RESUMO
The HLA system shows the most extensive polymorphism in the human genome. Allelic and haplotypic frequencies of HLA genes vary dramatically across human populations. Due to a complex history of migration, populations in Latin America show a broad variety of admixture proportions, usually varying not only between countries, but also within countries. Knowledge of HLA allele and haplotype frequencies is essential for medical fields such as transplantation, but also serves as a means to assess genetic diversity and ancestry in human populations. Here, we have determined high-resolution HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies in a sample of 713 healthy subjects from three Mestizo populations, one population of African descent, and Amerindians of five different groups from Costa Rica and Nicaragua and compared their profiles to a large set of indigenous populations from Iberia, Sub-Saharan Africa, and the Americas. Our results show a great degree of allelic and haplotypic diversity within and across these populations, with most extended haplotypes being private. Mestizo populations show alleles and haplotypes of putative European, Amerindian, and Sub-Saharan African origin, albeit with differential proportions. Despite some degree of gene flow, Amerindians and Afro-descendants show great similarity to other Amerindian and West African populations, respectively. This is the first comprehensive study reporting high-resolution HLA diversity in Central America, and its results will shed light into the genetic history of this region while also supporting the development of medical programs for organ and stem cell transplantation.
Assuntos
Genótipo , Antígenos HLA/genética , Indígenas Sul-Americanos , Alelos , População Negra , Costa Rica , Frequência do Gene , Humanos , Desequilíbrio de Ligação , Nicarágua , Polimorfismo Genético , TransplanteRESUMO
Hematopoietic stem cell transplantation (HSCT) with sibling donors (s.d.) is a life-saving intervention for patients with hematological malignancies. Numerous genetic factors have a role in transplant outcome. Several functional polymorphisms have been identified in TGF-ß1 gene, such as single-nucleotide polymorphism (SNP) at +29C>T within exon 1. Two hundred and forty five patient/donor pairs who underwent a s.d. HSCT in our centers were genotyped for this SNP. In the myeloablative cohort, +29CC donors were associated with an increase in severe chronic GvHD (32% vs 16%, hazard ratio (HR) 9.0, P=0.02). Regarding survival outcomes, +29CC patients developed higher non relapse mortality (NRM) (1-5 years CC 28-32% vs TC/TT 7-10%; HR 5.1, P=0.01). Recipients of +29TT donors experienced a higher relapse rate (1-5 years TT 37-51% vs TC 19-25% vs CC 13%-19%; HR 2.4, P=0.01) with a decreased overall survival (OS) (1-5 years TT 69-50% vs TC/CC 77-69%; HR 1.9, P=0.05). Similar to previous myeloablative unrelated donors HSCT results, we confirmed that +29CC patients had higher NRM. In addition we found that +29TT donors might be associated with a higher relapse rate and lower OS. These results should be confirmed in larger series. Identification of these SNPs will allow personalizing transplant conditioning and immunosuppressant regimens, as well as assisting in the choice of the most appropriate donor.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doadores de Tecidos , Fator de Crescimento Transformador beta1/genética , Adulto , Seleção do Doador/métodos , Feminino , Genótipo , Doença Enxerto-Hospedeiro/genética , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Masculino , Agonistas Mieloablativos/uso terapêutico , Polimorfismo de Nucleotídeo Único , Recidiva , Irmãos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Resultado do TratamentoRESUMO
Surface defects are believed to govern the adsorption behavior of reducible oxides. We challenge this perception on the basis of a combined scanning-tunneling-microscopy and density-functional-theory study, addressing the Au adsorption on reduced CeO_{2-x}(111). Despite a clear thermodynamic preference for oxygen vacancies, individual Au atoms were found to bind mostly to regular surface sites. Even at an elevated temperature, aggregation at step edges and not decoration of defects turned out to be the main consequence of adatom diffusion. Our findings are explained with the polaronic nature of the Au-ceria system, which imprints a strong diabatic character onto the diffusive motion of adatoms. Diabatic barriers are generally higher than those in the adiabatic regime, especially if the hopping step couples to an electron transfer into the ad-gold. As the population of O vacancies always requires a charge exchange, defect decoration by Au atoms becomes kinetically hindered. Our study demonstrates that polaronic effects determine not only electron transport in reducible oxides but also the adsorption characteristics and therewith the surface chemistry.
