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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Macromolecules 20 (1987), S. 1965-1975 
    ISSN: 1520-5835
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Macromolecules 20 (1987), S. 2833-2840 
    ISSN: 1520-5835
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    International Journal of Radiation Applications & Instrumentation. Part 37 (1986), S. 491-495 
    ISSN: 0883-2889
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    International orthopaedics 17 (1993), S. 214-218 
    ISSN: 1432-5195
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Nombre de travaux ont été effectués récemment afin d'expliquer l'évolution vers l'arthrose après méniscectomie. Les modifications mécaniques entraînant une concentration des contraintes sont considérées comme une des causes majeures. Mais il n'y a que peu d'études expérimentales concernant les différences de pression sur la surface de contact et le type de distribution des contraintes après méniscectomie partielle ou totale. En utilisant un film sensible à la pression (Pressensor) nous avons pu mesurer la surface de contact et son type de distribution dans les trois situations: ménisque intact, méniscectomie partielle et méniscectomie totale. Le matériel d'expérimentation consistait en cinq pièces d'amputation de cuisse. Pendant l'expérimentation le genou était placé en extension complète et fixé à la machine Instrom par une barre d'aluminium et une monture de résine. La charge était transmise par la machine à l'articulation fémoro-tibiale et au film Pressensor pré-inséré, dans les limites physiologiques. L'analyse de la surface de contact dans les trois situations a été permise par l'examen du film. En mesurant la surface de contact après méniscectomie nous avons montré que la fonction du ménisque est d'assurer la transmission des charges et l'absorption d'énergie dans le genou. La comparaison de la surface de contact interne de l'articulation avec la surface de contact externe montre que, lorsque le ménisque est intact, la première est toujours plus étendue que la seconde (le rapport est de 1.36). La différence diminue légérement en cas de méniscectomie partielle et beaucoup plus après méniscectomie totale. Le degré de concentration des contraintes augmente selon que le ménisque est intact, partiellement ou totalement réséqué. Il n'y a que de minimes modifications de la surface de contact du côté opposé de l'articulation après méniscectomie partielle, mais elles sont importantes après méniscectomie totale.
    Notes: Summary Many investigators have attempted to find the cause of the osteoarthritic changes after meniscectomy. Alteration of the mechanical factors resulting in stress concentration, is now thought to be one of the most important causes but few experimental studies have reported the differences in contact area and pressure distribution after partial or total meniscectomy. By using pressure sensitive film, we have calculated the contact area and the pattern of weight distribution in three different situations; intact meniscus, partial and total meniscectomy. The experimental materials were obtained from 5 above knee amputation specimens. The knee joint was fixed in full extension to an Instron machine using an aluminium box and mounting resin. Load was transmitted to the tibiofemoral joint containing the special film, within a physiological range. Analysis of the contact area for each situation (intact meniscus, partial and total meniscectomy) was made by reviewing the film, By measuring the contact area after meniscectomy, we showed that the meniscus performs a load transmitting function in the knee joint. The medial contact area of the tibiofemoral joint with an intact meniscus is always larger than the lateral compartment (1.36:1), but in partial and total meniscectomy the difference between them gradually decreased. There was a minor decrease in contact area after partial meniscectomy and a much greater decrease after total meniscectomy. The degree of stress concentration in the contact area was increased when part or all the meniscus was excised. There was little change of contact area in the opposite, intact side of the joint after partial meniscectomy, but marked change after total meniscectomy.
