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361.
Methylation demand: a key determinant of homocysteine metabolism 总被引:3,自引:0,他引:3
Elevated plasma homocysteine is a risk factor for cardiovascular disease and Alzheimer's disease. To understand the factors that determine the plasma homocysteine level it is necessary to appreciate the processes that produce homocysteine and those that remove it. Homocysteine is produced as a result of methylation reactions. Of the many methyltransferases, two are, normally, of the greatest quantitative importance. These are guanidinoacetate methyltransferase (that produces creatine) and phosphatidylethanolamine N-methyltransferase (that produces phosphatidylcholine). In addition, methylation of DOPA in patients with Parkinson's disease leads to increased homocysteine production. Homocysteine is removed either by its irreversible conversion to cysteine (transsulfuration) or by remethylation to methionine. There are two separate remethylation reactions, catalyzed by betaine:homocysteine methyltransferase and methionine synthase, respectively. The reactions that remove homocysteine are very sensitive to B vitamin status as both the transsulfuration enzymes contain pyridoxal phosphate, while methionine synthase contains cobalamin and receives its methyl group from the folic acid one-carbon pool. There are also important genetic influences on homocysteine metabolism. 相似文献
362.
Inducible heat shock protein 70 promotes myelin autoantigen presentation by the HLA class II 总被引:2,自引:0,他引:2
Mycko MP Cwiklinska H Szymanski J Szymanska B Kudla G Kilianek L Odyniec A Brosnan CF Selmaj KW 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(1):202-213
In this study, we investigated the role of the inducible form of heat shock protein 70 (hsp70) in the presentation of the major putative autoantigen in multiple sclerosis, myelin basic protein (MBP), in the context of appropriate MHC class II. By coimmunoprecipitation, we found that MBP is associated with hsp70 in APC in an ATP/ADP-dependent manner. Additionally, using confocal microscopy, hsp70 was detected in the endocytic pathway of APC, where it colocalized with MBP and HLA-DR. The immunodominant epitopes of MBP 85-99 and 80-99 were shown to bind selectively and specifically to hsp70 by surface plasmon resonance. The functional significance of MBP interaction with hsp70 was demonstrated by the detection of enhanced responses of an MBP-specific T cell hybridoma to MBP and MBP 80-99 with increasing levels of hsp70 and reduced responses when hsp70 expression was diminished within APC-expressing DRA*0101, DRB1*1501 (DR1501). However, when MBP 85-99 was used as the stimulus, T cell hybridoma responses were not enhanced by hsp70 overexpression within APC, suggesting that hsp70 contributes to Ag processing rather than Ag presentation. The importance of a direct association between MBP and hsp70 in the presentation pathways was demonstrated by enhanced efficacy of MBP presentation by APC transfected with a plasmid vector encoding a fusion hsp70-MBP protein. This is the first report on the involvement of self-inducible hsp70 in MHC class II-dependent autoantigen processing by APC. It implicates that aberrant self hsp expression may lead to the enhancement/modulation of autoimmune responses. 相似文献
363.
The study of reciprocal altruism, or the exchange of goods and services between individuals, requires attention to both evolutionary
explanations and proximate mechanisms. Evolutionary explanations have been debated at length, but far less is known about
the proximate mechanisms of reciprocity. Our own research has focused on the immediate causes and contingencies underlying
services such as food sharing, grooming, and cooperation in brown capuchin monkeys and chimpanzees. Employing both observational
and experimental techniques, we have come to distinguish three types of reciprocity. Symmetry-based reciprocity is cognitively
the least complex form, based on symmetries inherent in dyadic relationships (e.g., mutual association, kinship). Attitudinal
reciprocity, which is more cognitively complex, is based on the mirroring of social attitudes between partners and is exhibited
by both capuchin monkeys and chimpanzees. Finally, calculated reciprocity, the most cognitively advanced form, is based on
mental scorekeeping and is found only in humans and possibly chimpanzees.
Sarah F. Brosnan is a graduate student in the Population Biology, Ecology, and Evolution Program at Emory University. Her
interests include proximate mechanisms of cooperation and reciprocity in primates, and social learning in primates and other
species.
Frans B. M. de Waal is the C. H. Candler Professor of Psychology and the director of the Living Links Center at Emory University.
His interests include social behavior and cognition of monkeys and apes, and their relevance for questions on the evolution
of human politics, economy, morality, and culture. 相似文献
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366.
