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71.
Coelho M Luiselli D Bertorelle G Lopes AI Seixas S Destro-Bisol G Rocha J 《Human genetics》2005,117(4):329-339
The levels of haplotype diversity within the lineages defined by two single-nucleotide polymorphisms (SNPs) (–13910 C/T and –22018 G/A) associated with human lactase persistence were assessed with four fast-evolving microsatellite loci in 794 chromosomes from Portugal, Italy, Fulbe from Cameroon, São Tomé and Mozambique. Age estimates based on the intraallelic microsatellite variation indicate that the –13910*T allele, which is more tightly associated with lactase persistence, originated in Eurasia before the Neolithic and after the emergence of modern humans outside Africa. We detected significant departures from neutrality for the –13910*T variant in geographically and evolutionary distant populations from southern Europe (Portuguese and Italians) and Africa (Fulbe) by using a neutrality test based on the congruence between the frequency of the allele and the levels of intraallelic variability measured by the number of mutations in adjacent microsatellites. This result supports the role of selection in the evolution of lactase persistence, ruling out possible confounding effects from recombination suppression and population history. Reevaluation of the available evidence on variation of the –13910 and –22018 loci indicates that lactase persistence probably originated from different mutations in Europe and most of Africa, even if 13910*T is not the causal allele, suggesting that selective pressure could have promoted the convergent evolution of the trait. Our study shows that a limited number of microsatellite loci may provide sufficient resolution to reconstruct key aspects of the evolutionary history of lactase persistence, providing an alternative to approaches based on large numbers of SNPs.Electronic supplementary material Supplementary material is available for this article at 相似文献
72.
Mitochondrial respiratory chain complex I undergoes transitions from active to de-activated forms. We have investigated the phenomenon in sub-mitochondrial particles from Neurospora crassa wild-type and a null-mutant lacking the 29.9 kDa nuclear-coded subunit of complex I. Based on enzymatic activities, genetic crosses and analysis of mitochondrial proteins in sucrose gradients, we found that about one-fifth of complex I with catalytic properties similar to the wild-type enzyme is assembled in the mutant. Mutant complex I still displays active/de-active transitions, indicating that other proteins are involved in the phenomenon. However, the kinetic characteristics of complex I active/de-active transitions in nuo29.9 differ from wild-type. The spontaneous de-activation of the mutant enzyme is much slower, implicating the 29.9 kDa polypeptide in this event. We suggest that the fungal 29.9 kDa protein and its homologues in other organisms may modulate the active/de-active transitions of complex I. 相似文献
73.
Gales L Cortes L Almeida C Melo CV Costa MC Maciel P Clarke DT Damas AM Macedo-Ribeiro S 《Journal of molecular biology》2005,353(3):642-654
Machado-Joseph's disease is caused by a CAG trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract in the protein ataxin-3. Except for the polyglutamine region, proteins associated with polyglutamine diseases are unrelated, and for all of these diseases aggregates containing these proteins are the major components of the nuclear proteinaceous deposits found in the brain. Aggregates of the expanded proteins display amyloid-like morphological and biophysical properties. Human ataxin-3 containing a non-pathological number of glutamine residues (14Q), as well as its Caenorhabditis elegans (1Q) orthologue, showed a high tendency towards self-interaction and aggregation, under near-physiological conditions. In order to understand the discrete steps in the assembly process leading to ataxin-3 oligomerization, we have separated chromatographically high molecular mass oligomers as well as medium mass multimers of non-expanded ataxin-3. We show that: (a) oligomerization occurs independently of the poly(Q)-repeat and it is accompanied by an increase in beta-structure; and (b) the first intermediate in the oligomerization pathway is a Josephin domain-mediated dimer of ataxin-3. Furthermore, non-expanded ataxin-3 oligomers are recognized by a specific antibody that targets a conformational epitope present in soluble cytotoxic species found in the fibrillization pathway of expanded polyglutamine proteins and other amyloid-forming proteins. Imaging of the oligomeric forms of the non-pathological protein using electron microscopy reveals globular particles, as well as short chains of such particles that likely mimic the initial stages in the fibrillogenesis pathway occurring in the polyglutamine-expanded protein. Thus, they constitute potential targets for therapeutic approaches in Machado-Joseph's disease, as well as valuable diagnostic markers in disease settings. 相似文献
74.
