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101.
102.
Padhukasahasram B Halperin E Wessel J Thomas DJ Silver E Trumbower H Cargill M Stephan DA 《PloS one》2010,5(12):e14338
The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies. 相似文献
103.
Stem-like cells in human hepatoblastoma. 总被引:9,自引:0,他引:9
Henning C Fiegel Sylvia Glüer Beate Roth Johannes Rischewski Dietrich von Schweinitz Benno Ure Wolfgang Lambrecht Dietrich Kluth 《The journal of histochemistry and cytochemistry》2004,52(11):1495-1501
Hepatoblastoma is a pediatric liver tumor with epithelial components resembling embryonal and fetal liver cells. The existence of teratoid hepatoblastoma suggests the presence of stem cells in hepatoblastoma. The aim of this study was to analyze the expression of stem cell markers in hepatoblastomas. We studied specimens from 10 hepatoblastomas. Five of the hepatoblastomas were of epithelial and five of mixed type. Immunohistochemistry (IHC) for the stem cell markers CD34, Thy1, c-kit, and the hepatic or biliary lineage markers CK-18, OCH, CK-7, and CD56 was performed. Double IHC for stem cell and lineage markers was used to identify putative liver stem cells. The different markers showed distinct distributions on the tumor cells. Cells in atypical ducts were found to express simultaneously stem cell markers and hepatocytic or biliary lineage markers. Other cells in connective tissue showed c-kit expression, but not hepatic or biliary marker expression. The data show the presence of different cell populations bearing stem cell markers in human hepatoblastoma. Ductal cells co-expressing stem cell markers and hepatic lineage markers phenotypically resemble hepatic stem-like cells. These findings support the thesis that stem cells play a role in the histogenesis of hepatoblastoma. 相似文献
104.
I. Zimmer E. Usleber H. Klaffke R. Weber P. Majerus H. Otteneder M. Gareis R. Dietrich E. Märtlbauer 《Mycotoxin Research》2008,24(1):40-52
In order to calculate the dietary fumonisin intake of the German consumer, a large survey was carried out on a variety of
potentially contaminated products in the period between December 1998 and July 2001. A total of 1960 food samples comprising
all known relevant groups of products were analysed for fumonisins. Furthermore, 272 of these samples were also analysed for
hydrolysed fumonisins (HFB). For routine analysis enzyme immunoassay was used, confirmatory and control analyses were performed
using HPLC-FLD after precolumn derivatisation, or by LC-MS/MS. Daily intake of fumonisins was calculated by combining fumonisin
contamination data obtained in this study with available food consumption data for Germany. In a “mean case” scenario, median
fumonisin levels in foods and mean food intake values were used. To generate a “bad case” scenario, the 90th percentile of fumonisin levels in foods and mean food intake values were combined. The overall daily fumonisin intake by
the German consumer was 1.1 μg in the “mean case” scenario, and 21 μg in the “bad case” scenario. It was concluded that in
general there is no increased risk for the German consumer in aspects of exceeding the recommended tolerable daily intake
of fumonisins (2 μg/kg body weight). However, certain products (and certain brands of products) were repeatedly found to contain
elevated fumonisin levels, which in a “worst case” scenario (“high” food intake of maize-based products) could pose a potential
risk for the consumer, in particular concerning foods for infants and young children. High fumonisin levels were found in
infant foods in 1999, but contamination levels decreased strongly in the following years. HFBs (mostly HFB1) were frequently found in processed cereals such as corn flakes, but in relatively low concentrations. According to our findings,
the new European Union maximum levels for fumonisins are suitable to eliminate peak contamination levels of fumonisins in
foods, but would lead to a regular excess of the TDI for infants and young children if these maximum levels would indeed be
exhausted.
Financial support: This work was financially supported by the German Federal Ministry for Nutrition, Agriculture and Consumer
Protection, research grant 415-6080-1/60 (BMG alt). 相似文献
105.
ER–mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem‐like cells 下载免费PDF全文
Valentina Chiusolo Guillaume Jacquemin Emma Boydell Sebastian Zamorano Cristina Riccadonna Serena Pellegatta Nicolas Hulo Valérie Dutoit Madiha Derouazi Pierre Yves Dietrich Paul R Walker Denis Martinvalet 《The EMBO journal》2017,36(11):1493-1512
Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem‐like cells (GSC) being more sensitive to cytotoxic lymphocyte‐mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER–mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER–mitochondria contacts compared to GDCs. Forced ER–mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER–mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma. 相似文献
106.
