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  • Articles  (28)
  • National Academy of Sciences  (23)
  • Wiley-Blackwell  (5)
  • 2015-2019  (17)
  • 2005-2009  (6)
  • 1990-1994  (4)
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  • Biology  (28)
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  • Articles  (28)
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  • 1
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 22 (1992), S. 81-91 
    ISSN: 0886-1544
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Additional Material: 2 Ill.
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 15 (1973), S. 377-393 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A general mathematical model of the chemostat system is developed in order to define an experimental program of dynamic testing. A glucose-limited culture ofSaccharomyces cerevisiae was grown in a chemostat using chemically defined medium. The chemostat was perturbed from an initial steady state by changes in input glucose concentration, dilution rate, pH, and temperature. Dynamic responses of cell mass, glucose, cell number, RNA, and protein concentrations were measured. A number of simulation techniques were used in developing a dynamic mathematical model and in comparing the developed model with experimental data as well as the Monod model. The resulting model was found to be quantitatively accurate and superior to the Monod model. The developed model was interpreted in the light of cell physiology. Adjustment of intracellular RNA fraction was found to be rate limiting in acceleration of cell specific growth rate.
    Additional Material: 14 Ill.
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 159 (1994), S. 1-10 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Plasmin (Pm) is a broad action serine protease implicated in numerous physiological functions. In bone, Pm may play a role in growth, resorption, metastasis, and the activation of growth factors. The various components of the Pm system are known to bind and function on the cell surface of various cell types, but no pertinent data are available describing membrane-bound Pm or its zymogen, plasminogen (Pg), in either normal or neoplastic bone cells. We report here that Pg binds to the surface of the human osteosarcoma cell line MG-63 and is activated to Pm by endogenous urokinase plasminogen activator (uPA). These conclusions are based on experiments utilizing radiolabeled compounds and a cell surface proteolytic assay measuring amidolytic activity of Pm. 125I-Pg binding to cells was time dependent, saturable, reversible, and specific. Binding was characterized by a relatively low affinity (Kd ∼0.9 μM) and a high capacity (∼7.5 x 106 sites/cell). The binding of 125I-Pg was associated with lysine binding sites of the plasminogen molecule. Activation of 125I-Pg to 125I-Pm occurred on the cell surface and was dependent upon cell bound uPA, as determined by inhibitory antibodies. Binding of Pg to MG-63 monolayers represented ∼80% bound specifically to the cell surface and the remainder to the surrounding extracellular matrix. Either co-incubation with uPA or pre-incubation with Pm resulted in increased 125I-Pg binding to osteosarcoma cells. Cell surface Pm proteolytic activity was confirmed by an amidolytic chromogenic assay. Both Pm and Pg bound to cells with Pg being activated by endogenous uPA. Plasmin activated on the cell surface was partially protected from inhibition by α2-antiPm (requiring Pm lysine binding site interaction) but inhibited by aprotinin, (interacting directly with the Pm catalytic site). Resistance of cell bound Pm to α2-antiPm inhibition suggests that cell surface proteolysis can occur in the presence of a soluble Pm inhibitor known to exist in the extracellular space. Based on these results, we speculate that the various bone physiological processes implicating Pm may occur at or near the bone cell surface. © 1994 wiley-Liss, Inc.
    Additional Material: 7 Ill.
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  • 4
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Lack of estrogen receptor (ER) and presence of vimentin (VIM) associate with poor prognosis in human breast cancer. We have explored the relationships between ER, VIM, and invasiveness in human breast cancer cell lines. In the matrigel outgrowth assay, ER+/VIM- (MCF-7, T47D, ZR-75-1), and ER-/VIM- (MDA-MB-468, SK-Br-3) cell lines were uninvasive, while ER-/VIM+ (BT549, MDA-MB-231, MDA-MB-435, MDA-MB-436, Hs578T) lines formed invasive, penetrating colonies. Similarly, ER-/VIM+ cell lines were significantly more invasive than either the ER+/VIM- or ER-/VIM- cell lines in the Boyden chamber chemoinvasion assay. Invasive activity in nude mice was only seen with ER-/VIM+ cell lines MDA-MB-231, MDA-MB-435 and MDA-MB-436. Hs578T cells (ER-/VIM +) showed hematogenous dissemination to the lungs in one of five mice, but lacked local invasion. The ER-/VIM+ MCF-7ADR subline was significantly more active than the MCF-7 cells in vitro, but resembled the wild-type MCF-7 parent in in vivo activity. Data from these cell lines suggest that human breast cancer progression results first in the loss of ER, and subsequently in VIM acquisition, the latter being associated with increased metastatic potential through enhanced invasiveness. The MCF-7ADR data provide evidence that this transition can occur in human breast cancer cells. Vimentin expression may provide useful insights into mechanisms of invasion and/or breast cancer cell progression.
