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  • 1
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    Nicked-site substrates for a serine recombinase reveal enzyme-DNA communications and an essential tethering role of covalent enzyme-DNA linkages (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-12
    Description: To analyse the mechanism and kinetics of DNA strand cleavages catalysed by the serine recombinase Tn 3 resolvase, we made modified recombination sites with a single-strand nick in one of the two DNA strands. Resolvase acting on these sites cleaves the intact strand very rapidly, giving an abnormal half-site product which accumulates. We propose that these reactions mimic second-strand cleavage of an unmodified site. Cleavage occurs in a synapse of two sites, held together by a resolvase tetramer; cleavage at one site stimulates cleavage at the partner site. After cleavage of a nicked-site substrate, the half-site that is not covalently linked to a resolvase subunit dissociates rapidly from the synapse, destabilizing the entire complex. The covalent resolvase–DNA linkages in the natural reaction intermediate thus perform an essential DNA-tethering function. Chemical modifications of a nicked-site substrate at the positions of the scissile phosphodiesters result in abolition or inhibition of resolvase-mediated cleavage and effects on resolvase binding and synapsis, providing insight into the serine recombinase catalytic mechanism and how resolvase interacts with the substrate DNA.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Particle-in-cell simulations of collisionless magnetic reconnection with a non-uniform guide field (2016)
    American Institute of Physics (AIP)
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    Publication Date: 2016-03-03
    Description: Results are presented of a first study of collisionless magnetic reconnection starting from a recently found exact nonlinear force-free Vlasov–Maxwell equilibrium. The initial state has a Harris sheet magnetic field profile in one direction and a non-uniform guide field in a second direction, resulting in a spatially constant magnetic field strength as well as a constant initial plasma density and plasma pressure. It is found that the reconnection process initially resembles guide field reconnection, but that a gradual transition to anti-parallel reconnection happens as the system evolves. The time evolution of a number of plasma parameters is investigated, and the results are compared with simulations starting from a Harris sheet equilibrium and a Harris sheet plus constant guide field equilibrium.
    Print ISSN: 1070-664X
    Electronic ISSN: 1089-7674
    Topics: Physics
    Published by American Institute of Physics (AIP)
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  • 3
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    Contributions to the magnetospheric parallel electric field (2011)
    Wiley
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    Publication Date: 2011-07-20
    Description: Upward field-aligned currents and their associated parallel electric fields couple the ionosphere to the magnetosphere. It is desirable to know how such a potential drop is distributed along the flux tube, what controls its variation, and how it is balanced by the plasma. By considering the motion of the ionospheric and magnetospheric electrons and ions, under the influence of electrostatic and magnetic mirror forces, a quasi steady state, quasi-neutral electric field distribution along the magnetic flux tube can be obtained. A feature of the potential profiles is the occurrence of a potential jump that splits the profile into three distinct regions: below the jump, within the jump, and above the jump. Within a kinetic framework, we analyze how the plasma velocity distributions evolve along the flux tube, taking into account ionospheric, magnetospheric, mirroring, and precipitating electron populations. By calculating the moments of the governing Vlasov equation, we ascertain what balances the parallel electric field (E$\parallel$) and how it is maintained, establishing a dynamical equilibrium. Our calculations show that (1) earthward of the jump E$\parallel$ ≈ −(p$\perp$/enB)$\nabla$$\parallel$B associated with the ionospheric electrons, except for at the base of the F region where p$\parallel$ contributions become more significant; (2) within the jump magnetosphere electrons dominate and E$\parallel$ ≈ −(1/en)$\nabla$$\parallel$p$\parallel$; and (3) above the jump mirroring magnetospheric electrons make a principal contribution of E$\parallel$ ≈ −(1/en)$\nabla$$\parallel$p$\parallel$, with a secondary contribution of −(p$\perp$ − p$\parallel$)$\nabla$$\parallel$B/(ne) becoming comparable beyond ≈3 RE. Additionally, we found that although the precipitating electrons carry the field-aligned current, it is the mirroring population that determines where E$\parallel$ is concentrated and hence where precipitating electrons are accelerated.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 4
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    Interhomolog recombination and loss of heterozygosity in wild-type and Bloom syndrome helicase (BLM)-deficient mammalian cells [Genetics] (2011)
    National Academy of Sciences
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    Publication Date: 2011-07-20