RESUMO
The lack of available transcriptome data for plants of no economic or agronomic importance limits the identification of miRNAs in many species. Considering the possible similarity of the transcriptome between related species, the present study used expressed sequence tags (ESTs) of Suaeda salsa and Suaeda glauca to identify conserved miRNAs, which were validated in a halophyte, Suaeda maritima, with the aim of identifying salt-responsive miRNAs from naturally salt-tolerant plants, information on which is limited. In this study, computational analysis predicted three miRNA sequences by mapping non-redundant miRNA sequences from miRBase 16.0 on 1534 ESTs of S. salsa and S. glauca. The expression of one could be validated in S. maritima, and was named sma-miR1867. This miRNA was downregulated in response to NaCl treatment. It was predicted to target ferredoxin-thioredoxin reductase (FTR), cell division control protein 6 (CDC6), and ubiquitin-protein ligase (UPL) in S. salsa and/or S. glauca. However, only UPL could be amplified in S. maritima, and RT-qPCR showed that it was upregulated in response to NaCl treatment. These results indicate that, in halophytes, FTR and CDC6 may promote carbon metabolism and cell division, respectively, in the presence of salt, while UPL may regulate the abundance of proteins that are important for salt tolerance in halophytes. Thus, sma-miR1867 could be an essential component of salt resistance in halophytes.
Assuntos
Chenopodiaceae/genética , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Proteínas de Plantas/genética , RNA de Plantas/genética , Transcriptoma , Sequência de Bases , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Chenopodiaceae/efeitos dos fármacos , Chenopodiaceae/metabolismo , Biologia Computacional , Proteínas Ferro-Enxofre/genética , Proteínas Ferro-Enxofre/metabolismo , MicroRNAs/metabolismo , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Oxirredutases/genética , Oxirredutases/metabolismo , Proteínas de Plantas/metabolismo , RNA de Plantas/metabolismo , Tolerância ao Sal/genética , Plantas Tolerantes a Sal , Alinhamento de Sequência , Cloreto de Sódio/farmacologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Transforming growth factor ß-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiologic and pathogenic processes with pleiotropic effects. Regulatory activity for this gene has been shown for 3.0 kb between positions -2665 and +423 from its translational start site. At least 17 TGFB1 regulatory region and exon 1 alleles have been defined on the basis of 18 polymorphic sites. Polymorphisms in TGFB1's regulatory region have been associated with differential levels of expression of this cytokine and to genetic risk in cancer and transplantation. In this report, we present 19 novel TGFB1 regulatory region and exon 1 alleles: p018-p036. Amplification of TGFB1's regulatory region was performed with an in-house protocol, and novel alleles were defined by either allele-specific amplification and/or molecular cloning of the amplicons, followed by sequencing in isolation. Three of these novel alleles (p018, p019, and p020) are shown to be formed by novel combinations of the aforementioned known polymorphic positions. Another 16 novel alleles are shown to carry additional known and unknown single-nucleotide polymorphisms. Polymorphism in TGFB1's regulatory region could have an impact on important processes, including embryogenesis, hematopoiesis, carcinogenesis, angiogenesis, fibrosis, immune responses, and transplantation, making its characterization necessary.
Assuntos
Fator de Crescimento Transformador beta1/genética , Regiões 5' não Traduzidas/genética , Alelos , Clonagem Molecular , Escherichia coli , Éxons/genética , Humanos , Polimorfismo de Nucleotídeo Único , Proteínas Recombinantes de Fusão/genética , Sequências Reguladoras de Ácido Nucleico/genética , Alinhamento de Sequência , Análise de Sequência de DNA , Transplante de Células-Tronco , Doadores de Tecidos , Fator de Crescimento Transformador beta1/fisiologiaRESUMO
The new HLA-A*74:23 allele differs from the closest allele A*74:01 by a nucleotide change in exon 3 at codon 97.