Pereira HS Barão A Delgado M Morais-Cecílio L Viegas W 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(5):871-878
The complete sequence of the first retrotransposon isolated in Vitis vinifera, Gret1, was used to design primers that permitted its analysis in the genome of grapevine cultivars. This retroelement was found
to be dispersed throughout the genome with sites of repeated insertions. Fluorescent in situ hybridization indicated multiple
Gret1
loci distributed throughout euchromatic portions of chromosomes. REMAP and IRAP proved to be useful as molecular markers in grapevine.
Both of these techniques showed polymorphisms between cultivars but not between clones of the same cultivar, indicating differences
in Gret1 distribution between cultivars. The combined cytological and molecular results suggest that Gret1 may have a role in gene regulation and in explaining the enormous phenotypic variability that exists between cultivars. 相似文献
75.
Patrocínio LG Goulart IM Goulart LR Patrocínio JA Ferreira FR Fleury RN 《FEMS immunology and medical microbiology》2005,44(3):311-316
Several discoveries about leprosy indicate that Mycobacterium leprae transmission mainly occurs by inhalation, and the nose is major port of entry and exit. The present study evaluated the clinical application of PCR for detection of M. leprae DNA in nasal mucosa biopsies in untreated leprosy patients (52) and their contacts (99) from the State Reference Center in Sanitary Dermatology and Leprosy, Uberlandia, MG, Brazil. PCR detection of a 372-base pair DNA fragment from M. leprae was accomplished in 36 (69.2%) patients, from which 34 (91.9%) of them were multibacillaries. Furthermore, PCR was positive in 3 (16.7%) of 18 slit-skin smear negative, 4 (25.0%) of 16 skin lesion BI negative, 8 (33.3%) of 24 nasal mucosa BI negative patients, and 10 of 99 contacts (10.1%). The presence of bacilli in 10.1% of the contacts may potentially reflect an occult leprosy, and these patients must be accompanied, followed by a chemoprophylaxy treatment. Considering all PCR results against clinical and BI classification of patients and controls, we have found a sensitivity of 69.2%, a specificity of 89.9%, and an accuracy of 82.8%. It has been demonstrated here through PCR of nasal biopsies that the bacillus invades the mucosa, passing through the nasal inferior turbinate to reach peripheral blood. Therefore, the molecular investigation of invasive nasal biopsies by PCR tests has proven to be useful in defining patients of higher risk of transmission and risk-group contacts, which is an important step to reach the World Health Organization objective towards the elimination of leprosy as a public health problem. 相似文献
76.
The diversity and composition of drift invertebrate assemblages were evaluated along a longitudinal gradient of an altitudinal stream in southeastern Brazil. The main goal of this study was to evaluate the influence of seasonality, stream order, and some abiotic factors on invertebrate drift and the use of drifting invertebrate assemblages to assess aquatic invertebrate diversity. Drift samples were collected over a 24 h period using nets (open area of 0.08 m2; mesh 0.250 mm), partially submerged (60%) in the water column. Taxonomic richness, Pielou evenness (J), Shannon–Wiener diversity (H), and total density of drift invertebrate assemblages were used in unpaired t-tests, Kruskal–Wallis and stepwise multiple regression analysis. The results showed a high taxonomic richness of aquatic invertebrates, with 91 taxa found. Chironomidae and Ephemeroptera represented together c. 80% of the total density of drift organisms. The drift approach allowed the collection of new and rare taxa, besides the knowledge of pupae stage of several chironomid genera. Significant differences in the taxonomic richness and diversity of drift invertebrate assemblages were found between the rainy and dry periods, indicating a significant influence of seasonality. An increase in water flow and electrical conductivity were associated with the increase in the taxonomic richness and diversity in the rainy period. No significant differences were found among the other abiotic variables among the stream orders. 相似文献
77.
