RESUMO
Aiming to investigate fine-scale patterns of genetic heterogeneity in modern humans from a geographic perspective, a genetic geostatistical approach framed within a geographic information system is presented. A sample collected for prospective studies in a small area of southern Germany was analyzed. None indication of genetic heterogeneity was detected in previous analysis. Socio-demographic and genotypic data of German citizens were analyzed (212 SNPs; n = 728). Genetic heterogeneity was evaluated with observed heterozygosity (H O ). Best-fitting spatial autoregressive models were identified, using socio-demographic variables as covariates. Spatial analysis included surface interpolation and geostatistics of observed and predicted patterns. Prediction accuracy was quantified. Spatial autocorrelation was detected for both socio-demographic and genetic variables. Augsburg City and eastern suburban areas showed higher H O values. The selected model gave best predictions in suburban areas. Fine-scale patterns of genetic heterogeneity were observed. In accordance to literature, more urbanized areas showed higher levels of admixture. This approach showed efficacy for detecting and analyzing subtle patterns of genetic heterogeneity within small areas. It is scalable in number of loci, even up to whole-genome analysis. It may be suggested that this approach may be applicable to investigate the underlying genetic history that is, at least partially, embedded in geographic data.
RESUMO
Recipients of extended-criteria donor (ECD) kidneys have poorer long-term outcomes compared to standard-criteria donor kidney recipients. We report 3-year outcomes from a randomized, phase III study in recipients of de novo ECD kidneys (n = 543) assigned (1:1:1) to either a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine. Three hundred twenty-three patients completed treatment by year 3. Patient survival with a functioning graft was comparable between groups (80% in MI, 82% in LI, 80% in cyclosporine). Mean calculated GFR (cGFR) was 11 mL/min higher in belatacept-treated versus cyclosporine-treated patients (42.7 in MI, 42.2 in LI, 31.5 mL/min in cyclosporine). More cyclosporine-treated patients (44%) progressed to GFR <30 mL/min (chronic kidney disease [CKD] stage 4/5) than belatacept-treated patients (27-30%). Acute rejection rates were similar between groups. Posttransplant lymphoproliferative disorder (PTLD) occurrence was higher in belatacept-treated patients (two in MI, three in LI), most of which occurred during the first 18 months; four additional cases (3 in LI, 1 in cyclosporine) occurred after 3 years. Tuberculosis was reported in two MI, four LI and no cyclosporine patients. In conclusion, at 3 years after transplantation, immunosuppression with belatacept resulted in similar patient survival, graft survival and acute rejection, with better renal function compared with cyclosporine. As previously reported, PTLD and tuberculosis were the principal safety findings associated with belatacept in this study population.
Assuntos
Rejeição de Enxerto/prevenção & controle , Imunoconjugados/uso terapêutico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Complicações Pós-Operatórias , Abatacepte , Adulto , Ciclosporina/uso terapêutico , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/complicações , Testes de Função Renal , Transtornos Linfoproliferativos/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de SobrevidaRESUMO
We developed nine polymorphic microsatellite markers for the Mexican spadefoot toad, Spea multiplicata. Allele numbers range from five to 12, with observed heterozygosities from 0.48 to 0.87. Because two loci are in linkage disequilibrium, these nine loci provide eight independent markers. Three loci exhibit departure from Hardy-Weinberg equilibrium, possibly resulting from null alleles or population admixture. These markers will be useful for assessing population structure and relatedness in S. multiplicata. Based on our success at cross-amplification in the Plains spadefoot toad (Spea bombifrons), these loci also may be useful in this species with additional optimization.
RESUMO
Mutations in the gene uvsH of Aspergillus nidulans result in increased spontaneous chromosome instability and increased intragenic and intergenic mitotic recombination in homozygous diploids. The aim of the present work was to obtain a uvs mutant of A. nidulans and to use it for the isolation of asexual recombinants (parameiotic segregants). The mutant uvsH, named B511, showed normal frequency of meiotic recombination in sexual crosses and high frequency of parameiotic segregants in the parasexual crossings with master strains (B511//A757 and B511//A288). Asexual haploid recombinants (parameiotic segregants), diploid and aneuploid segregants were recovered directly from the uvs//uvs+ heterokaryons (B511//A757 and B511// A288). Parameiotic segregants originated through mitotic crossing-over and independent assortment of chromosomes.
