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AIM: Evaluate insulin resistance (IR) as a mediator of the effect of body fat distribution on liver fat infiltration and stiffness (LSt) in young adults using structural equation modeling (SEM). METHODS: We invited 500 first year students from two universities and evaluated their family history to determine the risk for cardiometabolic disease. Of these, 174 students (age 19 ± 1 years) were assessed for total body fat percentage (BF%), LSt, fat infiltration (Coefficient attenuated parameter CAP), and serum biochemical analysis. We performed a mediation analysis using two different structural equation models to determine the relationship between BMI, BF%, abdominal obesity (AO), IR, LSt, and fat infiltration using standardized ß coefficients. The symbol "->" means "explains/causes". RESULTS: Model#1 supported that mediation analysis and had a better fit than the direct effect. AO->IR (b = 0.62, p = 0.005), AO->CAP (b = 0.63, p <0.001), and CAP->IR (b = 0.23, p = 0.007), with negligible effect of BMI on CAP and IR. Model#2 showed direct effect of BMI on LSt was a better fit than mediation. BMI->LSt (b = 0.17, p = 0.05) but no effect AO->LSt. Interestingly, LSt->IR (b = 0.18, p = 0.001), but bi-directional IR->LSt (b = 0.23, p = 0.001). CONCLUSIONS: AO and BMI in young adults have differential phenotypic effects on liver CAP and LSt. Visceral fat had a direct effect on IR and CAP. Meanwhile, BMI was associated with LSt. Our findings shed light on the complex interplay of factors influencing liver stiffness, particularly in young individuals. Further research is needed to elucidate the precise mechanisms underlying these associations and their implications for liver health.
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Resistência à Insulina , Adulto Jovem , Humanos , Adolescente , Adulto , Índice de Massa Corporal , Obesidade Abdominal/complicações , Obesidade/complicações , Fígado , InsulinaRESUMO
In this review, we described the history of vaccination, the different types of vaccines, and how vaccination coverage has been affected by the current COVID-19 pandemic. The effectiveness of the vaccines under metabolic host conditions is analyzed, especially when people have lost their immunocompetence, such as in patients with chronic kidney disease who are in dialysis treatment. Vaccines are produced in a variety of industrial methods, modifying costs. The novel field of vaccinomics includes the set of immune responses, the satisfactory levels of neutralizing antibodies, the production of metabolites, and the induction of protein expression. Finally, an analysis is made of the confusing messages regarding vaccination that are disseminated on social networks, and general recommendations are given.
En esta revisión se describen el historial de vacunación, los diferentes tipos de vacunas y cómo la cobertura de vacunación se ha visto afectada por la pandemia actual de COVID-19. Se analiza la efectividad de las vacunas en condiciones metabólicas del huésped, especialmente cuando las personas han perdido su inmunocompetencia, como los pacientes con enfermedad renal crónica que están en tratamiento de diálisis. Las vacunas se producen con una variedad de métodos industriales, modificando los costos. El nuevo campo de la vacunómica incluye el conjunto de respuestas inmunitarias, los niveles satisfactorios de anticuerpos neutralizantes, la producción de metabolitos y la inducción de la expresión de proteínas. Finalmente, se analizan los confusos mensajes sobre vacunación que se difunden en las redes sociales y se dan recomendaciones generales.
