged because they are usually found after being sliced. Therefore, identifying muscle-parasitizing didymozoids is difficult because of the difficulty in collecting non-damaged worms and observing their organs as key points for morphological identification. Moreover, muscle-parasitizing didymozoids are not easily found because they parasitize at the trunk muscles. Therefore, muscle-parasitizing didymozoid classification has not progressed because there are few opportunities to detect them. Our recent report was the first to describe the usefulness of sequencing analysis for discrimination among muscle-parasitizing didymozoids. Recently, we found a didymozoid in the trunk muscle of a chub mackerel Scomber japonicus. The present study genetically compares the present isolate with other muscle-parasitizing didymozoids. The present isolate differs markedly from the previously unidentified didymozoid from an Atlantic mackerel S. scombrus by phylogenetic analysis of 18S rDNA. It also differs from other muscle-parasitizing didymozoids from other host species based on phylogenetic analyses of 18S, 28S rDNAs, and coxI loci. These results suggest that sequencing analysis is useful for the discrimination of muscle-parasitizing didymozoids. Combining the present data with earlier data for sequencing analysis, muscle-parasitizing didymozoids from seven marine fish species were classified as seven species. We proposed appellations for six distinct muscle-parasitizing didymozoids for future analysis: sweetlips fish type from Diagramma pictum and Plectorhinchus cinctus, red sea bream type from Pagrus major, flying fish type from Cypselurus heterurus, Atlantic mackerel type from Scomber scombrus, chub mackerel type from S. japonicus, and purple rockcod type from Epinephelus cyanopodus. PMID:26204013

  14. Hammock: a hidden Markov model-based peptide clustering algorithm to identify protein-interaction consensus motifs in large datasets

    PubMed Central

    Krejci, Adam; Hupp, Ted R.; Lexa, Matej; Vojtesek, Borivoj; Muller, Petr

    2016-01-01

    Motivation: Proteins often recognize their interaction partners on the basis of short linear motifs located in disordered regions on proteins’ surface. Experimental techniques that study such motifs use short peptides to mimic the structural properties of interacting proteins. Continued development of these methods allows for large-scale screening, resulting in vast amounts of peptide sequences, potentially containing information on multiple protein-protein interactions. Processing of such datasets is a complex but essential task for large-scale studies investigating protein-protein interactions. Results: The software tool presented in this article is able to rapidly identify multiple clusters of sequences carrying shared specificity motifs in massive datasets from various sources and generate multiple sequence alignments of identified clusters. The method was applied on a previously published smaller dataset containing distinct classes of ligands for SH3 domains, as well as on a new, an order of magnitude larger dataset containing epitopes for several monoclonal antibodies. The software successfully identified clusters of sequences mimicking epitopes of antibody targets, as well as secondary clusters revealing that the antibodies accept some deviations from original epitope sequences. Another test indicates that processing of even much larger datasets is computationally feasible. Availability and implementation: Hammock is published under GNU GPL v. 3 license and is freely available as a standalone program (from http://www.recamo.cz/en/software/hammock-cluster-peptides/) or as a tool for the Galaxy toolbox (from https://toolshed.g2.bx.psu.edu/view/hammock/hammock). The source code can be downloaded from https://github.com/hammock-dev/hammock/releases. Contact: muller@mou.cz Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26342231

  15. Large-Scale Phenomics Identifies Primary and Fine-Tuning Roles for CRKs in Responses Related to Oxidative Stress

    PubMed Central

    Rayapuram, Channabasavangowda; Idänheimo, Niina; Hunter, Kerri; Kimura, Sachie; Merilo, Ebe; Vaattovaara, Aleksia; Oracz, Krystyna; Kaufholdt, David; Pallon, Andres; Anggoro, Damar Tri; Glów, Dawid; Lowe, Jennifer; Zhou, Ji; Mohammadi, Omid; Puukko, Tuomas; Albert, Andreas; Lang, Hans; Ernst, Dieter; Kollist, Hannes; Brosché, Mikael; Durner, Jörg; Borst, Jan Willem; Collinge, David B.; Karpiński, Stanisław; Lyngkjær, Michael F.; Robatzek, Silke; Wrzaczek, Michael; Kangasjärvi, Jaakko

    2015-01-01

    Cysteine-rich receptor-like kinases (CRKs) are transmembrane proteins characterized by the presence of two domains of unknown function 26 (DUF26) in their ectodomain. The CRKs form one of the largest groups of receptor-like protein kinases in plants, but their biological functions have so far remained largely uncharacterized. We conducted a large-scale phenotyping approach of a nearly complete crk T-DNA insertion line collection showing that CRKs control important aspects of plant development and stress adaptation in response to biotic and abiotic stimuli in a non-redundant fashion. In particular, the analysis of reactive oxygen species (ROS)-related stress responses, such as regulation of the stomatal aperture, suggests that CRKs participate in ROS/redox signalling and sensing. CRKs play general and fine-tuning roles in the regulation of stomatal closure induced by microbial and abiotic cues. Despite their great number and high similarity, large-scale phenotyping identified specific functions in diverse processes for many CRKs and indicated that CRK2 and CRK5 play predominant roles in growth regulation and stress adaptation, respectively. As a whole, the CRKs contribute to specificity in ROS signalling. Individual CRKs control distinct responses in an antagonistic fashion suggesting future potential for using CRKs in genetic approaches to improve plant performance and stress tolerance. PMID:26197346

  16. Comparative genome analysis of a large Dutch Legionella pneumophila strain collection identifies five markers highly correlated with clinical strains

    PubMed Central

    2010-01-01

    Background Discrimination between clinical and environmental strains within many bacterial species is currently underexplored. Genomic analyses have clearly shown the enormous variability in genome composition between different strains of a bacterial species. In this study we have used Legionella pneumophila, the causative agent of Legionnaire's disease, to search for genomic markers related to pathogenicity. During a large surveillance study in The Netherlands well-characterized patient-derived strains and environmental strains were collected. We have used a mixed-genome microarray to perform comparative-genome analysis of 257 strains from this collection. Results Microarray analysis indicated that 480 DNA markers (out of in total 3360 markers) showed clear variation in presence between individual strains and these were therefore selected for further analysis. Unsupervised statistical analysis of these markers showed the enormous genomic variation within the species but did not show any correlation with a pathogenic phenotype. We therefore used supervised statistical analysis to identify discriminating markers. Genetic programming was used both to identify predictive markers and to define their interrelationships. A model consisting of five markers was developed that together correctly predicted 100% of the clinical strains and 69% of the environmental strains. Conclusions A novel approach for identifying predictive markers enabling discrimination between clinical and environmental isolates of L. pneumophila is presented. Out of over 3000 possible markers, five were selected that together enabled correct prediction of all the clinical strains included in this study. This novel approach for identifying predictive markers can be applied to all bacterial species, allowing for better discrimination between strains well equipped to cause human disease and relatively harmless strains. PMID:20630115

  17. The Protein Precursors of Peptides That Affect the Mechanics of Connective Tissue and/or Muscle in the Echinoderm Apostichopus japonicus

    PubMed Central

    Elphick, Maurice R.

    2012-01-01

    Peptides that cause muscle relaxation or contraction or that modulate electrically-induced muscle contraction have been discovered in the sea cucumber Apostichopus japonicus (Phylum Echinodermata; Class Holothuroidea). By analysing transcriptome sequence data, here the protein precursors of six of these myoactive peptides (the SALMFamides Sticho-MFamide-1 and -2, NGIWYamide, stichopin, GN-19 and GLRFA) have been identified, providing novel insights on neuropeptide and endocrine-type signalling systems in echinoderms. The A. japonicus SALMFamide precursor comprises eight putative neuropeptides including both L-type and F-type SALMFamides, which contrasts with previous findings from the sea urchin Strongylocentrotus purpuratus where L-type and F-type SALMFamides are encoded by different genes. The NGIWYamide precursor contains five copies of NGIWYamide but, unlike other NG peptide-type neuropeptide precursors in deuterostomian invertebrates, the NGIWYamide precursor does not have a C-terminal neurophysin domain, indicating loss of this character in holothurians. NGIWYamide was originally discovered as a muscle contractant, but it also causes stiffening of mutable connective tissue in the body wall of A. japonicus, whilst holokinins (PLGYMFR and derivative peptides) cause softening of the body wall. However, the mechanisms by which these peptides affect the stiffness of body wall connective tissue are unknown. Interestingly, analysis of the A. japonicus transcriptome reveals that the only protein containing the holokinin sequence PLGYMFR is an alpha-5 type collagen. This suggests that proteolysis of collagen may generate peptides (holokinins) that affect body wall stiffness in sea cucumbers, providing a novel perspective on mechanisms of mutable connective tissue in echinoderms. PMID:22952987

  18. The SNARE Protein SYP71 Expressed in Vascular Tissues Is Involved in Symbiotic Nitrogen Fixation in Lotus japonicus Nodules1[W][OA

    PubMed Central

    Hakoyama, Tsuneo; Oi, Ryo; Hazuma, Kazuya; Suga, Eri; Adachi, Yuka; Kobayashi, Mayumi; Akai, Rie; Sato, Shusei; Fukai, Eigo; Tabata, Satoshi; Shibata, Satoshi; Wu, Guo-Jiang; Hase, Yoshihiro; Tanaka, Atsushi; Kawaguchi, Masayoshi; Kouchi, Hiroshi; Umehara, Yosuke; Suganuma, Norio

    2012-01-01

    Soluble N-Ethylmaleimide Sensitive Factor Attachment Protein Receptor (SNARE) proteins are crucial for signal transduction and development in plants. Here, we investigate a Lotus japonicus symbiotic mutant defective in one of the SNARE proteins. When in symbiosis with rhizobia, the growth of the mutant was retarded compared with that of the wild-type plant. Although the mutant formed nodules, these exhibited lower nitrogen fixation activity than the wild type. The rhizobia were able to invade nodule cells, but enlarged symbiosomes were observed in the infected cells. The causal gene, designated LjSYP71 (for L. japonicus syntaxin of plants71), was identified by map-based cloning and shown to encode a Qc-SNARE protein homologous to Arabidopsis (Arabidopsis thaliana) SYP71. LjSYP71 was expressed ubiquitously in shoot, roots, and nodules, and transcripts were detected in the vascular tissues. In the mutant, no other visible defects in plant morphology were observed. Furthermore, in the presence of combined nitrogen, the mutant plant grew almost as well as the wild type. These results suggest that the vascular tissues expressing LjSYP71 play a pivotal role in symbiotic nitrogen fixation in L. japonicus nodules. PMID:22858633

  19. Analysis of the essential oil of Dipsacus japonicus flowering aerial parts and its insecticidal activity against Sitophilus zeamais and Tribolium castaneum.

    PubMed

    Liu, Zhi Long; Jiang, Guo Hua; Zhou, Ligang; Liu, Qi Zhi

    2013-01-01

    Water-distilled essential oil from the aerial parts of Dipsacus japonicus Miq. (Dipsacaceae) at the flowering stage was analysed by gas chromatography-mass spectrometry (GC-MS). Forty-six compounds, accounting for 96.76% of the total oil, were identified and the main compounds of the essential oil were linalool (11.78%), trans-geraniol (8.58%), 1,8-cineole (7.91%), beta-caryophyllene (5.58%), alpha-terpineol (5.32%), beta-selinene (5.15%), and spathulenol (5.04%). The essential oil of D. japonicus possessed contact toxicity against two grain storage insects, Sitophilus zeamais and Tribolium castaneum adults, with LD50 values of 18.32 microg/ adult and 13.45 microg/adult, respectively. The essential oil of D. japonicus also exhibited pronounced fumigant toxicity against S. zeamais (LC50 = 10.11 mg/l air) and T. castaneum adults (LC50 = 5.26 mg/l air). Of the three major compounds, 1,8-cineole exhibited stronger fumigant toxicity than the crude essential oil against S. zeamais and T. castaneum adults with LC50 values of 2.96 mg/l air and 4.86 mg/l air, respectively. PMID:23659168

  20. Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.

    PubMed

    Saxena, Richa; Elbers, Clara C; Guo, Yiran; Peter, Inga; Gaunt, Tom R; Mega, Jessica L; Lanktree, Matthew B; Tare, Archana; Castillo, Berta Almoguera; Li, Yun R; Johnson, Toby; Bruinenberg, Marcel; Gilbert-Diamond, Diane; Rajagopalan, Ramakrishnan; Voight, Benjamin F; Balasubramanyam, Ashok; Barnard, John; Bauer, Florianne; Baumert, Jens; Bhangale, Tushar; Böhm, Bernhard O; Braund, Peter S; Burton, Paul R; Chandrupatla, Hareesh R; Clarke, Robert; Cooper-DeHoff, Rhonda M; Crook, Errol D; Davey-Smith, George; Day, Ian N; de Boer, Anthonius; de Groot, Mark C H; Drenos, Fotios; Ferguson, Jane; Fox, Caroline S; Furlong, Clement E; Gibson, Quince; Gieger, Christian; Gilhuijs-Pederson, Lisa A; Glessner, Joseph T; Goel, Anuj; Gong, Yan; Grant, Struan F A; Grobbee, Diederick E; Hastie, Claire; Humphries, Steve E; Kim, Cecilia E; Kivimaki, Mika; Kleber, Marcus; Meisinger, Christa; Kumari, Meena; Langaee, Taimour Y; Lawlor, Debbie A; Li, Mingyao; Lobmeyer, Maximilian T; Maitland-van der Zee, Anke-Hilse; Meijs, Matthijs F L; Molony, Cliona M; Morrow, David A; Murugesan, Gurunathan; Musani, Solomon K; Nelson, Christopher P; Newhouse, Stephen J; O'Connell, Jeffery R; Padmanabhan, Sandosh; Palmen, Jutta; Patel, Sanjey R; Pepine, Carl J; Pettinger, Mary; Price, Thomas S; Rafelt, Suzanne; Ranchalis, Jane; Rasheed, Asif; Rosenthal, Elisabeth; Ruczinski, Ingo; Shah, Sonia; Shen, Haiqing; Silbernagel, Günther; Smith, Erin N; Spijkerman, Annemieke W M; Stanton, Alice; Steffes, Michael W; Thorand, Barbara; Trip, Mieke; van der Harst, Pim; van der A, Daphne L; van Iperen, Erik P A; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V; Verweij, Niek; Wolffenbuttel, Bruce H R; Young, Taylor; Zafarmand, M Hadi; Zmuda, Joseph M; Boehnke, Michael; Altshuler, David; McCarthy, Mark; Kao, W H Linda; Pankow, James S; Cappola, Thomas P; Sever, Peter; Poulter, Neil; Caulfield, Mark; Dominiczak, Anna; Shields, Denis C; Bhatt, Deepak L; Bhatt, Deepak; Zhang, Li; Curtis, Sean P; Danesh, John; Casas, Juan P; van der Schouw, Yvonne T; Onland-Moret, N Charlotte; Doevendans, Pieter A; Dorn, Gerald W; Farrall, Martin; FitzGerald, Garret A; Hamsten, Anders; Hegele, Robert; Hingorani, Aroon D; Hofker, Marten H; Huggins, Gordon S; Illig, Thomas; Jarvik, Gail P; Johnson, Julie A; Klungel, Olaf H; Knowler, William C; Koenig, Wolfgang; März, Winfried; Meigs, James B; Melander, Olle; Munroe, Patricia B; Mitchell, Braxton D; Bielinski, Susan J; Rader, Daniel J; Reilly, Muredach P; Rich, Stephen S; Rotter, Jerome I; Saleheen, Danish; Samani, Nilesh J; Schadt, Eric E; Shuldiner, Alan R; Silverstein, Roy; Kottke-Marchant, Kandice; Talmud, Philippa J; Watkins, Hugh; Asselbergs, Folkert W; Asselbergs, Folkert; de Bakker, Paul I W; McCaffery, Jeanne; Wijmenga, Cisca; Sabatine, Marc S; Wilson, James G; Reiner, Alex; Bowden, Donald W; Hakonarson, Hakon; Siscovick, David S; Keating, Brendan J

