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  • 1
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    EFICAz2.5: application of a high-precision enzyme function predictor to 396 proteomes (2012)
    Oxford University Press
    Details
    Publication Date: 2012-10-11
    Description: : High-quality enzyme function annotation is essential for understanding the biochemistry, metabolism and disease processes of organisms. Previously, we developed a multi-component high-precision enzyme function predictor, EFICAz 2 (enzyme function inference by a combined approach). Here, we present an updated improved version, EFICAz 2.5 , that is trained on a significantly larger data set of enzyme sequences and PROSITE patterns. We also present the results of the application of EFICAz 2.5 to the enzyme reannotation of 396 genomes cataloged in the ENSEMBL database. Availability: The EFICAz 2.5 server and database is freely available with a use-friendly interface at http://cssb.biology.gatech.edu/EFICAz2.5 . Contact: skolnick@gatech.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 2
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    Lithospheric structure of southern Indian shield and adjoining oceans: integrated modelling of topography, gravity, geoid and heat flow data (2013)
    Oxford University Press
    Details
    Publication Date: 2013-06-11
    Description: For the present 2-D lithospheric density modelling, we selected three geotransects of more than 1000 km in length each crossing the southern Indian shield, south of 16°N, in N–S and E–W directions. The model is based on the assumption of local isostatic equilibrium and is constrained by the topography, gravity and geoid anomalies, by geothermal data, and where available by seismic data. Our integrated modelling approach reveals a crustal configuration with the Moho depth varying from ~40 km beneath the Dharwar Craton, and ~39 km beneath the Southern Granulite Terrane to about 15–20 km beneath the adjoining oceans. The lithospheric thickness varies significantly along the three profiles from ~70–100 km under the adjoining oceans to ~130–135 km under the southern block of Southern Granulite Terrane including Sri Lanka and increasing gradually to ~165–180 km beneath the northern block of Southern Granulite Terrane and the Dharwar Craton. This step-like lithosphere–asthenosphere boundary (LAB) structure indicates a normal lithospheric thickness beneath the adjoining oceans, the northern block of Southern Granulite Terrane and the Dharwar Craton. The thin lithosphere below the southern block of Southern Granulite Terrane including Sri Lanka is, however, atypical considering its age. Our results suggest that the southern Indian shield as a whole cannot be supported isostatically only by thickened crust; a thin and hot lithosphere beneath the southern block of Southern Granulite Terrane including Sri Lanka is required to explain the high topography, gravity, geoid and crustal temperatures. The widespread thermal perturbation during Pan-African (550 Ma) metamorphism and the breakup of Gondwana during late Cretaceous are proposed as twin cause mechanism for the stretching and/or convective removal of the lower part of lithospheric mantle and its replacement by hotter and lighter asthenosphere in the southern block of Southern Granulite Terrane including Sri Lanka. Unusually thinned LAB beneath the region near Bangalore apparently indicates the preserved tectonocompositional effect of late Proterozoic rifted margin of Dharwar Craton.
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 3
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    Comparative genomic analysis of Helicobacter pylori from Malaysia identifies three distinct lineages suggestive of differential evolution (2015)
    Oxford University Press
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    Publication Date: 2015-01-10
    Description: The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host–pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    ModuleBlast: identifying activated sub-networks within and across species (2015)
    Oxford University Press
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    Publication Date: 2015-02-18
    Description: Identifying conserved and divergent response patterns in gene networks is becoming increasingly important. A common approach is integrating expression information with gene association networks in order to find groups of connected genes that are activated or repressed. In many cases, researchers are also interested in comparisons across species (or conditions). Finding an active sub-network is a hard problem and applying it across species requires further considerations (e.g. orthology information, expression data and networks from different sources). To address these challenges we devised ModuleBlast, which uses both expression and network topology to search for highly relevant sub-networks. We have applied ModuleBlast to expression and interaction data from mouse, macaque and human to study immune response and aging. The immune response analysis identified several relevant modules, consistent with recent findings on apoptosis and NFB activation following infection. Temporal analysis of these data revealed cascades of modules that are dynamically activated within and across species. We have experimentally validated some of the novel hypotheses resulting from the analysis of the ModuleBlast results leading to new insights into the mechanisms used by a key mammalian aging protein.