Assuntos
Aspergillus nidulans/genética , Troca Genética , Genes Fúngicos/genética , Mutação/genética , Reprodução Assexuada/genética , Aspergillus nidulans/fisiologia , Haploidia , Meiose/genética , Meiose/fisiologia , Mitose/genética , Mitose/fisiologia , Reprodução Assexuada/fisiologiaRESUMO
Striking conservation in various organisms suggests that cellular nucleic acid binding protein (CNBP) plays a fundamental biological role across different species. Recently, it was reported that CNBP is required for forebrain formation during chick and mouse embryogenesis. In this study, we have used the zebrafish model system to expand and contextualize the basic understanding of the molecular mechanisms of CNBP activity during vertebrate head development. We show that zebrafish cnbp is expressed in the anterior CNS in a similar fashion as has been observed in early chick and mouse embryos. Using antisense morpholino oligonucleotide knockdown assays, we show that CNBP depletion causes forebrain truncation while trunk development appears normal. A substantial reduction in cell proliferation and an increase in cell death were observed in the anterior regions of cnbp morphant embryos, mainly within the cnbp expression territory. In situ hybridization assays show that CNBP depletion does not affect CNS patterning while it does cause depletion of neural crest derivatives. Our data suggest an essential role for CNBP in mediating neural crest expansion by controlling proliferation and cell survival rather than via a cell fate switch during rostral head development. This possible role of CNBP may not only explain the craniofacial anomalies observed in zebrafish but also those reported for mice and chicken and, moreover, demonstrates that CNBP plays an essential and conserved role during vertebrate head development.
Assuntos
Proliferação de Células , Cabeça/embriologia , Crista Neural/fisiologia , Proteínas de Ligação a RNA/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Animais , Morte Celular/fisiologia , Sobrevivência Celular/fisiologia , Embrião não Mamífero/embriologia , Embrião não Mamífero/metabolismo , Embrião não Mamífero/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Hibridização In Situ , Microinjeções , Crista Neural/citologia , Oligonucleotídeos Antissenso/farmacologia , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
Mutations in the gene uvsH of Aspergillus nidulans result in increased spontaneous chromosome instability and increased intragenic and intergenic mitotic recombination in homozygous diploids. The aim of the present work was to obtain a uvs mutant of A. nidulans and to use it for the isolation of asexual recombinants (parameiotic segregants). The mutant uvsH, named B511, showed normal frequency of meiotic recombination in sexual crosses and high frequency of parameiotic segregants in the parasexual crossings with master strains (B511//A757 and B511//A288). Asexual haploid recombinants (parameiotic segregants), diploid and aneuploid segregants were recovered directly from the uvs//uvs+ heterokaryons (B511//A757 and B511// A288). Parameiotic segregants originated through mitotic crossing-over and independent assortment of chromosomes.
Assuntos
Aspergillus nidulans/genética , Troca Genética , Genes Fúngicos/genética , Mutação/genética , Reprodução Assexuada/genética , Aspergillus nidulans/fisiologia , Haploidia , Meiose/genética , Meiose/fisiologia , Mitose/genética , Mitose/fisiologia , Reprodução Assexuada/fisiologiaRESUMO
OBJECTIVES: This study evaluates time trends in colon and rectal cancer incidence and mortality among the three major race/ethnic groups (Hispanics, American Indians, and non-Hispanic Whites) in New Mexico (United States). METHODS: We used data from the New Mexico Tumor Registry (NMTR) and computed average annual age-standardized incidence and mortality rates. Colon cancer incidence rates were further examined by anatomical subsite. Estimated annual percent change (EAPC) in incidence and mortality over time were computed using Poisson regression. RESULTS: Invasive colorectal cancer incidence rates increased from 1969-89 in all three race/ethnic groups, but decreased among non-Hispanic Whites in 1990-94, while rates continued to increase among minority populations, especially among minority men. Over the 26-year period, EAPC in colon cancer incidence among men was 3.6 percent for Hispanics, 4.7 percent for American Indians, and 0.7 percent for non-Hispanic Whites. Right-sided colon cancers were more common among American Indian women, and among all women aged 65 years and older. Mortality rates decreased steadily among non-Hispanic Whites over the study period, especially among women. CONCLUSIONS: Studies are needed to identify important modifiable risk factors and to develop strategies to increase the use of colorectal cancer screening-procedures among the minority populations.