    2012-03-01

    To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 × 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 × 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 × 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 × 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 × 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups. PMID:22325160

  1. Natural nitric oxide (NO) inhibitors from Chloranthus japonicus.

    PubMed

    Guo, Yan-Qiong; Zhao, Jing-Jun; Li, Zhen-Zhen; Tang, Gui-Hua; Zhao, Zhi-Min; Yin, Sheng

    2016-07-01

    Eight new lindenane sesquiterpenoid dimers, chlojapolides A-H (1-8), along with 11 known analogues were isolated from the whole plant of Chloranthus japonicus. Their structures including absolute configurations were elucidated by spectral and chemical methods. All the compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and compounds 1, 11, 13, and 17 exhibited pronounced inhibition with IC50 values in the range of 6.91-15.75μM, being more active than the positive control, quercetin (IC50=15.90μM). PMID:27177824

  2. Characterization of phenoloxidase from the sea cucumber Apostichopus japonicus.

    PubMed

    Jiang, Jingwei; Zhou, Zunchun; Dong, Ying; Guan, Xiaoyan; Wang, Bai; Jiang, Bei; Yang, Aifu; Chen, Zhong; Gao, Shan; Sun, Hongjuan

    2014-06-01

    Phenoloxidase (PO) is a crucial immune-related enzyme in invertebrates. In this study, three POs of the sea cucumber Apostichopus japonicus were detected in coelomic fluid using linear-gradient native-PAGE combined with catechol staining and then partially purified by gel excising. The results showed that the three POs had a color of mahogany (AjPO1), yellow (AjPO2) and purple (AjPO3) respectively with molecular weights smaller than 21kDa in native-PAGE after staining with catechol. Enzymatic activities analysis revealed that AjPO1, AjPO2 and AjPO3 had optimal temperature of 45, 95 and 85°C and pH of 5.0, 8.0 and 8.0, respectively. Kinetic analysis showed that the Km values of AjPO1 for catechol, l-DOPA, dopamine and hydroquinone were 3.23, 0.86, 3.98 and 1.20mmol/l, respectively, those of AjPO2 were 0.31, 0.38, 2.05 and 1.30mmol/l, respectively, and those of AjPO3 were 5.95, 1.28, 5.81 and 0.62mmol/l, respectively. These results suggest that the three POs are laccase-type phenoloxidase. The activities of all three A. japonicus POs were significantly promoted by Ca(2+), Mg(2+) and Mn(2+), and strongly inhibited by ethylenediamine tetraacetic acid disodium (EDTA), sodium diethyldithiocarbamate (DETC) and some common antioxidants. The inhibitions by EDTA and DETC suggest that the three A. japonicus POs are copper-containing metalloenzymes. Immune-responsive analysis showed that the total PO activities in coelomocytes (TPAC) increased greatly after lipopolysaccharide (LPS) challenge and declined significantly after polyinosinic-polycytidylic acid (PolyI:C) challenge, implying that A. japonicus PO immune system, which is composed of several isoenzymes with different characteristics, is closely involved in the defense against the infection of Gram-negative bacteria and double-stranded RNA viruses. PMID:24631331

  3. Large Impact Melt Flow Feature identified across the floor of Copernicus Crater by Moon Mineralogy Mapper (M3)

    NASA Astrophysics Data System (ADS)

    Dhingra, D.; Pieters, C. M.; Head, J. W.

    2011-12-01

    Impact melt is normally one of the primary products of a large cratering event. The production of melt, its geographic distribution and the timing of its formation in the sequence of events during the cratering process depends on several parameters including size and velocity of the impactor, angle of impact, nature of pre-existing topography and target lithology. All of these parameters influence the size of the resulting crater as well as the character and fate of the melt produced during the event. We report here a very large impact melt flow feature across the floor of Copernicus crater identified with near-infrared spectra from M3. Copernicus is a relatively young impact crater ~100 km in diameter, located on the equatorial nearside of the Moon. The NW quadrant of the crater appears to contain a thick pool of impact melt. The new flow feature, with a length of ~30 km and flow lobes ~4-6 km wide, lies across the eastern portion of this melt deposit. Principal component analysis of M3 spectral data reveals this feature prominently in the 5th principal component. Spectroscopically, the flow feature differs from its surroundings mostly at longer M3 NIR wavelengths. Further analysis of the M3 data will focus on the compositional aspects and physical properties of this flow feature and its relation to nearby regions. An interesting aspect of the flow feature is its restricted occurrence between the northern wall and central peaks of the Copernicus crater. Several hypotheses, concerning this geologic setting, sourcing of the melt in the flow feature and its flow direction, are being explored. Two hypotheses in context of the melt sourcing include: 1) accumulation of the scattered melted material and drainage along a preferred slope or 2) fallback of large volume of melt that was lofted in a preferred direction during the impact event. The occurrence of such a large sized flow feature also suggests that the impact melt was very mobile and therefore probably poor in

  4. Ubiquity of synonymity: almost all large binary trees are not uniquely identified by their spectra or their immanantal polynomials

    PubMed Central

    2012-01-01

    Background There are several common ways to encode a tree as a matrix, such as the adjacency matrix, the Laplacian matrix (that is, the infinitesimal generator of the natural random walk), and the matrix of pairwise distances between leaves. Such representations involve a specific labeling of the vertices or at least the leaves, and so it is natural to attempt to identify trees by some feature of the associated matrices that is invariant under relabeling. An obvious candidate is the spectrum of eigenvalues (or, equivalently, the characteristic polynomial). Results We show for any of these choices of matrix that the fraction of binary trees with a unique spectrum goes to zero as the number of leaves goes to infinity. We investigate the rate of convergence of the above fraction to zero using numerical methods. For the adjacency and Laplacian matrices, we show that the a priori more informative immanantal polynomials have no greater power to distinguish between trees. Conclusion Our results show that a generic large binary tree is highly unlikely to be identified uniquely by common spectral invariants. PMID:22613173

  5. Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations, 1: Review and Comparison of Techniques

    SciTech Connect

    Kleijnen, J.P.C.; Helton, J.C.

    1999-03-24

    The robustness of procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses is investigated. These procedures are based on attempts to detect increasingly complex patterns in the scatterplots under consideration and involve the identification of (i) linear relationships with correlation coefficients, (ii) monotonic relationships with rank correlation coefficients, (iii) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (iv) trends in variability as defined by variances and interquartile ranges, and (v) deviations from randomness as defined by the chi-square statistic. The following two topics related to the robustness of these procedures are considered for a sequence of example analyses with a large model for two-phase fluid flow: the presence of Type I and Type II errors, and the stability of results obtained with independent Latin hypercube samples. Observations from analysis include: (i) Type I errors are unavoidable, (ii) Type 11errors can occur when inappropriate analysis procedures are used, (iii) physical explanations should always be sought for why statistical procedures identify variables as being important, and (iv) the identification of important variables tends to be stable for independent Latin hypercube samples.

  6. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

    PubMed Central

    2012-01-01

    Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9 (HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes. PMID:22306652

  7. A Large-Scale Rheumatoid Arthritis Genetic Study Identifies Association at Chromosome 9q33.2

    PubMed Central

    Chang, Monica; Rowland, Charles M.; Garcia, Veronica E.; Schrodi, Steven J.; Catanese, Joseph J.; van der Helm-van Mil, Annette H. M.; Ardlie, Kristin G.; Amos, Christopher I.; Criswell, Lindsey A.; Kastner, Daniel L.; Gregersen, Peter K.; Kurreeman, Fina A. S.; Toes, Rene E. M.; Huizinga, Tom W. J.; Seldin, Michael F.; Begovich, Ann B.

    2008-01-01

    Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease affecting both joints and extra-articular tissues. Although some genetic risk factors for RA are well-established, most notably HLA-DRB1 and PTPN22, these markers do not fully account for the observed heritability. To identify additional susceptibility loci, we carried out a multi-tiered, case-control association study, genotyping 25,966 putative functional SNPs in 475 white North American RA patients and 475 matched controls. Significant markers were genotyped in two additional, independent, white case-control sample sets (661 cases/1322 controls from North America and 596 cases/705 controls from The Netherlands) identifying a SNP, rs1953126, on chromosome 9q33.2 that was significantly associated with RA (ORcommon = 1.28, trend Pcomb = 1.45E-06). Through a comprehensive fine-scale-mapping SNP-selection procedure, 137 additional SNPs in a 668 kb region from MEGF9 to STOM on 9q33.2 were chosen for follow-up genotyping in a staged-approach. Significant single marker results (Pcomb<0.01) spanned a large 525 kb region from FBXW2 to GSN. However, a variety of analyses identified SNPs in a 70 kb region extending from the third intron of PHF19 across TRAF1 into the TRAF1-C5 intergenic region, but excluding the C5 coding region, as the most interesting (trend Pcomb: 1.45E-06 → 5.41E-09). The observed association patterns for these SNPs had heightened statistical significance and a higher degree of consistency across sample sets. In addition, the allele frequencies for these SNPs displayed reduced variability between control groups when compared to other SNPs. Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential. PMID:18648537

  8. High-Throughput Genetic Screens Identify a Large and Diverse Collection of New Sporulation Genes in Bacillus subtilis

    PubMed Central

    Brady, Jacqueline; Lim, Hoong Chuin; Bernhardt, Thomas G.; Rudner, David Z.

    2016-01-01

    The differentiation of the bacterium Bacillus subtilis into a dormant spore is among the most well-characterized developmental pathways in biology. Classical genetic screens performed over the past half century identified scores of factors involved in every step of this morphological process. More recently, transcriptional profiling uncovered additional sporulation-induced genes required for successful spore development. Here, we used transposon-sequencing (Tn-seq) to assess whether there were any sporulation genes left to be discovered. Our screen identified 133 out of the 148 genes with known sporulation defects. Surprisingly, we discovered 24 additional genes that had not been previously implicated in spore formation. To investigate their functions, we used fluorescence microscopy to survey early, middle, and late stages of differentiation of null mutants from the B. subtilis ordered knockout collection. This analysis identified mutants that are delayed in the initiation of sporulation, defective in membrane remodeling, and impaired in spore maturation. Several mutants had novel sporulation phenotypes. We performed in-depth characterization of two new factors that participate in cell–cell signaling pathways during sporulation. One (SpoIIT) functions in the activation of σE in the mother cell; the other (SpoIIIL) is required for σG activity in the forespore. Our analysis also revealed that as many as 36 sporulation-induced genes with no previously reported mutant phenotypes are required for timely spore maturation. Finally, we discovered a large set of transposon insertions that trigger premature initiation of sporulation. Our results highlight the power of Tn-seq for the discovery of new genes and novel pathways in sporulation and, combined with the recently completed null mutant collection, open the door for similar screens in other, less well-characterized processes. PMID:26735940

  9. How do you assign persistent identifiers to extracts from large, complex, dynamic data sets that underpin scholarly publications?

    NASA Astrophysics Data System (ADS)

    Wyborn, Lesley; Car, Nicholas; Evans, Benjamin; Klump, Jens

    2016-04-01

    Persistent identifiers in the form of a Digital Object Identifier (DOI) are becoming more mainstream, assigned at both the collection and dataset level. For static datasets, this is a relatively straight-forward matter. However, many new data collections are dynamic, with new data being appended, models and derivative products being revised with new data, or the data itself revised as processing methods are improved. Further, because data collections are becoming accessible as services, researchers can log in and dynamically create user-defined subsets for specific research projects: they also can easily mix and match data from multiple collections, each of which can have a complex history. Inevitably extracts from such dynamic data sets underpin scholarly publications, and this presents new challenges. The National Computational Infrastructure (NCI) has been experiencing and making progress towards addressing these issues. The NCI is large node of the Research Data Services initiative (RDS) of the Australian Government's research infrastructure, which currently makes available over 10 PBytes of priority research collections, ranging from geosciences, geophysics, environment, and climate, through to astronomy, bioinformatics, and social sciences. Data are replicated to, or are produced at, NCI and then processed there to higher-level data products or directly analysed. Individual datasets range from multi-petabyte computational models and large volume raster arrays, down to gigabyte size, ultra-high resolution datasets. To facilitate access, maximise reuse and enable integration across the disciplines, datasets have been organized on a platform called the National Environmental Research Data Interoperability Platform (NERDIP). Combined, the NERDIP data collections form a rich and diverse asset for researchers: their co-location and standardization optimises the value of existing data, and forms a new resource to underpin data-intensive Science. New publication

  10. Biosynthesis of rhodiocyanosides in Lotus japonicus: rhodiocyanoside A is synthesized from (Z)-2-methylbutanaloxime via 2-methyl-2-butenenitrile.

    PubMed

    Saito, Shigeki; Motawia, Mohammed Saddik; Olsen, Carl Erik; Møller, Birger Lindberg; Bak, Søren

    2012-05-01

    Lotus japonicus contains the two cyanogenic glucosides, linamarin and lotaustralin, and the non cyanogenic hydroxynitriles, rhodiocyanoside A and D, with rhodiocyanoside A as the major rhodiocyanoside. Rhodiocyanosides are structurally related to cyanogenic glucosides but are not cyanogenic. In vitro administration of intermediates of the lotaustralin pathway to microsomes prepared from selected L. japonicus accessions identified 2-methyl-2-butenenitrile as an intermediate in the rhodiocyanoside biosynthetic pathway. In vitro inhibitory studies with carbon monoxide and tetcyclacis indicate that the conversion of (Z)-2-methylbutanal oxime to 2-methyl-2-butenenitrile is catalyzed by cytochrome P450(s). Carbon monoxide inhibited cyanogenic glucosides as well as rhodiocyanosides synthesis, but inhibition of the latter pathway was much stronger. These results demonstrate that the cyanogenic glucoside and rhodiocyanosides pathways share CYP79Ds to obtain (Z)-2-methylbutanaloxime from l-isoleucine, whereas the subsequent conversions are catalyzed by different P450s. The aglycon of rhodiocyanoside A forms the cyclic product 3-methyl-2(5H)-furanone. Furanones are known to possess antimicrobial properties indicating that rhodiocyanoside A may have evolved to serve as a phytoanticipin that following β-glucosidase activation and cyclization of the aglycone formed, give rise to a potent defense compound. PMID:22385904

  11. 16S rRNA gene phylogenesis of culturable predominant bacteria from diseased Apostichopus japonicus (Holothuroidea, Echinodermata)

    NASA Astrophysics Data System (ADS)

    Ma, Haiyan; Jiang, Guoliang; Wu, Zhiqiang; Wang, Xin

    2009-06-01

    Cultured Apostichopus japonicus in China suffers from a kind of skin ulceration disease that has caused severe economic loss in recent years. The disease, pathogens of which are supposed to be bacteria by most researchers, is highly infectious and can often cause all individuals in the same culture pool to die in a very short time. The 16S rRNA gene phylogenesis of the culturable bacteria from the lesions of diseased individuals was conducted to study the biodiversity of the bacterial communities in the lesions and to identify probable pathogen(s) associated with this kind of disease. S. japonica samples were selected from a hatchery located in the eastern part of Qingdao, China. Bacterial universal primers GM5F and DS907R were used to amplify the 16S rRNA gene of bacteria colonies, and touchdown PCR was performed to amplify the target sequences. The results suggest that γ- proteobacteria (Alteromonadales and Vibrionales) of CFB group, many strains of which have been also determined as pathogens in other marine species, are the predominant bacterial genera of the diseased Apostichopus japonicus individuals.

