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51.
Admixture in Mexico City: implications for admixture mapping of Type 2 diabetes genetic risk factors
Martinez-Marignac VL Valladares A Cameron E Chan A Perera A Globus-Goldberg R Wacher N Kumate J McKeigue P O'Donnell D Shriver MD Cruz M Parra EJ 《Human genetics》2007,120(6):807-819
Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases
showing prevalence differences between major continental groups. Type 2 diabetes (T2D) is at least twice as prevalent in Native
American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis
of this complex disease. We have characterized the admixture proportions in a sample of 286 unrelated T2D patients and 275
controls from Mexico City and we discuss the implications of the results for admixture mapping studies. Admixture proportions
were estimated using 69 autosomal ancestry-informative markers (AIMs). Maternal and paternal contributions were estimated
from geographically informative mtDNA and Y-specific polymorphisms. The average proportions of Native American, European and,
West African admixture were estimated as 65, 30, and 5%, respectively. The contributions of Native American ancestors to maternal
and paternal lineages were estimated as 90 and 40%, respectively. In a logistic model with higher educational status as dependent
variable, the odds ratio for higher educational status associated with an increase from 0 to 1 in European admixture proportions
was 9.4 (95%, credible interval 3.8–22.6). This association of socioeconomic status with individual admixture proportion shows
that genetic stratification in this population is paralleled, and possibly maintained, by socioeconomic stratification. The
effective number of generations back to unadmixed ancestors was 6.7 (95% CI 5.7–8.0), from which we can estimate that genome-wide
admixture mapping will require typing about 1,400 evenly distributed AIMs to localize genes underlying disease risk between
populations of European and Native American ancestry. Sample sizes of about 2,000 cases will be required to detect any locus
that contributes an ancestry risk ratio of at least 1.5. 相似文献
52.
Jessica Tauany Andrade Geisa Fantini de Figueiredo Luisa Ferreira Cruz Sarah Eliza de Morais Carla Daiane Ferreira Souza Flávia Carmo Horta Pinto Jaqueline Maria Siqueira Ferreira Marcelo Gonzaga de Freitas Araújo 《Revista iberoamericana de micología》2019,36(4):192-199
BackgroundCandida albicans is the main agent that causes vulvovaginal candidiasis. Resistance among isolates to azole antifungal agents has been reported.AimsDue to the well-known antifungal potential of curcumin, the purpose of this work was to evaluate the in vitro anticandidal activity of curcumin and its effect in the treatment of experimental vulvovaginal candidiasis.MethodsThe anticandidal activity of curcumin was investigated against eight Candida strains by the broth microdilution assay, and its mechanism of action was evaluated by testing the binding to ergosterol. Then, the effect of curcumin in the treatment of vulvovaginal candidiasis was evaluated in an immunosuppressed, estrogen treated rat model.ResultsCurcumin showed minimum inhibitory concentration values of 125–1000 μg/ml, and the best result was observed against Candida glabrata. The compound was shown to be able to bind to the ergosterol present in the membrane, event that may be the mechanism of action. In addition, in the in vivo model of vulvovaginal candidiasis with C. albicans, treatments reduced the vaginal fungal burden in infected rats after seven days of treatment with different doses.ConclusionsCurcumin could be considered a promising effective antifungal agent in the treatment of vulvovaginal candidiasis. 相似文献
53.
Mariluze P. Cruz Cassya M. F. Andrade Kelle O. Silva Erika P. de Souza Regiane Yatsuda Lucas M. Marques Juceni P. David Jorge M. David Marcelo H. Napimoga Juliana T. Clemente-Napimoga 《PloS one》2016,11(3)
The bark of Mimosa tenuiflora (Willd.) Poiret (Leguminosae family), popularly known as “jurema preta” in Brazil, is used by the population of Contendas of Sincorá (Bahia State, Brazil) for the treatment of coughs and wound healing. Thus, the aim of this study was to evaluate the antinociceptive and anti-inflammatory activities of the bark ethanol extract (EEMT) and solvent soluble fractions (hexane—H, DCM—D, EtOAc—E and BuOH—B) of the extract in vivo. Additionally, we synthesized 5,7-dihidroxy-4’-methoxyflavanone (isosakuranetin) and isolated the compound sakuranetin, and both compounds were also tested. The anti-inflammatory and antinociceptive assays performed were: writhing test; nociception induced by intraplantar formalin injection; leukocyte recruitment to the peritoneal cavity; evaluation of vascular permeability (Evans blue test); and evaluation of mechanical hypernociception (von Frey test). Production of TNF-α, IL-10, myeloperoxidase and the expression of ICAM-1 were also evaluated. Statistical analysis was performed by one-way ANOVA followed by the Bonferroni post-test (n = 8), with P < 0.05. The EEMT showed antinociceptive activities in writhing test (100–200 mg/kg), in the second phase of the formalin test (50–200 mg/kg), and in mechanical hypernociception (100 mg/kg). EEMT showed an anti-inflammatory effect by reducing neutrophil migration to the peritoneal cavity and in the plantar tissue detected by the reduction of myeloperoxidase activity (100 mg/kg), reduction of IL-10 levels and expression of ICAM-1 in the peritoneal exudate and the mesentery (100 mg/kg), respectively. The four soluble EEMT fractions showed good results in tests for antinociceptive (H, D, E, B) and anti-inflammation (H, D, E). Only sakuranetin showed reduction of the writhing and neutrophil migration (200 mg/kg). Thus, the EEMT and soluble fractions of M. tenuiflora bark demonstrated great antinociceptive and anti-inflammatory activities, as also sakuranetin. More studies should be conducted to elucidate the mechanism of action of this compound. To the best of our knowledge, this is the first report on the antinociceptive activity of the M. tenuiflora fractions and the bioactive isolated compound sakuranetin in vivo. 相似文献
54.
