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71.
72.
Empty class II major histocompatibility complex created by peptide photolysis establishes the role of DM in peptide association 总被引:1,自引:0,他引:1
Grotenbreg GM Nicholson MJ Fowler KD Wilbuer K Octavio L Yang M Chakraborty AK Ploegh HL Wucherpfennig KW 《The Journal of biological chemistry》2007,282(29):21425-21436
DM catalyzes the exchange of peptides bound to Class II major histocompatibility complex (MHC) molecules. Because the dissociation and association components of the overall reaction are difficult to separate, a detailed mechanism of DM catalysis has long resisted elucidation. UV irradiation of DR molecules loaded with a photocleavable peptide (caged Class II MHC molecules) enabled synchronous and verifiable evacuation of the peptide-binding groove and tracking of early binding events in real time by fluorescence polarization. Empty DR molecules generated by photocleavage rapidly bound peptide but quickly resolved into species with substantially slower binding kinetics. DM formed a complex with empty DR molecules that bound peptide with even faster kinetics than empty DR molecules just having lost their peptide cargo. Mathematical models demonstrate that the peptide association rate of DR molecules is substantially higher in the presence of DM. We therefore unequivocally establish that DM contributes directly to peptide association through formation of a peptide-loading complex between DM and empty Class II MHC. This complex rapidly acquires a peptide analogous to the MHC class I peptide-loading complex. 相似文献
73.
74.
Bacterial mechanosensitive channels are activated by increases in tension in the lipid bilayer of the cytoplasmic membrane, where they transiently create large pores in a controlled manner. Mechanosensitive channel research has benefited from advances in electrophysiology, genomics and molecular genetics as well as from the application of biophysical techniques. Most recently, new analytical methods have been used to complement existing knowledge and generate insights into the molecular interactions that take place between mechanosensitive channel proteins and the surrounding membrane lipids. This article reviews the latest developments. 相似文献
75.
Böhme H Rudloff E Schöne F Schumann W Hüther L Flachowsky G 《Archives of animal nutrition》2007,61(4):308-316
The nutritive value of genetically modified myristic acid-rich rapeseed, in which a acyl-thioesterase gene inserted, was studied. Crude nutrients, amino acid and fatty acid profiles as well as mineral and glucosinolate contents were determined and compared with those of the non-transgenic parental cultivar. The concentration of crude nutrients, minerals and amino acids were found to be within the range of natural variance. The myristic and palmitic acid content increased from 0.1 - 11.4% and from 3.6-20%, respectively, at the expense of oleic acid, which decreased from 68.6-42.6% of total fatty acids. The glucosinolate contents increased from 12.4 micromol/g in the parental plant to 19 micromol/g DM in the GM-plant. Full-fat rapeseed of both cultivars was incorporated in pig diets at a level of 15%, and the digestibility and the production efficiency were tested under ad libitum feeding conditions with ten pigs each over the growing finishing period from 32-105 kg BW. The experimental diets did not show significant differences in digestibility and energetic feeding value. However, feed intake and weight gain decreased presumably due to the increasing glucosinolate intake associated with the feeding of transgenic rapeseed. The dietary fatty acids profile influenced the fatty acid profile of body fat. Myristic acid accumulated in back fat and intramuscular fat while the oleic acid content decreased. The increased glucosinolate intake affected the weight of thyroid glands and their iodine concentration. 相似文献
76.
Schumann B Dänicke S Meyer U Ueberschär KH Breves G 《Archives of animal nutrition》2007,61(5):357-370
The aim of the present study was to examine long-term effects of low levels of ergot alkaloids on growing bulls. Natural grown ergot with a mean total alkaloid concentrations of 633 mg/kg, and ergotamine (25%), ergocristine (15%) and ergosine (13%) as the most prominent alkaloids, was used. In a dose-response study 38 Holstein Friesian bulls were fed with three different doses of this ergot (0, 0.45 and 2.25 g/kg concentrate corresponding to an average total alkaloid concentration of the daily ration of 0, 69 and 421 microg/kg DM) over a period of approximately 230 days. Live weight, feed intake and health condition were monitored over the entire test period. The bulls were slaughtered at a live weight of approximately 550 kg. Carcass composition and quality were recorded and samples of liver, muscle, kidneys, fat, bile, urine and blood were analysed for ergot alkaloids. Liver enzyme activities and total bilirubin were measured in the blood. Statistically, no significant differences were detectable between the three feeding groups. Mean live weight gain over all groups was 1.41 kg/d with a mean dry matter intake of 7.35 kg/d. No carry over into tissues could be proved out of the experiment. To derive a no-effect level for beef cattle further research including higher ergot doses will be necessary. 相似文献
77.