    Additional Material: 6 Ill.
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  • 5
    ISSN: 0173-0835
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Lipoprotein(a) resembles low density lipoprotein in structure, except that a unique apolipoprotein (apo), apo(a), is linked to apo B-100. Variations in the number of sequence repeats in the apo(a) gene give rise to a range of isoforms. Depending on the method used, 6-30 apo(a) isoforms have been observed; however, the correspondence of these different isoforms has not been reported, making between-study comparisons difficult. In the present study we address this question by characterizing the apo(a) phenotypes of 48 sera using two previously reported separation methods, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE, 3-12% gels) and SDS-agarose gel electrophoresis. In addition, the molecular weight of each isoform was estimated using haptoglobin 2-2 polymers as molecular weight standards. Among the 48 sera, 15 distinct apo(a) isoforms were separated by SDS-PAGE and 28 by SDS-agarose gel electrophoresis. There was excellent correlation between the two nomenclature systems (r = -0.97, p 〈 0.001, by rank correlation), and the ranges were totally overlapping, with the same two isoforms being identified as the largest and smallest by either method. The apparent molecular mass range for the isoforms was 294-624 kDa, which is in close agreement with the theoretical molecular mass range of 238-643 kDa, calculated from the sequence and carbohydrate content of recombinant apo(a). The disparity in number of isoforms between methods was expected, due to the poorer separation of apo(a) by SDS-PAGE; 3.1 ± 1.7 (median, 2.0) SDS-agarose isoforms were combined for each SDS-PAGE isoform. The present study demonstrates that the nomenclature systems for apo(a) isoforms separated by SDS-PAGE or by SDS-agarose gel electrophoresis are well correlated mathematically and encompass the same size range; however, the better resolution of SDS-agarose electrophoresis suggests that it is the method of choice for apo(a) phenotyping. As further apo(a) isoforms are identified, it will be important to address the question of a standardized nomenclature, in order to facilitate between-study comparisons.
    Additional Material: 3 Ill.
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  • 6
    Publication Date: 2017-11-27
    Description: During the Mid-Pleistocene Transition (MPT; 1,200–800 kya), Earth’s orbitally paced ice age cycles intensified, lengthened from ∼40,000 (∼40 ky) to ∼100 ky, and became distinctly asymmetrical. Testing hypotheses that implicate changing atmospheric CO2 levels as a driver of the MPT has proven difficult with available observations. Here, we use orbitally resolved, boron isotope CO2 data to show that the glacial to interglacial CO2 difference increased from ∼43 to ∼75 μatm across the MPT, mainly because of lower glacial CO2 levels. Through carbon cycle modeling, we attribute this decline primarily to the initiation of substantive dust-borne iron fertilization of the Southern Ocean during peak glacial stages. We also observe a twofold steepening of the relationship between sea level and CO2-related climate forcing that is suggestive of a change in the dynamics that govern ice sheet stability, such as that expected from the removal of subglacial regolith or interhemispheric ice sheet phase-locking. We argue that neither ice sheet dynamics nor CO2 change in isolation can explain the MPT. Instead, we infer that the MPT was initiated by a change in ice sheet dynamics and that longer and deeper post-MPT ice ages were sustained by carbon cycle feedbacks related to dust fertilization of the Southern Ocean as a consequence of larger ice sheets.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 7
    Publication Date: 2016-05-16
    Description: Isoprene photooxidation is a major driver of atmospheric chemistry over forested regions. Isoprene reacts with hydroxyl radicals (OH) and molecular oxygen to produce isoprene peroxy radicals (ISOPOO). These radicals can react with hydroperoxyl radicals (HO2) to dominantly produce hydroxyhydroperoxides (ISOPOOH). They can also react with nitric oxide (NO) to largely produce methyl vinyl ketone (MVK) and methacrolein (MACR). Unimolecular isomerization and bimolecular reactions with organic peroxy radicals are also possible. There is uncertainty about the relative importance of each of these pathways in the atmosphere and possible changes because of anthropogenic pollution. Herein, measurements of ISOPOOH and MVK + MACR concentrations are reported over the central region of the Amazon basin during the wet season. The research site, downwind of an urban region, intercepted both background and polluted air masses during the GoAmazon2014/5 Experiment. Under background conditions, the confidence interval for the ratio of the ISOPOOH concentration to that of MVK + MACR spanned 0.4–0.6. This result implies a ratio of the reaction rate of ISOPOO with HO2 to that with NO of approximately unity. A value of unity is significantly smaller than simulated at present by global chemical transport models for this important, nominally low-NO, forested region of Earth. Under polluted conditions, when the concentrations of reactive nitrogen compounds were high (〉1 ppb), ISOPOOH concentrations dropped below the instrumental detection limit (
