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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Macromolecules 16 (1983), S. 1243-1244 
    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.] : Nature Publishing Group
    Nature 271 (1978), S. 665-666 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Sera were initially obtained from two normal donors and two myasthenia gravis patients who had undergone thymectomy (samples by kind permission of Dr J. Posner, Memorial Hospital and Dr G. Genkins, Mt Sinai Hospital, New York City). As described by Astaldi et al.2, we separated the fresh serum into ...
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Die Makromolekulare Chemie 182 (1981), S. 941-947 
    ISSN: 0025-116X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Monodispersed N-and C-protected linear homo-oligomers of S-methyl-L-cysteine (n = 2 - 7) are studied by measurements of circular dichroism in the vacuum-ultraviolet region. In the solid state higher members of the series take up a β-conformation. The results are compared with earlier circular dichroism and infrared absorption measurements on the same series, and also with the related norvaline and methionine series.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2018-03-08
    Description: This article reports the results of a study of submarine groundwater discharge (SGD) to coastal waters of Majorca (NW Mediterranean). The overall aim is to evaluate the relevance of SGD of the island and chemically characterize the components that are supplied to the coastal waters through this pathway. Although other discharge areas are identified, we particularly focus on SGD in bays and areas of increased sea water residence time where effects of the discharges are expected to be most notable. Analysis at four selected embayments with different land-use characteristics indicated a link between human activities (mainly agriculture and urban) and compounds arriving to the coast. A pathway for these elements is the diffuse discharge along the shoreline, as suggested by the inverse relationship between salinity and nutrients in nearshore porewaters. A general survey was conducted at 46 sites around the island, and used dissolved radium as a qualitative indicator of SGD. Measurements of nutrients (P and N), pCO2 and TOC were performed to characterize the elements delivered to the coastal environment. Most nearshore samples showed 224Ra enrichment (mean ± SE, 7.0 ± 0.6 dpm 100 l−1) with respect to offshore waters (1.1 ± 0.2 dpm 100 l−1); however, 224Ra measurements along the coast were highly variable (1.0–38.1 dpm 100 l−1). Coastal samples with enhanced radium levels showed elevated pCO2 with respect to atmospheric concentrations, which together with high pCO2 in groundwater (〉5,000 ppm) indicates that SGD is an important vector of CO2 to coastal waters. Moreover, a relationship between 224Ra and phytoplankton biomass was established, suggesting an important impact of SGD on coastal productivity. The results presented here provide a first approximation of the SGD effect in the coastal waters of Majorca, and indicate that SGD could be an important source of nutrients and CO2 to the coast, strongly influencing the productivity and biogeochemical cycling of the coastal waters of Majorca.
    Type: Article , PeerReviewed
    Format: text
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  • 5
    Publication Date: 2013-05-29
    Description: Establishment and maintenance of apico-basolateral trafficking pathways are critical to epithelial homeostasis. Loss of polarity and trafficking fidelity are thought to occur as a consequence of transformation; however, here we report that selective mistrafficking of the epidermal growth factor receptor (EGFR) ligand epiregulin (EREG) from the basolateral to the apical...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2014-04-16
    Description: Purpose: Apoptosis, or programmed cell death, can be leveraged as a surrogate measure of response to therapeutic interventions in medicine. Cysteine aspartic acid–specific proteases, or caspases, are essential determinants of apoptosis signaling cascades and represent promising targets for molecular imaging. Here, we report development and in vivo validation of [ 18 F]4-fluorobenzylcarbonyl–Val–Ala–Asp(OMe)–fluoromethylketone ([ 18 F]FB-VAD-FMK), a novel peptide-based molecular probe suitable for quantification of caspase activity in vivo using positron emission tomography (PET). Experimental Design: Supported by molecular modeling studies and subsequent in vitro assays suggesting probe feasibility, the labeled pan-caspase inhibitory peptide, [ 18 F]FB-VAD-FMK, was produced in high radiochemical yield and purity using a simple two-step, radiofluorination. The biodistribution of [ 18 F]FB-VAD-FMK in normal tissue and its efficacy to predict response to molecularly targeted therapy in tumors was evaluated using microPET imaging of mouse models of human colorectal cancer. Results: Accumulation of [ 18 F]FB-VAD-FMK was found to agree with elevated caspase-3 activity in response to Aurora B kinase inhibition as well as a multidrug regimen that combined an inhibitor of mutant BRAF and a dual PI3K/mTOR inhibitor in V600E BRAF colon cancer. In the latter setting, [ 18 F]FB-VAD-FMK PET was also elevated in the tumors of cohorts that exhibited reduction in size. Conclusions: These studies illuminate [ 18 F]FB-VAD-FMK as a promising PET imaging probe to detect apoptosis in tumors and as a novel, potentially translatable biomarker for predicting response to personalized medicine. Clin Cancer Res; 20(8); 2126–35. ©2014 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 7
    Publication Date: 2017-02-10
    Description: The relationship between iron and β-cell dysfunction has long been recognized as individuals with iron overload display an increased incidence of diabetes. This link is usually attributed to the accumulation of excess iron in β-cells leading to cellular damage and impaired function. Yet, the molecular mechanism(s) by which human β-cells take up iron has not been determined. In the present study, we assessed the contribution of the metal-ion transporters ZRT/IRT-like protein 14 and 8 (ZIP14 and ZIP8) and divalent metal-ion transporter-1 (DMT1) to iron uptake by human β-cells. Iron was provided to the cells as nontransferrin-bound iron (NTBI), which appears in the plasma during iron overload and is a major contributor to tissue iron loading. We found that overexpression of ZIP14 and ZIP8, but not DMT1, resulted in increased NTBI uptake by βlox5 cells, a human β-cell line. Conversely, siRNA-mediated knockdown of ZIP14, but not ZIP8, resulted in 50% lower NTBI uptake in βlox5 cells. In primary human islets, knockdown of ZIP14 also reduced NTBI uptake by 50%. Immunofluorescence analysis of islets from human pancreatic sections localized ZIP14 and DMT1 nearly exclusively to β-cells. Studies in primary human islets suggest that ZIP14 protein levels do not vary with iron status or treatment with IL-1β. Collectively, these observations identify ZIP14 as a major contributor to NTBI uptake by β-cells and suggest differential regulation of ZIP14 in primary human islets compared with other cell types such as hepatocytes.