Schöneberg T Hermsdorf T Engemaier E Engel K Liebscher I Thor D Zierau K Römpler H Schulz A 《Purinergic signalling》2007,3(4):255-268
Metabotropic pyrimidine and purine nucleotide receptors (P2Y receptors) belong to the superfamily of G protein-coupled receptors
(GPCR). They are distinguishable from adenosine receptors (P1) as they bind adenine and/or uracil nucleotide triphosphates
or diphosphates depending on the subtype. Over the past decade, P2Y receptors have been cloned from a variety of tissues and
species, and as many as eight functional subtypes have been characterized. Most recently, several members of the P2Y12-like receptor group, which includes the clopidogrel-sensitive ADP receptor P2Y12, have been deorphanized. The P2Y12-like receptor group comprises several structurally related GPCR which, however, display heterogeneous agonist specificity
including nucleotides, their derivatives, and lipids. Besides the established function of P2Y12 in platelet activation, expression in macrophages, neuronal and glial cells as well as recent results from functional studies
implicate that several members of this group may have specific functions in neurotransmission, inflammation, chemotaxis, and
response to tissue injury. This review focuses specifically on the structure-function relation and shortly summarizes some
aspects of the physiological relevance of P2Y12-like receptor members. 相似文献
78.
Over the past decade, many lines of investigation have shown that receptor-mediated signaling exhibits greater diversity than
previously appreciated. Signal diversity arises from numerous factors, which include the formation of receptor dimers and
interplay between different receptors. Using adenosine A1 receptors as a paradigm of G protein-coupled receptors, this review focuses on how receptor-receptor interactions may contribute
to regulation of the synaptic transmission within the central nervous system. The interactions with metabotropic dopamine,
adenosine A2A, A3, neuropeptide Y, and purinergic P2Y1 receptors will be described in the first part. The second part deals with interactions between A1Rs and ionotropic receptors, especially GABAA, NMDA, and P2X receptors as well as ATP-sensitive K+ channels. Finally, the review will discuss new approaches towards treating neurological disorders. 相似文献
79.
Sorg UR Kleff V Fanaei S Schumann A Moellmann M Opalka B Thomale J Moritz T 《DNA Repair》2007,6(8):1197-1209
As haematopoietic stem cell gene therapy utilizing O(6)-methylguanine-DNA-methyltransferase has reached the clinical stage, safety-related questions become increasingly important. These issues concern insertional mutagenesis of viral vectors, the acute toxicity of pre-transplant conditioning protocols and in vivo selection regimens as well as potential genotoxic side effects of the alkylating drugs administered in this context. To address these questions, we have investigated toxicity-reduced conditioning regimens combining low-dose alkylator application with sublethal irradiation and have analysed their influence on engraftment and subsequent selectability of transduced haematopoietic stem cells. In addition, a strategy to monitor the acute and long-term genotoxic effects of drugs with high guanine-O(6) alkylating potential, such as chloroethylnitrosoureas or temozolomide is introduced. For this purpose, assays were implemented which allow an assessment of the generation and fate of primary drug-induced adducts as well as their long-term effect on chromosomal integrity at the single cell level. 相似文献
80.
Otte Kathrin A. Effertz Christoph Fröhlich Thomas Arnold Georg J. Laforsch Christian von Elert Eric 《Hydrobiologia》2019,846(1):27-38
Hydrobiologia - The crustacean genus Daphnia holds a key position in aquatic ecosystems rendering it an important model organism in environmental research. Its enormous sensitivity to environmental... 相似文献