Neurospora strains harboring mitochondrial disease-associated mutations in iron-sulfur subunits of complex I 下载免费PDF全文
We subjected the genes encoding the 19.3-, 21.3c-, and 51-kDa iron-sulfur subunits of respiratory chain complex I from Neurospora crassa to site-directed mutagenesis to mimic mutations in human complex I subunits associated with mitochondrial diseases. The V135M substitution was introduced into the 19.3-kDa cDNA, the P88L and R111H substitutions were separately introduced into the 21.3c-kDa cDNA, and the A353V and T435M alterations were separately introduced into the 51-kDa cDNA. The altered cDNAs were expressed in the corresponding null-mutants under the control of a heterologous promoter. With the exception of the A353V polypeptide, all mutated subunits were able to promote assembly of a functional complex I, rescuing the phenotypes of the respective null-mutants. Complex I from these strains displays spectroscopic and enzymatic properties similar to those observed in the wild-type strain. A decrease in total complex I amounts may be the major impact of the mutations, although expression levels of mutant genes from the heterologous promoter were sometimes lower and may also account for complex I levels. We discuss these findings in relation to the involvement of complex I deficiencies in mitochondrial disease. 相似文献
78.
Amado M Yan Q Comelli EM Collins BE Paulson JC 《The Journal of biological chemistry》2004,279(35):36689-36697
Following activation in the periphery, murine CD8+ T cells exhibit a characteristic increased binding of peanut agglutinin (PNA), reflecting an increased expression of hyposialylated O-linked glycans (Galbeta1-3GalNAcalpha-O-Thr/Ser) on the cell surface. In this report, we show that the majority of the PNA receptors expressed on activated CD8+ T cells are carried by CD45. Other glycoproteins (e.g. CD8) and the glycolipid asialo-GM1 also carry PNA receptors, although to a much lesser extent. Analysis of enzymes involved in the sialylation/de-sialylation pathways showed that generation of PNA receptors in activated CD8+ T cells is not due to up-regulation of endogenous sialidases. Instead, our results indicate that the PNA(high) phenotype results from de novo synthesis of CD45 carrying reduced sialylated core 1 O-glycans. 相似文献
79.
Zhao H Bernardo MM Osenkowski P Sohail A Pei D Nagase H Kashiwagi M Soloway PD DeClerck YA Fridman R 《The Journal of biological chemistry》2004,279(10):8592-8601
The membrane type (MT)-matrix metalloproteinases (MMPs) constitute a subgroup of membrane-anchored MMPs that are major mediators of pericellular proteolysis and physiological activators of pro-MMP-2. The MT-MMPs also exhibit differential inhibition by members of the tissue inhibitor of metalloproteinase (TIMP) family. Here we investigated the processing, catalytic activity, and TIMP inhibition of MT3-MMP (MMP-16). Inhibitor profile and mutant enzyme studies indicated that MT3-MMP is regulated on the cell surface by autocatalytic processing and ectodomain shedding. Inhibition kinetic studies showed that TIMP-3 is a high affinity inhibitor of MT3-MMP when compared with MT1-MMP (K(i) = 0.008 nm for MT3-MMP versus K(i) = 0.16 nm for MT1-MMP). In contrast, TIMP-2 is a better inhibitor of MT1-MMP. MT3-MMP requires TIMP-2 to accomplish full pro-MMP-2 activation and this process is enhanced in marimastatpretreated cells, consistent with regulation of active enzyme turnover by synthetic MMP inhibitors. TIMP-3 also enhances the activation of pro-MMP-2 by MT3-MMP but not by MT1-MMP. TIMP-4, in contrast, cannot support pro-MMP-2 activation with either enzyme. Affinity chromatography experiments demonstrated that pro-MMP-2 can assemble trimolecular complexes with a catalytic domain of MT3-MMP and TIMP-2 or TIMP-3 suggesting that pro-MMP-2 activation by MT3-MMP involves ternary complex formation on the cell surface. These results demonstrate that TIMP-3 is a major regulator of MT3-MMP activity and further underscores the unique interactions of TIMPs with MT-MMPs in the control of pericellular proteolysis. 相似文献
80.