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COVID-19 , Vacinas , Humanos , Pandemias , SARS-CoV-2 , VacinaçãoRESUMO
Mexicans and Mexican Americans share culture, genetic background, and predisposition for chronic complications associated with obesity and diabetes making imperative efficacious treatments and prevention. Obesity has been treated for centuries focused-on weight loss while other treatments on associated conditions like gout, diabetes (T2D), and hypertriglyceridemia. To date, there is no systematic review that synthesizes the origin of obesity clinics in Mexico and the efforts to investigate treatments for obesity tested by randomized clinical trials (RCT). We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve anti-obesity RCT through 2019 and without an inferior temporal limit. The systematic review included RCT of anti-obesity treatments in the Mexican adult population, covering alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions reporting metabolism-associated traits such as BMI, weight, waist circumference, triglycerides, glucose, among others. Only the studies with at least 3 months of treatment were included in the meta-analyses in order to reduce placebo effects. We found 634 entries, after removal of duplicates and screening the studies based on eligibility criteria, we analyzed 43 national, and 2 multinational-collaborative studies. Most of the national studies had small sample sizes, and the implemented strategies do not have replications in the population. The nutrition/behavioral interventions were difficult to blind, and most studies have medium-to-high risk of bias. Nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like pure water instead of sweet beverages decrease triglycerides and systolic blood pressure. Dark chocolate showed the highest effect for BMI and high blood pressure, and treatment with insulin increased weight in those with T2D. The study of obesity in Mexico has been on-going for more than four decades, the interest on RCT just increased until this millennium, but with small sample sizes and lack of replication. The interventions affect different cardiometabolic associated traits, which should be analyzed in detail in the population living near the Mexico-U.S. border; therefore, bi-national collaboration is desirable to disentangle the cultural effects on this population's treatment response. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020221436, identifier: CRD42020221436.
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High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and ß-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and ß-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and ß-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between ß-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and ß-carotenoids rather than that of ß-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.
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Carotenoides/sangue , Resistência à Insulina/etnologia , Resistência à Insulina/fisiologia , Americanos Mexicanos , Adolescente , beta-Criptoxantina/sangue , Índice de Massa Corporal , Criança , HDL-Colesterol/sangue , Cromatografia Líquida/métodos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Dieta , Feminino , Humanos , Licopeno/sangue , Masculino , Obesidade/sangue , Obesidade/metabolismo , Fenótipo , Fatores de Risco , Texas , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
La epidemia de COVID-19 ha modificado la cultura de la comunicación. La solución para los problemas de salud puede ser asertiva cuando es consensuada. El método Delphi es una herramienta de consenso que emplea rondas de listas de preguntas para recopilar información del conocimiento de un panel de expertos que analizan planteamientos y posibles soluciones a problemas. Se basa en la premisa de que, con la libertad del anonimato, la inteligencia combinada mejora el juicio individual y captura la opinión colectiva experta. El proceso del método es muy flexible, pues las rondas de preguntas pueden realizarse de manera presencial o remota. En este artículo se describe cómo implementar el método Delphi convencional en tiempos de confinamiento, y se analizan la utilidad y las limitaciones del método para su uso por expertos en salud para la resolución de problemas de tratamiento, diagnóstico o administrativos. Las tecnologías actuales para recolectar los datos permiten gran flexibilidad en el formato de los cuestionarios y facilitan la recopilación de la opinión experta. Gracias a su adaptabilidad, el método Delphi se está convirtiendo en una estrategia popular que involucra los ámbitos cualitativo y cuantitativo.
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Betacoronavirus , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Betacoronavirus/imunologia , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Reações Falso-Positivas , Humanos , México/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , SARS-CoV-2 , Sensibilidade e Especificidade , Vigilância de Evento Sentinela , Testes Sorológicos/métodos , Análise Espectral Raman/métodos , Avaliação de SintomasRESUMO
AIM: Acanthosis nigricans (AN) is a strong correlate of obesity and is considered a marker of insulin resistance (IR). AN is associated with various other cardiometabolic risk factors (CMRFs). However, the direct causal relationship of IR with AN in obesity has been debated. Therefore, we aimed to examine the complex causal relationships among the troika of AN, obesity, and IR in Mexican Americans (MAs). METHODS: We used data from 670 non-diabetic MA children, aged 6-17 years (49% girls). AN (prevalence 33%) severity scores (range 0-5) were used as a quasi-quantitative trait (AN-q) for analysis. We used the program SOLAR for determining phenotypic, genetic, and environmental correlations between AN-q and CMRFs (e.g., BMI, HOMA-IR, lipids, blood pressure, hs-C-reactive protein (CRP), and Harvard physical fitness score (PFS)). The genetic and environmental correlations were subsequently used in mediation analysis (AMOS program). Model comparisons were made using goodness-of-fit indexes. RESULTS: Heritability of AN-q was 0.75 (p<0.0001). It was positively/significantly (p<0.05) correlated with traits such as BMI, HOMA-IR, and CRP, and negatively with HDL-C and PFS. Of the models tested, indirect mediation analysis of BMIâHOMA-IRâAN-q yielded lower goodness-of-fit than a partial mediation model where BMI explained the relationship with both HOMA-IR and AN-q simultaneously. Using complex models, BMI was associated with AN-q and IR mediating most of the CMRFs; but no relationship between IR and AN-q. CONCLUSION: Our study suggests that obesity explains the association of IR with AN, but no causal relationship between IR and AN in Mexican American children.
