排序方式: 共有82条查询结果,搜索用时 31 毫秒
51.
52.
53.
Christina Ulm Mona Saffarzadeh Poornima Mahavadi Sandra Müller Gerlinde Prem Farhan Saboor Peter Simon Ralf Middendorff Hildegard Geyer Ingrid Henneke Nils Bayer Susanne Rinné Thomas Lütteke Eva Böttcher-Friebertshäuser Rita Gerardy-Schahn David Schwarzer Martina Mühlenhoff Klaus T. Preissner Andreas Günther Rudolf Geyer Sebastian P. Galuska 《Cellular and molecular life sciences : CMLS》2013,70(19):3695-3708
Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity. Here, we describe a novel function of polysialylated NCAM (polySia-NCAM) in innate immunity of the lung. In mature lung tissue of healthy donors, polySia was exclusively attached to the transmembrane isoform NCAM-140 and located to intracellular compartments of epithelial cells. In patients with chronic obstructive pulmonary disease, however, increased polySia levels and processing of the NCAM carrier were observed. Processing of polysialylated NCAM was reproduced in a mouse model by bleomycin administration leading to an activation of the inflammasome and secretion of interleukin (IL)-1β. As shown in a cell culture model, polySia-NCAM-140 was kept in the late trans-Golgi apparatus of lung epithelial cells and stimulation by IL-1β or lipopolysaccharide induced metalloprotease-mediated ectodomain shedding, resulting in the secretion of soluble polySia-NCAM. Interestingly, polySia chains of secreted NCAM neutralized the cytotoxic activity of extracellular histones as well as DNA/histone-network-containing “neutrophil extracellular traps”, which are formed during invasion of microorganisms. Thus, shedding of polySia-NCAM by lung epithelial cells may provide a host-protective mechanism to reduce tissue damage during inflammatory processes. 相似文献
54.
Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure. 总被引:21,自引:0,他引:21
R Birkenh?ger E Otto M J Schürmann M Vollmer E M Ruf I Maier-Lutz F Beekmann A Fekete H Omran D Feldmann D V Milford N Jeck M Konrad D Landau N V Knoers C Antignac R Sudbrak A Kispert F Hildebrandt 《Nature genetics》2001,29(3):310-314
Antenatal Bartter syndrome (aBS) comprises a heterogeneous group of autosomal recessive salt-losing nephropathies. Identification of three genes that code for renal transporters and channels as responsible for aBS has resulted in new insights into renal salt handling, diuretic action and blood-pressure regulation. A gene locus of a fourth variant of aBS called BSND, which in contrast to the other forms is associated with sensorineural deafness (SND) and renal failure, has been mapped to chromosome 1p. We report here the identification by positional cloning, in a region not covered by the human genome sequencing projects, of a new gene, BSND, as the cause of BSND. We examined ten families with BSND and detected seven different mutations in BSND that probably result in loss of function. In accordance with the phenotype, BSND is expressed in the thin limb and the thick ascending limb of the loop of Henle in the kidney and in the dark cells of the inner ear. The gene encodes a hitherto unknown protein with two putative transmembrane alpha-helices and thus might function as a regulator for ion-transport proteins involved in aBS, or else as a new transporter or channel itself. 相似文献
55.
Arne C. Rufer Ralf Thoma Michael Hennig 《Cellular and molecular life sciences : CMLS》2009,66(15):2489-2501
The control of fatty acid translocation across the mitochondrial membrane is mediated by the carnitine palmitoyltransferase
(CPT) system. Modulation of its functionality has simultaneous effects on fatty acid and glucose metabolism. This encourages
use of the CPT system as drug target for reduction of gluconeogenesis and restoration of lipid homeostasis, which are beneficial
in the treatment of type 2 diabetes mellitus and obesity. Recently, crystal structures of CPT-2 were determined in uninhibited
forms and in complexes with inhibitory substrate-analogs with anti-diabetic properties in animal models and in clinical studies.
The CPT-2 crystal structures have advanced understanding of CPT structure–function relationships and will facilitate discovery
of novel inhibitors by structure-based drug design. However, a number of unresolved questions regarding the biochemistry and
pharmacology of CPT enzymes remain and are addressed in this review. 相似文献
56.
Damian Miles Bailey Peter Bärtsch Michael Knauth Ralf W. Baumgartner 《Cellular and molecular life sciences : CMLS》2009,66(22):3583-3594
Acute mountain sickness (AMS) is a neurological disorder that typically affects mountaineers who ascend to high altitude.
The symptoms have traditionally been ascribed to intracranial hypertension caused by extracellular vasogenic edematous brain
swelling subsequent to mechanical disruption of the blood–brain barrier in hypoxia. However, recent diffusion-weighted magnetic
resonance imaging studies have identified mild astrocytic swelling caused by a net redistribution of fluid from the “hypoxia-primed”
extracellular space to the intracellular space without any evidence for further barrier disruption or additional increment
in brain edema, swelling or pressure. These findings and the observation of minor vasogenic edema present in individuals with
and without AMS suggest that the symptoms are not explained by cerebral edema. This has led to a re-evaluation of the relevant
pathogenic events with a specific focus on free radicals and their interaction with the trigeminovascular system. (Part of
a multi-author review.) 相似文献
57.
In the present study we report on the development and test results of a Cartesian ARIMA Search Algorithm, designed for automatic generation of univariate models for time series data within specified parameter intervals of the identification and estimation stages. Model retention is determined within a preselected set of statistics. By interpreting these statistics as dimensions of the constructed criterion space, we obtain a subset of non-dominated models according to the rule of maximum dispersion over the efficient set. The CARIMA algorithm allows free specification of the number of criteria used in the runs. The algorithm was tested with both simulated and real economic data. The results based on simulated data indicate that the precision of the CARIMA algorithm is lower for seasonal models and higher for non-seasonal ones, thus suggesting an inverse relationship between algorithm performance and model complexity. 相似文献
58.
59.
RNA molecules stimulate prion protein conversion 总被引:3,自引:0,他引:3
Much evidence supports the hypothesis that the infectious agents of prion diseases are devoid of nucleic acid, and instead are composed of a specific infectious protein. This protein, PrP(Sc), seems to be generated by template-induced conformational change of a normally expressed glycoprotein, PrP(C) (ref. 2). Although numerous studies have established the conversion of PrP(C) to PrP(Sc) as the central pathogenic event of prion disease, it is unknown whether cellular factors other than PrP(C) might be required to stimulate efficient PrP(Sc) production. We investigated the biochemical amplification of protease-resistant PrP(Sc)-like protein (PrPres) using a modified version of the protein-misfolding cyclic amplification method. Here we report that stoichiometric transformation of PrP(C) to PrPres in vitro requires specific RNA molecules. Notably, whereas mammalian RNA preparations stimulate in vitro amplification of PrPres, RNA preparations from invertebrate species do not. Our findings suggest that host-encoded stimulatory RNA molecules may have a role in the pathogenesis of prion disease. They also provide a practical approach to improve the sensitivity of diagnostic techniques based on PrPres amplification. 相似文献
60.