Assuntos
Alelos , Antígenos HLA-A/genética , Costa Rica , Humanos , MasculinoRESUMO
OBJECTIVE: In the United States of America, 6.2 million individuals are using elliptical motion trainers in fitness centres. However, graded exercise test protocols to estimate peak oxygen consumption (VO(2peak)) using elliptical motion trainers have not been developed for the general population. METHODS: Fifty-nine subjects (mean age: 23.5 +/- 4.1 years) were randomly divided into a validation (VAL: n = 39) or cross-validation (XVAL: n = 20) group. Peak oxygen consumption (ml x kg(-1) x min(-1)) was measured via indirect calorimetry on an elliptical motion trainer for both groups. Subjects exercised at 150 strides x min(-1) against a resistance of four and a crossramp of 8%. The resistance was increased every two minutes by two units until exhaustion. For the VAL group, a stepwise regression analysis was used to predict VO(2peak) from resistance, maximal heart rate (HR(max)), body mass index (BMI), height and gender (female = 0, male = 1). RESULTS: The prediction equation derived from this study was VO(2peak) (ml x kg(-1) x min(-1)) = 187.39403 + 12.97271 (gender) - 1.45311 (height) - 1.21604 (BMI) - 0.19613 (HR(max)) + 1.57093 (resistance) (R2 = 0.76, SEE = 4.47, p < 0.05). Using this equation, the predicted VO(2peak) of the XVAL group was 45.18 +/- 6.42 ml x kg(-1) x min(-1), while the measured VO(2peak) was 43.55 +/- 6.23 ml x kg(-1) x min(-1) CONCLUSION: No significant difference was found between the measured and predicted VO(2peak) in the XVAL group. Therefore, it appears this protocol and equation will allow individuals to accurately estimate their VO(2peak) without using direct calorimetry. However future studies should investigate the validity of this protocol with diverse populations.
Assuntos
Teste de Esforço/métodos , Exercício Físico/fisiologia , Consumo de Oxigênio/fisiologia , Adulto , Algoritmos , Teste de Esforço/instrumentação , Feminino , Humanos , Masculino , Análise de Regressão , Adulto JovemRESUMO
OBJECTIVE: To explore gender and racial profiling of percentage body fat of 1136 urban South African children attending public schools in Pretoria Central. METHODS: This is a cross-sectional survey of 1136 randomly selected children (548 boys and 588 girls) aged 9-13 years in urban (Pretoria Central) South Africa. Body mass, stature, skinfolds (subscapular and triceps) were measured. Data were analysed using descriptive statistics (means and standard deviations). Differences in the mean body fat percentage were examined for boys and girls according to their age group/race, using independent t-test samples. RESULTS: Girls had a significantly (p = 0.001) higher percentage body fat (22.7 ± 5.7%, 95% CI = 22.3, 23.2) compared to boys (16.1 ± 7.7%, 95% CI = 15.5, 16.8). Percentage body fat fluctuated with age in both boys and girls. Additionally, girls had significantly (p = 0.001) higher percentage body fat measurements at all ages compared to boys. Viewed racially, black children (20.1 ± 7.5) were significantly (p = 0.010) fatter than white children (19.0 ± 7.4) with a mean difference of 4.0. Black children were fatter than white children at ages 9, 10, 12 and 13 years, with a significant difference (p = 0.009) observed at age 12 years. CONCLUSION: There was a considerably higher level of excessive percentage body fat among school children in Central Pretoria, South Africa, with girls having significantly higher percentage body fat compared to boys. Racially, black children were fatter than white children. The excessive percentage body fat observed among the children in this study has implications for their health and fitness. Therefore, an intervention programme must be instituted in schools to prevent and control possible excessive percentage body fat in this age group.