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Acantose Nigricans/fisiopatologia , Doenças Cardiovasculares/etiologia , Resistência à Insulina , Síndrome Metabólica/etiologia , Americanos Mexicanos/estatística & dados numéricos , Obesidade/epidemiologia , Adolescente , Biomarcadores/metabolismo , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Criança , Feminino , Humanos , Incidência , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Obesidade/complicações , Estados Unidos/epidemiologiaRESUMO
Dengue virus (DENV) evolution has had a significant impact on disease pathogenesis, virulence, and epidemiology in Mexico. Novel genotypic variation in DENV serotypes and genotypes may influence the magnitude and severity of dengue epidemics, as evidenced by 2009 data from Veracruz State. The data presented herein is related to the publication entitled "Epidemiological Implications of the Genetic Diversification of Dengue Virus (DENV) Serotypes and Genotypes in Mexico" [1]. Raw data and trees provide epidemiological data on DENV prevalence and a comprehensive phylogeny of both representative sequences collected from an NCBI repository, and 28 additional isolates from acute-phase plasma samples diagnosed with dengue fever or severe dengue (Raw sequencing data is hosted in the public repository Mendeley Data (http://dx.doi.org/10.17632/bf2kdhhf6x.2). Phylogenetic trees for each DENV serotype (DENV-1, -2, -3 and -4) were constructed using these sequences by a maximum likelihood methodology as well as a Bayesian Markov chain Monte Carlo (MCMC) integration approach. Phylogenetic trees exhibited: (1) DENV-1, genotype V, (2) the DENV-2 Asian/American and Asian II genotypes, (3) DENV-3, genotype III, and (4) DENV-4, genotype I. This data can be beneficial for future analyses on DENV serotype and genotype structure and the introduction of novel DENV genotype sequences in the Americas, for the further elucidation of dengue etiology.
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Variation and clade shifts in dengue virus (DENV) genotypes are responsible for numerous dengue fever outbreaks throughout Latin America in the past decade. Molecular analyses of dengue serotypes have revealed extensive genetic diversification and the emergence of new genotypes in Brazil (DENV-4 genotype I) and elsewhere in tropical and subtropical America. The goal of the present study is to assess the extent to which the adventitious introduction of DENV genotypes and their increasing genetic diversity affects dengue epidemiology in Mexico. A nuanced sequence inspection and phylogenetic analysis of the C-prM nucleotide region of DENV was performed for specimens collecting in 2009 from the Veracruz State, Mexico. Findings were contrasted with specimens collected in adjacent years and analysed based on the epidemiological patterns reported between 1990 and 2019. Additionally, the identification process of various DENV genotypes was assessed, including: (1) DENV-1, genotype V, (2) the DENV-2 Asian/American and Asian II genotypes (3) DENV-3, genotype III, and (4) DENV-4, genotype I. This resulted in the discovery of a distinct genetic cladistic pattern for serotype DENV-2. Lastly, study findings suggest that a correlation exists between the emergence of novel genotypes and genetic diversification, with the increasing incidence of DENV infections in Mexico in 2009.