Abstract: Aggregation pheromone of the Australian population of New Guinea sugarcane weevil, Rhabdoscelus obscurus (Boisduval), in conjunction with other semiochemicals, was used to develop an efficient trapping method for the weevil population in Guam. In a field experiment at Yigo, plastic bucket traps baited with the lure of the Australian R. obscurus population in combination with ethyl acetate and cut sugarcane captured significantly more weevils than traps baited with pheromone + ethyl acetate, pheromone + sugarcane or individual lure components alone. Traps baited with various semiochemical-based lures and treated with insecticide captured significantly greater numbers of weevils than those not treated with insecticide. Traps baited with cut sugarcane caught significantly more weevils than those without sugarcane. Semiochemical-based trapping in weevil management has potential either in mass trapping or as part of an integrated pest management (IPM) programme. Based on the present findings, a future line of work for the control of this weevil is proposed. 相似文献
55.
Fiuza SM Gomes C Teixeira LJ Girão da Cruz MT Cordeiro MN Milhazes N Borges F Marques MP 《Bioorganic & medicinal chemistry》2004,12(13):3581-3589
The antiproliferative and cytotoxic properties of polyphenolic acid derivatives, structurally related with the natural models caffeic and gallic acids, have been tested in human cervix adenocarcinoma cells (HeLa). Simultaneous structural information was obtained for these compounds through theoretical ab initio methods. This study was conducted for the following esters: methyl caffeate (MC, 1), propyl caffeate (PC, 2), octyl caffeate (OC, 3), methyl gallate (MG, 4), propyl gallate (PG, 5) and octyl gallate (OG, 6). A significant growth-inhibition effect was assessed for some of these compounds, clearly dependent on their structural characteristics. Marked structure-activity relationships (SARs)--namely the number of hydroxyl ring substituents--were found to rule the biological effect of such systems. 相似文献
56.
Fermin M. Sanchez-Guijo Juan F. Blanco Graciela Cruz Sandra Muntion Maria Gomez Soraya Carrancio Olga Lopez-Villar Maria-Victoria Barbado Luis-Ignacio Sanchez-Abarca Belén Blanco Jesus G. Briñon Maria-Consuelo del Cañizo 《Cell and tissue research》2009,336(3):501-507
Trabecular bone fragments from femoral heads are sometimes used as bone grafts and have been described as a source of mesenchymal
progenitor cells. Nevertheless, mesenchymal stromal cells (MSC) from trabecular bone have not been directly compared with
MSC obtained under standard conditions from iliac crest aspiration of the same patients. This is the ideal control to avoid
inter-individual variation. We have obtained MSC by a novel method (grinding bone fragments with a bone mill without enzymatic
digestion) from the femoral heads of 11 patients undergoing hip replacement surgery and compared them with MSC obtained by
standard iliac crest aspiration of bone marrow from the same patients. We have shown that trabecular bone MSC obtained by
mechanically fragmented femoral heads fulfil the immunophenotypic and multilineage (adipogenic, osteogenic and chondrogenic)
differentiation criteria used to define MSC. We have also differentially compared cellular yields, growth kinetics, cell cycle
assessment, and colony-forming unit-fibroblast content of MSC from both sources and conclude that these parameters do not
significantly differ. Nevertheless, the finding of slight differences, such as a higher expression of the immature marker
CD90, a lower expansion time through the different passages, and a higher percentage of cycling cells in the trabecular bone
MSC, warrants further studies with the isolation method proposed here in order to gain further knowledge of the status of
MSC in this setting.
The present study was partially supported by grant HUS01B07 from the Consejería de Educación and by grant SAN196/SA13/07 from
the Consejería de Sanidad, Junta de Castilla y León, Spain. 相似文献
57.