  12. Network of GRAS Transcription Factors Involved in the Control of Arbuscule Development in Lotus japonicus1[OPEN

    PubMed Central

    Xue, Li; Cui, Haitao; Buer, Benjamin; Vijayakumar, Vinod; Delaux, Pierre-Marc; Junkermann, Stefanie; Bucher, Marcel

    2015-01-01

    Arbuscular mycorrhizal (AM) fungi, in symbiosis with plants, facilitate acquisition of nutrients from the soil to their host. After penetration, intracellular hyphae form fine-branched structures in cortical cells termed arbuscules, representing the major site where bidirectional nutrient exchange takes place between the host plant and fungus. Transcriptional mechanisms underlying this cellular reprogramming are still poorly understood. GRAS proteins are an important family of transcriptional regulators in plants, named after the first three members: GIBBERELLIC ACID-INSENSITIVE, REPRESSOR of GAI, and SCARECROW. Here, we show that among 45 transcription factors up-regulated in mycorrhizal roots of the legume Lotus japonicus, expression of a unique GRAS protein particularly increases in arbuscule-containing cells under low phosphate conditions and displays a phylogenetic pattern characteristic of symbiotic genes. Allelic rad1 mutants display a strongly reduced number of arbuscules, which undergo accelerated degeneration. In further studies, two RAD1-interacting proteins were identified. One of them is the closest homolog of Medicago truncatula, REDUCED ARBUSCULAR MYCORRHIZATION1 (RAM1), which was reported to regulate a glycerol-3-phosphate acyl transferase that promotes cutin biosynthesis to enhance hyphopodia formation. As in M. truncatula, the L. japonicus ram1 mutant lines show compromised AM colonization and stunted arbuscules. Our findings provide, to our knowledge, new insight into the transcriptional program underlying the host’s response to AM colonization and propose a function of GRAS transcription factors including RAD1 and RAM1 during arbuscule development. PMID:25560877

  13. An apposition-like compound eye with a layered rhabdom in the small diving beetle Agabus japonicus (Coleoptera, Dytiscidae).

    PubMed

    Jia, Lei-Po; Liang, Ai-Ping

    2014-11-01

    The fine structure of the compound eyes of the adult diving beetle Agabus japonicus is described with light, scanning, and transmission electron microscopy. The eye of A. japonicus is mango-shaped and consists of about 985 ommatidia. Each ommatidium is composed of a corneal facet lens, an eucone type of crystalline cone, a fused layered rhabdom with a basal rhabdomere, seven retinula cells (including six distal cells and one basal cell), two primary pigment cells and an undetermined number of secondary pigment cells that are restricted to the distalmost region of the eye. A clear-zone, separating dioptric apparatus from photoreceptive structures, is not developed and the eye thus resembles an apposition eye. The cross-sectional areas of the rhabdoms are relatively large indicative of enhanced light-sensitivity. The distal and central region of the rhabdom is layered with interdigitating microvilli suggesting polarization sensitivity. According to the features mentioned above, we suggest that 1) the eye, seemingly of the apposition type, occurs in a taxon for which the clear-zone (superposition) eye is characteristic; 2) the eye possesses adaptations to function in a dim-light environment; 3) the eye may be sensitive to underwater polarized light or linearly water-reflected polarized light. PMID:24889009

  14. Effects of rearing temperature and density on growth, survival and development of sea cucumber larvae, Apostichopus japonicus (Selenka)

    NASA Astrophysics Data System (ADS)

    Liu, Guangbin; Yang, Hongsheng; Liu, Shilin

    2010-07-01

    In laboratory conditions, effects of rearing temperature and stocking density were examined on hatching of fertilized egg and growth of auricularia larvae of Apostichopus japonicus respectively. Data series like larval length and density, metamorphic time, and survival rate of the larvae were recorded. Statistics showed that for A. japonicus, survival rate (from fertilized egg to late auricularia) decreased significantly with the increasing rearing temperature ( P<0.05). At different temperatures SGR was statistically significant as well ( P<0.05) from day 1, and maximal SGR was found on day 9 at 24°C (159.26±3.28). This study clearly indicated that at low temperature (<24°C), metamorphic rate was remarkably higher than at higher temperature (>26°C). Hatching rate was significantly different between 0.2-5 ind./ml groups and 20-50 ind./ml groups. Rearing larvae at the higher density had the smaller maximal-length, whereas needed longer time to complete metamorphosis. This study suggested that 21°C and 0.4 ind./ml can be used as the most suitable rearing temperature and stocking density for large -scale artificial breeding of A. japonicus’s larvae.

  15. Air quality models and unusually large ozone increases: Identifying model failures, understanding environmental causes, and improving modeled chemistry

    NASA Astrophysics Data System (ADS)

    Couzo, Evan A.

    Several factors combine to make ozone (O3) pollution in Houston, Texas, unique when compared to other metropolitan areas. These include complex meteorology, intense clustering of industrial activity, and significant precursor emissions from the heavily urbanized eight-county area. Decades of air pollution research have borne out two different causes, or conceptual models, of O 3 formation. One conceptual model describes a gradual region-wide increase in O3 concentrations "typical" of many large U.S. cities. The other conceptual model links episodic emissions of volatile organic compounds to spatially limited plumes of high O3, which lead to large hourly increases that have exceeded 100 parts per billion (ppb) per hour. These large hourly increases are known to lead to violations of the federal O 3 standard and impact Houston's status as a non-attainment area. There is a need to further understand and characterize the causes of peak O 3 levels in Houston and simulate them correctly so that environmental regulators can find the most cost-effective pollution controls. This work provides a detailed understanding of unusually large O 3 increases in the natural and modeled environments. First, we probe regulatory model simulations and assess their ability to reproduce the observed phenomenon. As configured for the purpose of demonstrating future attainment of the O3 standard, the model fails to predict the spatially limited O3 plumes observed in Houston. Second, we combine ambient meteorological and pollutant measurement data to identify the most likely geographic origins and preconditions of the concentrated O3 plumes. We find evidence that the O3 plumes are the result of photochemical activity accelerated by industrial emissions. And, third, we implement changes to the modeled chemistry to add missing formation mechanisms of nitrous acid, which is an important radical precursor. Radicals control the chemical reactivity of atmospheric systems, and perturbations to

  16. Social Network Analysis and Mining to Monitor and Identify Problems with Large-Scale Information and Communication Technology Interventions

    PubMed Central

    da Silva, Aleksandra do Socorro; de Brito, Silvana Rossy; Vijaykumar, Nandamudi Lankalapalli; da Rocha, Cláudio Alex Jorge; Monteiro, Maurílio de Abreu; Costa, João Crisóstomo Weyl Albuquerque; Francês, Carlos Renato Lisboa

    2016-01-01

    The published literature reveals several arguments concerning the strategic importance of information and communication technology (ICT) interventions for developing countries where the digital divide is a challenge. Large-scale ICT interventions can be an option for countries whose regions, both urban and rural, present a high number of digitally excluded people. Our goal was to monitor and identify problems in interventions aimed at certification for a large number of participants in different geographical regions. Our case study is the training at the Telecentros.BR, a program created in Brazil to install telecenters and certify individuals to use ICT resources. We propose an approach that applies social network analysis and mining techniques to data collected from Telecentros.BR dataset and from the socioeconomics and telecommunications infrastructure indicators of the participants’ municipalities. We found that (i) the analysis of interactions in different time periods reflects the objectives of each phase of training, highlighting the increased density in the phase in which participants develop and disseminate their projects; (ii) analysis according to the roles of participants (i.e., tutors or community members) reveals that the interactions were influenced by the center (or region) to which the participant belongs (that is, a community contained mainly members of the same region and always with the presence of tutors, contradicting expectations of the training project, which aimed for intense collaboration of the participants, regardless of the geographic region); (iii) the social network of participants influences the success of the training: that is, given evidence that the degree of the community member is in the highest range, the probability of this individual concluding the training is 0.689; (iv) the North region presented the lowest probability of participant certification, whereas the Northeast, which served municipalities with similar

  17. Early science with the Large Millimeter Telescope: observations of extremely luminous high-z sources identified by Planck

    NASA Astrophysics Data System (ADS)

    Harrington, K. C.; Yun, Min S.; Cybulski, R.; Wilson, G. W.; Aretxaga, I.; Chavez, M.; De la Luz, V.; Erickson, N.; Ferrusca, D.; Gallup, A. D.; Hughes, D. H.; Montaña, A.; Narayanan, G.; Sánchez-Argüelles, D.; Schloerb, F. P.; Souccar, K.; Terlevich, E.; Terlevich, R.; Zeballos, M.; Zavala, J. A.

    2016-06-01

    We present 8.5 arcsec resolution 1.1-mm continuum imaging and CO spectroscopic redshift measurements of eight extremely bright submillimetre galaxies identified from the Planck and Herschel surveys, taken with the Large Millimeter Telescope's AzTEC and Redshift Search Receiver instruments. We compiled a candidate list of high-redshift galaxies by cross-correlating the Planck Surveyor mission's highest frequency channel (857 GHz, full width at half-maximum = 4.5 arcmin) with the archival Herschel Spectral and Photometric Imaging Receiver imaging data, and requiring the presence of a unique, single Herschel counterpart within the 150-arcsec search radius of the Planck source positions with 350-μm flux density larger than 100 mJy, excluding known blazars and foreground galaxies. All eight candidate objects observed are detected in 1.1 mm continuum by AzTEC bolometer camera, and at least one CO line is detected in all cases with a spectroscopic redshift between 1.3 < zCO < 3.3. Their infrared (IR) spectral energy distributions (SEDs) mapped using the Herschel and AzTEC photometry are consistent with cold dust emission with characteristic temperature between Td = 43 and 84 K. With apparent IR luminosity of up to LIR = 3 × 1014μ-1 L⊙, they are some of the most luminous galaxies ever found (with yet unknown gravitational magnification factor μ). The analysis of their SEDs suggests that star formation is powering the bulk of their extremely large IR luminosities. Derived molecular gas masses of M_{H_2}=(0.6-7.8)× 10^{11} M_{odot } (for μ ≈ 10) also make them some of the most gas-rich high-redshift galaxies ever detected.

  18. Social Network Analysis and Mining to Monitor and Identify Problems with Large-Scale Information and Communication Technology Interventions.

    PubMed

    da Silva, Aleksandra do Socorro; de Brito, Silvana Rossy; Vijaykumar, Nandamudi Lankalapalli; da Rocha, Cláudio Alex Jorge; Monteiro, Maurílio de Abreu; Costa, João Crisóstomo Weyl Albuquerque; Francês, Carlos Renato Lisboa

    2016-01-01

    The published literature reveals several arguments concerning the strategic importance of information and communication technology (ICT) interventions for developing countries where the digital divide is a challenge. Large-scale ICT interventions can be an option for countries whose regions, both urban and rural, present a high number of digitally excluded people. Our goal was to monitor and identify problems in interventions aimed at certification for a large number of participants in different geographical regions. Our case study is the training at the Telecentros.BR, a program created in Brazil to install telecenters and certify individuals to use ICT resources. We propose an approach that applies social network analysis and mining techniques to data collected from Telecentros.BR dataset and from the socioeconomics and telecommunications infrastructure indicators of the participants' municipalities. We found that (i) the analysis of interactions in different time periods reflects the objectives of each phase of training, highlighting the increased density in the phase in which participants develop and disseminate their projects; (ii) analysis according to the roles of participants (i.e., tutors or community members) reveals that the interactions were influenced by the center (or region) to which the participant belongs (that is, a community contained mainly members of the same region and always with the presence of tutors, contradicting expectations of the training project, which aimed for intense collaboration of the participants, regardless of the geographic region); (iii) the social network of participants influences the success of the training: that is, given evidence that the degree of the community member is in the highest range, the probability of this individual concluding the training is 0.689; (iv) the North region presented the lowest probability of participant certification, whereas the Northeast, which served municipalities with similar

  19. A large-scale functional screen identifies Nova1 and Ncoa3 as regulators of neuronal miRNA function

    PubMed Central

    Störchel, Peter H; Thümmler, Juliane; Siegel, Gabriele; Aksoy-Aksel, Ayla; Zampa, Federico; Sumer, Simon; Schratt, Gerhard

    2015-01-01

    MicroRNAs (miRNAs) are important regulators of neuronal development, network connectivity, and synaptic plasticity. While many neuronal miRNAs were previously shown to modulate neuronal morphogenesis, little is known regarding the regulation of miRNA function. In a large-scale functional screen, we identified two novel regulators of neuronal miRNA function, Nova1 and Ncoa3. Both proteins are expressed in the nucleus and the cytoplasm of developing hippocampal neurons. We found that Nova1 and Ncoa3 stimulate miRNA function by different mechanisms that converge on Argonaute (Ago) proteins, core components of the miRNA-induced silencing complex (miRISC). While Nova1 physically interacts with Ago proteins, Ncoa3 selectively promotes the expression of Ago2 at the transcriptional level. We further show that Ncoa3 regulates dendritic complexity and dendritic spine maturation of hippocampal neurons in a miRNA-dependent fashion. Importantly, both the loss of miRNA activity and increased dendrite complexity upon Ncoa3 knockdown were rescued by Ago2 overexpression. Together, we uncovered two novel factors that control neuronal miRISC function at the level of Ago proteins, with possible implications for the regulation of synapse development and plasticity. PMID:26105073

  20. A large-scale functional screen identifies Nova1 and Ncoa3 as regulators of neuronal miRNA function.

    PubMed

    Störchel, Peter H; Thümmler, Juliane; Siegel, Gabriele; Aksoy-Aksel, Ayla; Zampa, Federico; Sumer, Simon; Schratt, Gerhard

    2015-09-01

    MicroRNAs (miRNAs) are important regulators of neuronal development, network connectivity, and synaptic plasticity. While many neuronal miRNAs were previously shown to modulate neuronal morphogenesis, little is known regarding the regulation of miRNA function. In a large-scale functional screen, we identified two novel regulators of neuronal miRNA function, Nova1 and Ncoa3. Both proteins are expressed in the nucleus and the cytoplasm of developing hippocampal neurons. We found that Nova1 and Ncoa3 stimulate miRNA function by different mechanisms that converge on Argonaute (Ago) proteins, core components of the miRNA-induced silencing complex (miRISC). While Nova1 physically interacts with Ago proteins, Ncoa3 selectively promotes the expression of Ago2 at the transcriptional level. We further show that Ncoa3 regulates dendritic complexity and dendritic spine maturation of hippocampal neurons in a miRNA-dependent fashion. Importantly, both the loss of miRNA activity and increased dendrite complexity upon Ncoa3 knockdown were rescued by Ago2 overexpression. Together, we uncovered two novel factors that control neuronal miRISC function at the level of Ago proteins, with possible implications for the regulation of synapse development and plasticity. PMID:26105073

  1. A Large-Scale RNAi-Based Mouse Tumorigenesis Screen Identifies New Lung Cancer Tumor Suppressors that Repress FGFR Signaling

    PubMed Central

    Lin, Ling; Chamberlain, Lynn; Pak, Magnolia L.; Nagarajan, Arvindhan; Gupta, Romi; Zhu, Lihua J.; Wright, Casey M.; Fong, Kwun M.; Wajapeyee, Narendra; Green, Michael R.