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Vírus da Dengue/genética , Dengue/epidemiologia , Dengue/virologia , Aedes , Animais , Linhagem Celular , Humanos , Incidência , México/epidemiologia , Filogenia , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sorotipagem , Fatores de TempoAssuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Disseminação de Informação/métodos , Aprendizado de Máquina , Pandemias , Pneumonia Viral/epidemiologia , Rede Social , Animais , Betacoronavirus/classificação , COVID-19 , Quirópteros/virologia , Biologia Computacional , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , História Medieval , Humanos , Modelos Estatísticos , Pandemias/história , Peste/história , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , SARS-CoV-2RESUMO
Mexican Maya populations have a notably high prevalence of type 2 diabetes (T2D) as a consequence of the interaction between environmental factors and a genetic component. To assess the impact of 24 single nucleotide variants (SNVs) located in 18 T2D risk genes, we conducted a family-based association evaluation in samples from Maya communities with a high incidence of the disease. A total of four hundred individuals were recruited from three Maya communities with a high T2D incidence. Family pedigrees (100) and 49 nuclear families were included. Genotyping was performed by allelic discrimination with TaqMan probes. This study also included the family-based association test (FBAT) statistic U to assess the genetic associations with T2D, and the multivariate statistical and haplotype analyses. A positive association with TD2 risk was found for WFS1 rs6446482 (p = 0.046, Z = 1.994) under an additive model, and SIRT1 rs7896005 (p = 0.038, Z = 2.073) under the dominant model. Multivariate model analysis, including T2D status, age, and body mass index (BMI), displayed significant covariance in PPARGC-1α rs8192678; SIRT1 rs7896005; TCF7L2 rs7903146 and rs122243326; UCP3 rs3781907; and HHEX rs1111875 with a P < 0.05. This study revealed an association of SIRT1 and WFS1 with T2D risk.
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Diabetes Mellitus Tipo 2/genética , Proteínas de Membrana/genética , Sirtuína 1/genética , Adulto , Idoso , Alelos , Índice de Massa Corporal , Estudos de Casos e Controles , Etnicidade/genética , Família , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Haplótipos , Humanos , Masculino , México , Pessoa de Meia-Idade , Linhagem , Polimorfismo de Nucleotídeo Único/genética , Grupos Populacionais/genética , Fatores de RiscoRESUMO
Maya communities have been shown to exhibit type 2 diabetes (T2D) with high prevalence compared with Mexican mestizo populations. Furthermore, some variants associated with the risk for T2D have been described. In this study, we describe the results of a pilot genome wide association study (GWAS) using 817,823 single nucleotide polymorphisms (SNPs) to identify candidate variants for replication in future studies. Herein, we present the GWAS study data, which were divided into three parts: first, 1289 ancestry informative markers (AIMs) were selected for Latino populations containing European, African, and Native American SNPs obtained from the literature; second, a GWAS hypothesis free to select candidate genes associated with T2D was performed, which identified 24 candidate genes; and third, 39 SNPs previously associated with T2D or related traits were replicated. This article is associated with the original article published in "Gene" under the title "Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population".
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INTRODUCTION: Genetic variants have been replicated for association with type 2 diabetes mellitus (T2D) and many of them with diabetes-related traits. Because T2D is highly prevalent in Mexico, this study aimed to test the association of CDKN2A/B, PPARGC1A, VEGFA, SIRT1 and UCP2 gene polymorphisms (rs10811661, rs8192678, rs2010963, rs7896005 and rs659366 respectively) with metabolic traits in 415 unrelated Mexican mestizos with T2D under three models of inheritance. MATERIAL AND METHODS: A total of 415 unrelated Mexican mestizos were genotyped by TaqMan assays. Triglycerides, cholesterol, glucose, high-density lipoprotein cholesterol (HDL-C), insulin and anthropometric measurements were determined and the HOMA-IR was calculated. Association studies were tested by the Kruskal-Wallis test, linear regression, statistical power analysis, Bonferroni correction, paired SNP analysis, and physical interaction by GeneMANIA. RESULTS: All polymorphisms were in Hardy-Weinberg equilibrium, and the association by genotype with T2D-related traits displayed nominal significance for rs8192678 with glucose (p = 0.023) and triglycerides (p = 0.013); rs2010963 with diastolic blood pressure (DBP) (p = 0.012) and cholesterol (p = 0.013); rs7896005 with DBP (p = 0.012) and insulin (p = 0.011); and rs659366 with cholesterol (p = 0.034), glucose (p = 0.031) and triglycerides (p = 0.028); and the association of rs2010963 with HDL-C (p = 0.0007) was significant. Linear regression performed with three models of inheritance, adjusted by age + sex + BMI and corrected with Bonferroni, showed a significant association of rs2010963 with HDL-C in an additive model (p = 0.007); and rs7896005 was significantly associated with DBP in the recessive model (p = 0.006). CONCLUSIONS: Rigorous analysis evidenced the association of VEGFA rs2010963 and SIRT1 rs7896005 with HDL-C and DBP respectively; these traits are known predictors of cardiovascular complications, which increase the risk of cardiovascular diseases in this population.