    Description: Genomic integrity often is compromised in tumor cells, as illustrated by genetic alterations leading to loss of heterozygosity (LOH). One mechanism of LOH is mitotic crossover recombination between homologous chromosomes, potentially initiated by a double-strand break (DSB). To examine LOH associated with DSB-induced interhomolog recombination, we analyzed recombination events using a reporter in mouse embryonic stem cells derived from F1 hybrid embryos. In this study, we were able to identify LOH events although they occur only rarely in wild-type cells (≤2.5%). The low frequency of LOH during interhomolog recombination suggests that crossing over is rare in wild-type cells. Candidate factors that may suppress crossovers include the RecQ helicase deficient in Bloom syndrome cells (BLM), which is part of a complex that dissolves recombination intermediates. We analyzed interhomolog recombination in BLM-deficient cells and found that, although interhomolog recombination is slightly decreased in the absence of BLM, LOH is increased by fivefold or more, implying significantly increased interhomolog crossing over. These events frequently are associated with a second homologous recombination event, which may be related to the mitotic bivalent structure and/or the cell-cycle stage at which the initiating DSB occurs.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    Pulsar electrodynamics: Relativistic kinetic theory of radiative plasmas—collective phenomena and their radiation (2011)
    American Physical Society (APS)
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    Publication Date: 2011-01-20
    Description: Author(s): A. A. da Costa, D. A. Diver, E. W. Laing, C. R. Stark, and L. F. A. Teodoro The classical modeling of radiation by accelerated charged particles in pulsars predicts a cutoff in photon energy at around 25 GeV. While this is broadly consistent with observations, the classical treatment is not self-consistent, and cannot be extended to explain the rare high-energy detections ... [Phys. Rev. D 83, 023013] Published Wed Jan 19, 2011
    Keywords: D15
    Print ISSN: 0556-2821
    Electronic ISSN: 1089-4918
    Topics: Physics
    Published by American Physical Society (APS)
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  • 6
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    Morphological and physiological traits in relation to carbon balance in a diverse clade of dryland mosses (2019)
    Details
    Publication Date: 2019
    Description: Abstract Plant functional trait analyses have focused almost exclusively on vascular plants, but bryophytes comprise ancient and diverse plant lineages that have widespread global distributions and important ecological functions in terrestrial ecosystems. We examined a diverse clade of dryland mosses, Syntrichia, and studied carbon balance during a precipitation event (C‐balance), a functional trait related to physiological functioning, desiccation tolerance, survival, and ecosystem carbon and nitrogen cycling. We examined variability in C‐balance among 14 genotypes of Syntrichia and measured an additional 10 physiological and 13 morphological traits at the cell, leaf, shoot, and clump level. C‐balance varied 20‐fold among genotypes, and highest C‐balances were associated with long, narrow leaves with awns, and small cells with thick cell walls, traits that may influence water uptake and retention during a precipitation event. Ordination analyses revealed that the axis most strongly correlated with C‐balance included the maximum chlorophyll fluorescence, Fm, indicating the importance of photosystem II health for C exchange. C‐balance represents a key functional trait in bryophytes, but its measurement is time intensive and not feasible to measure on large scales. We propose two models (using physiological and morphological traits) to predict C‐balance, whereby identifying simpler to measure traits for trait databases.
    Print ISSN: 0140-7791
    Electronic ISSN: 1365-3040
    Topics: Biology
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  • 7
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    Defective TNF-alpha-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases (1997)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1997-12-31
    Description: Signal transducers and activators of transcription (STATs) enhance transcription of specific genes in response to cytokines and growth factors. STAT1 is also required for efficient constitutive expression of the caspases Ice, Cpp32, and Ich-1 in human fibroblasts. As a consequence, STAT1-null cells are resistant to apoptosis by tumor necrosis factor alpha (TNF-alpha). Reintroduction of STAT1alpha restored both TNF-alpha-induced apoptosis and the expression of Ice, Cpp32, and Ich-1. Variant STAT1 proteins carrying point mutations that inactivate domains required for STAT dimer formation nevertheless restored protease expression and sensitivity to apoptosis, indicating that the functions of STAT1 required for these activities are different from those that mediate induced gene expression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kumar, A -- Commane, M -- Flickinger, T W -- Horvath, C M -- Stark, G R -- P01 CA62220/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1997 Nov 28;278(5343):1630-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9374464" target="_blank"〉PubMed〈/a〉