    Keywords: Computational Methods
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Diminished Systemic and Antigen-Specific Type 1, Type 17, and Other Proinflammatory Cytokines in Diabetic and Prediabetic Individuals With Latent Mycobacterium tuberculosis Infection (2014)
    Oxford University Press
    Details
    Publication Date: 2014-10-25
    Description: Background.  Diabetes mellitus type 2 (DM) is known to be a major risk factor for the development of active tuberculosis, although its influence on latent Mycobacterium tuberculosis infection (hereafter, "latent infection") remains poorly characterized. Methods.  We examined circulating plasma cytokine levels in individuals with latent infection with DM or pre-DM (ie, intermediate hyperglycemia) and compared them to levels in patients with latent infection and normal glycemic control. Results.  In persons with DM or pre-DM, latent infection is characterized by diminished circulating levels of type 1 (interferon , interleukin 2, and tumor necrosis factor α) and type 17 (interleukin 17F) cytokines. This was associated with decreased systemic levels of other proinflammatory cytokines (interleukin 1β and interleukin 18) and the antiinflammatory cytokine interleukin 10 but not with decreased systemic levels of type 2 cytokines. Moreover, latently infected individuals with DM had diminished levels of spontaneous and M. tuberculosis antigen–specific levels of type 1 and type 17 cytokines when antigen-stimulated whole blood was examined. Finally, there was no significant correlation between the levels of any of the cytokines measured (with the exception of interleukin 22) with hemoglobin A1c levels. Conclusions.  Our data reveal that latent infection in the presence of DM or pre-DM, is characterized by diminished production of cytokines, implicated in the control of M. tuberculosis activation, allowing for a potential immunological mechanism that could account for the increased risk of active tuberculosis in latently infected individuals with DM.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
    Published by Oxford University Press on behalf of The Infectious Diseases Society of America (IDSA).
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  • 6
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    HPMCD: the database of human microbial communities from metagenomic datasets and microbial reference genomes (2016)
    Oxford University Press
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    Publication Date: 2016-01-07
    Description: The Human Pan-Microbe Communities (HPMC) database ( http://www.hpmcd.org/ ) provides a manually curated, searchable, metagenomic resource to facilitate investigation of human gastrointestinal microbiota. Over the past decade, the application of metagenome sequencing to elucidate the microbial composition and functional capacity present in the human microbiome has revolutionized many concepts in our basic biology. When sufficient high quality reference genomes are available, whole genome metagenomic sequencing can provide direct biological insights and high-resolution classification. The HPMC database provides species level, standardized phylogenetic classification of over 1800 human gastrointestinal metagenomic samples. This is achieved by combining a manually curated list of bacterial genomes from human faecal samples with over 21000 additional reference genomes representing bacteria, viruses, archaea and fungi with manually curated species classification and enhanced sample metadata annotation. A user-friendly, web-based interface provides the ability to search for (i) microbial groups associated with health or disease state, (ii) health or disease states and community structure associated with a microbial group, (iii) the enrichment of a microbial gene or sequence and (iv) enrichment of a functional annotation. The HPMC database enables detailed analysis of human microbial communities and supports research from basic microbiology and immunology to therapeutic development in human health and disease.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    A Chat about Insurance: Experimental Results from Rural Bangladesh (2015)
    Oxford University Press
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    Publication Date: 2015-08-11
    Description: Farmers throughout the developing world face multiple sources of uninsured risk to agricultural production and household assets. In this paper, we present results from an experimental demand-elicitation exercise in rural Bangladesh to shed light on smallholder farmers' interest in formal insurance products. We propose a suite of insurance and savings products, and we randomly vary the price of one insurance option (area-yield insurance) and the presence of one of the savings options (group savings). Consistent with economic theory, farmers buy more of the insurance products that cover the risks they primarily face. However, because farmers are subject to a variety of risks, they do not focus on only one type of insurance; instead, they evenly split their endowment between life and disability insurance and agricultural insurance. Demand for area-yield insurance falls with price; we also observe important cross-price elasticities with other insurance products. The presence of group savings does not alter demand for insurance, though group savings is found to be a particularly popular risk management tool, especially when decisions are made in groups.
    Keywords: C93 - Field Experiments, G22 - Insurance ; Insurance Companies, O13 - Agriculture ; Natural Resources ; Energy ; Environment ; Other Primary Products, O16 - Economic Development: Financial Markets ; Saving and Capital Investment ; Corporate Finance and, Q14 - Agricultural Finance
    Print ISSN: 2040-5790
    Electronic ISSN: 2040-5804
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Economics
    Published by Oxford University Press
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  • 8
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    Complementary expression and phosphorylation of Cx46 and Cx50 during development and following gene deletion in mouse and in normal and orchitic mink testes (2015)
    The American Physiological Society (APS)
    Details
    Publication Date: 2015-08-03
    Description: Gap junction-mediated communication helps synchronize interconnected Sertoli cell activities. Besides, coordination of germ cell and Sertoli cell activities depends on gap junction-mediated Sertoli cell–germ cell communication. This report assesses mechanisms underlying the regulation of connexin 46 (Cx46) and Cx50 in mouse testis and those accompanying a "natural" seasonal and a pathological arrest of spermatogenesis, resulting from autoimmune orchitis (AIO) in mink. Furthermore, the impact of deleting Cx46 or Cx50 on the expression, phosphorylation of junction proteins, and spermatogenesis is evaluated. Cx46 mRNA and protein expression increased, whereas Cx50 decreased with adulthood in normal mice and mink. Cx46 mRNA and protein expression increased, whereas Cx50 decreased with adulthood in normal mice and mink. During the mink active spermatogenic phase, Cx50 became phosphorylated and localized to the site of the blood-testis barrier. By contrast, Cx46 was dephosphorylated and associated with annular junctions, suggesting phosphorylation/dephosphorylation of Cx46 and Cx50 involvement in the barrier dynamics. Cx46-positive annular junctions in contact with lipid droplets were found. Cx46 and Cx50 expression and localization were altered in mink with AIO. The deletion of Cx46 or Cx50 impacted on other connexin expression and phosphorylation and differently affected tight and adhering junction protein expression. The level of apoptosis, determined by ELISA, and a number of Apostain-labeled spermatocytes and spermatids/tubules were higher in mice lacking Cx46 ( Cx46–/– ) than wild-type and Cx50–/– mice, arguing for life-sustaining Cx46 gap junction-mediated exchanges in late-stage germ cells secluded from the blood by the barrier. The data show that expression and phosphorylation of Cx46 and Cx50 are complementary in seminiferous tubules.