    2014-01-01

    To discover new tumor suppressor genes (TSGs), we developed a functional genomics approach in which immortalized but non-tumorigenic cells were stably transduced with large-scale short hairpin RNA (shRNA) pools and tested for tumor formation in mice. Identification of shRNAs in resulting tumors revealed candidate TSGs, which were validated experimentally and by analyzing expression in human tumor samples. Using this approach, we identified 24 TSGs that were significantly down-regulated in human lung squamous cell carcinomas (hLSCCs). Amplification of fibroblast growth factor receptor 1 (FGFR1), which aberrantly increases FGFR signaling, is a common genetic alteration in hLSCCs. Remarkably, we found that 17 of the TSGs encode repressors of FGFR signaling. Knockdown of 14 of these TSGs transformed immortalized human bronchial epithelial cells and, in most cases, rendered them sensitive to FGFR inhibitors. Our results indicate that increased FGFR signaling promotes tumorigenesis in many hLSCCs that lack FGFR1 amplification or activating mutations. PMID:25015643

  2. Germination rate of Phyllospadix japonicus seeds relative to storage methods and periods

    NASA Astrophysics Data System (ADS)

    Park, Jung-Im; Lee, Kun-Seop; Son, Min Ho

    2014-03-01

    To determine the optimal storage method and longest possible storage period of Phyllospadix japonicus seeds, we examined post-storage germination rates using different storage methods and periods for P. japonicus seeds harvested in Korean coastal waters. P. japonicus seeds are classified as recalcitrant seeds with an average moisture content of 45.4%. Germination rates of P. japonicus seeds stored in seawater at 4 °C, seawater at room temperature with air supply, and an aquarium with continuous seawater circulation ranged from 35.0% to 43.5%, whereas seeds stored in seawater at 30°C, a refrigerator at -20°C, and a desiccator at room temperature did not germinate. Seeds stored at 4°C maintained germination rates of 72.5˜73.0% until 30 days of storage, but showed rapidly decreasing germination rates after 60 days and no germination after 180 days. Since few studies have investigated seed storage of P. japonicus, these results will serve as useful data for seed-based P. japonicus habitat restoration.

  3. Dietary Apostichopus japonicus enhances the respiratory and intestinal mucosal immunity in immunosuppressive mice.

    PubMed

    Zheng, Rong; Li, Xuemin; Cao, Binbin; Zuo, Tao; Wu, Juan; Wang, Jingfeng; Xue, Changhu; Tang, Qingjuan

    2015-01-01

    Although Apostichopus japonicus is recognized as a food and drug resource with significant immunomodulatory activity, its role in regulating the mucosal immunity remains unclear. This study aimed to explore the effects of dietary A. japonicus on mucosal immunity with an immunosuppressive mouse model. The expression of lysozyme, secretory immunoglobulin A(sIgA), and immunoglobulin A(IgA) as well as polymeric immunoglobulin receptor(pIgR) in respiratory and intestine organs was investigated. The results showed that A. japonicus could improve both the systematic and mucosal immunity. The expression of lysozyme, sIgA, and IgA in the respiratory organ was increased more significantly. Consumption of A. japonicus with the dose of 512 mg kg(-1), which equals to (1)/2 sea cucumber per day for adults, showed better effects. This study elucidated positive effects of A. japonicus on mucosal immunity for the first time, suggesting that moderate consumption of A. japonicus is helpful in improving mucosal immunity and preventing exogenous infection. PMID:25186733

  4. Identifying the Irritability Dimension of ODD: Application of a Modified Bifactor Model Across Five Large Community Samples of Children

    PubMed Central

    Burke, Jeffrey D.; Boylan, Khrista; Rowe, Richard; Duku, Eric; Stepp, Stephanie D.; Hipwell, Alison E.; Waldman, Irwin D.

    2014-01-01

    The importance of irritability as measured among the symptoms of oppositional defiant disorder (ODD) has dramatically come to the fore in recent years. New diagnostic categories rely on the distinct clinical utility of irritability, and models of psychopathology suggest it plays a key role in explaining developmental pathways within and between disorders into adulthood. However, only a few studies have tested multidimensional models of ODD, and the results have been conflicting. Further, consensus has not been reached regarding which symptoms best identify irritability. The present analyses use data from five large community data sets with five different measures of parent-reported ODD, comprising 16,280 youth in total, to help resolve these questions. Across the samples, ages ranged from 5 to 18, and included both boys and girls. Confirmatory factor analyses demonstrated that a modified bifactor model showed the best fit in each of the five data sets. The structure of the model included two correlated specific factors (irritability and oppositional behavior) in addition to a general ODD factor. In four of the five models, the best fit was obtained using the items of being touchy, angry and often losing temper as indicators of irritability. Given the structure of the models and the generally high correlation between the specific dimensions, the results suggest that irritability may not be sufficiently distinct from oppositional behavior to support an entirely independent diagnosis. Rather, irritability may be better understood as a dimension of psychopathology that can be distinguished within ODD, and which may be related to particular forms of psychopathology apart from ODD. PMID:25314267

  5. Transcriptome comparisons identify new cell markers for theca interna and granulosa cells from small and large antral ovarian follicles.

    PubMed

    Hatzirodos, Nicholas; Hummitzsch, Katja; Irving-Rodgers, Helen F; Rodgers, Raymond J

    2015-01-01

    In studies using isolated ovarian granulosa and thecal cells it is important to assess the degree of cross contamination. Marker genes commonly used for granulosa cells include FSHR, CYP19A1 and AMH while CYP17A1 and INSL3 are used for thecal cells. To increase the number of marker genes available we compared expression microarray data from isolated theca interna with that from granulosa cells of bovine small (n = 10 for both theca and granulosa cells; 3-5 mm) and large (n = 4 for both theca and granulosa cells, > 9 mm) antral follicles. Validation was conducted by qRT-PCR analyses. Known markers such as CYP19A1, FSHR and NR5A2 and another 11 genes (LOC404103, MGARP, GLDC, CHST8, CSN2, GPX3, SLC35G1, CA8, CLGN, FAM78A, SLC16A3) were common to the lists of the 50 most up regulated genes in granulosa cells from both follicle sizes. The expression in theca interna was more consistent than in granulosa cells between the two follicle sizes. Many genes up regulated in theca interna were common to both sizes of follicles (MGP, DCN, ASPN, ALDH1A1, COL1A2, FN1, COL3A1, OGN, APOD, COL5A2, IGF2, NID1, LHFP, ACTA2, DUSP12, ACTG2, SPARCL1, FILIP1L, EGFLAM, ADAMDEC1, HPGD, COL12A1, FBLN5, RAMP2, COL15A1, PLK2, COL6A3, LOXL1, RARRES1, FLI1, LAMA2). Many of these were stromal extracellular matrix genes. MGARP, GLDC, CHST8, GPX3 were identified as new potential markers for granulosa cells, while FBLN5, OGN, RAMP2 were significantly elevated in the theca interna. PMID:25775029

  6. Transcriptome Comparisons Identify New Cell Markers for Theca Interna and Granulosa Cells from Small and Large Antral Ovarian Follicles

    PubMed Central

    Hatzirodos, Nicholas; Hummitzsch, Katja; Irving-Rodgers, Helen F.; Rodgers, Raymond J.

    2015-01-01

    In studies using isolated ovarian granulosa and thecal cells it is important to assess the degree of cross contamination. Marker genes commonly used for granulosa cells include FSHR, CYP19A1 and AMH while CYP17A1 and INSL3 are used for thecal cells. To increase the number of marker genes available we compared expression microarray data from isolated theca interna with that from granulosa cells of bovine small (n = 10 for both theca and granulosa cells; 3-5 mm) and large (n = 4 for both theca and granulosa cells, > 9 mm) antral follicles. Validation was conducted by qRT-PCR analyses. Known markers such as CYP19A1, FSHR and NR5A2 and another 11 genes (LOC404103, MGARP, GLDC, CHST8, CSN2, GPX3, SLC35G1, CA8, CLGN, FAM78A, SLC16A3) were common to the lists of the 50 most up regulated genes in granulosa cells from both follicle sizes. The expression in theca interna was more consistent than in granulosa cells between the two follicle sizes. Many genes up regulated in theca interna were common to both sizes of follicles (MGP, DCN, ASPN, ALDH1A1, COL1A2, FN1, COL3A1, OGN, APOD, COL5A2, IGF2, NID1, LHFP, ACTA2, DUSP12, ACTG2, SPARCL1, FILIP1L, EGFLAM, ADAMDEC1, HPGD, COL12A1, FBLN5, RAMP2, COL15A1, PLK2, COL6A3, LOXL1, RARRES1, FLI1, LAMA2). Many of these were stromal extracellular matrix genes. MGARP, GLDC, CHST8, GPX3 were identified as new potential markers for granulosa cells, while FBLN5, OGN, RAMP2 were significantly elevated in the theca interna. PMID:25775029

  7. RNAseq versus genome-predicted transcriptomes: a large population of novel transcripts identified in an Illumina-454 Hydra transcriptome

    PubMed Central

    2013-01-01

    Background Evolutionary studies benefit from deep sequencing technologies that generate genomic and transcriptomic sequences from a variety of organisms. Genome sequencing and RNAseq have complementary strengths. In this study, we present the assembly of the most complete Hydra transcriptome to date along with a comparative analysis of the specific features of RNAseq and genome-predicted transcriptomes currently available in the freshwater hydrozoan Hydra vulgaris. Results To produce an accurate and extensive Hydra transcriptome, we combined Illumina and 454 Titanium reads, giving the primacy to Illumina over 454 reads to correct homopolymer errors. This strategy yielded an RNAseq transcriptome that contains 48’909 unique sequences including splice variants, representing approximately 24’450 distinct genes. Comparative analysis to the available genome-predicted transcriptomes identified 10’597 novel Hydra transcripts that encode 529 evolutionarily-conserved proteins. The annotation of 170 human orthologs points to critical functions in protein biosynthesis, FGF and TOR signaling, vesicle transport, immunity, cell cycle regulation, cell death, mitochondrial metabolism, transcription and chromatin regulation. However, a majority of these novel transcripts encodes short ORFs, at least 767 of them corresponding to pseudogenes. This RNAseq transcriptome also lacks 11’270 predicted transcripts that correspond either to silent genes or to genes expressed below the detection level of this study. Conclusions We established a simple and powerful strategy to combine Illumina and 454 reads and we produced, with genome assistance, an extensive and accurate Hydra transcriptome. The comparative analysis of the RNAseq transcriptome with genome-predicted transcriptomes lead to the identification of large populations of novel as well as missing transcripts that might reflect Hydra-specific evolutionary events. PMID:23530871

  8. Molecular characterization of two novel molecular chaperones in bacterial-challenged Apostichopus japonicus.

    PubMed

    Wang, Haihong; Shao, Yina; Zhang, Weiwei; Li, Chenghua; Lv, Zhimeng; Jin, Chunhua

    2015-10-01

    Molecular chaperones of 78 kDa glucose-regulated protein (GRP78) and protein disulfide isomerase (PDI) are involved in protein folding and assembly in the endoplasmic reticulum (ER). Increasing evidences also suggest that these two molecules play an important role in immune response. In the present study, we cloned and characterized GRP78 and PDI genes from Apostichopus japonicus by RNA-seq and RACE approaches (designated as AjGRP78 and AjPDI, respectively). The AjGRP78 cDNA was of 2355bp including an open reading frame (ORF) of 2013 bp encoding a protein of 670 amino acids with three heat shock protein 70 (HSP70) family signatures. AjGRP78 contained a 23-amino acid signal peptide at the N-terminus and a HDEL motif at the C-terminus, which supported the location of the protein in the ER. The full length cDNA of AjPDI was of 1893 bp with a 5' untranslated region (UTR) of 153 bp, a 3' UTR of 228 bp and an ORF of 1512 bp encoding a protein of 503 amino acids. A 17-amino acid signal peptide, two thioredoxin domains with two active sites of CGHC, and KDEL retention signal were totally conserved in the deduced amino acid of AjPDI. Phylogenic analysis and multiple alignments have shown that both genes shared remarkably higher degree of structural conservation and sequence identities with other counterparts from invertebrates and vertebrates, further supporting that the two proteins were novel members of molecular chaperone family. Spatial expression analysis revealed that AjGRP78 mRNA transcripts were dominantly expressed in the tentacle, while AjPDI mRNA levels were abundant in the muscle, intestine and respiratory trees. For Vibrio splendidus challenged sea cucumber, the peak expression of AjGRP78 and AjPDI mRNAs in coelomocytes were detected at 24h with 1.73-fold increase and at 6h with 1.83-fold increase compared with the control group, respectively. Similarly, a significant increase in the relative mRNA levels of AjGRP78 and AjPDI was also identified in 1 μg mL(-1

  9. Novel episomal vectors and a highly efficient transformation procedure for the fission yeast Schizosaccharomyces japonicus.

    PubMed

    Aoki, Keita; Nakajima, Reiko; Furuya, Kanji; Niki, Hironori

    2010-12-01

    Schizosaccharomyces japonicus is a fission yeast for which new genetic tools have recently been developed. Here, we report novel plasmid vectors with high transformation efficiency and an electroporation method for Sz. japonicus. We isolated 44 replicating segments from 12 166 transformants of Sz. japonicus genomic fragments and found a chromosomal fragment, RS1, as a new replicating sequence that conferred high transformation activity to Sz. japonicus cells. This sequence was cloned into a pUC19 vector with ura4(+) of Sz. pombe (pSJU11) or the kan gene on the kanMX6 module (pSJK11) as selection markers. These plasmids transformed Sz. japonicus cells in the early-log phase by electroporation at a frequency of 123 cfu/µg for pSJK11 and 301 cfu/µg for pSJU11, which were higher than previously reported autonomously replicating sequences. Although a portion of plasmids remained in host cells by integration into the chromosome via RS1 segment, the plasmids could be recovered from transformants. The plasmid copy number was estimated to be 1.88 copies per cell by Southern blot analysis using a Sz. pombe ura4(+) probe. The plasmid containing ade6(+) suppressed the auxotrophic growth of the ade6-domE mutant, indicating that the plasmid would be useful for suppressor screening and complementation assays in Sz. japonicus. Furthermore, pSJU11 transformed Sz. pombe cells with the same frequency as the pREP2 plasmid. This study is a report to demonstrate practical use of episomal plasmid vectors for genetic research in Sz. japonicus. PMID:20737410

  10. MiR-200 modulates coelomocytes antibacterial activities and LPS priming via targeting Tollip in Apostichopus japonicus.