    Keywords: *Apoptosis ; Caspase 1 ; Caspase 2 ; Caspase 3 ; *Caspases ; Cell Line ; Cysteine Endopeptidases/genetics/*metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Dactinomycin/pharmacology ; Dimerization ; Gene Expression Regulation, Enzymologic ; Humans ; Interferon-gamma/pharmacology ; Phosphorylation ; Point Mutation ; Proteins/genetics/*metabolism ; STAT1 Transcription Factor ; Signal Transduction ; Trans-Activators/chemistry/genetics/*metabolism ; Transfection ; Tumor Necrosis Factor-alpha/*pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    TRAF4 binds to the juxtamembrane region of EGFR directly and promotes kinase activation [Cell Biology] (2018)
    National Academy of Sciences
    Details
    Publication Date: 2018-11-07
    Description: The activation of the epidermal growth factor receptor (EGFR) is crucial for triggering diverse cellular functions, including cell proliferation, migration, and differentiation, and up-regulation of EGFR expression or activity is a key factor in triggering the development of cancer. Here we show that overexpression of a scaffold protein, tumor necrosis...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 9
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    Progesterone receptor modulates ERalpha action in breast cancer (2015)
    Nature Publishing Group (NPG)
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    Publication Date: 2015-07-15
    Description: Progesterone receptor (PR) expression is used as a biomarker of oestrogen receptor-alpha (ERalpha) function and breast cancer prognosis. Here we show that PR is not merely an ERalpha-induced gene target, but is also an ERalpha-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERalpha to direct ERalpha chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited oestrogen-mediated growth of ERalpha(+) cell line xenografts and primary ERalpha(+) breast tumour explants, and had increased anti-proliferative effects when coupled with an ERalpha antagonist. Copy number loss of PGR, the gene coding for PR, is a common feature in ERalpha(+) breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERalpha chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650274/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650274/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohammed, Hisham -- Russell, I Alasdair -- Stark, Rory -- Rueda, Oscar M -- Hickey, Theresa E -- Tarulli, Gerard A -- Serandour, Aurelien A -- Birrell, Stephen N -- Bruna, Alejandra -- Saadi, Amel -- Menon, Suraj -- Hadfield, James -- Pugh, Michelle -- Raj, Ganesh V -- Brown, Gordon D -- D'Santos, Clive -- Robinson, Jessica L L -- Silva, Grace -- Launchbury, Rosalind -- Perou, Charles M -- Stingl, John -- Caldas, Carlos -- Tilley, Wayne D -- Carroll, Jason S -- 242664/European Research Council/International -- 5P30CA142543/CA/NCI NIH HHS/ -- A10178/Cancer Research UK/United Kingdom -- England -- Nature. 2015 Jul 16;523(7560):313-7. doi: 10.1038/nature14583. Epub 2015 Jul 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK. ; Dame Roma Mitchell Cancer Research Laboratories and the Adelaide Prostate Cancer Research Centre, School of Medicine, Hanson Institute Building, University of Adelaide, Adelaide, South Australia 5005, Australia. ; Department of Urology, University of Texas, Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA. ; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 450 West Drive, CB7295, Chapel Hill, North Carolina 27599, USA. ; 1] Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK [2] Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 2QQ, UK [3] Cambridge Experimental Cancer Medicine Centre, Cambridge CB2 0RE, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26153859" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/drug therapy/*genetics/*metabolism/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Chromatin/drug effects/genetics/metabolism ; DNA Copy Number Variations/genetics ; Disease Progression ; Estrogen Receptor alpha/antagonists & inhibitors/*metabolism ; Estrogens/metabolism/pharmacology ; Female ; *Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Ligands ; Mice ; Progesterone/metabolism/pharmacology ; Protein Binding/drug effects ; Receptors, Progesterone/genetics/*metabolism ; Transcription, Genetic/drug effects ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 10
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    Corrigendum: Progesterone receptor modulates ERalpha action in breast cancer (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohammed, Hisham -- Russell, I Alasdair -- Stark, Rory -- Rueda, Oscar M -- Hickey, Theresa E -- Tarulli, Gerard A -- Serandour, Aurelien A -- Birrell, Stephen N -- Bruna, Alejandra -- Saadi, Amel -- Menon, Suraj -- Hadfield, James -- Pugh, Michelle -- Raj, Ganesh V -- Brown, Gordon D -- D'Santos, Clive -- Robinson, Jessica L L -- Silva, Grace -- Launchbury, Rosalind -- Perou, Charles M -- Stingl, John -- Caldas, Carlos -- Tilley, Wayne D -- Carroll, Jason S -- England -- Nature. 2015 Oct 1;526(7571):144. doi: 10.1038/nature14959. Epub 2015 Aug 5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26245370" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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