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  • 1
    ISSN: 0921-4534
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 2
    Keywords: CELLS ; PROTEIN ; COMPONENTS ; MICE ; KERATINOCYTES ; COLLAGEN TYPE-IV ; EPITHELIAL MORPHOGENESIS ; MOUSE NIDOGEN-2 ; BINDING-SITE ; LAMININ GAMMA-1 CHAIN
    Abstract: Nidogen-1 and nidogen-2 are homologous proteins found in all basement membranes (BMs). They show comparable binding activities in vitro and partially redundant functions in vivo. Previously, we showed that in skin organotypic cocultures, BM formation was prevented in the absence of nidogens and that either nidogen was able to rescue this failure. We now dissected the two nidogens to identify the domains required for BM deposition. For that purpose, HaCaT cells were grown on collagen matrices containing nidogen-deficient, murine fibroblasts. After addition of nidogen-1 or nidogen-2 protein fragments comprising different binding domains, BM deposition was analyzed by immunofluorescence and electron microscopy. We could demonstrate that the rod-G3 domain of nidogen-2 was sufficient to achieve deposition of BM components at the epidermal-collagen interface. In contrast, for nidogen-1, both the G2 and G3 domains were required. Immunoblot analysis confirmed that all BM components were present in comparable amounts under all culture conditions. This finding demonstrates that nidogens, although homologous proteins, exert their effect on BM assembly through different binding domains, which may in turn result in alterations of BM structure and functions, thus providing an explanation for the phenotypical differences observed between nidogen-1 and -2 deficient mice.
    Type of Publication: Journal article published
    PubMed ID: 22623588
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  • 3
    Abstract: Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Data Sources: Genomewide association studies (GWAS) published up to January 15, 2015. Study Selection: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Data Extraction and Synthesis: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Main Outcomes and Measures: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Results: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420081 cases (median cases, 2526 per disease) and 1093105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). Conclusions and Relevance: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
    Type of Publication: Journal article published
    PubMed ID: 28241208
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS); 20120613-20120616; Leipzig; DOCMI.05.03 /20120604/
    Publication Date: 2012-06-05
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 5
    Keywords: ANGIOGENESIS ; EXPRESSION ; INVASION ; MOLECULES ; FAMILY ; DOMAIN ; BINDING ; PROGRESSION ; METASTASIS ; EXTRACELLULAR-MATRIX PROTEINS
    Abstract: Balance between pro-tumor and anti-tumor effects may be affected by molecular interactions within tumor microenvironment. On this basis we searched for molecular partners of ADAMTS-12, a secreted metalloprotease that shows both oncogenic and tumor-suppressive effects. Using its spacer region as a bait in a yeast two-hybrid screen, we identified fibulin-2 as a potential ADAMTS-12-interacting protein. Fibulins are components of basement membranes and elastic matrix fibers in connective tissue. Besides this structural function, fibulins also play crucial roles in different biological events, including tumorigenesis. To examine the functional consequences of the ADAMTS-12/fibulin-2 interaction, we performed different in vitro assays using two breast cancer cell lines: the poorly invasive MCF-7 and the highly invasive MDA-MB-231. Overall our data indicate that this interaction promotes anti-tumor effects in breast cancer cells. To assess the in vivo relevance of this interaction, we induced tumors in nude mice using MCF-7 cells expressing both ADAMTS-12 and fibulin-2 that showed a remarkable growth deficiency. Additionally, we also found that ADAMTS-12 may elicit pro-tumor effects in the absence of fibulin-2. Immunohistochemical staining of breast cancer samples allowed the detection of both ADAMTS-12 and fibulin-2 in the connective tissue surrounding tumor area in less aggressive carcinomas. However, both proteins are hardly detected in more aggressive tumors. These data and survival analysis plots of breast cancer patients suggest that concomitant detection of ADAMTS-12 and fibulin-2 could be a good prognosis marker in breast cancer diagnosis.