Rym Chamakh-Ayari Rachel Bras-Gon?alves Narges Bahi-Jaber Elodie Petitdidier Wafa Markikou-Ouni Karim Aoun Javier Moreno Eugenia Carrillo Poonam Salotra Himanshu Kaushal Narender Singh Negi Jorge Arevalo Francesca Falconi-Agapito Angela Privat Maria Cruz Julie Pagniez Gérard-Marie Papierok Faten Bel Haj Rhouma Pilar Torres Jean-Loup Lemesre Mehdi Chenik Amel Meddeb-Garnaoui 《PloS one》2014,9(5)
PSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in several Leishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice. We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in a L. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L. braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals were subdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantum infection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high or low levels of IFN-γ in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detected in sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more. No significant cytokine response was observed in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increase in CD4+ T cells producing IFN-γ after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ. We showed that the LaPSA-38S protein was able to induce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infection indicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection. 相似文献
58.
DEAD-box proteins are ATPase enzymes that destabilize and unwind duplex RNA. Quantitative knowledge of the ATPase cycle parameters is critical for developing models of helicase activity. However, limited information regarding the rate and equilibrium constants defining the ATPase cycle of RNA helicases is available, including the distribution of populated biochemical intermediates, the catalytic step(s) that limits the enzymatic reaction cycle, and how ATP utilization and RNA interactions are linked. We present a quantitative kinetic and equilibrium characterization of the ribosomal RNA (rRNA)-activated ATPase cycle mechanism of DbpA, a DEAD-box rRNA helicase implicated in ribosome biogenesis. rRNA activates the ATPase activity of DbpA by promoting a conformational change after ATP binding that is associated with hydrolysis. Chemical cleavage of bound ATP is reversible and occurs via a γ-phosphate attack mechanism. ADP-Pi and RNA binding display strong thermodynamic coupling, which causes DbpA-ADP-Pi to bind rRNA with > 10-fold higher affinity than with bound ATP, ADP or in the absence of nucleotide. The rRNA-activated steady-state ATPase cycle of DbpA is limited both by ATP hydrolysis and by Pi release, which occur with comparable rates. Consequently, the predominantly populated biochemical states during steady-state cycling are the ATP- and ADP-Pi-bound intermediates. Thermodynamic linkage analysis of the ATPase cycle transitions favors a model in which rRNA duplex destabilization is linked to strong rRNA and nucleotide binding. The presented analysis of the DbpA ATPase cycle reaction mechanism provides a rigorous kinetic and thermodynamic foundation for developing testable hypotheses regarding the functions and molecular mechanisms of DEAD-box helicases. 相似文献
59.
Members of the HERC (domain homologous to E6 associated protein carboxy-terminus and RCC1 domain protein) family may function both as guanine nucleotide exchange factors and E3 ubiquitin ligases. Here we identify an unstudied member, HERC3. This protein was recognized by specific antibodies in different cell types. HERC3 was located in the cytosol and in vesicular-like structures containing beta-COP, ARF and Rab5 proteins. Involvement of HERC3 in the ubiquitin system was suggested by its ability to interact with ubiquitin. The conserved cysteine in HECT proteins was not essential for this non-covalent binding. Moreover, HERC3 was a substrate of ubiquitination being degraded by the proteasome. These observations indicate a fine regulation of HERC3 and suggest a role in vesicular traffic and ubiquitin-dependent processes. 相似文献
60.
Jaqueline Inês Alves de Andrade Eduardo Akifumi Ono Glauber Cruz de Menezes Elenice Martins Brasil Rodrigo Roubach Elisabeth Criscuolo Urbinati Marcos Tavares-Dias Jaydione Luiz Marcon Elizabeth Gusmo Affonso 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,146(4):576
This study evaluated the influence of diets supplemented with 500, 800, 1200 mg kg− 1 of vitamin C (ascorbic acid or AA) and vitamin E (α-tocopherol or α-T) on the physiological responses of pirarucu fed for 2 months. Weight and mortality were not affected by dietary vitamin type or their concentrations. Significant increase (p < 0.05) on the red blood cells count was obtained on treatments with 800 and 1200 mg AA kg− 1 and on the hemoglobin concentration on treatment with 500 mg α-T kg− 1 relatively to control. Mean corpuscular volume presented a significant decrease (p < 0.05) on treatment with 800 and 1200 mg AA kg−1 when compared to control. Mean corpuscular hemoglobin concentration was significantly high (p < 0.05) on treatment with 500 mg α-T kg− 1. Only in vitamin C treatments, we noticed a significant increase (p < 0.05) in the number of leucocytes relative to control. All fish in the vitamin-supplemented treatments, except 500 mg AA kg− 1, had high total protein values compared to control. Fish treated with 800 or 1200 mg α-T kg− 1 also showed increases in plasma glucose concentrations. Our results suggest that 800 and 1200 mg AA kg− 1 are probably the most suitable concentrations for pirarucu diets, although high vitamin E diets are not necessary for quantitative leucocyte increases for this species. 相似文献