    Type of Medium: Electronic Resource
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  • 5
    Publication Date: 2013-07-02
    Description: To study the genomic plasticity of somatic cells without ectopic genetic manipulation, we cultured mouse fibroblasts with ovarian cells, embryonic fibroblasts of different strains, and parthenogenetic embryonic stem cells (ESCs). Of 41 trials, cell aggregation resembling nascent ESC colony from inner cell mass was detected in 9 cases (22%), and 6 cases (67%) yielded fibroblast-derived colonies with ESC morphology. Cells used in coculture provided the critical ( P =0.0061) inducing factor for the aggregation. These colony-forming fibroblasts (CFFs) showed similar characteristics to those in ESCs and induced pluripotent stem cells (iPSCs), including pluripotency gene expression, in vitro differentiation, and teratoma formation. Furthermore, CFFs produced somatic chimera, although none showed germline chimerism. CFFs had a tetraploid-like karyotype, and their imprinting patterns differed from parthenogenetic ESCs, thereby confirming their nongermline transmissibility. We observed dysregulation of cell cycle-related proteins, as well as both homologous and heterologous recombination of genomic single-nucleotide polymorphisms in CFFs. Our observations provide information on somatic cell plasticity, resulting in stemness or tumorigenesis, regardless of colony-forming cell progenitors in the fibroblast population. The plasticity of somatic genomes under environmental influences, as well as acquisition of pluripotency by cell fusion, is also implicated.—Lee, S. T., Gong, S. P., Yum, K. E., Lee, E. J., Lee, C. H., Choi, J. H., Kim, D. Y., Han, H., Kim, K.-S., Hysolli, E., Ahn, J. Y., Park, I.-H., Han, J. Y., Jeong, J.-W., Lim, J. M. Transformation of somatic cells into stem cell-like cells under a stromal niche.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
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  • 6
    Publication Date: 2011-11-30
    Description: ES cells proliferate with very short gap phases yet maintain their capacity to differentiate. It had been thought that the levels of cyclins and other substrates of ubiquitin ligase APC/C remain nearly constant and Cdk activity remains constitutively high in mouse ES cells. Here we demonstrate that APC/C (anaphase-promoting complex/cyclosome) enzyme is active in ES cells but attenuated by high levels of the Emi1 (early mitotic inhibitor-1) protein. Despite the presence of high Cdk activity during the G1 phase, chromatin can be effectively licensed for DNA replication and fast entry into the S phase can still occur. High Cdk activity during S-G2-M phases produces high levels of the DNA replication factor Cdt1, and this leads to efficient Mcm proteins loading on chromatin after mitotic exit. Although disturbing the usual balance between Cdk activity and APC/C activity found in somatic cells, a few key adaptations allow normal progression of a very rapid cell cycle.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
    Publication Date: 2014-01-24
    Description: In the large-quantity production of α2,3- and α2,6-sialyllactose (Neu5Ac(α2,3)Galβ1,4Glc (3'-SL) and Neu5Ac(α2,6)Galβ1,4Glc (6'-SL)) using sialyltransferases (STs), there are major hurdles to overcome for further improvement in yield and productivity of the enzyme reactions. Specifically, Pasteurella multocida α2,3-sialyltransferase (α2,3PST) forms a by-product to a certain extent, owing to its multifunctional activity at pH below 7.0, and Photobacterium damselae α2,6-sialyltransferase (α2,6PdST) shows relatively low ST activity. In this study, α2,3PST and α2,6PdST were successfully engineered using a hybrid approach that combines rational design with site-saturation mutagenesis. Narrowly focused on the substrate-binding pocket of the STs, putative functional residues were selected by multiple sequence alignment and alanine scanning, and subsequently subjected to site-saturation mutagenesis. In the case of α2,3PST, R313N single mutation improved its activity slightly (by a factor of 1.5), and further improvement was obtained by making the double mutants (R313N/T265S and R313H/T265S) resulting in an overall 2-fold improvement in its specific α2,3 ST activity, which is mainly caused by the increase in k cat . It was revealed that the R313 mutations to N, D, Y, H or T greatly reduced the α2,6 ST side-reaction activity of α2,3PST at below pH 7.0. In the case of α2,6PdST, single-mutation L433S/T and double-mutation I411T/L433T exhibited 3- and 5-fold enhancement of the α2,6 ST-specific activity compared with the wild-type, respectively, via increase in k cat values. Our results show a very good model system for enhancing ST activity and demonstrate that the generated mutants could be used efficiently for the mass production of 3'-SL and 6'-SL with enhanced productivity and yield.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