    Type of Publication: Journal article published
    PubMed ID: 24457941
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  • 6
    ISSN: 1588-2780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Distribution coefficients /Kd/ of lanthanide elements on layered hydrous titanium dioxide, H2Ti4O9.nH2O /where n=1.2–1.3/, have been determined as a function of the pH of the aqueous phase. The plots of 1g Kd vs. pH gave straight lines with slopes equal to +3 except for the data for heavier lanthanides, suggesting ideal ion-exchange equilibria between tervalent cations in the aqueous phase and hydrogen ions in the hydrous oxide. Mutual separations of La−Cs and La−Ba have been achieved on a column of this material on the basis of large differences in affinities between the metal ion pairs.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1617-4623
    Keywords: Key words Mitochondria ; Gene transfer ; Ribosomal protein S10 ; Rice ; 5′ Untranslated region (UTR)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Mitochondrial ribosomal protein S10 (rps10) is encoded by the mitochondrial genome in potato and pea. Here we show that the rps10 gene is absent from the mitochondrial genome of rice and has been transferred to the nucleus. Cloning and transcriptional analysis show that there are two rps10 genes in the rice nuclear genome and that their transcripts differ in abundance. Western analysis detected the RPS10 protein in the soluble fraction of rice mitochondria, although neither RPS10 has any obvious N-terminal presequence for targeting to mitochondria. This result suggests that targeting information is present in the internal region of rice RPS10. Genomic sequence analysis indicated that each rps10 gene has an intron in the 5′ untranslated region (5′ UTR) and that these intron sequences are homologous to each other. This result strongly suggests that a duplication event occurred after transfer of the rps10 gene to the nucleus. The duplicated rps10 genes have since been translocated to different chromosomes, because the two rps10 genes were mapped on chromosomes 6 and 12 by RFLP analysis. Interestingly, the 5′ UTR and the intron of the rice rps10 genes are homologous to sequences found in several rice genes with various functions, such as osk4, EF-1β2 and RAG1, suggesting a common origin and a functional role for the 5′ UTR. Acquisition of the 5′ flanking region might have accelerated the activation of the mitochondrial rps10 gene which was transferred to the nuclear genome.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ehrlich ascites tumor-bearing mice were subjected to 14CO2 radiorespirometric analysis after administration of [U-14C]glucose, and the results were compared with the levels of host liver glycolytic enzyme activities and the uptake of the radioactivity into the liver. After IP administration of [U-14C]glucose, there was a progressive decline in respiratory 14CO2 after the transplantation of the Ehrlich ascites tumor cells. The peak time (PT) was about 10 min on day 1, but thereafter was increasingly delayed, and could not be determined on day 13. Peak height (PH) and yield value (YV) were both considerably decreased, and again the magnitudes of the changes increased with the time after transplantation of the tumor cells. Glycolytic enzyme activities in the host liver were at normal levels 13 days after transplantation of the tumor cells. The uptake of the radioactivity into the liver after IP administration of [U-14C]glucose began to decline from day 5 and was 50% the value in normal mice 13 days after transplantation of the tumor cells. These results indicate that the radiorespirometric patterns with [U-14C]glucose reflects hepatic biochemical changes rather well.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1612-1112
    Keywords: Thin-layer chromatography ; 2-Dimensional development ; Bile acid conjugates ; Tetra-n-butylammonium phosphate ; Methyl β-cyclodextrin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary This paper describes a method for the separation, by high-performance thin-layer chromatography (HPTLC), of a series of polar, ionic, and hydrophilic double conjugates of bile acids amidated at the C-24 carboxyl group with glycine or taurine and sulfonated or glucosylated at hydroxyl groups in the 5β-steroid nucleus. The method involves two-dimensional (2D) reversed-phase (RP) HPTLC with the combined use of tetra-n-butylammonium phosphate (TBAP) and methyl β-cyclodextrin (Me-β-CD) as mobile phase additives. Complete separation of the hydrophilic bile acid conjugates, particularly of the recalcitrant pairs of chenodeoxycholic acid and deoxycholic acid conjugates in each group, was achieved by 2D inclusion RPHPTLC by developing with methanol-water-0.5 mol L−1 TBAP, 90:10:5–75:25:5 (ν/ν) in the first dimension and the same mobile phase containing 5mm Me-β-CD in the second dimension. The method could be usefully applied to biosynthetic and metabolic studies of bile acids in biological materials.
    Type of Medium: Electronic Resource
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