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51.
Apart from cleaving C1s, we demonstrate for the first time that: 1) at concentrations found in serum, the activated forms of the complement components C1r in addition to C1s can cleave the heavy chain of MHC class I antigens, 2) the cleavage by C1r and C1s is seemingly dependent upon a native configuration of the MHC class I antigen, since heat denaturation of the HLA antigens reduce the cleavage. The proteolytic fragments following C1 cleavage were characterized by precipitation with Con A-Sepharose, anti-MHC class I and anti-beta 2-microglobulin antibodies. The proteolysis of the alpha-chain of MHC class I was shown to take place between the alpha 2- and alpha 3- domains as estimated by the Con A-Sepharose precipitation pattern on SDS-PAGE. The alpha 1/alpha 2 fragment was still shown to interact with beta 2-microglobulin as shown by immunoprecipitation. 相似文献
52.
Mark E. Nissen 《Flexible Services and Manufacturing Journal》2000,12(4):321-339
Manufacturing enterprises face intensive competitive pressures, and many firms are forced to redesign processes just to stay even with the competition. But process redesign is an expensive, time-consuming, and labor-intensive activity, and first-generation computer-based tools are inadequate for redesign today. Alternatively, knowledge-based systems and intelligent tools have the ability to address the key intellectual activities required for effective process redesign. The research described in this article addresses an intelligent redesign tool called KOPeR. The article describes the KOPeR design and implementation and highlights its use and mechanics in the context of a manufacturing supply-chain example. It then turns to application of KOPeR as a redesign tool in the field, through an “industrial-strength” reengineering engagement, to redesign major supply-chain processes. The field results reveal insights into the use, utility, and potential of this tool in procurement, manufacturing, and beyond. The article closes with a number of promising future directions for related research. 相似文献
53.
Summary By ultracentrifugation of homogenates of rat renal papillae, a low density layer composed of small primary fluorescing lipid droplets was isolated. Probably the isolated lipid material originates mainly from the primary fluorescing lipid droplets of the renal interstitial cells. The isolated lipid droplets were mainly triglycerides, cholesterol esters and free longchain fatty acids. The long-chain fatty acid composition of the main components differed markedly from that of the analogous components of plasma and depot fat. The findings suggest that the complex lipids of the isolated lipid droplets are synthetized by the renal papilla and probably by the renal interstitial cells. The prostaglandin precursor arachidonic acid constitutes a significant fraction of the triglyceride long-chain fatty acids. Usually also small quantities of prostaglandins were present. Altogether the results suggest that the lipid droplets of the renal interstitial cells may function as a storage site for prostaglandin precursor.This work was supported by a grant from the Danish State Research Foundation. — The authors wish to acknowledge the support and inspiration given by E. Bojesen, M.D., Ph.D., the Institute of Experimental Medicine, Division of Endocrinology. — The authors wish to thank Dr. John E. Pike of the Upjohn Company, Kalamazoo, Michigan, for supplying the Prostaglandins used in this study. 相似文献
54.
Melanoma is the most lethal cutaneous cancer with a highly aggressive and metastatic phenotype. While recent genetic and epigenetic studies have shed new insights into the mechanism of melanoma development, the involvement of regulatory non‐coding RNAs remain unclear. Long non‐coding RNAs (lncRNAs) are a group of endogenous non‐protein‐coding RNAs with the capacity to regulate gene expression at multiple levels. Recent evidences have shown that lncRNAs can regulate many cellular processes, such as cell proliferation, differentiation, migration and invasion. In the melanoma, deregulation of a number of lncRNAs, such as HOTAIR, MALAT1, BANCR, ANRIL, SPRY‐IT1 and SAMMSON, have been reported. Our review summarizes the functional role of lncRNAs in melanoma and their potential clinical application for diagnosis, prognostication and treatment. 相似文献
55.
Changes in odor quality discrimination following recovery from olfactory nerve transection 总被引:4,自引:2,他引:2
Following recovery from olfactory nerve transection, animals regain their
ability to discriminate between odors. Odor discrimination is restored
after new neurons establish connections with the olfactory bulb. However,
it is not known if the new connections alter odor quality perception. To
address this question, 20 adult hamsters were first trained to discriminate
between cinnamon and strawberry odors. After reaching criterion (> or =
90% correct response), half of the animals received a bilateral nerve
transection (BTX) and half a surgical sham procedure. Animals were not
tested again until day 40, a point in recovery when connections are
re-established with the bulb. When BTX animals were tested without food
reinforcement, they could not perform the odor discrimination task. Sham
animals, however, could discriminate, demonstrating that the behavioral
response had not been extinguished during the 40 day period. When
reinforcement was resumed, BTX animals were able to discriminate between
cinnamon and strawberry after four test sessions. In addition, their
ability to discriminate between these two familiar odors was no different
than that of BTX and sham animals tested with two novel odors, baby powder
and coffee. These findings suggest that, after recovery from nerve
transection, there are alterations in sensory perception and that
restoration of odor quality discrimination requires that the animal must
again learn to associate individual odor sensations with a behavioral
response.