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Type 2 diabetes mellitus (T2D) is one of the two leading causes of mortality in Mexico. However, most studies have focused on Caucasians or Asians, and there are a small number of studies investigating Maya populations. Furthermore, to the best of our knowledge, there is no information on isolated Maya communities with T2D frequencies of 20% that are primarily attributed to ethnicity. Consequently, this study focused on assessing which genetic risk variants could be involved in the high rates of T2D in 92 individuals with Maya ancestry; 47 were diagnosed with T2D, and 45 were classified as healthy individuals. A pilot genome-wide association study was performed using the Affymetrix Axiom Genome-wide LAT1 array. The population structure was determined with the ADMIXTURE software using 1289 Latin American selected polymorphisms, and 39 polymorphisms associated with T2D were included for replication. Association tests were performed using the Statistical Analysis System (SAS) using the allelic, genotype and Armitage trend tests. The results indicated that population structure analysis displayed no differences between T2D patients and healthy individuals; 24 loci located were identified for probable association with T2D (pâ¯>â¯1.288â¯×â¯10-7 and pâ¯<â¯1.348â¯×â¯10-4); the polymorphism AGTR2 rs1914711 in chromosome X was identified by the allele test (ORâ¯=â¯6.824; pâ¯=â¯1.448â¯×â¯10-9) as a candidate gene for association with T2D; and ARL15 rs4311394 was associated as a T2D protector by genotype and the Armitage trend test (ORâ¯=â¯0.318; pâ¯=â¯0.001). In conclusion, this study proposes 24 candidate SNPs associated with T2D for replication studies and one for protective association with T2D.
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Diabetes Mellitus Tipo 2/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Alelos , Estudos de Casos e Controles , Etnicidade/genética , Feminino , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Projetos Piloto , Polimorfismo de Nucleotídeo Único/genética , Risco , População Branca/genéticaRESUMO
Type 2 diabetes (T2D) is a disease with a prevalence of 9.4% in Mexicans. Its etiology is complex involving environmental and genetic factors. The aim of this study was to analyse the association between PPARG rs1801282, PPARGC1A rs8192678, VEGFA rs2010963, ADRA2A rs553668, KCNQ1 rs2237892, SIRT1 rs7896005, IGF2BP2 rs4402960, and UCP3 rs3781907 single nucleotide variants (SNVs) with T2D and metabolic traits in a case-control study of a population from Mexico City. A total of 831 blood samples of non-diabetic, with healthy control participants (416) and individuals with T2D (415) were collected over a five-year period. After DNA extraction, genotyping was performed with TaqMan probes using real-time PCR. The genotypes were analysed for association with T2D in linear and logistic regressions adjusting for age, sex, and body mass index using the dominant, recessive, and additive models with a Bonferroni correction for multiple comparisons pâ¯<â¯0.001 and for association with related T2D traits fixed with a pâ¯<â¯2.3â¯×â¯10-4. The univariate analysis gives a significant (pâ¯<â¯1â¯×â¯10-4) for sex, triglycerides, and HOMA-IR. Significant association with T2D was found for ADRA2A rs553668 under the recessive model (ORâ¯=â¯3.640 and 95% CI of 2.330-5.690 (pâ¯<â¯1â¯×â¯10-4); statistical power 0.999) and under the additive model (ORâ¯=â¯1.640 and 95% CI of 1.340-2.000 (pâ¯<â¯1â¯×â¯10-4); statistical power 0.997). Variants PPARG rs1801282, PPARGC1A rs8192678, SIRT1 rs7896005, IGF2BP2 rs4402960 and UCP3 rs3781907 were nominally associated (pâ¯>â¯0.001 and <0.050). Results describe association of ADRA2A rs553668 with T2D in a Mexican population. Variants with nominal association with T2D require to be replicated in additional Mexican populations.