Plant mitochondria actively import DNA via the permeability transition pore complex 总被引:6,自引:0,他引:6 下载免费PDF全文
Plant mitochondria are remarkable with respect to their content in foreign, alien and plasmid-like DNA, raising the question of the transfer of this information into the organelles. We demonstrate the existence of an active, transmembrane potential-dependent mechanism of DNA uptake into plant mitochondria. The process is restricted to double-strand DNA, but has no obvious sequence specificity. It is most efficient with linear fragments up to a few kilobase pairs. When containing appropriate information, imported sequences are transcribed within the organelles. The uptake likely involves the voltage-dependent anion channel and the adenine nucleotide translocator, i.e. the core components of the mitochondrial permeability transition pore complex in animal cells, but it does not rely on known mitochondrial membrane permeabilization processes. We conclude that DNA import into plant mitochondria might represent a physiological phenomenon with some functional relevance. 相似文献
107.
Lebeau L Lach F Vénien-Bryan C Renault A Dietrich J Jahn T Palmgren MG Kühlbrandt W Mioskowski C 《Journal of molecular biology》2001,308(4):639-647
Two-dimensional crystals of a membrane protein, the proton ATPase from plant plasma membranes, have been obtained by a new strategy based on the use of functionalized, fluorinated lipids spread at the air-water interface. Monolayers of the fluorinated lipids are stable even in the presence of high concentrations of various detergents as was established by ellipsometry measurements. A nickel functionalized fluorinated lipid was spread into a monolayer at the air-water interface. The overexpressed His-tagged ATPase solubilized by detergents was added to the subphase. 2D crystals of the membrane protein, embedded in a lipid bilayer, formed as the detergent was removed by adsorption. Electron microscopy indicated that the 2D crystals were single layers with dimensions of 10 microm or more. Image processing yielded a projection map at 9 A resolution, showing three well-separated domains of the membrane-embedded proton ATPase. 相似文献
108.
Kaleczyc J Timmermans JP Majewski M Lakomy M Scheuermann DW 《Histochemistry and cell biology》1999,111(3):217-228
Immunohistochemical studies have been performed to investigate the occurrence and coexistence of two catecholamine-synthesising
enzymes, tyrosine hydroxylase and dopamine-β-hydroxylase, and several neuropeptides, including neuropeptide Y, vasoactive
intestinal polypeptide, Leu5-enkephalin, somatostatin, calcitonin gene-related peptide and substance P, in nerve fibres supplying porcine accessory genital
glands, the seminal vesicles, prostate (body and the disseminated part) and bulbourethral glands. Three major populations
of nerve fibres supplying non-vascular elements of the glands have been distinguished (from the largest to the smallest one):
(1) noradrenergic fibres, the majority of which contain Leu5-enkephalin, neuropeptide Y or, to a lesser extent, somatostatin, (2) non-noradrenergic, putative cholinergic fibres containing
vasoactive intestinal polypeptide, neuropeptide Y and/or somatostatin and, (3) non-noradrenergic, presumably sensory fibres,
containing calcitonin gene-related peptide and substance P. Whilst the coexistence patterns within nerves supplying particular
glands are similar, the density of innervation varies between the organs. The innervation of the seminal vesicles and prostatic
body is more developed than that of the disseminated part of the prostate and bulbourethral glands. The majority of noradrenergic
fibres related to blood vessels contain neuropeptide Y only, while the non-noradrenergic nerves contain mainly vasoactive
intestinal polypeptide. The possible function and origin of particular nerve fibre populations are discussed.
Accepted: 16 November 1998 相似文献
109.
110.
AtPTR1, a plasma membrane peptide transporter expressed during seed germination and in vascular tissue of Arabidopsis 总被引:1,自引:0,他引:1
Dietrich D Hammes U Thor K Suter-Grotemeyer M Flückiger R Slusarenko AJ Ward JM Rentsch D 《The Plant journal : for cell and molecular biology》2004,40(4):488-499
For the efficient translocation of organic nitrogen, small peptides of two to three amino acids are posited as an important alternative to amino acids. A new transporter mediating the uptake of di- and tripeptides was isolated from Arabidopsis thaliana by heterologous complementation of a peptide transport-deficient Saccharomyces cerevisiae mutant. AtPTR1 mediated growth of S. cerevisiae cells on different di- and tripeptides and caused sensitivity to the phytotoxin phaseolotoxin. The spectrum of substrates recognized by AtPTR1 was determined in Xenopus laevis oocytes injected with AtPTR1 cRNA under voltage clamp conditions. AtPTR1 not only recognized a broad spectrum of di- and tripeptides, but also substrates lacking a peptide bond. However, amino acids, omega-amino fatty acids or peptides with more than three amino acid residues did not interact with AtPTR1. At pH 5.5 AtPTR1 had an apparent lower affinity (K(0.5) = 416 microm) for Ala-Asp compared with Ala-Ala (K(0.5) = 54 microm) and Ala-Lys (K(0.5) = 112 microm). Transient expression of AtPTR1/GFP fusion proteins in tobacco protoplasts showed that AtPTR1 is localized at the plasma membrane. In addition, transgenic plants expressing the beta-glucuronidase (uidA) gene under control of the AtPTR1 promoter demonstrated expression in the vascular tissue throughout the plant, indicative of a role in long-distance transport of di- and tripeptides. 相似文献