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Possible Functional Implications (possible + functional_implication)
Selected AbstractsCombined homology modelling and evolutionary significance evaluation of missense mutations in blood clotting factor VIII to highlight aspects of structure and functionHAEMOPHILIA, Issue 4 2009A. MARKOFF Summary., Most small lesions in the factor VIII (FVIII) gene that cause haemophilia A (HA) are single nucleotide substitutions resulting in amino acid replacing (missense) mutations and leading to various phenotypes, ranging from mild to severe. We took a combined approach of homology modelling and quantitative evaluation of evolutionary significance of amino acid replacing alterations using the Grantham Matrix Score (GMS) to assess their structural effects and significance of pathological expression. Comparative homology models of all amino acid substitutions summarized in the FVIII mutations database plus these identified and reported lately by us or by our collaborators were evaluated. Altogether 640 amino acid replacing mutations were scored for potential distant or local conformation changes, influence on the molecular stability and predicted contact residues, using available FVIII domain models. The average propensity to substitute amino acid residues by mutation was found comparable to the overall probability of de novo mutations. Missense changes reported with various HA phenotypes were all confirmed significant using GMS. The fraction of these, comprising residues apparently involved in intermolecular interactions, exceeds the average proportion of such residues for FVIII. Predicted contact residues changed through mutation were visualized on the surface of FVIII domains and their possible functional implications were verified from the literature and are discussed considering available structural information. Our predictive modelling adds on the current view of domain interface molecular contacts. This structural insight could aid in part to the design of engineered FVIII constructs for therapy, to possibly enhance their stability and prolong circulating lifetime. [source] Polymorphism of LMP2, TAP1, LMP7 and TAP2 in Brazilian Amerindians and Caucasoids: implications for the evolution of allelic and haplotypic diversityINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2000F. Rueda Faucz In the class II region of the major histocompatibility complex (MHC), four genes implicated in processing of MHC class I-presented antigens have been described. Two of these (TAP1 and TAP2) code for endoplasmic reticulum membrane transporter proteins and the other two (LMP2 and LMP7) for proteasome subunits. These genes are polymorphic, although much less so than classical MHC class I and II genes. There is controversy concerning the possible functional implications of this variation. Population genetics is one of the means of investigating the evolutionary and functional significance of genetic polymorphisms; however, few populations have been analysed with respect to TAP and LMP diversity. We present here the polymorphism of TAP1, TAP2, LMP2 and LMP7 genes in the Kaingang and Guarani Amerindian tribes, and in the Caucasoid population of the Brazilian State of Paraná. Allele frequencies found in the Caucasoids were close to those described for similar populations. Amerindians had a somewhat more restricted polymorphism, and allele and haplotype frequencies differed greatly between the two tribes. Overall linkage disequilibrium (LD) between the four genes was low in the Caucasoids, but high in the Amerindians, for which significant LD was seen for all informative pairs of loci. Comparing results of this and previous studies we observed that, whenever significant LD occurs in non-Amerindians, it tends to be similar in the different ethnic groups. While this might be interpreted as evidence of co-evolution of genes in the TAP-LMP region, the high haplotypic diversity in all populations and low LD in non-Amerindians indicate absence of co-evolution of the different genes. Distributions of allele and genotype frequencies are consistent with the hypothesis of selective neutrality. We conclude that genetic polymorphism of the human TAP and LMP genes and haplotypes is of little, if any, functional significance. [source] Effect of the Photoperiod and Administration of Melatonin on the Pars Tuberalis of Viscacha (Lagostomus maximus maximus): An Ultrastructural StudyTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 5 2010Edith Perez Romera Abstract The pituitary pars tuberalis (PT) is a glandular zone exhibiting well-defined structural characteristics. Morphologically, it is formed by specific secretory cells, folliculostellate cells, and migratory cells coming from the pars distalis. The purpose of this work was to investigate differences in specific cellular characteristics in the PT of viscachas captured in summer (long photoperiod) and winter (short photoperiod), as well as the effects of chronic melatonin administration in viscachas captured in summer and kept under long photoperiod. In summer, the PT-specific cells exhibited cell-like characteristics with an important secretory activity and a moderate amount of glycogen. In winter, the PT-specific granulated cells showed ultrastructural variations with signs of a reduced synthesis activity. Also, PT showed a high amount of glycogen and a great number of cells in degeneration. After melatonin administration, the ultrastructural characteristics were similar to those observed in winter, but the amount of glycogen was higher. These results suggest possible functional implications as a result of morphological differences between long and short photoperiods, and are in agreement with the variations of the pituitary-gonadal axis, probably in response to the natural photoperiod changes through the pineal melatonin. The ultrastructural differences observed in PT, after melatonin administration, were similar to those observed in the short photoperiod, thus supporting the hypothesis that these cytological changes are induced by melatonin. Anat Rec, 293:871,878, 2010. © 2010 Wiley-Liss, Inc. [source] Distribution of Lectin-Bindings in the Testis of the Lesser Mouse Deer, Tragulus javanicusANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 3 2009S. Agungpriyono Summary The distribution of lectin bindings in the testis of the smallest ruminant, lesser mouse deer (Tragulus javanicus), was studied using 12 biotinylated lectins specific for d -galactose (peanut agglutinin PNA, Ricinus communis agglutinin RCA I), N -acetyl- d -galactosamine (Dolichos biflorus agglutinin DBA, Vicia villosa agglutinin VVA, Soybean agglutinin SBA), N -acetyl- d -glucosamine and sialic acid (wheat germ agglutinin WGA, s-WGA), d -mannose and d -glucose (Lens culinaris agglutinin LCA, Pisum sativum agglutinin PSA, Concanavalin A Con A), l -fucose (Ulex europaeus agglutinin UEA I), and oligosaccharide (Phaseolus vulgaris agglutinin PHA-E) sugar residues. In Golgi-, cap-, and acrosome-phase spermatids, lectin-bindings were found in the acrosome (PNA, RCA I, VVA, SBA, WGA and s-WGA), and in the cytoplasm (PNA, RCA I, VVA, SBA, WGA, LCA, PSA, Con A and PHA-E). s-WGA binding was confined to the spermatid acrosome, but other lectins were also observed in spermatocytes. In spermatogonia, VVA, WGA, Con A, and PHA-E bindings were observed. Sertoli cells were intensely stained with DBA and Con A, and weakly with PHA-E. In interstitial Leydig cells, RCA I, DBA, VVA, Con A, PSA, LCA, WGA and PHA-E were positive. UEA I was negative in all cell types including spermatogenic cells. Unusual distribution of lectin-bindings noted in the testis of lesser mouse deer included the limited distribution of s-WGA only in the spermatid acrosome, the distribution of DBA in Sertoli cells, Leydig cells and lamina propria, and the absence of UEA I in all type cells. The present results were discussed in comparison with those of other animals and their possible functional implications. [source] | |||||||||||||