    PubMed

    Lv, Zhimeng; Li, Chenghua; Zhang, Pengjuan; Wang, Zhenhui; Zhang, Weiwei; Jin, Chun-Hua

    2015-08-01

    In order to explore the potential roles of microRNAs (miRNAs) in regulating Toll-like receptor (TLR) pathways, we identified Toll interacting protein as a putative target of miR-200 in Apostichopus japonicus coelomocytes by RNA-seq screening (denoted as AjTollip). The positive expression profiles of miR-200 and AjTollip were detected in both LPS exposure primary coelomocytes and Vibrio splendidus challenge sea cucumber. Co-infection miR-200 mimics significantly elevated the expression of AjTollip and its down-stream molecules. In contrast, miR-200 inhibitor significantly repressed the expression of these TLR-pathway members. More importantly, miR-200 displayed not only to enhance coelomocytes antibacterial activities, but to suppress LPS priming in vitro. Overall, all these results will enhance our understanding on miR-200 regulatory roles in anti-bacterial process in sea cucumber. PMID:25910848

  11. Change of digestive physiology in sea cucumber Apostichopus japonicus (Selenka) induced by corn kernels meal and soybean meal in diets

    NASA Astrophysics Data System (ADS)

    Yu, Haibo; Gao, Qinfeng; Dong, Shuanglin; Hou, Yiran; Wen, Bin

    2016-05-01

    The present study was conducted to determine the change of digestive physiology in sea cucumber Apostichopus japonicus (Selenka) induced by corn kernels meal and soybean meal in diets. Four experimental diets were tested, in which Sargassum thunbergii was proportionally replaced by the mixture of corn kernels meal and soybean meal. The growth performance, body composition and intestinal digestive enzyme activities in A. japonicus fed these 4 diets were examined. Results showed that the sea cucumber exhibited the maximum growth rate when 20% of S. thunbergii in the diet was replaced by corn kernels meal and soybean meal, while 40% of S. thunbergii in the diet can be replaced by the mixture of corn kernels meal and soybean meal without adversely affecting growth performance of A. japonicus. The activities of intestinal trypsin and amylase in A. japonicus can be significantly altered by corn kernels meal and soybean meal in diets. Trypsin activity in the intestine of A. japonicus significantly increased in the treatment groups compared to the control, suggesting that the supplement of corn kernels meal and soybean meal in the diets might increase the intestinal trypsin activity of A. japonicus. However, amylase activity in the intestine of A. japonicus remarkably decreased with the increasing replacement level of S. thunbergii by the mixture of corn kernels meal and soybean meal, suggesting that supplement of corn kernels meal and soybean meal in the diets might decrease the intestinal amylase activity of A. japonicus.

  12. Change of digestive physiology in sea cucumber Apostichopus japonicus (Selenka) induced by corn kernels meal and soybean meal in diets

    NASA Astrophysics Data System (ADS)

    Yu, Haibo; Gao, Qinfeng; Dong, Shuanglin; Hou, Yiran; Wen, Bin

    2016-08-01

    The present study was conducted to determine the change of digestive physiology in sea cucumber Apostichopus japonicus (Selenka) induced by corn kernels meal and soybean meal in diets. Four experimental diets were tested, in which Sargassum thunbergii was proportionally replaced by the mixture of corn kernels meal and soybean meal. The growth performance, body composition and intestinal digestive enzyme activities in A. japonicus fed these 4 diets were examined. Results showed that the sea cucumber exhibited the maximum growth rate when 20% of S. thunbergii in the diet was replaced by corn kernels meal and soybean meal, while 40% of S. thunbergii in the diet can be replaced by the mixture of corn kernels meal and soybean meal without adversely affecting growth performance of A. japonicus. The activities of intestinal trypsin and amylase in A. japonicus can be significantly altered by corn kernels meal and soybean meal in diets. Trypsin activity in the intestine of A. japonicus significantly increased in the treatment groups compared to the control, suggesting that the supplement of corn kernels meal and soybean meal in the diets might increase the intestinal trypsin activity of A. japonicus. However, amylase activity in the intestine of A. japonicus remarkably decreased with the increasing replacement level of S. thunbergii by the mixture of corn kernels meal and soybean meal, suggesting that supplement of corn kernels meal and soybean meal in the diets might decrease the intestinal amylase activity of A. japonicus.

  13. CYTOKININ OXIDASE/DEHYDROGENASE3 Maintains Cytokinin Homeostasis during Root and Nodule Development in Lotus japonicus.

    PubMed

    Reid, Dugald E; Heckmann, Anne B; Novák, Ondřej; Kelly, Simon; Stougaard, Jens

    2016-02-01

    Cytokinins are required for symbiotic nodule development in legumes, and cytokinin signaling responses occur locally in nodule primordia and in developing nodules. Here, we show that the Lotus japonicus Ckx3 cytokinin oxidase/dehydrogenase gene is induced by Nod factor during the early phase of nodule initiation. At the cellular level, pCkx3::YFP reporter-gene studies revealed that the Ckx3 promoter is active during the first cortical cell divisions of the nodule primordium and in growing nodules. Cytokinin measurements in ckx3 mutants confirmed that CKX3 activity negatively regulates root cytokinin levels. Particularly, tZ and DHZ type cytokinins in both inoculated and uninoculated roots were elevated in ckx3 mutants, suggesting that these are targets for degradation by the CKX3 cytokinin oxidase/dehydrogenase. The effect of CKX3 on the positive and negative roles of cytokinin in nodule development, infection and regulation was further clarified using ckx3 insertion mutants. Phenotypic analysis indicated that ckx3 mutants have reduced nodulation, infection thread formation and root growth. We also identify a role for cytokinin in regulating nodulation and nitrogen fixation in response to nitrate as ckx3 phenotypes are exaggerated at increased nitrate levels. Together, these findings show that cytokinin accumulation is tightly regulated during nodulation in order to balance the requirement for cell divisions with negative regulatory effects of cytokinin on infection events and root development. PMID:26644503

  14. Identification and characterization a novel transcription factor activator protein-1 in the sea cucumber Apostichopus japonicus.

    PubMed

    Yang, Limeng; Li, Chenghua; Chang, Yaqing; Gao, Yinxue; Wang, Yi; Wei, Jing; Song, Jian; Sun, Ping

    2015-08-01

    The transcription factor activator protein-1 (AP-1) is an important gene expression regulator with typical Jun and region-leucine zipper (bZIP) domains and can respond to a plethora of physiological and pathological stimulus. In this study, we identified a novel AP-1 gene in Apostichopus japonicus by transcriptome sequencing and RACE approaches (designated as AjAP-1). The full-length of AjAP-1 was of 2944 bp including a 5' untranslated region (UTR) of 201 bp, a 3' UTR of 1753 bp and a putative open reading frame of 990 bp encoding a polypeptide of 329 amino acid residues. Two representative domains of Jun and bZIP as well as two nuclear localization signals (NLSs) were also detected in deduced amino acid of AjAP-1. Spatial distribution expression indicated that AjAP-1 was ubiquitously expressed in all examined tissues with predominant expression in the body wall, moderate in the tube feet, respiratory tree and colemocytes and slightly weak in the intestine and longitudinal muscle. Time-course expression analysis in intestine and coelomocytes revealed that AjAP-1 both reached its peak expression at 4 h after Vibrio splendidus challenge with a 2.6 and 8.2-fold increase compared to their control groups, respectively. Taken together, all these results suggested that AjAP-1 was a novel immune factor and might be involved in the processes of anti-bacteria response in sea cucumber. PMID:26093208

  15. A metabolic gene cluster in Lotus japonicus discloses novel enzyme functions and products in triterpene biosynthesis.

    PubMed

    Krokida, Afrodite; Delis, Costas; Geisler, Katrin; Garagounis, Constantine; Tsikou, Daniela; Peña-Rodríguez, Luis M; Katsarou, Dimitra; Field, Ben; Osbourn, Anne E; Papadopoulou, Kalliope K

    2013-11-01

    Genes for triterpene biosynthetic pathways exist as metabolic gene clusters in oat and Arabidopsis thaliana plants. We characterized the presence of an analogous gene cluster in the model legume Lotus japonicus. In the genomic regions flanking the oxidosqualene cyclase AMY2 gene, genes for two different classes of cytochrome P450 and a gene predicted to encode a reductase were identified. Functional characterization of the cluster genes was pursued by heterologous expression in Nicotiana benthamiana. The gene expression pattern was studied under different developmental and environmental conditions. The physiological role of the gene cluster in nodulation and plant development was studied in knockdown experiments. A novel triterpene structure, dihydrolupeol, was produced by AMY2. A new plant cytochrome P450, CYP71D353, which catalyses the formation of 20-hydroxybetulinic acid in a sequential three-step oxidation of 20-hydroxylupeol was characterized. The genes within the cluster are highly co-expressed during root and nodule development, in hormone-treated plants and under various environmental stresses. A transcriptional gene silencing mechanism that appears to be involved in the regulation of the cluster genes was also revealed. A tightly co-regulated cluster of functionally related genes is involved in legume triterpene biosynthesis, with a possible role in plant development. PMID:23909862

  16. Down-regulated Lotus japonicus GCR1 plants exhibit nodulation signalling pathways alteration.

    PubMed

    Rogato, Alessandra; Valkov, Vladimir Totev; Alves, Ludovico Martins; Apone, Fabio; Colucci, Gabriella; Chiurazzi, Maurizio

    2016-06-01

    G Protein Coupled Receptor (GPCRs) are integral membrane proteins involved in various signalling pathways by perceiving many extracellular signals and transducing them to heterotrimeric G proteins, which further transduce these signals to intracellular downstream effectors. GCR1 is the only reliable plant candidate as a member of the GPCRs superfamily. In the legume/rhizobia symbiotic interaction, G proteins are involved in signalling pathways controlling different steps of the nodulation program. In order to investigate the putative hierarchic role played by GCR1 in these symbiotic pathways we identified and characterized the Lotus japonicus gene encoding the seven transmembrane GCR1 protein. The detailed molecular and topological analyses of LjGCR1 expression patterns that are presented suggest a possible involvement in the early steps of nodule organogenesis. Furthermore, phenotypic analyses of independent transgenic RNAi lines, showing a significant LjGCR1 expression down regulation, suggest an epistatic action in the control of molecular markers of nodulation pathways, although no macroscopic symbiotic phenotypes could be revealed. PMID:27095401

  17. Identification and assessment of differentially expressed genes involved in growth regulation in Apostichopus japonicus.

    PubMed

    Zhu, L; Li, C H; Su, X R; Guo, C Y; Wang, Z; Jin, C H; Li, Y; Li, T W

    2013-01-01

    Rapid and efficient growth is a major consideration and challenge for global mariculture. The differential growth rate of the sea cucumber, Apostichopus japonicus, has significantly hampered the total production of the industry. In the present study, forward and reverse suppression subtractive hybridization libraries were constructed and sequenced from a fast-growth group and a slow-growth group of the sea cucumber. A total of 142 differentially expressed sequence tags (ESTs) with insertions longer than 150 bp were identified and further analyzed. Fifty-seven of these ESTs (approximately 40%) were functionally annotated for cell structure, energy metabolism, immunity response, and growth factor categories. Six candidate genes, arginine kinase, cytochrome c oxidase subunit I, HSP70, β-actin, ferritin, and the ADP-ribosylation factor, were further validated by quantitative PCR. Significant differences were found between the fast- and slow-growth groups (P < 0.05) for the expression levels of arginine kinase, cytochrome c oxidase, HSP70, the ADP-ribosylation factor, and β-actin. However, no significant difference was observed for ferritin. Our results provide promising candidate gene markers for practical size screening, and also further promote marker-assisted selective breeding of this species. PMID:24065658

  18. Evolution of NIN-like proteins in Arabidopsis, rice, and Lotus japonicus.

    PubMed

    Schauser, Leif; Wieloch, Wioletta; Stougaard, Jens

    2005-02-01

    Genetic studies in Lotus japonicus and pea have identified Nin as a core symbiotic gene required for establishing symbiosis between legumes and nitrogen fixing bacteria collectively called Rhizobium. Sequencing of additional Lotus cDNAs combined with analysis of genome sequences from Arabidopsis and rice reveals that Nin homologues in all three species constitute small gene families. In total, the Arabidopsis and rice genomes encode nine and three NIN-like proteins (NLPs), respectively. We present here a bioinformatics analysis and prediction of NLP evolution. On a genome scale we show that in Arabidopsis, this family has evolved through segmental duplication rather than through tandem amplification. Alignment of all predicted NLP protein sequences shows a composition with six conserved modules. In addition, Lotus and pea NLPs contain segments that might characterize NIN proteins of legumes and be of importance for their function in symbiosis. The most conserved region in NLPs, the RWP-RK domain, has secondary structure predictions consistent with DNA binding properties. This motif is shared by several other small proteins in both Arabidopsis and rice. In rice, the RWP-RK domain sequences have diversified significantly more than in Arabidopsis. Database searches reveal that, apart from its presence in Arabidopsis and rice, the motif is also found in the algae Chlamydomonas and in the slime mold Dictyostelium discoideum. Thus, the origin of this putative DNA binding region seems to predate the fungus-plant divide. PMID:15785851

  19. Mutagenic effects of carbon ion beam irradiations on dry Lotus japonicus seeds

    NASA Astrophysics Data System (ADS)

    Luo, Shanwei; Zhou, Libin; Li, Wenjian; Du, Yan; Yu, Lixia; Feng, Hui; Mu, Jinhu; Chen, Yuze

    2016-09-01

    Carbon ion beam irradiation is a powerful method for creating mutants and has been used in crop breeding more and more. To investigate the effects of carbon ion beams on Lotus japonicus, dry seeds were irradiated by 80 MeV/u carbon ion beam at dosages of 0, 100, 200, 300, 400, 500 and 600 Gy. The germination rate, survival rate and root length of M1 populations were explored and the dose of 400 Gy was selected as the median lethal dose (LD50) for a large-scale mutant screening. Among 2472 M2 plants, 127 morphological mutants including leaf, stem, flower and fruit phenotypic variation were found, and the mutation frequency was approximately 5.14%. Inter simple sequence repeat (ISSR) assays were utilized to investigate the DNA polymorphism between seven mutants and eight plants without phenotypic variation from M2 populations. No remarkable differences were detected between these two groups, and the total polymorphic rate was 0.567%.