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Diabetes Mellitus Tipo 2/genética , Variação Genética , Receptores Adrenérgicos alfa 2/genética , Estudos de Casos e Controles , Feminino , Humanos , Masculino , México , Pessoa de Meia-IdadeRESUMO
Here; we have described and tested a microarray based-method for the screening of dengue virus (DENV) serotypes. This DNA microarray assay is specific and sensitive and can detect dual infections with two dengue virus serotypes and single-serotype infections. Other methodologies may underestimate samples containing more than one serotype. This technology can be used to discriminate between the four DENV serotypes. Single-stranded DNA targets were covalently attached to glass slides and hybridised with specific labelled probes. DENV isolates and dengue samples were used to evaluate microarray performance. Our results demonstrate that the probes hybridized specifically to DENV serotypes; with no detection of unspecific signals. This finding provides evidence that specific probes can effectively identify single and double infections in DENV samples.
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Técnicas Biossensoriais/instrumentação , DNA Viral/genética , Vírus da Dengue/genética , Vírus da Dengue/isolamento & purificação , Dengue/diagnóstico , Dengue/virologia , Análise de Sequência com Séries de Oligonucleotídeos/instrumentação , Vírus da Dengue/classificação , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , SorogrupoRESUMO
The main vector of dengue in America is the mosquito Aedes aegypti, which is infected by dengue virus (DENV) through receptors of midgut epithelial cells. The envelope protein (E) of dengue virus binds to receptors present on the host cells through its domain III that has been primarily recognized to bind cell receptors. In order to identify potential receptors, proteins from mosquito midgut tissue and C6/36 cells were purified by affinity using columns with the recombinant E protein domain III (rE-DIII) or DENV particles bound covalently to Sepharose 4B to compare and evaluate their performance to bind proteins including putative receptors from female mosquitoes of Ae. aegypti. To determine their identity mass spectrometric analysis of purified proteins separated by polyacrylamide gel electrophoresis was performed. Our results indicate that both viral particles and rE-DIII bound proteins with the same apparent molecular weights of 57 and 67 kDa. In addition, viral particles bound high molecular weight proteins. Purified proteins identified were enolase, beta-adrenergic receptor kinase (beta-ARK), translation elongation factor EF-1 alpha/Tu, and cadherin.
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Aedes/genética , Vírus da Dengue/metabolismo , Dengue/genética , Proteínas/isolamento & purificação , Aedes/virologia , Animais , Proteínas de Transporte , Dengue/transmissão , Dengue/virologia , Vírus da Dengue/genética , Vírus da Dengue/patogenicidade , Células Epiteliais/metabolismo , Humanos , Proteínas/química , Proteínas/metabolismo , ProteômicaRESUMO
Patterns of gene flow vary greatly among Aedes aegypti populations throughout Mexico. The populations are panmictic along the Pacific coast, isolated by distance in northeast Mexico, and exhibit moderate gene flow across the Yucatan peninsula. Nine Ae. aegypti collections from 6 cities in Oaxaca, Mexico, were taken to examine the local patterns of gene flow. Genetic variation was examined in a 387-bp region of the nicotinamide adenine dinucleotide dehydrogenase subunit 4 mitochondrial gene (ND4) using single-strand conformation polymorphism analysis, and 3 haplotypes were detected. Cluster analysis on the linearized FST genetic distances failed to group collections in geographic proximity. Regression analysis of linear or road distances on linearized F(ST) indicated that proximal collections were as diverse as distant collections across an approximately 800-km range. The geographical distribution of the Mexican mosquito haplotype frequencies was determined for the ND4 sequences from 524 individuals from Oaxaca (this study) and 2,043 individuals from our previous studies. Herein, we report on yet another pattern dominated by genetic drift among 9 Ae. aegypti collections from 6 cities in Oaxaca, Mexico, and compare it to those reported in other regions of Mexico. Molecular analysis of variance showed that there was as much genetic variation among collections 4 km apart as there was among all collections. The numbers of haplotypes and the amount of genetic diversity among the collections from Oaxaca were much lower than detected in previous studies in other regions of Mexico and may reflect the effects of control efforts or adaptations to the altitudinal limits (1,500 m) of the species in Mexico. The geographical distribution of mosquito haplotypes in Mexico is also reported. Furthermore, based on the distribution of the mosquito haplotypes in America, we suggest that mosquito dispersion is very efficient, most likely due to commercial transportation.