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  • 8
    Publication Date: 2014-01-24
    Description: Rett syndrome (RTT) is one of the most prevalent female mental disorders. De novo mutations in methyl CpG-binding protein 2 (MeCP2) are a major cause of RTT. MeCP2 regulates gene expression as a transcription regulator as well as through long-range chromatin interaction. Because MeCP2 is present on the X chromosome, RTT is manifested in an X-linked dominant manner. Investigation using murine MeCP2 null models and post-mortem human brain tissues has contributed to understanding the molecular and physiological function of MeCP2. In addition, RTT models using human induced pluripotent stem cells derived from RTT patients (RTT-iPSCs) provide novel resources to elucidate the regulatory mechanism of MeCP2. Previously, we obtained clones of female RTT-iPSCs that express either wild-type or mutant MECP2 due to the inactivation of one X chromosome. Reactivation of the X chromosome also allowed us to have RTT-iPSCs that express both wild-type and mutant MECP2 . Using these unique pluripotent stem cells, we investigated the regulation of gene expression by MeCP2 in pluripotent stem cells by transcriptome analysis. We found that MeCP2 regulates genes encoding mitochondrial membrane proteins. In addition, loss of function in MeCP2 results in de-repression of genes on the inactive X chromosome. Furthermore, we showed that each mutation in MECP2 affects a partly different set of genes. These studies suggest that fundamental cellular physiology is affected by mutations in MECP2 from early development, and that a therapeutic approach targeting to unique forms of mutant MeCP2 is needed.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 9
    Publication Date: 2011-08-24
    Description: Rett syndrome (RTT) is one of the most prevalent female neurodevelopmental disorders that cause severe mental retardation. Mutations in methyl CpG binding protein 2 (MeCP2) are mainly responsible for RTT. Patients with classical RTT exhibit normal development until age 6–18 mo, at which point they become symptomatic and display loss of language and motor skills, purposeful hand movements, and normal head growth. Murine genetic models and postmortem human brains have been used to study the disease and enable the molecular dissection of RTT. In this work, we applied a recently developed reprogramming approach to generate a novel in vitro human RTT model. Induced pluripotent stem cells (iPSCs) were derived from RTT fibroblasts by overexpressing the reprogramming factors OCT4, SOX2, KLF4, and MYC. Intriguingly, whereas some iPSCs maintained X chromosome inactivation, in others the X chromosome was reactivated. Thus, iPSCs were isolated that retained a single active X chromosome expressing either mutant or WT MeCP2, as well as iPSCs with reactivated X chromosomes expressing both mutant and WT MeCP2. When these cells underwent neuronal differentiation, the mutant monoallelic or biallelelic RTT-iPSCs displayed a defect in neuronal maturation consistent with RTT phenotypes. Our in vitro model of RTT is an important tool allowing the further investigation of the pathophysiology of RTT and the development of the curative therapeutics.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 10
    Publication Date: 2012-04-11
    Description: Transactive response DNA-binding (TDP-43) protein is the dominant disease protein in amyotrophic lateral sclerosis (ALS) and a subgroup of frontotemporal lobar degeneration (FTLD-TDP). Identification of mutations in the gene encoding TDP-43 (TARDBP) in familial ALS confirms a mechanistic link between misaccumulation of TDP-43 and neurodegeneration and provides an opportunity to study TDP-43 proteinopathies in human neurons generated from patient fibroblasts by using induced pluripotent stem cells (iPSCs). Here, we report the generation of iPSCs that carry the TDP-43 M337V mutation and their differentiation into neurons and functional motor neurons. Mutant neurons had elevated levels of soluble and detergent-resistant TDP-43 protein, decreased survival in longitudinal studies, and increased vulnerability to antagonism of the PI3K pathway. We conclude that expression of physiological levels of TDP-43 in human neurons is sufficient to reveal a mutation-specific cell-autonomous phenotype and strongly supports this approach for the study of disease mechanisms and for drug screening.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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