Assuntos
Composição Corporal , Nível de Saúde , Aptidão Física , População Urbana/estatística & dados numéricos , Tecido Adiposo , Adolescente , População Negra/estatística & dados numéricos , Criança , Estudos Transversais , Feminino , Humanos , Masculino , África do Sul/epidemiologia , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: With ageing, the ability to mobilize fat is reduced and this, coupled with gradual decrease in lean body mass (LBM) from lessened exercise, allows for an increased body fat percentage (%BF). Exercising is considered a key to maintaining an appropriate body mass (BM), as it improves fat oxidation, while maintaining LBM. Although the effects of endurance and/or resistance training on fat mass (FM) and LBM in the elderly have well been established, limited data are forthcoming regarding the effects of Pilates as a training modality on these variables in the elderly. OBJECTIVE: The present study was therefore conducted to determine the effects of a mat Pilates programme on body fat in elderly women. METHODS: Fifty sedentary, apparently healthy females aged 60 years and older were randomly assigned a control (CG, n = 25) or an intervention (IG, n = 25) group. The IG took part in an eight-week progressive mat Pilates exercise programme, three times weekly while the CG were instructed to maintain their normal daily activities throughout the eight-week experimental period. All subjects underwent pre- and post-test in which FM and LBM were assessed. RESULTS: Eight weeks of mat Pilates demonstrated a significant (p ≤ 0.05) decrease in % BF (p = 0.016) and FM (p = 0.038), with a significant increase in LBM (p = 0.006), while not showing any significant changes (p ≥ 0.05) in BM (p = 0.979) and BMI (p = 0.992). The CG, however, did not produce any significant (p ≥ 0.05) changes in any of the tested anthropometric variables (BM: p = 0.266; BMI: p = 0.123; % BF: p = 0.516; FM: p = 0.937 and LBM: p = 0.522) after completion of the eight-week Pilates programme. CONCLUSION: An eight-week mat Pilates exercise programme may contradict or even reverse some of the most serious consequences of ageing associated with an increased fat mass and reduced lean body mass in elderly females.
Assuntos
Composição Corporal , Técnicas de Exercício e de Movimento , Tecido Adiposo , Idoso , Composição Corporal/fisiologia , Índice de Massa Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Dobras CutâneasRESUMO
OBJECTIVE: Little is known concerning the applicability of receiver operating characteristic (ROC) curve analysis in detecting excess adiposity in preadolescent South African children. Therefore, the purpose of this study was to evaluate the sensitivity and specificity of body mass index (BMI) and skinfold thickness: BMI (subcutaneous to overall fat) in detecting excess adiposity in preadolescent urban South African school children. METHODS: This was a cross-sectional survey of 1136 randomly selected children (548 boys and 588 girls) aged 9-13 years old in urban (Pretoria Central) South Africa. Body mass, stature, skinfolds (subscapular, triceps, supraspinale and biceps) and waist circumference were measured. Receiver operating characteristic curve analysis was used to assess the sensitivity and specificity of BMI, and log10 SF4:BMI to detect excess adiposity. Excess adiposity was defined as levels of log10 SF4 greater than the internally derived 85th percentile (log10 SF4 > 85th percentile). RESULTS: Compared to log10 SF4:BMI, BMI had a high specificity (0.88; 95% CI 0.84, 0.90). The log10 SF4:BMI identified excess adiposity with a sensitivity and specificity of 0.62 (95% CI 0.60, 0.67) and 0.68 (95% CI 0.64, 0.70), respectively. Besides, a decrease in overall misclassification with the use of log10 SF4:BMI instead of BMI at the 95th percentile (9.7% versus 27.1%) was observed. CONCLUSION: Similar to other studies, although with varying degrees, the present study confirms that log10 SF4:BMI at conventional cut-off points has a relatively high sensitivity and specificity in detecting excess adiposity, and therefore could be used to identify the excess adiposity in South African children. As such, defining obesity based on population-specific percentiles rather than using cut-off points derived from other geographical settings with contrasting levels of socio-economic development becomes imperative.