相似文献
56.
57.
Cutting edge: TCR stimulation by antibody and bacterial superantigen induces Stat3 activation in human T cells. 总被引:3,自引:0,他引:3
J Gerwien M Nielsen T Labuda M H Nissen A Svejgaard C Geisler C R?pke N Odum 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(4):1742-1745
Recent data show that TCR/CD3 stimulation induces activation of Stat5 in murine T cells. Here, we show that CD3 ligation by mAb and Staphylococcal enterotoxin (SE) induce a rapid, gradually accumulating, long-lasting tyrosine, and serine phosphorylation of Stat3 (but not Stat5) in allogen-specific human CD4+ T cell lines. In contrast, IL-2 induces a rapid and transient tyrosine and serine phosphorylation of Stat3. Compared with IL-2, CD3 ligation induces a delayed Stat3 binding to oligonucleotide probes from the ICAM-1 and IL-2R alpha promoter. CD3-mediated activation of Stat3 is almost completely inhibited by a Src kinase inhibitor (PP1), whereas IL-2-induced Stat3 activation is unaffected. In conclusion, we show that CD3 ligation by mAb and SE triggers a rapid, PP1-sensitive tyrosine and serine phosphorylation of Stat3 in human CD4+ T cells. Moreover, we provide evidence that TCR/CD3 and IL-2 induce Stat3 activation via distinct signaling pathways. 相似文献
58.
Laura F. McNair Rasmus Kornfelt Anne B. Walls Jens V. Andersen Blanca I. Aldana Jakob D. Nissen Arne Schousboe Helle S. Waagepetersen 《Neurochemical research》2017,42(3):810-826
Brain slice preparations from rats, mice and guinea pigs have served as important tools for studies of neurotransmission and metabolism. While hippocampal slices routinely have been used for electrophysiology studies, metabolic processes have mostly been studied in cerebral cortical slices. Few comparative characterization studies exist for acute hippocampal and cerebral cortical slices, hence, the aim of the current study was to characterize and compare glucose and acetate metabolism in these slice preparations in a newly established incubation design. Cerebral cortical and hippocampal slices prepared from 16 to 18-week-old mice were incubated for 15–90 min with unlabeled glucose in combination with [U-13C]glucose or [1,2-13C]acetate. Our newly developed incubation apparatus allows accurate control of temperature and is designed to avoid evaporation of the incubation medium. Subsequent to incubation, slices were extracted and extracts analyzed for 13C-labeling (%) and total amino acid contents (µmol/mg protein) using gas chromatography–mass spectrometry and high performance liquid chromatography, respectively. Release of lactate from the slices was quantified by analysis of the incubation media. Based on the measured 13C-labeling (%), total amino acid contents and relative activity of metabolic enzymes/pathways, we conclude that the slice preparations in the current incubation apparatus exhibited a high degree of metabolic integrity. Comparison of 13C-labeling observed with [U-13C]glucose in slices from cerebral cortex and hippocampus revealed no significant regional differences regarding glycolytic or total TCA cycle activities. On the contrary, results from the incubations with [1,2-13C]acetate suggest a higher capacity of the astrocytic TCA cycle in hippocampus compared to cerebral cortex. Finally, we propose a new approach for assessing compartmentation of metabolite pools between astrocytes and neurons using 13C-labeling (%) data obtained from mass spectrometry. Based on this approach we suggest that cellular metabolic compartmentation in hippocampus and cerebral cortex is very similar. 相似文献
59.
Transient protein interactions are paramount to life where fast and efficient transfer of information and cargo are often integral to pathways and networks. However, complexes formed by transient protein interactions are often times resistant to direct structural characterization due to their inherent, dynamic nature, so our knowledge to date typically derives from biochemical, biophysical and computational methods. In this issue, Shimada and co‐authors present the crystal structure of the mammalian cytochrome c oxidase in complex with its electron donor cytochrome c, identifying a new class of protein–protein interaction termed “soft and specific”. 相似文献
60.
Dueholm MS Nielsen SB Hein KL Nissen P Chapman M Christiansen G Nielsen PH Otzen DE 《Biochemistry》2011,50(39):8281-8290
The amyloid fold is usually considered a result of protein misfolding. However, a number of studies have recently shown that the amyloid structure is also used in nature for functional purposes. CsgA is the major subunit of Escherichia coli curli, one of the most well-characterized functional amyloids. Here we show, using a highly efficient approach to prepare monomeric CsgA, that in vitro fibrillation of CsgA occurs under a wide variety of environmental conditions and that the resulting fibrils exhibit similar structural features. This highlights how fibrillation is "hardwired" into amyloid that has evolved for structural purposes in a fluctuating extracellular environment and represents a clear contrast to disease-related amyloid formation. Furthermore, we show that CsgA polymerization in vitro is preceded by the formation of thin needlelike protofibrils followed by aggregation of the amyloid fibrils. 相似文献