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Aedes/genética , DNA Mitocondrial/genética , Fluxo Gênico , Variação Genética , Animais , Análise por Conglomerados , Geografia , Haplótipos , América Latina , México , FilogeniaRESUMO
Since Mexican mestizos are an admixed population, it is necessary to determine the effects that the substructure of the population has on genetic and forensic parameters. With this aim, a study was performed with 15 STR loci (CODIS plus D2S1338 and D19S433) on 1,640 unrelated Mexican mestizos. We determine allele and genotypic frequencies observing departure from Hardy-Weinberg expectation (12 out of 15 loci, with an excess of homozygotes, Fis > 0), as well as pairs of loci in an apparent linkage disequilibrium (13 of 92 loci). We conducted a test for genetic population stratification, the results show that the Mexican mestizo population is substructured into three subgroups, which are in HW and linkage equilibrium. The combination of the 15 loci in the whole population has high forensic efficiency with the capacity to genetically discriminate one individual in one quintillion (1/10(18)). Our data potentially validates the use of these 15 STR loci to establish forensic identity and parentage testing for legal purposes, and offers a powerful tool for genetic variation analysis. However, given that the population is stratified, we highly recommend applying a correction with the inbreeding coefficient in calculations of paternity and forensic studies to avoid erroneous assumptions.
Assuntos
População Negra/genética , Indígenas Norte-Americanos/genética , Repetições de Microssatélites , População Branca/genética , Genética Forense , Frequência do Gene , Loci Gênicos , Testes Genéticos , Genótipo , Humanos , Desequilíbrio de Ligação , México , Modelos Genéticos , Modelos Estatísticos , PaternidadeRESUMO
BACKGROUND: Culex spp. mosquitoes are considered to be the most important vectors of West Nile virus (WNV) detected in at least 34 species of mosquitoes in the United States. In North America, Culex pipiens pipiens, Culex pipiens quinquefasciatus, and Culex tarsalis are all competent vectors of WNV, which is considered to be enzootic in the United States and has also been detected in equines and birds in many states of Mexico and in humans in Nuevo Leon. There is potential for WNV to be introduced into Mexico City by various means including infected mosquitoes on airplanes, migrating birds, ground transportation and infected humans. Little is known of the geographic distribution of Culex pipiens complex mosquitoes and hybrids in Mexico City. Culex pipiens pipiens preferentially feed on avian hosts; Culex pipiens quinquefasciatus have historically been considered to prefer mammalian hosts; and hybrids of these two species could theoretically serve as bridge vectors to transmit WNV from avian hosts to humans and other mammalian hosts. In order to address the potential of WNV being introduced into Mexico City, we have determined the identity and spatial distribution of Culex pipiens complex mosquitoes and their hybrids. RESULTS: Mosquito larvae collected from 103 sites throughout Mexico City during 2004-2005 were identified as Culex, Culiseta or Ochlerotatus by morphological analysis. Within the genus Culex, specimens were further identified as Culex tarsalis or as belonging to the Culex pipiens complex. Members of the Culex pipiens complex were separated by measuring the ratio of the dorsal and ventral arms (DV/D ratio) of the male genitalia and also by using diagnostic primers designed for the Ace.2 gene. Culex pipiens quinquefasciatus was the most abundant form collected. CONCLUSIONS: Important WNV vectors species, Cx. p. pipiens, Cx. p. quinquefasciatus and Cx. tarsalis, are all present in Mexico City. Hybrids of Cx. p. pipiens and Cx. p. quinquefasciatus were also collected and identified. The presence and abundance of these WNV competent vectors is a cause for concern. Understanding the distribution of these vectors can help improve viral surveillance activities and mosquito control efforts in Mexico City.