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The genes of the major histocompatibility complex (MHC) code for proteins involved in antigen recognition and triggering of the adaptive immune response, and are therefore likely to be under selection from parasites. These selection regimes may vary in space and time. Here we report a strong geographical structure in MHC class II B genes of a migrating bird, the great snipe (Gallinago media). Genetic differentiation in the MHC between two ecologically distinct distributional regions (Scandinavian mountain populations vs. East European lowland populations) was still present after statistically controlling for the effect of selectively neutral variation (microsatellites) using partial Mantel tests. This suggests a role for selection in generating this spatial structure and that it represents local adaptation to different environments. Differentiation between populations within the two regions was negligible. Overall, we found a high number of MHC alleles (50, from 175 individuals). This, together with a tendency for a higher rate of nonsynonymous than synonymous substitutions in the peptide binding sites, and high Tajima's D in certain regions of the gene, suggests a history of balancing selection. MHC variation is often thought to be maintained by some form of balancing selection, but the nature of this selection remains unclear. Our results support the hypothesis that spatial variation in selection regimes contributes to the high polymorphism.  相似文献   
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When mice were exposed to a total dose of 240 rad of fission neutrons divided into two, four, or six fractions given at 1-week intervals, more life shortening was observed than was seen after a single exposure. Maximum life shortening was observed with four fractions, although the value for six fractions was not significantly lower. Much of the augmentation effect was attributable to an increase in early deaths during the first 200-300 days after exposure, although differences persisted throughout the lifetime of the animals. The changes in life shortening were associated with changes in the distribution of causes of death; however, decrementation of the populations for any given specific cause of death failed to eliminate completely the differences in mean aftersurvival time.  相似文献   
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The terminal modification of glycans by β4 addition of N-acetylgalactosamine to N-acetylglucosamine with formation of the N,N-diacetyllactosediamine (LacdiNAc) moiety has been well documented for a number of N-linked glycoproteins and peptides, like neurohormones. Much less is known about O-glycoproteins in this regard because only human zona pellucida glycoprotein 3 (ZP3) and bovine proopiomelanocortin were reported to be LacdiNAc-modified. In searching for mammalian proteins modified with O-linked LacdiNAc we identified six positive species among nine endogenous and recombinant O-glycoproteins, which were extracellular matrix, or matrix-related proteins. These are ZP3 and the five novel LacdiNAc-positive species ECM1, AMACO, nidogen-1, α-dystroglycan, and neurofascin. The mass spectrometric analyses revealed a core 2-based tetrasaccharide as the common structural basis of O-linked LacdiNAc that could be further modified, similar to the type 2 LacNAc termini, with fucose, sialic acid, or sulfate. Here, we provide structural evidence for a novel type of mucin-type O-glycans that is strictly specific for LacdiNAc termini: sugar phosphorylation with formation of GalNAcβ1-4(phospho-)GlcNAc. The structural details of the phosphatase-labile compound were elucidated by MS(2) analysis of tetralysine complexes and by MS(n) measurements of the permethylated glycan alditols. Phospho-LacdiNAc was detected in human HEK-293 as well as in mouse myoblast cells and in bovine brain tissue.  相似文献   
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The heritability, subcellular location, and tissue distribution of liver protein alterations found in the two-dimensional electrophoresis patterns of 4 offspring from male mice treated with N-ethyl-N-nitrosourea (ENU) were studied. Mice homozygous for each of the 4 ENU-induced protein variants were found to be viable and fertile, although the number of homozygous offspring from crosses between heterozygous carriers of one variant (ENU 2) was less than that expected for a nondetrimental trait. Two of the proteins altered by ENU-induced mutations were associated with the crude mitochondrial fraction, another was found predominantly in the microsomal fraction, and the fourth was associated with the mitochondrial, microsomal, and cytosol fractions. All of the ENU-induced mutations affected proteins that were not liver-specific; i.e., the proteins were found in other tissues in addition to the liver.  相似文献   
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Effects of chemical modification of lysine residues in trypsin   总被引:3,自引:0,他引:3  
Chemical modifications are a simple method to identify and modify functional determinants of enzymes. In the case of serine proteases, it is possible to induce characteristics which are advantageous for peptide synthesis. In this work, we investigated the influence of guanylation and succinylation of lysine residues on the S′-subsite specificity, the catalytic behavior and stability of trypsin. We have found, that succinylation leads to an about 10-fold better acceptance of basic residues in P1′, whereas guanylation shows no remarkable effects. Furthermore, guanylation enhances, succinylation reduces the general enzyme–substrate interactions in P2′. The structural fundamentals of these specificity changes are discussed. The catalytic behavior of trypsin was not influenced by guanylation and succinylation but an enhancement of the stability against autolytic processes by introducing additional negative charges into the protein was observed.  相似文献   
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