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  • 1
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Chemie Ingenieur Technik - CIT 65 (1993), S. 72-75 
    ISSN: 0009-286X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Chemie Ingenieur Technik - CIT 63 (1991), S. 486-488 
    ISSN: 0009-286X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    BioEssays 15 (1993), S. 799-805 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The pathogenic, Gram-negative bacteria, Neisseria gon-orrhoeae, Neisseria meningitidis and Haemophilus influenzae, secrete immunoglobulin A1 proteases into their extracellular surroundings. An extraordinary feature in the secretory pathway of these putative virulence factors is a self-directed outer membrane transport step allowing the proteins to be secreted autonomously, even from foreign Gram-negative host cells like Escherichia coli. Here we summarize recent achievements in the understanding of IgA protease outer membrane translocation.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2014-02-08
    Description: Background: Accurate estimation of parameters of biochemical models is required to characterize the dynamics of molecular processes. This problem is intimately linked to identifying the most informative experiments for accomplishing such tasks. While significant progress has been made, effective experimental strategies for parameter identification and for distinguishing among alternative network topologies remain unclear. We approached these questions in an unbiased manner using a unique community-based approach in the context of the DREAM initiative (Dialogue for Reverse Engineering Assessment of Methods). We created an in silico test framework under which participants could probe a network with hidden parameters by requesting a range of experimental assays; results of these experiments were simulated according to a model of network dynamics only partially revealed to participants. Results: We proposed two challenges; in the first, participants were given the topology and underlying biochemical structure of a 9-gene regulatory network and were asked to determine its parameter values. In the second challenge, participants were given an incomplete topology with 11 genes and asked to find three missing links in the model. In both challenges, a budget was provided to buy experimental data generated in silico with the model and mimicking the features of different common experimental techniques, such as microarrays and fluorescence microscopy. Data could be bought at any stage, allowing participants to implement an iterative loop of experiments and computation. Conclusions: A total of 19 teams participated in this competition. The results suggest that the combination of state-of-the-art parameter estimation and a varied set of experimental methods using a few datasets, mostly fluorescence imaging data, can accurately determine parameters of biochemical models of gene regulation. However, the task is considerably more difficult if the gene network topology is not completely defined, as in challenge 2. Importantly, we found that aggregating independent parameter predictions and network topology across submissions creates a solution that can be better than the one from the best-performing submission.
    Electronic ISSN: 1752-0509
    Topics: Biology
    Published by BioMed Central
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  • 5
    Publication Date: 2013-06-29
    Description: Background: Multiple solutes are retained in uremia, but it is currently unclear which solutes are toxic. Small studies suggest that protein-bound solutes, such as p-cresol sulfate and indoxyl sulfate and intracellular solutes, such as methylamine (MMA) and dimethylamine (DMA), may be toxic. Our objective was to test whether elevated levels of these solutes were associated with mortality. Methods: We conducted a prospective cohort study in 521 U.S. incident hemodialysis patients to evaluate associations between these solutes and all-cause and cardiovascular mortality. P-cresol sulfate, indoxyl sulfate, MMA and DMA levels were measured from frozen plasma samples obtained 2 to 6 months after initiation of dialysis. Mortality data was available through 2004 using the National Death Index. Results: Elevated (greater than the population median) p-cresol sulfate, MMA or DMA levels were not associated with all-cause or cardiovascular mortality. Elevated indoxyl sulfate levels were associated with all-cause mortality but not cardiovascular mortality (hazard ratio 1.30 (95% confidence interval 1.01, 1.69) p-value 0.043). Conclusions: In this cohort of 521 incident hemodialysis patients, only elevated indoxyl sulfate levels were associated with all-cause mortality. Further research is needed to identify causes of the toxicity of uremia to provide better care for patients with kidney disease.
    Electronic ISSN: 1471-2369
    Topics: Medicine
    Published by BioMed Central
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  • 6
    Publication Date: 2013-09-26
    Description: Background: The identification of the loci and specific alleles underlying variation in quantitative traits is an important goal for evolutionary biologists and breeders. Despite major advancements in genomics technology, moving from QTL to causal alleles remains a major challenge in genetics research. Near-isogenic lines are the ideal raw material for QTL validation, refinement of QTL location and, ultimately, gene discovery. Results: In this study, a population of 75 Arabidopsis thaliana near-isogenic lines was developed from an existing recombinant inbred line (RIL) population derived from a cross between physiologically divergent accessions Kas-1 and Tsu-1. First, a novel algorithm was developed to utilize genome-wide marker data in selecting RILs fully isogenic to Kas-1 for a single chromosome. Seven such RILs were used in 2 generations of crossing to Tsu-1 to create BC1 seed. BC1 plants were genotyped with SSR markers so that lines could be selected that carried Kas-1 introgressions, resulting in a population carrying chromosomal introgressions spanning the genome. BC1 lines were genotyped with 48 genome-wide SSRs to identify lines with a targeted Kas-1 introgression and the fewest genomic introgressions elsewhere. 75 such lines were selected and genotyped at an additional 41 SNP loci and another 930 tags using 2b-RAD genotyping by sequencing. The final population carried an average of 1.35 homozygous and 2.49 heterozygous introgressions per line with average introgression sizes of 5.32 and 5.16 Mb, respectively. In a simple case study, we demonstrate the advantage of maintaining heterozygotes in our library whereby fine-mapping efforts are conducted simply by self-pollination. Crossovers in the heterozygous interval during this single selfing generation break the introgression into smaller, homozygous fragments (sub-NILs). Additionally, we utilize a homozygous NIL for validation of a QTL underlying stomatal conductance, a low heritability trait. Conclusions: The present results introduce a new and valuable resource to the Brassicaceae research community that enables rapid fine-mapping of candidate loci in parallel with QTL validation. These attributes along with dense marker coverage and genome-wide chromosomal introgressions make this population an ideal starting point for discovery of genes underlying important complex traits of agricultural and ecological significance.