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
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  • 8
    Publication Date: 2017-07-31
    Description: Binding-site water is often displaced upon ligand recognition, but is commonly neglected in structure-based ligand discovery. Inhomogeneous solvation theory (IST) has become popular for treating this effect, but it has not been tested in controlled experiments at atomic resolution. To do so, we turned to a grid-based version of this method, GIST, readily implemented in molecular docking. Whereas the term only improves docking modestly in retrospective ligand enrichment, it could be added without disrupting performance. We thus turned to prospective docking of large libraries to investigate GIST’s impact on ligand discovery, geometry, and water structure in a model cavity site well-suited to exploring these terms. Although top-ranked docked molecules with and without the GIST term often overlapped, many ligands were meaningfully prioritized or deprioritized; some of these were selected for testing. Experimentally, 13/14 molecules prioritized by GIST did bind, whereas none of the molecules that it deprioritized were observed to bind. Nine crystal complexes were determined. In six, the ligand geometry corresponded to that predicted by GIST, for one of these the pose without the GIST term was wrong, and three crystallographic poses differed from both predictions. Notably, in one structure, an ordered water molecule with a high GIST displacement penalty was observed to stay in place. Inclusion of this water-displacement term can substantially improve the hit rates and ligand geometries from docking screens, although the magnitude of its effects can be small and its impact in drug binding sites merits further controlled studies.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
    Publication Date: 2018-01-18
    Description: Growth/differentiation factor 8 (GDF8), or myostatin, negatively regulates muscle mass. GDF8 is held in a latent state through interactions with its N-terminal prodomain, much like TGF-β. Using a combination of small-angle X-ray scattering and mutagenesis, we characterized the interactions of GDF8 with its prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully latent state and an activated or “triggered” state where the prodomain remains in complex with the mature domain. However, these states are not reversible, indicating the latent GDF8 is “spring-loaded.” Structural analysis shows that the prodomain:GDF8 complex adopts an “open” configuration, distinct from the latency state of TGF-β and more similar to the open state of Activin A and BMP9 (nonlatent complexes). We determined that GDF8 maintains similar features for latency, including the alpha-1 helix and fastener elements, and identified a series of mutations in the prodomain of GDF8 that alleviate latency, including I56E, which does not require activation by the protease Tolloid. In vivo, active GDF8 variants were potent negative regulators of muscle mass, compared with WT GDF8. Collectively, these results help characterize the latency and activation mechanisms of GDF8.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
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  • 10
    Publication Date: 2019-05-20
    Description: The hydroxyl radical (OH) fuels tropospheric ozone production and governs the lifetime of methane and many other gases. Existing methods to quantify global OH are limited to annual and global-to-hemispheric averages. Finer resolution is essential for isolating model deficiencies and building process-level understanding. In situ observations from the Atmospheric Tomography (ATom) mission demonstrate that remote tropospheric OH is tightly coupled to the production and loss of formaldehyde (HCHO), a major hydrocarbon oxidation product. Synthesis of this relationship with satellite-based HCHO retrievals and model-derived HCHO loss frequencies yields a map of total-column OH abundance throughout the remote troposphere (up to 70% of tropospheric mass) over the first two ATom missions (August 2016 and February 2017). This dataset offers unique insights on near-global oxidizing capacity. OH exhibits significant seasonality within individual hemispheres, but the domain mean concentration is nearly identical for both seasons (1.03 ± 0.25 × 106 cm−3), and the biseasonal average North/South Hemisphere ratio is 0.89 ± 0.06, consistent with a balance of OH sources and sinks across the remote troposphere. Regional phenomena are also highlighted, such as a 10-fold OH depression in the Tropical West Pacific and enhancements in the East Pacific and South Atlantic. This method is complementary to budget-based global OH constraints and can help elucidate the spatial and temporal variability of OH production and methane loss.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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