  20. Expression of immune-related genes in embryos and larvae of sea cucumber Apostichopus japonicus.

    PubMed

    Yang, Aifu; Zhou, Zunchun; Dong, Ying; Jiang, Bei; Wang, Xiaoyu; Chen, Zhong; Guan, Xiaoyan; Wang, Bai; Sun, Dapeng

    2010-11-01

    The echinoderm immunity system has been extensively investigated in adults in several classes such as echinoid and holothuroidea. However, the defense mechanism in embryos and larvae remains largely unexplored. To profile the immune-related genes expression in embryos and larvae and to monitor the stimulation of the innate immune response by lipopolysaccharides (LPS) challenge, we investigated the expression patterns of nine immune-related genes in embryos and larvae of sea cucumber (Apostichopus japonicus) at eleven developmental stages using quantitative real-time PCR (qRT-PCR). The expression of six encoding proteins including heat shock protein70 (Hsp70), Hsp90, Hsp gp96, thymosin-beta, ferritin and DD104 protein was detected at all eleven development stages according to mRNA expression data. However, the expression of mannan-binding C-type lectin (MBCL) was detected at early auricularia to juvenile stages, while lysozyme and serine proteinase inhibitor (SPI) were detected only at juvenile stage. Out of these nine genes, three (MBCL, lysozyme and SPI) were found to be up-regulated in mRNA expression upon LPS challenge, whereas the other six showed no significant change. Our study presents a first preliminary view into the expression patterns of immune-related genes at different developmental stages of sea cucumber, which increases the available information on echinoderm immunity. PMID:20673800

  1. iTRAQ-based proteomics reveals novel members involved in pathogen challenge in sea cucumber Apostichopus japonicus.

    PubMed

    Zhang, Pengjuan; Li, Chenghua; Zhang, Peng; Jin, Chunhua; Pan, Daodong; Bao, Yongbo

    2014-01-01

    Skin ulceration syndrome (SUS) is considered to be a major constraint for the stable development of Apostichopus japonicus culture industries. In this study, we investigated protein changes in the coelomocytes of A. japonicus challenged by Vibrio splendidus using isobaric tags for relative and absolute quantification (iTRAQ) over a 96 h time course. Consequently, 228 differentially expressed proteins were identified in two iTRAQs. A comparison of the protein expression profiles among different time points detected 125 proteins primarily involved in response to endogenous stimuli at 24 h. At 48 h, the number of differentially expressed proteins decreased to 67, with their primary function being oxidation reduction. At the end of pathogen infection, proteins responsive to amino acid stimuli and some metabolic processes were classified as the predominant group. Fifteen proteins were differentially expressed at all time points, among which eight proteins related to pathologies in higher animals were shown to be down-regulated after V. splendidus infection: paxillin, fascin-2, aggrecan, ololfactomedin-1, nesprin-3, a disintegrin-like and metallopeptidase with thrombospondin type 1 motif (Adamts7), C-type lectin domain family 4 (Clec4g) and n-myc downstream regulated gene 1 (Ndrg1). To gain more insight into two SUS-related miRNA (miR-31 and miR-2008) targets at the protein level, all 129 down-regulated proteins were further analyzed in combination with RNA-seq. Twelve and eight proteins were identified as putative targets for miR-31 and miR-2008, respectively, in which six proteins (5 for miR-31 and 1 for miR-2008) displayed higher possibilities to be regulated at the level of translation. Overall, the present work enhances our understanding of the process of V. splendidus-challenged sea cucumber and provides a new method for screening miRNAs targets at the translation level. PMID:24949634

  2. iTRAQ-Based Proteomics Reveals Novel Members Involved in Pathogen Challenge in Sea Cucumber Apostichopus japonicus

    PubMed Central

    Zhang, Pengjuan; Li, Chenghua; Zhang, Peng; Jin, Chunhua; Pan, Daodong; Bao, Yongbo

    2014-01-01

    Skin ulceration syndrome (SUS) is considered to be a major constraint for the stable development of Apostichopus japonicus culture industries. In this study, we investigated protein changes in the coelomocytes of A. japonicus challenged by Vibrio splendidus using isobaric tags for relative and absolute quantification (iTRAQ) over a 96 h time course. Consequently, 228 differentially expressed proteins were identified in two iTRAQs. A comparison of the protein expression profiles among different time points detected 125 proteins primarily involved in response to endogenous stimuli at 24 h. At 48 h, the number of differentially expressed proteins decreased to 67, with their primary function being oxidation reduction. At the end of pathogen infection, proteins responsive to amino acid stimuli and some metabolic processes were classified as the predominant group. Fifteen proteins were differentially expressed at all time points, among which eight proteins related to pathologies in higher animals were shown to be down-regulated after V. splendidus infection: paxillin, fascin-2, aggrecan, ololfactomedin-1, nesprin-3, a disintegrin-like and metallopeptidase with thrombospondin type 1 motif (Adamts7), C-type lectin domain family 4 (Clec4g) and n-myc downstream regulated gene 1 (Ndrg1). To gain more insight into two SUS-related miRNA (miR-31 and miR-2008) targets at the protein level, all 129 down-regulated proteins were further analyzed in combination with RNA-seq. Twelve and eight proteins were identified as putative targets for miR-31 and miR-2008, respectively, in which six proteins (5 for miR-31 and 1 for miR-2008) displayed higher possibilities to be regulated at the level of translation. Overall, the present work enhances our understanding of the process of V. splendidus-challenged sea cucumber and provides a new method for screening miRNAs targets at the translation level. PMID:24949634

  3. Phylogenetic differentiation between Atlantic Scomber colias and Pacific Scomber japonicus based on nuclear DNA sequences.

    PubMed

    Infante, Carlos; Blanco, Enrique; Zuasti, Eugenia; Crespo, Aniela; Manchado, Manuel

    2007-05-01

    In the classical taxonomy, three Scomber species are distinguished: S. scombrus, S. australasicus, and S. japonicus. Yet, some fish taxonomists have recently recognized Scomber colias, inhabiting the Atlantic Ocean, as a separate species from S. japonicus, distributed in the Pacific Ocean. Such proposal was based on significant mitochondrial DNA divergence as well as great phenotypic variation among individuals from these two ocean basins. However, in the absence of nuclear DNA data this issue remains still controversial. In this study, a phylogenetic analysis of nuclear 5S rDNA sequences was performed. A total of 30 individuals of S. colias collected in the Atlantic and 34 specimens of S. japonicus from the Pacific were characterized. Moreover, nine individuals of Pacific S. australasicus and eight of Atlantic S. scombrus were included. Maximum likelihood, maximum parsimony, and neighbor-joining analyses revealed the presence of two well-supported distinct clades corresponding to S. colias and S. japonicus, respectively. Altogether, morphologic and genetic data are in agreement with the recognition of two different species, S. colias in the Atlantic, and S. japonicus in the Pacific. PMID:16897460

  4. Community Ecology of Container Mosquitoes (Diptera: Culicidae) in Virginia Following Invasion by Aedes japonicus

    PubMed Central

    ARMISTEAD, JENNIFER S.; NISHIMURA, NAOYA; ARIAS, JORGE R.; LOUNIBOS, L. PHILIP

    2012-01-01

    The success of an invasive species in a new region depends on its interactions with ecologically similar resident species. Invasions by disease vector mosquitoes are important as they may have ecological and epidemiological consequences. Potential interactions of a recent invasive mosquito, Aedes japonicus Theobald, with resident species in Virginia were evaluated by sampling larvae from containers and trapping adults. Distinct species compositions were observed for artificial containers and rock pools, with Ae. albopictus most abundant in the former and Ae. japonicus in the latter. However, these two species were found to co-occur in 21.2% of containers sampled. Among the six mosquito species most common in containers from May through September, 2006, only interspecific associations of Ae.japonicus with Aedesalbopictus(Skuse) and Aedestriseriatus(Say) were significant, and both were negative. In addition to differences in habitat preference, mean crowding estimates suggest that interspecific repulsion may contribute to the significant negative associations observed between these species. High relative abundances of late instars and pupae of Ae. japonicus seem to provide this species with a mechanism of evading competition with Ae. albopictus, facilitating their coexistence in artificial containers. Although annual fluctuations were observed, trends in adult populations over a 6-yr period provide no evidence of declines. In summary, this survey of diverse container types and all life stages provided only limited evidence for competitive displacements or reductions of resident container species by Ae. japonicus, as observed elsewhere in its invasive range. PMID:23270159

  5. An effective seeding method for restoring the surfgrass Phyllospadix japonicus using an aartificial reef

    NASA Astrophysics Data System (ADS)

    Park, Jung-Im; Son, Min Ho; Kim, Jeong Bae; Lee, Kun-Seop

    2014-12-01

    Phyllospadix japonicus is an abundant surfgrass that thrives mainly along the exposed rocky shores of Northeastern Asia. On the eastern coast of Korea, surfgrass populations have been adversely affected by increasing human pressures. We developed a seeding method using an artificial reef for the restoration of P. japonicus. In January 2005, we planted P. japonicus seeds on the lower part of coarse hemp-plant brush that was embedded densely on the concave surface on the top of artificial reefs. The reefs were then installed on an exposed rocky shore. To evaluate the feasibility of this seed-based surfgrass restoration technique, we monitored the seedling/shoot density and morphological characteristics of the shoots over a 2-year period. Seedlings began to emerge within the first month after seeding, reaching densities of up to 275.0 shoots m-2 by April 2005. After an initial decline, shoot density increased through the production of lateral shoots, and densities of up to 997.1 shoots m-2 were observed by the end of the experiment. Shoot height, the number of leaves, and leaf width rapidly increased during the first year after seeding, whereas the number of rhizome internodes and rhizome length rapidly increased during the second year. The P. japonicus shoots exhibited approximately 63.4 mm of rhizome elongation during the study period. Because seeded P. japonicus on the artificial reefs were successfully established at the study site, this seeding method using an artificial reef may offer an effective approach to restoring surfgrass habitat.

  6. Interspecific Larval Competition Between Aedes albopictus and Aedes japonicus (Diptera: Culicidae) in Northern Virginia

    PubMed Central

    Armistead, J. S.; Arias, J. R.; Nishimura, N.; Lounibos, L. P.

    2008-01-01

    Aedes albopictus (Skuse) and Aedes japonicus (Theobald) are two of the most recent and widespread invasive mosquito species to have become established in the United States. The two species co-occur in water-filled artificial containers, where crowding and limiting resources are likely to promote inter- or intraspecific larval competition. The performance of northern Virginia populations of Ae. japonicus and Ae. albopictus competing as larvae under field conditions was evaluated. Per capita rates of population increase for each species were estimated, and the effects of species composition and larval density were determined. In water-containing cups provided with oak leaves, Ae. albopictus larvae exhibited a competitive advantage over Ae. japonicus as a consequence of higher survivorship, shorter developmental time, and a significantly higher estimated population growth rate under conditions of interspecific competition. Intraspecific competition constrained population performance of Ae. albopictus significantly more than competition with Ae. japonicus. In the context of the Lotka-Volterra model of competition, these findings suggest competitive exclusion of Ae. japonicus in those habitats where this species co-occurs with Ae. albopictus. PMID:18714861

  7. Sustainability evaluation of different systems for sea cucumber ( Apostichopus japonicus) farming based on emergy theory

    NASA Astrophysics Data System (ADS)

    Wang, Guodong; Dong, Shuanglin; Tian, Xiangli; Gao, Qinfeng; Wang, Fang

    2015-06-01

    Emergy analysis is effective for analyzing ecological economic systems. However, the accuracy of the approach is affected by the diversity of economic level, meteorological and hydrological parameters in different regions. The present study evaluated the economic benefits, environmental impact, and sustainability of indoor, semi-intensive and extensive farming systems of sea cucumber ( Apostichopus japonicus) in the same region. The results showed that A. japonicus indoor farming system was high in input and output (yield) whereas pond extensive farming system was low in input and output. The output/input ratio of indoor farming system was lower than that of pond extensive farming system, and the output/input ratio of semi-intensive farming system fell in between them. The environmental loading ratio of A. japonicus extensive farming system was lower than that of indoor farming system. In addition, the emergy yield and emergy exchange ratios, and emergy sustainability and emergy indexes for sustainable development were higher in extensive farming system than those in indoor farming system. These results indicated that the current extensive farming system exerted fewer negative influences on the environment, made more efficient use of available resources, and met more sustainable development requirements than the indoor farming system. A. japonicus farming systems showed more emergy benefits than fish farming systems. The pond farming systems of A. japonicus exploited more free local environmental resources for production, caused less potential pressure on the local environment, and achieved higher sustainability than indoor farming system.

  8. Expression of Apostichopus japonicus lysozyme in the methylotrophic yeast Pichia pastoris.

    PubMed

    Wang, Tingting; Xu, Yongping; Liu, Wenjia; Sun, Yongxin; Jin, Liji

    2011-05-01

    Apostichopus japonicus (sea cucumber) is one of the economically important farmed echinoderm species in Northern China. As a crucial enzyme in innate immunity, lysozyme plays a key role in the overall defense against pathogens in A. japonicus. In the present study, a lysozyme gene from A. japonicus was cloned by PCR and expressed in Pichia pastoris using the expression vector pPIC9K. The expressed lysozyme had a molecular mass of ∼14 kD, as shown by SDS-PAGE and Western-blotting. The expression condition was optimized, and the highest expression level was achieved by induction with 1% methanol at pH 5.0 for 120 h. The recombinant lysozyme was purified by affinity chromatography using a Ni-NTA column. The specific activity of the purified lysozyme was 34,000 U/mg using Micrococcus lysodeikticus as substrates. It exhibited antimicrobial activity toward M.lysodeikticus, as detected by growth inhibition on agar plate and turbidity assay, suggesting a potential application of A. japonicus lysozyme as an antimicrobial agent in A. japonicus aquaculture. PMID:21241808

  9. Using Exploratory and Confirmatory Methods to Identify the Cognitive Dimensions in a Large-Scale Science Assessment

    ERIC Educational Resources Information Center

    Leighton, Jacqueline P.; Gokiert, Rebecca J.; Cui, Ying

    2007-01-01

    Studies of test dimensionality indicate that many large-scale science assessments measure multiple dimensions. These findings have reinforced the perspective that science achievement is an inherently dynamic process and that there is benefit in reporting subscores in science. A limitation with some of these studies is that they fail to indicate…

  10. Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya.

    PubMed

    Tremblay, M; Dahm, J S; Wamae, C N; De Glanville, W A; Fèvre, E M; Döpfer, D

    2015-12-01

    Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization. PMID:25876816

  11. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.

    PubMed

    Nalls, Mike A; Pankratz, Nathan; Lill, Christina M; Do, Chuong B; Hernandez, Dena G; Saad, Mohamad; DeStefano, Anita L; Kara, Eleanna; Bras, Jose; Sharma, Manu; Schulte, Claudia; Keller, Margaux F; Arepalli, Sampath; Letson, Christopher; Edsall, Connor; Stefansson, Hreinn; Liu, Xinmin; Pliner, Hannah; Lee, Joseph H; Cheng, Rong; Ikram, M Arfan; Ioannidis, John P A; Hadjigeorgiou, Georgios M; Bis, Joshua C; Martinez, Maria; Perlmutter, Joel S; Goate, Alison; Marder, Karen; Fiske, Brian; Sutherland, Margaret; Xiromerisiou, Georgia; Myers, Richard H; Clark, Lorraine N; Stefansson, Kari; Hardy, John A; Heutink, Peter; Chen, Honglei; Wood, Nicholas W; Houlden, Henry; Payami, Haydeh; Brice, Alexis; Scott, William K; Gasser, Thomas; Bertram, Lars; Eriksson, Nicholas; Foroud, Tatiana; Singleton, Andrew B

    2014-09-01

    We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation. PMID:25064009

  12. Large-Scale Computational Screening Identifies First in Class Multitarget Inhibitor of EGFR Kinase and BRD4

    PubMed Central

    Allen, Bryce K.; Mehta, Saurabh; Ember, Stewart W. J.; Schonbrunn, Ernst; Ayad, Nagi; Schürer, Stephan C.