    Print ISSN: 0363-6119
    Electronic ISSN: 1522-1490
    Topics: Medicine
    Published by The American Physiological Society (APS)
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  • 9
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    The anti-inflammatory peptide Ac-SDKP is released from thymosin-{beta}4 by renal meprin-{alpha} and prolyl oligopeptidase (2016)
    The American Physiological Society (APS)
    Details
    Publication Date: 2016-05-20
    Description: N -acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural tetrapeptide with anti-inflammatory and antifibrotic properties. Previously, we have shown that prolyl oligopeptidase (POP) is involved in the Ac-SDKP release from thymosin-β4 (Tβ4). However, POP can only hydrolyze peptides shorter than 30 amino acids, and Tβ4 is 43 amino acids long. This indicates that before POP hydrolysis takes place, Tβ4 is hydrolyzed by another peptidase that releases NH 2 -terminal intermediate peptide(s) with fewer than 30 amino acids. Our peptidase database search pointed out meprin-α metalloprotease as a potential candidate. Therefore, we hypothesized that, prior to POP hydrolysis, Tβ4 is hydrolyzed by meprin-α. In vitro, we found that the incubation of Tβ4 with both meprin-α and POP released Ac-SDKP, whereas no Ac-SDKP was released when Tβ4 was incubated with either meprin-α or POP alone. Incubation of Tβ4 with rat kidney homogenates significantly released Ac-SDKP, which was blocked by the meprin-α inhibitor actinonin. In addition, kidneys from meprin-α knockout (KO) mice showed significantly lower basal Ac-SDKP amount, compared with wild-type mice. Kidney homogenates from meprin-α KO mice failed to release Ac-SDKP from Tβ4. In vivo, we observed that rats treated with the ACE inhibitor captopril increased plasma concentrations of Ac-SDKP, which was inhibited by the coadministration of actinonin (vehicle, 3.1 ± 0.2 nmol/l; captopril, 15.1 ± 0.7 nmol/l; captopril + actinonin, 6.1 ± 0.3 nmol/l; P 〈 0.005). Similar results were obtained with urinary Ac-SDKP after actinonin treatment. We conclude that release of Ac-SDKP from Tβ4 is mediated by successive hydrolysis involving meprin-α and POP.
    Print ISSN: 1931-857X
    Electronic ISSN: 1522-1466
    Topics: Medicine
    Published by The American Physiological Society (APS)
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  • 10
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    PKC{alpha} and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation (2016)
    Oxford University Press
    Details
    Publication Date: 2016-09-20
    Description: Harmful oxidation of proteins, lipids and nucleic acids is observed when reactive oxygen species (ROS) are produced excessively and/or the antioxidant capacity is reduced, causing ‘oxidative stress’. Nuclear poly-ADP-ribose (PAR) formation is thought to be induced in response to oxidative DNA damage and to promote cell death under sustained oxidative stress conditions. However, what exactly triggers PAR induction in response to oxidative stress is incompletely understood. Using reverse phase protein array (RPPA) and in-depth analysis of key stress signaling components, we observed that PAR formation induced by H 2 O 2 was mediated by the PLC/IP3R/Ca 2+ /PKCα signaling axis. Mechanistically, H 2 O 2 -induced PAR formation correlated with Ca 2+ -dependent DNA damage, which, however, was PKCα-independent. In contrast, PAR formation was completely lost upon knockdown of PKCα, suggesting that DNA damage alone was not sufficient for inducing PAR formation, but required a PKCα-dependent process. Intriguingly, the loss of PAR formation observed upon PKCα depletion was overcome when the chromatin structure-modifying protein HMGB1 was co-depleted with PKCα, suggesting that activation and nuclear translocation of PKCα releases the inhibitory effect of HMGB1 on PAR formation. Together, these results identify PKCα and HMGB1 as important co-regulators involved in H 2 O 2 -induced PAR formation, a finding that may have important relevance for oxidative stress-associated pathophysiological conditions.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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