    Print ISSN: 0363-6143
    Electronic ISSN: 1522-1563
    Topics: Medicine
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  • 8
    Publication Date: 2013-03-02
    Description: Selective inhibition of oncogenic targets and associated signaling pathways forms the basis of personalized cancer medicine. The clinical success of V600E BRAF inhibition in melanoma, coupled with the emergence of acquired resistance, underscores the importance of rigorously validating quantitative biomarkers of treatment response in this and similar settings. Because constitutive activation of BRAF leads to proliferation in tumors, we explored 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) PET to noninvasively quantify changes in tumor proliferation that are associated with pharmacologic inhibition of V600E BRAF downstream effectors and that precede changes in tumor volume. Methods: Human colorectal cancer (CRC) cell lines expressing V600E BRAF were used to explore relationships between upregulation of p27 and phosphorylation of BRAF downstream effectors on small-molecule V600E BRAF inhibitor exposure. Athymic nude mice bearing V600E BRAF -expressing human CRC cell line xenografts were treated with a small-molecule V600E BRAF inhibitor (or vehicle) daily for 10 d. Predictive 18 F-FLT PET was conducted before changes in tumor volume occurred. Correlations were evaluated among PET, inhibition of phosphorylated MEK (p-MEK) and phosphorylated-ERK (p-ERK) by Western blot, tumor proliferation by histology, and small-molecule exposure by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). Results: Treatment of CRC cell lines with PLX4720 reduced proliferation associated with target inhibition and upregulation of p27. In vivo, PLX4720 treatment reduced 18 F-FLT uptake, but not 18 F-FDG uptake, in Lim2405 xenografts before quantifiable differences in xenograft volume. Reduced 18 F-FLT PET reflected a modest, yet significant, reduction of Ki67 immunoreactivity, inhibition of p-MEK and p-ERK, and elevated tumor cell p27 protein levels. Both 18 F-FLT PET and 18 F-FDG PET accurately reflected a lack of response in HT-29 xenografts, which MALDI imaging mass spectrometry suggested may have stemmed from limited PLX4720 exposure. Conclusion: We used preclinical models of CRC to demonstrate 18 F-FLT PET as a sensitive predictor of response to V600E BRAF inhibitors. Because 18 F-FLT PET predicted reduced proliferation associated with attenuation of BRAF downstream effectors, yet 18 F-FDG PET did not, these data suggest that 18 F-FLT PET may represent an alternative to 18 F-FDG PET for quantifying clinical responses to BRAF inhibitors.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 9
    Publication Date: 2014-07-02
    Description: Individuals with familial adenomatous polyposis (FAP) harbor a germline mutation in adenomatous polyposis coli ( APC ). The major clinical manifestation is development of multiple colonic tumors at a young age due to stochastic loss of the remaining APC allele. Extracolonic features, including periampullary tumors, gastric abnormalities, and congenital hypertrophy of the retinal pigment epithelium, may occur. The objective of this study was to develop a mouse model that simulates these features of FAP. We combined our Lrig1-CreERT2/ + mice with Apcfl/ + mice, eliminated one copy of Apc in leucine-rich repeats and immunoglobulin-like domains protein 1 (Lrig1)-positive (Lrig1 + ) progenitor cells with tamoxifen injection, and monitored tumor formation in the colon by colonoscopy and PET. Initial loss of one Apc allele in Lrig1 + cells results in a predictable pattern of preneoplastic changes, culminating in multiple distal colonic tumors within 50 days of induction, as well as the extracolonic manifestations of FAP mentioned above. We show that tumor formation can be monitored by noninvasive PET imaging. This inducible stem cell-driven model recapitulates features of FAP and offers a tractable platform on which therapeutic interventions can be monitored over time by colonoscopy and noninvasive imaging.
    Print ISSN: 0193-1857
    Electronic ISSN: 1522-1547
    Topics: Medicine
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  • 10
    Publication Date: 2014-06-26
    Description: IL-17 has emerged as a key player in the immune system, exhibiting roles in protection from infectious diseases and promoting inflammation in autoimmunity. Initially thought to be CD4 T-cell-derived, the sources of IL-17 are now known to be varied and belong to both the innate and adaptive arms of the immune system. Mechanisms for inducing IL-17 production in lymphoid cells are thought to rely on appropriate antigenic stimulation in the context of TGF-β1, IL-6 and/or IL-1β. Using culture protocols adapted from human studies, we have effectively induced both bovine CD4+ and WC1+ γδ T-cells to produce IL-17 termed Th17 and γδ17 cells, respectively. The negative regulatory effect of IFN-γ on mouse and human IL-17 production can be extended to the bovine model, as addition of IFN-γ decreases IL-17 production in both cell types. Furthermore we show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a γδ17 phenotype that preferentially kills infected target cells. Our study identifies two T-cell sources of IL-17, and is the first to demonstrate a protective effect of IL-17+ T-cells in ruminants. Our findings offer further opportunities for future adjuvants or vaccines which could benefit from inducing these responses. Scientific Reports 4 doi: 10.1038/srep05431
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
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