    2015-01-01

    Inhibition of cancer-promoting kinases is an established therapeutic strategy for the treatment of many cancers, although resistance to kinase inhibitors is common. One way to overcome resistance is to target orthogonal cancer-promoting pathways. Bromo and Extra-Terminal (BET) domain proteins, which belong to the family of epigenetic readers, have recently emerged as promising therapeutic targets in multiple cancers. The development of multitarget drugs that inhibit kinase and BET proteins therefore may be a promising strategy to overcome tumor resistance and prolong therapeutic efficacy in the clinic. We developed a general computational screening approach to identify novel dual kinase/bromodomain inhibitors from millions of commercially available small molecules. Our method integrated machine learning using big datasets of kinase inhibitors and structure-based drug design. Here we describe the computational methodology, including validation and characterization of our models and their application and integration into a scalable virtual screening pipeline. We screened over 6 million commercially available compounds and selected 24 for testing in BRD4 and EGFR biochemical assays. We identified several novel BRD4 inhibitors, among them a first in class dual EGFR-BRD4 inhibitor. Our studies suggest that this computational screening approach may be broadly applicable for identifying dual kinase/BET inhibitors with potential for treating various cancers. PMID:26596901

  13. DNA Barcoding of genus Hexacentrus in China reveals cryptic diversity within Hexacentrus japonicus (Orthoptera, Tettigoniidae)

    PubMed Central

    Guo, Hui-Fang; Guan, Bei; Shi, Fu-Ming; Zhou, Zhi-Jun

    2016-01-01

    Abstract DNA barcoding has been proved successful to provide resolution beyond the boundaries of morphological information. Hence, a study was undertaken to establish DNA barcodes for all morphologically determined Hexacentrus species in China collections. In total, 83 specimens of five Hexacentrus species were barcoded using standard mitochondrial cytochrome c oxidase subunit I (COI) gene. Except for Hexacentrus japonicus, barcode gaps were present in the remaining Hexacentrus species. Taxon ID tree generated seven BOLD’s barcode index numbers (BINs), four of which were in agreement with the morphological species. For Hexacentrus japonicus, the maximum intraspecific divergence (4.43%) produced a minimal overlap (0.64%), and 19 specimens were divided into three different BINs. There may be cryptic species within the current Hexacentrus japonicus. This study adds to a growing body of DNA barcodes that have become available for katydids, and shows that a DNA barcoding approach enables the identification of known Hexacentrus species with a very high resolution. PMID:27408576

  14. Analysis of fatty acid composition of sea cucumber Apostichopus japonicus using multivariate statistics

    NASA Astrophysics Data System (ADS)

    Xu, Qinzeng; Gao, Fei; Xu, Qiang; Yang, Hongsheng

    2014-11-01

    Fatty acids (FAs) provide energy and also can be used to trace trophic relationships among organisms. Sea cucumber Apostichopus japonicus goes into a state of aestivation during warm summer months. We examined fatty acid profiles in aestivated and non-aestivated A. japonicus using multivariate analyses (PERMANOVA, MDS, ANOSIM, and SIMPER). The results indicate that the fatty acid profiles of aestivated and non-aestivated sea cucumbers differed significantly. The FAs that were produced by bacteria and brown kelp contributed the most to the differences in the fatty acid composition of aestivated and nonaestivated sea cucumbers. Aestivated sea cucumbers may synthesize FAs from heterotrophic bacteria during early aestivation, and long chain FAs such as eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) that produced from intestinal degradation, are digested during deep aestivation. Specific changes in the fatty acid composition of A. japonicus during aestivation needs more detailed study in the future.

  15. Reactive Oxygen Species (ROS)-Activated ATM-Dependent Phosphorylation of Cytoplasmic Substrates Identified by Large-Scale Phosphoproteomics Screen.

    PubMed

    Kozlov, Sergei V; Waardenberg, Ashley J; Engholm-Keller, Kasper; Arthur, Jonathan W; Graham, Mark E; Lavin, Martin

    2016-03-01

    Ataxia-telangiectasia, mutated (ATM) protein plays a central role in phosphorylating a network of proteins in response to DNA damage. These proteins function in signaling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair, and regulating gene expression. ATM kinase can be activated by a variety of stimuli, including oxidative stress. Here, we confirmed activation of cytoplasmic ATM by autophosphorylation at multiple sites. Then we employed a global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and ataxia-telangiectasia (A-T) cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,833 phosphorylation sites, including 6,686 high-confidence sites mapping to 2,536 unique proteins. A total of 62 differentially phosphorylated peptides were identified; of these, 43 were phosphorylated in control but not in A-T cells, and 19 varied in their level of phosphorylation. Motif enrichment analysis of phosphopeptides revealed that consensus ATM serine glutamine sites were overrepresented. When considering phosphorylation events, only observed in control cells (not observed in A-T cells), with predicted ATM sites phosphoSerine/phosphoThreonine glutamine, we narrowed this list to 11 candidate ATM-dependent cytoplasmic proteins. Two of these 11 were previously described as ATM substrates (HMGA1 and UIMCI/RAP80), another five were identified in a whole cell extract phosphoproteomic screens, and the remaining four proteins had not been identified previously in DNA damage response screens. We validated the phosphorylation of three of these proteins (oxidative stress responsive 1 (OSR1), HDGF, and ccdc82) as ATM dependent after H2O2 exposure, and another protein (S100A11) demonstrated ATM

  16. Construction of cDNA library from intestine, mesentery and coelomocyte of Apostichopus japonicus Selenka infected with Vibrio sp. and a preliminary analysis of immunity-related genes

    NASA Astrophysics Data System (ADS)

    Liu, Hongzhan; Zheng, Fengrong; Sun, Xiuqin; Cai, Yimei

    2012-06-01

    The aquaculture of sea cucumber Apostichopus japonicus (Echinodermata, Holothuroidea) has grown rapidly during recent years and has become an important sector of the marine industry in Northern China. However, with the rapid growth of the industry and the use of non-standard culture techniques, epidemic diseases of A. japonicus now pose increasing problems to the industry. To screen the genes with stress response to bacterial infection in sea cucumber at a genome wide level, we constructed a cDNA library from A. japonicus Selenka (Aspidochirotida: Stichopodidae) after infecting them with Vibrio sp. for 48 h. Total RNA was extracted from the intestine, mesentery and coelomocyte of infected sea cucumber using Trizol and mRNA was isolated by Oligotex mRNA Kits. The ligated cDNAs were transformed into DH5α, and a library of 3.24×105 clones (3.24×105 cfu mL-1) was obtained with the sizes of inserted fragments ranging from 0.8 to 2.5 kb. Sequencing the cDNA clones resulted in a total of 1106 ESTs that passed the quality control. BlastX and BlastN searches have identified 168 (31.5%) ESTs sharing significant homology with known sequences in NCBI protein or nucleotide databases. Among a panel of 25 putative immunity-related genes, serum lectin isoform, complement component 3, complement component 3-like genes were further studied by real-time PCR and they all increased more than 5 fold in response to Vibrio sp. challenge. Our library provides a valuable molecular tool for future study of invertebrate immunity against bacterial infection and our gene expression data indicates the importance of the immune system in the evolution and development of sea cucumber.

  17. [Molecular cloning of tubulin beta 3 (TUBB3) in Gekko japonicus and preparation of its polyclonal antibody].

    PubMed

    Li, Jing; Qin, Yong; Gu, Yun; Liu, Yan; Liu, Mei

    2012-08-01

    The tubulin beta III (TUBB3) gene encodes a class III member of the beta tubulin protein family that is primarily expressed in neurons and is considered to play a critical role in proper axon guidance and maintenance. This protein is generally used as a specific marker of neurons in the central nervous system. We obtained the full length cDNA sequence of TUBB3 by using the RACE method based on the EST fragment from the brain and spinal cord cDNA library of Gekko japonicus. We further investigated the multi-tissue expression pattern by RT-PCR and identified one transcript of TUBB3 about 1.8 kb in the central nervous system of Gekko japonicus by Northern blotting. The completed cDNA of gecko TUBB3 is 1 790 bp with an open reading frame of 1 350 bp, encoding a 450 amino-acid protein. The recombinant plasmid of pET-32a-TUBB3 was constructed and induced to express His-tagged TUBB3 protein in prokaryotic BL21 cells. The purified TUBB3 protein was then used to immunize rabbits to generate polyclonal antisera. The titer of the antiserum was more than 1:65 536 determined by ELISA. The result of western blotting showed that the TUBB3 antibody could specifically recognize the recombinant TUBB3 protein and endogenous TUBB3 protein. Our findings provide the tools to further understand the TUBB3 gene and investigate the regeneration of the central nervous system in Gekko japonicas. PMID:22855447

  18. Comparative transcriptome analysis of papilla and skin in the sea cucumber, Apostichopus japonicus

    PubMed Central

    Kong, Derong; Sun, He; Gu, Chenlei; Wang, Hongdi; Qiu, Xuemei; Chang, Yaqing; Liu, Zhanjiang

    2016-01-01

    Papilla and skin are two important organs of the sea cucumber. Both tissues have ectodermic origin, but they are morphologically and functionally very different. In the present study, we performed comparative transcriptome analysis of the papilla and skin from the sea cucumber (Apostichopus japonicus) in order to identify and characterize gene expression profiles by using RNA-Seq technology. We generated 30.6 and 36.4 million clean reads from the papilla and skin and de novo assembled in 156,501 transcripts. The Gene Ontology (GO) analysis indicated that cell part, metabolic process and catalytic activity were the most abundant GO category in cell component, biological process and molecular funcation, respectively. Comparative transcriptome analysis between the papilla and skin allowed the identification of 1,059 differentially expressed genes, of which 739 genes were expressed at higher levels in papilla, while 320 were expressed at higher levels in skin. In addition, 236 differentially expressed unigenes were not annotated with any database, 160 of which were apparently expressed at higher levels in papilla, 76 were expressed at higher levels in skin. We identified a total of 288 papilla-specific genes, 171 skin-specific genes and 600 co-expressed genes. Also, 40 genes in papilla-specific were not annotated with any database, 2 in skin-specific. Development-related genes were also enriched, such as fibroblast growth factor, transforming growth factor-β, collagen-α2 and Integrin-α2, which may be related to the formation of the papilla and skin in sea cucumber. Further pathway analysis identified ten KEGG pathways that were differently enriched between the papilla and skin. The findings on expression profiles between two key organs of the sea cucumber should be valuable to reveal molecular mechanisms involved in the development of organs that are related but with morphological differences in the sea cucumber. PMID:26989617

  19. Comparative transcriptome analysis of papilla and skin in the sea cucumber, Apostichopus japonicus.

    PubMed

    Zhou, Xiaoxu; Cui, Jun; Liu, Shikai; Kong, Derong; Sun, He; Gu, Chenlei; Wang, Hongdi; Qiu, Xuemei; Chang, Yaqing; Liu, Zhanjiang; Wang, Xiuli

    2016-01-01

    Papilla and skin are two important organs of the sea cucumber. Both tissues have ectodermic origin, but they are morphologically and functionally very different. In the present study, we performed comparative transcriptome analysis of the papilla and skin from the sea cucumber (Apostichopus japonicus) in order to identify and characterize gene expression profiles by using RNA-Seq technology. We generated 30.6 and 36.4 million clean reads from the papilla and skin and de novo assembled in 156,501 transcripts. The Gene Ontology (GO) analysis indicated that cell part, metabolic process and catalytic activity were the most abundant GO category in cell component, biological process and molecular funcation, respectively. Comparative transcriptome analysis between the papilla and skin allowed the identification of 1,059 differentially expressed genes, of which 739 genes were expressed at higher levels in papilla, while 320 were expressed at higher levels in skin. In addition, 236 differentially expressed unigenes were not annotated with any database, 160 of which were apparently expressed at higher levels in papilla, 76 were expressed at higher levels in skin. We identified a total of 288 papilla-specific genes, 171 skin-specific genes and 600 co-expressed genes. Also, 40 genes in papilla-specific were not annotated with any database, 2 in skin-specific. Development-related genes were also enriched, such as fibroblast growth factor, transforming growth factor-β, collagen-α2 and Integrin-α2, which may be related to the formation of the papilla and skin in sea cucumber. Further pathway analysis identified ten KEGG pathways that were differently enriched between the papilla and skin. The findings on expression profiles between two key organs of the sea cucumber should be valuable to reveal molecular mechanisms involved in the development of organs that are related but with morphological differences in the sea cucumber. PMID:26989617

  20. Identifying sensitive areas of adaptive observations for prediction of the Kuroshio large meander using a shallow-water model

    NASA Astrophysics Data System (ADS)

    Zou, Guang'an; Wang, Qiang; Mu, Mu

    2016-09-01

    Sensitive areas for prediction of the Kuroshio large meander using a 1.5-layer, shallow-water ocean model were investigated using the conditional nonlinear optimal perturbation (CNOP) and first singular vector (FSV) methods. A series of sensitivity experiments were designed to test the sensitivity of sensitive areas within the numerical model. The following results were obtained: (1) the eff ect of initial CNOP and FSV patterns in their sensitive areas is greater than that of the same patterns in randomly selected areas, with the eff ect of the initial CNOP patterns in CNOP sensitive areas being the greatest; (2) both CNOP- and FSV-type initial errors grow more quickly than random errors; (3) the eff ect of random errors superimposed on the sensitive areas is greater than that of random errors introduced into randomly selected areas, and initial errors in the CNOP sensitive areas have greater eff ects on final forecasts. These results reveal that the sensitive areas determined using the CNOP are more sensitive than those of FSV and other randomly selected areas. In addition, ideal hindcasting experiments were conducted to examine the validity of the sensitive areas. The results indicate that reduction (or elimination) of CNOP-type errors in CNOP sensitive areas at the initial time has a greater forecast benefit than the reduction (or elimination) of FSV-type errors in FSV sensitive areas. These results suggest that the CNOP method is suitable for determining sensitive areas in the prediction of the Kuroshio large-meander path.

  1. MUSI: an integrated system for identifying multiple specificity from very large peptide or nucleic acid data sets

    PubMed Central

    Kim, TaeHyung; Tyndel, Marc S.; Huang, Haiming; Sidhu, Sachdev S.; Bader, Gary D.; Gfeller, David; Kim, Philip M.