Assuntos
Neoplasias do Colo/epidemiologia , Hispânico ou Latino , Indígenas Norte-Americanos , Neoplasias Retais/epidemiologia , Fatores Etários , Neoplasias do Colo/mortalidade , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento , New Mexico , Neoplasias Retais/mortalidade , Fatores de Risco , Fatores Sexuais , População BrancaRESUMO
Hispanic women in New Mexico have recently experienced an increase in age-adjusted mortality compared with non-Hispanic white women. Since patients' knowledge of stroke risk factors may affect risk factor control, the present study was undertaken to characterize stroke risk factor understanding in Hispanic and non-Hispanic white women in New Mexico. We administered a stroke risk factor knowledge survey to 215 women hospitalized in Albuquerque, New Mexico. Patients were classified by each of three dichotomous groupings: stroke or nonstroke diagnosis; Hispanic or non-Hispanic white ethnicity; history of cardiovascular risk factors. The frequency of specific item responses was determined for each patient grouping. Two-way analysis of variance was used to determine whether composite knowledge score differed among patient groups. Stress was the attribute most commonly thought to be a risk factor for stroke. Although no ethnic differences were found on composite knowledge score, Hispanic women were significantly less likely to report hypertension as a stroke risk factor than non-Hispanic white women. We suggest that stroke risk factor understanding in Hispanic and non-Hispanic white women in New Mexico is inadequate. Insufficient understanding of the consequences of hypertension, including stroke, may diminish the degree of hypertension control that patients achieve. Further study of the relationship between stroke risk factor understanding and health behavior could enhance prevention efforts.
Assuntos
Transtornos Cerebrovasculares/etnologia , Transtornos Cerebrovasculares/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Hispânico ou Latino/psicologia , Educação de Pacientes como Assunto , População Branca/psicologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , New Mexico , Fatores de RiscoRESUMO
BACKGROUND: Although ethnic and radical differences in uterine corpus cancer incidence and mortality have been reported worldwide, few published data have addressed the epidemiology of uterine cancer among US American Indians and Hispanics. METHODS: We reviewed uterine corpus cancer incidence and survival data from New Mexico's population-based cancer registry collected from 1969 to 1992, and examined State vital records data for uterine cancer deaths collected from 1958 to 1992, focusing on ethnic differences in occurrence and outcomes of uterine malignancies. RESULTS: Non-Hispanic white women had age-adjusted incidence rates that were substantially higher (20.8 per 100,000) than rates for Hispanics (10.3) and American Indians (6.0) over the 24-year period. Uterine cancer mortality rates were also higher for non-Hispanic whites and Hispanics than for American Indian women, although mortality rates were substantially lower than incidence rates. Five-year survival for uterine cancer was comparable among all groups for all stages combined (87.3% for non-Hispanic whites, 81.4% for Hispanics, and 84.6% for American Indians). CONCLUSIONS: Our population-based data show ethnic differences in uterine corpus cancer incidence rates for non-Hispanic white women that were double those for Hispanics, and triple those for American Indian women. Ethnic differences in survival were comparable. Aetiologic studies are warranted to investigate the dramatic ethnic differences in occurrence of uterine cancer.
Assuntos
Povo Asiático , Neoplasias Uterinas/etnologia , População Branca , Adenocarcinoma/etnologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Comparação Transcultural , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Incidência , Indígenas Norte-Americanos/estatística & dados numéricos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , New Mexico/epidemiologia , Sistema de Registros , Fatores de Risco , Sarcoma/etnologia , Taxa de Sobrevida , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: New Mexico has had the highest motor vehicle fatality rate in the nation for many years. Our objective was to examine ethnic differences and trends in motor vehicle fatality rates. DESIGN: Using death certificate data from the New Mexico Bureau of Vital Records and Health Statistics, we compiled age-adjusted motor vehicle-related mortality rates from 1958-1990 among the three major ethnic groups in New Mexico--Hispanics, white non-Hispanics and American Indians. RESULTS: Over the 33-year study period, American Indians of both sexes had two to three times higher mortality rates than white non-Hispanics. Hispanic males also had higher motor vehicle death rates than white non-Hispanic males. During the 1970s fatality rates peaked, with age-adjusted death rates of 233/100,000 for American Indian males, 74.7 for Hispanic males and 49.3 for white non-Hispanics for the period 1973-1977. Evaluation of successive 5-year birth cohorts showed highest mortality rates for ages 15-29 years for each ethnic group and both sexes, and a dramatic decline in most ethnic, sex and age-specific rates during the last eight years of the study period. CONCLUSION: Although the recent trends indicate favorable changes in motor vehicle fatality rates, our data highlight the need for ethnic and age-specific interventions to further reduce rates of motor vehicle-related mortality in this state.