    Electronic ISSN: 1471-2164
    Topics: Biology
    Published by BioMed Central
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  • 7
    Publication Date: 2016-05-29
    Description: Article Protein aggregates are associated with a wide variety of diseases. Here, in order to address how protein aggregation affects cellular homoeostasis, the authors describe a method to rapidly create protein aggregates in living cells and organisms with precise spatial and temporal control. Nature Communications doi: 10.1038/ncomms11689 Authors: Yusuke Miyazaki, Kota Mizumoto, Gautam Dey, Takamasa Kudo, John Perrino, Ling-chun Chen, Tobias Meyer, Thomas J. Wandless
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2015-02-04
    Description: Nature Geoscience 8, 122 (2015). doi:10.1038/ngeo2349 Authors: Hanno Meyer, Thomas Opel, Thomas Laepple, Alexander Yu Dereviagin, Kirstin Hoffmann & Martin Werner Relative to the past 2,000 years, the Arctic region has warmed significantly over the past few decades. However, the evolution of Arctic temperatures during the rest of the Holocene is less clear. Proxy reconstructions, suggest a long-term cooling trend throughout the mid- to late Holocene, whereas climate model simulations show only minor changes or even warming. Here we present a record of the oxygen isotope composition of permafrost ice wedges from the Lena River Delta in the Siberian Arctic. The isotope values, which reflect winter season temperatures, became progressively more enriched over the past 7,000 years, reaching unprecedented levels in the past five decades. This warming trend during the mid- to late Holocene is in opposition to the cooling seen in other proxy records. However, most of these existing proxy records are biased towards summer temperatures. We argue that the opposing trends are related to the seasonally different orbital forcing over this interval. Furthermore, our reconstructed trend as well as the recent maximum are consistent with the greenhouse gas forcing and climate model simulations, thus reconciling differing estimates of Arctic and northern high-latitude temperature evolution during the Holocene.
    Print ISSN: 1752-0894
    Electronic ISSN: 1752-0908
    Topics: Geosciences
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  • 9
    Publication Date: 2013-10-05
    Description: The t(8;21) chromosomal translocation activates aberrant expression of the AML1-ETO (AE) fusion protein and is commonly associated with core binding factor acute myeloid leukaemia (CBF AML). Combining a conditional mouse model that closely resembles the slow evolution and the mosaic AE expression pattern of human t(8;21) CBF AML with global transcriptome sequencing, we find that disease progression was characterized by two principal pathogenic mechanisms. Initially, AE expression modified the lineage potential of haematopoietic stem cells (HSCs), resulting in the selective expansion of the myeloid compartment at the expense of normal erythro- and lymphopoiesis. This lineage skewing was followed by a second substantial rewiring of transcriptional networks occurring in the trajectory to manifest leukaemia. We also find that both HSC and lineage-restricted granulocyte macrophage progenitors (GMPs) acquired leukaemic stem cell (LSC) potential being capable of initiating and maintaining the disease. Finally, our data demonstrate that long-term expression of AE induces an indolent myeloproliferative disease (MPD)-like myeloid leukaemia phenotype with complete penetrance and that acute inactivation of AE function is a potential novel therapeutic option. This novel model system of AML1-ETO driven acute myeloid leukaemia addresses the concept of ‘oncogene addiction’. Better understanding of AML1-ETO need to maintain leukemia and rewire the transcriptome may help to design future therapies.
    Print ISSN: 1757-4676
    Electronic ISSN: 1757-4684
    Topics: Medicine
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  • 10
    Publication Date: 2012-06-16
    Description: Background: Solely in Europoe, Salmonella Typhimurium causes more than 100,000 infections per year.Improved detection of livestock colonised with S. Typhimurium is necessary to preventfoodborne diseases. Currently, commercially available ELISA assays are based on a mixtureof O-antigens (LPS) or total cell lysate of Salmonella and are hampered by cross-reaction.The identification of novel immunogenic proteins would be useful to develop ELISA baseddiagnostic assays with a higher specificity. Results: A phage display library of the entire Salmonella Typhimurium genome was constructed and47 immunogenic oligopeptides were identified using a pool of convalescent sera from pigsinfected with Salmonella Typhimurium. The corresponding complete genes of seven of theidentified oligopeptids were cloned. Five of them were produced in E. coli. The immunogeniccharacter of these antigens was validated with sera from pigs infeced with S. Tyhimurium andcontrol sera from non-infected animals. Finally, human antibody fragments (scFv) againstthese five antigens were selected using antibody phage display and characterised. Conclusion: In this work, we identified novel immunogenic proteins of Salmonella Typhimurium andgenerated antibody fragments against these antigens completely based on phage display. Fiveimmunogenic proteins were validated using a panel of positive and negative sera forprospective applications in diagnostics of Salmonela Typhimurium.
    Electronic ISSN: 1472-6750
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Published by BioMed Central
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