    2012-01-01

    Peptide recognition domains and transcription factors play crucial roles in cellular signaling. They bind linear stretches of amino acids or nucleotides, respectively, with high specificity. Experimental techniques that assess the binding specificity of these domains, such as microarrays or phage display, can retrieve thousands of distinct ligands, providing detailed insight into binding specificity. In particular, the advent of next-generation sequencing has recently increased the throughput of such methods by several orders of magnitude. These advances have helped reveal the presence of distinct binding specificity classes that co-exist within a set of ligands interacting with the same target. Here, we introduce a software system called MUSI that can rapidly analyze very large data sets of binding sequences to determine the relevant binding specificity patterns. Our pipeline provides two major advances. First, it can detect previously unrecognized multiple specificity patterns in any data set. Second, it offers integrated processing of very large data sets from next-generation sequencing machines. The results are visualized as multiple sequence logos describing the different binding preferences of the protein under investigation. We demonstrate the performance of MUSI by analyzing recent phage display data for human SH3 domains as well as microarray data for mouse transcription factors. PMID:22210894

  2. Rapid microsatellite development in Gekko japonicus using sequenced restriction-site associated DNA markers.

    PubMed

    Wei, L; Shao, W W; Zhou, H B; Ping, J; Li, L M; Zhang, Y P

    2015-01-01

    Twelve polymorphic microsatellite loci were isolated in the Japanese gecko, Gekko japonicus. We genotyped one population from Wenzhou, Zhejiang Province, China (N = 36). The mean number of observed alleles per locus was 7.3 (range 4 to 13). Observed and expected heterozygosity values ranged from 0.200 to 0.944 and from 0.395 to 0.797, respectively. One locus (GJ20) showed significant departure from Hardy-Weinberg equilibrium; no linkage disequilibrium was found between any two loci. These informative microsatellite markers will be useful for population genetic analyses of G. japonicus and other species in the genus Gekko. PMID:26535727

  3. Identifying sources of groundwater nitrate contamination in a large alluvial groundwater basin with highly diversified intensive agricultural production.

    PubMed

    Lockhart, K M; King, A M; Harter, T

    2013-08-01

    Groundwater quality is a concern in alluvial aquifers underlying agricultural areas worldwide. Nitrate from land applied fertilizers or from animal waste can leach to groundwater and contaminate drinking water resources. The San Joaquin Valley, California, is an example of an agricultural landscape with a large diversity of field, vegetable, tree, nut, and citrus crops, but also confined animal feeding operations (CAFOs, here mostly dairies) that generate, store, and land apply large amounts of liquid manure. As in other such regions around the world, the rural population in the San Joaquin Valley relies almost exclusively on shallow domestic wells (≤150 m deep), of which many have been affected by nitrate. Variability in crops, soil type, and depth to groundwater contribute to large variability in nitrate occurrence across the underlying aquifer system. The role of these factors in controlling groundwater nitrate contamination levels is examined. Two hundred domestic wells were sampled in two sub-regions of the San Joaquin Valley, Stanislaus and Merced (Stan/Mer) and Tulare and Kings (Tul/Kings) Counties. Forty six percent of well water samples in Tul/Kings and 42% of well water samples in Stan/Mer exceeded the MCL for nitrate (10mg/L NO3-N). For statistical analysis of nitrate contamination, 78 crop and landuse types were considered by grouping them into ten categories (CAFO, citrus, deciduous fruits and nuts, field crops, forage, native, pasture, truck crops, urban, and vineyards). Vadose zone thickness, soil type, well construction information, well proximity to dairies, and dominant landuse near the well were considered. In the Stan/Mer area, elevated nitrate levels in domestic wells most strongly correlate with the combination of very shallow (≤21 m) water table and the presence of either CAFO derived animal waste applications or deciduous fruit and nut crops (synthetic fertilizer applications). In Tulare County, statistical data indicate that elevated

  4. Identifying sources of groundwater nitrate contamination in a large alluvial groundwater basin with highly diversified intensive agricultural production

    NASA Astrophysics Data System (ADS)

    Lockhart, K. M.; King, A. M.; Harter, T.

    2013-08-01

    Groundwater quality is a concern in alluvial aquifers underlying agricultural areas worldwide. Nitrate from land applied fertilizers or from animal waste can leach to groundwater and contaminate drinking water resources. The San Joaquin Valley, California, is an example of an agricultural landscape with a large diversity of field, vegetable, tree, nut, and citrus crops, but also confined animal feeding operations (CAFOs, here mostly dairies) that generate, store, and land apply large amounts of liquid manure. As in other such regions around the world, the rural population in the San Joaquin Valley relies almost exclusively on shallow domestic wells (≤ 150 m deep), of which many have been affected by nitrate. Variability in crops, soil type, and depth to groundwater contribute to large variability in nitrate occurrence across the underlying aquifer system. The role of these factors in controlling groundwater nitrate contamination levels is examined. Two hundred domestic wells were sampled in two sub-regions of the San Joaquin Valley, Stanislaus and Merced (Stan/Mer) and Tulare and Kings (Tul/Kings) Counties. Forty six percent of well water samples in Tul/Kings and 42% of well water samples in Stan/Mer exceeded the MCL for nitrate (10 mg/L NO3-N). For statistical analysis of nitrate contamination, 78 crop and landuse types were considered by grouping them into ten categories (CAFO, citrus, deciduous fruits and nuts, field crops, forage, native, pasture, truck crops, urban, and vineyards). Vadose zone thickness, soil type, well construction information, well proximity to dairies, and dominant landuse near the well were considered. In the Stan/Mer area, elevated nitrate levels in domestic wells most strongly correlate with the combination of very shallow (≤ 21 m) water table and the presence of either CAFO derived animal waste applications or deciduous fruit and nut crops (synthetic fertilizer applications). In Tulare County, statistical data indicate that elevated

  5. Does induction of labor for constitutionally large-for-gestational-age fetuses identified in utero reduce maternal morbidity?

    PubMed Central

    2014-01-01

    Background The number of infants with a birth weight > 97th percentile for gestational age has increased over the years. Although some studies have examined the interest of inducing labor for fetuses with macrosomia suspected in utero, only a few have analyzed this suspected macrosomia according to estimated weight at each gestational age. Most studies have focused principally on neonatal rather than on maternal (and still less on perineal) outcomes. The principal aim of this study was to assess whether a policy of induction of labor for women with a constitutionally large-for-gestational-age fetus might reduce the occurrence of severe perineal tears; the secondary aims of this work were to assess whether this policy would reduce either recourse to cesarean delivery during labor or neonatal complications. Methods This historical cohort study (n = 3077) analyzed records from a French perinatal database. Women without diabetes and with a cephalic singleton term pregnancy were eligible for the study. We excluded medically indicated terminations of pregnancy and in utero fetal deaths. Among the pregnancies with fetuses suspected, before birth, of being large-for-gestational-age, we compared those for whom labor was induced from ≥ 37 weeks to ≤ 38 weeks+ 6 days (n = 199) to those with expectant obstetrical management (n = 2878). In this intention-to-treat analysis, results were expressed as crude and adjusted relative risks. Results The mean birth weight was 4012 g ± 421 g. The rate of perineal lesions did not differ between the two groups in either primiparas (aRR: 1.06; 95% CI: 0.86-1.31) or multiparas (aRR: 0.94; 95% CI: 0.84-1.05). Similarly, neither the cesarean rate (aRR: 1.11; 95% CI: 0.82-1.50) nor the risks of resuscitation in the delivery room or of death in the delivery room or in the immediate postpartum or of neonatal transfer to the NICU (aRR = 0.94; 95% CI: 0.59-1.50) differed between the two groups. Conclusions A

  6. Genome-wide association and large scale follow-up identifies 16 new loci influencing lung function

    PubMed Central

    Artigas, María Soler; Loth, Daan W; Wain, Louise V; Gharib, Sina A; Obeidat, Ma’en; Tang, Wenbo; Zhai, Guangju; Zhao, Jing Hua; Smith, Albert Vernon; Huffman, Jennifer E; Albrecht, Eva; Jackson, Catherine M; Evans, David M; Cadby, Gemma; Fornage, Myriam; Manichaikul, Ani; Lopez, Lorna M; Johnson, Toby; Aldrich, Melinda C; Aspelund, Thor; Barroso, Inês; Campbell, Harry; Cassano, Patricia A; Couper, David J; Eiriksdottir, Gudny; Franceschini, Nora; Garcia, Melissa; Gieger, Christian; Gislason, Gauti Kjartan; Grkovic, Ivica; Hammond, Christopher J; Hancock, Dana B; Harris, Tamara B; Ramasamy, Adaikalavan; Heckbert, Susan R; Heliövaara, Markku; Homuth, Georg; Hysi, Pirro G; James, Alan L; Jankovic, Stipan; Joubert, Bonnie R; Karrasch, Stefan; Klopp, Norman; Koch, Beate; Kritchevsky, Stephen B; Launer, Lenore J; Liu, Yongmei; Loehr, Laura R; Lohman, Kurt; Loos, Ruth JF; Lumley, Thomas; Al Balushi, Khalid A; Ang, Wei Q; Barr, R Graham; Beilby, John; Blakey, John D; Boban, Mladen; Boraska, Vesna; Brisman, Jonas; Britton, John R; Brusselle, Guy G; Cooper, Cyrus; Curjuric, Ivan; Dahgam, Santosh; Deary, Ian J; Ebrahim, Shah; Eijgelsheim, Mark; Francks, Clyde; Gaysina, Darya; Granell, Raquel; Gu, Xiangjun; Hankinson, John L; Hardy, Rebecca; Harris, Sarah E; Henderson, John; Henry, Amanda; Hingorani, Aroon D; Hofman, Albert; Holt, Patrick G; Hui, Jennie; Hunter, Michael L; Imboden, Medea; Jameson, Karen A; Kerr, Shona M; Kolcic, Ivana; Kronenberg, Florian; Liu, Jason Z; Marchini, Jonathan; McKeever, Tricia; Morris, Andrew D; Olin, Anna-Carin; Porteous, David J; Postma, Dirkje S; Rich, Stephen S; Ring, Susan M; Rivadeneira, Fernando; Rochat, Thierry; Sayer, Avan Aihie; Sayers, Ian; Sly, Peter D; Smith, George Davey; Sood, Akshay; Starr, John M; Uitterlinden, André G; Vonk, Judith M; Wannamethee, S Goya; Whincup, Peter H; Wijmenga, Cisca; Williams, O Dale; Wong, Andrew; Mangino, Massimo; Marciante, Kristin D; McArdle, Wendy L; Meibohm, Bernd; Morrison, Alanna C; North, Kari E; Omenaas, Ernst; Palmer, Lyle J; Pietiläinen, Kirsi H; Pin, Isabelle; Polašek, Ozren; Pouta, Anneli; Psaty, Bruce M; Hartikainen, Anna-Liisa; Rantanen, Taina; Ripatti, Samuli; Rotter, Jerome I; Rudan, Igor; Rudnicka, Alicja R; Schulz, Holger; Shin, So-Youn; Spector, Tim D; Surakka, Ida; Vitart, Veronique; Völzke, Henry; Wareham, Nicholas J; Warrington, Nicole M; Wichmann, H-Erich; Wild, Sarah H; Wilk, Jemma B; Wjst, Matthias; Wright, Alan F; Zgaga, Lina; Zemunik, Tatijana; Pennell, Craig E; Nyberg, Fredrik; Kuh, Diana; Holloway, John W; Boezen, H Marike; Lawlor, Debbie A; Morris, Richard W; Probst-Hensch, Nicole; Kaprio, Jaakko; Wilson, James F; Hayward, Caroline; Kähönen, Mika; Heinrich, Joachim; Musk, Arthur W; Jarvis, Deborah L; Gläser, Sven; Järvelin, Marjo-Riitta; Stricker, Bruno H Ch; Elliott, Paul; O’Connor, George T; Strachan, David P; London, Stephanie J; Hall, Ian P; Gudnason, Vilmundur; Tobin, Martin D

    2011-01-01

    Pulmonary function measures reflect respiratory health and predict mortality, and are used in the diagnosis of chronic obstructive pulmonary disease (COPD). We tested genome-wide association with the forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) in 48,201 individuals of European ancestry, with follow-up of top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P<5×10−8) with pulmonary function, in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1, and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. PMID:21946350

  7. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.

    PubMed

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian'an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tõnu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-09-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

  8. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

    PubMed Central

    Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian’an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O’Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tönu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

    2012-01-01

    Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

  9. Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits

    PubMed Central

    Hinckley, Jesse D; Abbott, Diana; Burns, Trudy L; Heiman, Meadow; Shapiro, Amy D; Wang, Kai; Di Paola, Jorge

    2013-01-01

    We characterized a large Amish pedigree and, in 384 pedigree members, analyzed the genetic variance components with covariate screen as well as genome-wide quantitative trait locus (QTL) linkage analysis of red blood cell count (RBC), hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count (PLT), and white blood cell count (WBC) using SOLAR. Age and gender were found to be significant covariates in many CBC traits. We obtained significant heritability estimates for RBC, MCV, MCH, MCHC, RDW, PLT, and WBC. We report four candidate loci with Logarithm of the odds (LOD) scores above 2.0: 6q25 (MCH), 9q33 (WBC), 10p12 (RDW), and 20q13 (MCV). We also report eleven candidate loci with LOD scores between 1.5 and <2.0. Bivariate linkage analysis of MCV and MCH on chromosome 20 resulted in a higher maximum LOD score of 3.14. Linkage signals on chromosomes 4q28, 6p22, 6q25, and 20q13 are concomitant with previously reported QTL. All other linkage signals reported herein represent novel evidence of candidate QTL. Interestingly rs1800562, the most common causal variant of hereditary hemochromatosis in HFE (6p22) was associated with MCH and MCHC in this family. Linkage studies like the one presented here will allow investigators to focus the search for rare variants amidst the noise encountered in the large amounts of data generated by whole-genome sequencing. PMID:24058921

  10. Midgut fungal and bacterial microbiota of Aedes triseriatus and Aedes japonicus shift in response to La Crosse virus infection.

    PubMed

    Muturi, Ephantus J; Bara, Jeffrey J; Rooney, Alejandro P; Hansen, Allison K

    2016-08-01

    Understanding how midgut microbial communities of field-collected mosquitoes interact with pathogens is critical for controlling vector infection and disease. We used 16S rRNA and internal transcribed spacer sequencing to characterize the midgut bacterial and fungal communities of adult females of Aedes triseriatus and Aedes japonicus collected as pupae in tree holes, plastic bins and waste tires and their response to La Crosse virus (LACV) infection. For both mosquito species and across all habitat and virus treatments, a total of 62 bacterial operational taxonomic units (OTUs) from six phyla and 21 fungal OTUs from two phyla were identified. The majority of bacterial (92%) and fungal (71%) OTUs were shared between the mosquito species; however, several OTUs were unique to each species. Bacterial and fungal communities of individuals that took either infectious or noninfectious bloodmeals were less diverse and more homogeneous compared to those of newly emerged adults. Interestingly, LACV-infected A. triseriatus and A. japonicus had higher bacterial richness and lower fungal richness compared to individuals that took a noninfectious bloodmeal, suggesting that viral infection was associated with an increase in bacterial OTUs and a decrease in fungal OTUs. For both mosquito species, several OTUs were identified that had both high fidelity and specificity to mosquito midguts that were infected with LACV. Overall, these findings demonstrate that bacterial and fungal communities that reside in mosquito midguts respond to host diet and viral infection and could play a role in modulating vector susceptibility to LACV. PMID:27357374