Interorgan metabolism of amino acids, glucose, lactate, glycerol and uric acid in the domestic fowl (Gallus domesticus). 总被引:2,自引:1,他引:1
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Arterial--venous differences for metabolites across liver, kidney and hindquarters were measured in fed or starved, artificially ventilated chickens. The results indicate that the liver takes up amino acids under both conditions. Urate and glucose are released by the liver in both the fed and the starved state. Lactate and amino acids are extracted from blood by the kidneys, and this increases in the starved chicken. Urate is removed from the circulation by the kidney in the fed and starved state and excreted. In the fed bird there is no significant arteriovenous difference of glucose across the kidney, but in the starved state the kidney releases glucose into the circulation. The hindquarters take up glucose in the fed but not in the starved state. The branched-chain amino acids valine and leucine were taken up by the hindquarters in the fed, but not the starved, chicken. Glycerol is released by the hindquarter of fed and starved chickens. In the starved state, alanine and glutamine represent 57% of the amino acids released by the hindquarter. Lactate is released by the hindquarter of starved chickens and represents the major gluconeogenic carbon source released by the hindquarter and taken up by kidney and liver. Although the liver is the major gluconeogenic organ in the starved chicken, the kidney accounts for approx. 30% of the glucose produced. 相似文献
367.
Evolution of the secondary structures and compensatory mutations of the ribosomal RNAs of Drosophila melanogaster 总被引:10,自引:0,他引:10
This paper examines the effects of DNA sequence evolution on RNA secondary
structures and compensatory mutations. Models of the secondary structures
of Drosophila melanogaster 18S ribosomal RNA (rRNA) and of the complex
between 2S, 5.8S, and 28S rRNAs have been drawn on the basis of comparative
and energetic criteria. The overall AU richness of the D. melanogaster
rRNAs allows the resolution of some ambiguities in the structures of both
large rRNAs. Comparison of the sequence of expansion segment V2 in D.
melanogaster 18S rRNA with the same region in three other Drosophila
species and the tsetse fly (Glossina morsitans morsitans) allows us to
distinguish between two models for the secondary structure of this region.
The secondary structures of the expansion segments of D. melanogaster 28S
rRNA conform to a general pattern for all eukaryotes, despite having highly
divergent sequences between D. melanogaster and vertebrates. The 70 novel
compensatory mutations identified in the 28S rRNA show a strong (70%) bias
toward A-U base pairs, suggesting that a process of biased mutation and/or
biased fixation of A and T point mutations or AT-rich slippage-generated
motifs has occurred during the evolution of D. melanogaster rDNA. This
process has not occurred throughout the D. melanogaster genome. The
processes by which compensatory pairs of mutations are generated and spread
are discussed, and a model is suggested by which a second mutation is more
likely to occur in a unit with a first mutation as such a unit begins to
spread through the family and concomitantly through the population.
Alternatively, mechanisms of proofreading in stem-loop structures at the
DNA level, or between RNA and DNA, might be involved. The apparent
tolerance of noncompensatory mutations in some stems which are otherwise
strongly supported by comparative criteria within D. melanogaster 28S rRNA
must be borne in mind when compensatory mutations are used as a criterion
in secondary-structure modeling. Noncompensatory mutation may extend to the
production of unstable structures where a stem is stabilized by RNA-
protein or additional RNA-RNA interactions in the mature ribosome. Of
motifs suggested to be involved in rRNA processing, one (CGAAAG) is
strongly overrepresented in the 28S rRNA sequence. The data are discussed
both in the context of the forces involved with the evolution of multigene
families and in the context of molecular coevolution in the rDNA family in
particular.
相似文献
368.
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370.
Heterologous expression of an engineered truncated form of human Lewis fucosyltransferase (Fuc-TIII) by the methylotrophic yeast Pichia pastoris 总被引:1,自引:0,他引:1
Gallet PF; Vaujour H; Petit JM; Maftah A; Oulmouden A; Oriol R; Le Narvor C; Guilloton M; Julien R 《Glycobiology》1998,8(9):919-925
A stable GS115 Pichia pastoris recombinant strain was constructed to
secrete a truncated form of the human alpha(1,3/4) fucosyltransferase
(amino acids 45-361). Enzyme production resulted from a secretory pathway
based on the pre-pro- alpha mating factor signal sequence of the yeast
Saccharomyces cerevisiae . Following its transit through the Golgi
apparatus, the enzyme accumulated in the periplasmic space before its
release in the culture broth (about 30 mg/l). Cell-enclosed enzyme (
approximately 0.16%) proved to be fairly stable for many freezing and
thawing cycles and could be used several times as an immobilized catalyst.
Soluble enzyme (>99.8%) representing the main protein of the culture
broth (10%) has been characterized by Western-blotting, substrate
specificities and kinetic parameters. The two forms (cell- enclosed and
soluble) of recombinant enzyme may be used for in vitro synthesis of
Lewisadeterminants.
相似文献