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1.
Food Chem ; 335: 127637, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32738535

RESUMEN

This study aimed to analyze physicochemical characteristics and phenolic profile of twenty-three sweet cherry cultivars from Fundão region, Portugal. The average length and width ranged between 1.9 and 2.6 and 2.1-2.8 cm, respectively. Weight varied between 4.9 and 11.8 g, firmness ranged from 7.3 to 20.1 N, moisture and ash contents ranged from 75.1 to 88.6% and 0.4 to 2.9%, respectively. Sunburst and Sweetheart presented high values of CIEL∗, a∗ and b∗, and low values regarding total soluble solids and maturity index. A total of 46 phenolic compounds were identified by HPLC-DAD-ESI/MSn and quantified by HPLC-DAD, namely 19 hydroxycinnamic acids, 2 hydroxybenzoic acids, 13 flavonols, 5 flavan-3-ols, 2 flavanones, 1 flavanonol and 4 anthocyanins. Sunburst and Brook's were the richest in non-colored phenolics, while Garnet and Tavora were the richest ones in anthocyanins. Therefore, our results revealed that sweet cherries represent a supply of high-value bioactive compounds, being greatly influenced by the cultivar.


Asunto(s)
Frutas/química , Frutas/genética , Genotipo , Fitoquímicos/química , Prunus avium/química , Prunus avium/genética , Fitoquímicos/análisis , Solubilidad , Gusto
2.
Gene ; 766: 145118, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32896588

RESUMEN

Insulin-like growth factor 1 (IGF1) is a multifunctional cell proliferation regulator that plays a critical role in regulating animal growth and development. In this study, the expression level of IGF1 gene in different tissues of Dezhou donkey in different periods was investigated by RT-qPCR. Meanwhile, two mutation sites were identified within the IGF1 gene and its effect on body size traits of Dezhou donkey was analysed. The results showed that the expression level of the adult donkey IGF1 gene in heart, liver, spleen, lung, renal and gastric tissues is higher than that of the young donkeys, but the young donkeys are significantly higher in muscle tissues than the adult donkeys. The IGF1-1 and IGF1-2 loci showed a trend that the GG mutant was larger than other genotypes in the growth traits of both male and female donkeys, among which the IGF1-1 loci had a significant association with the chest circumference and chest depth of male donkeys (P < 0.05), and the IGF1-2 loci had a significant association with the chest circumference of female donkeys. Haplotype combination Hap1Hap1 (GG-GG) showed a greater tendency than Hap2Hap2 (AA-GG) combination in terms of growth traits, reflecting that the results were consistent with the analysis results of genotypes, which also proved the analysis results of genotypes and growth traits had certain reliability. In summary, the IGF1 gene is a candidate gene for growth and development, and its polymorphisms can be used as the molecular markers for Dezhou donkey breeding.


Asunto(s)
Tamaño Corporal/genética , Equidae/genética , Factor I del Crecimiento Similar a la Insulina/genética , Transcriptoma/genética , Animales , Cruzamiento/métodos , Femenino , Genotipo , Haplotipos/genética , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple/genética
3.
Gene ; 766: 145143, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32911028

RESUMEN

We aimed to test the hypothesis that apelin (APLN) and its receptor AGTRL1 (APLNR) genes may contribute to the pathogenesis of myocardial infarction in Han Chinese. This is a hospital-based, case-control association study, involving 1067 patients with myocardial infarction and 942 healthy controls. Myocardial infarction is diagnosed by electrocardiogram or anatomopathological examination. Eight polymorphisms in APLN gene and 5 in APLNR gene were genotyped using the TaqMan assay. Risk was summarized as odds ratio (OR) and 95% confidence interval (CI). In males, rs56204867-G allele (adjusted OR, 95% CI, p: 0.21, 0.08-0.55, 0.002) and rs2235309-T allele (0.60, 0.42-0.84, 0.004) was associated with a significantly reduced risk of myocardial infarction, and the mutations of rs2235310 was associated with an increased risk (1.41, 1.06-2.52, 0.021), as well as for rs948847-GG genotype (1.85, 1.23-2.91, 0.007). In females, the presence of rs56204867-AG and -GG genotypes was significantly associated with 44% and 50% reduced risk (0.56 and 0.50, 0.40-8.04 and 0.29-0.86, 0.007 and 0.036), respectively; for rs2235310, CC genotype was associated with 72% increased risk (1.72, 1.09-3.22, 0.016), and the odds of myocardial infarction was 3.47 for rs9943582-TT genotype (95% CI: 1.53-7.57, 0.009). The gender-specific association of APLN and APLNR genes with myocardial infarction was reinforced by further linkage and haplotype analyses. Finally, nomograms based on significant polymorphisms are satisfactory, with the C-indexes over 80% for both genders. Taken together, our findings indicate that APLN and APLNR genes are potential candidates in the pathogenesis of myocardial infarction in Han Chinese, and importantly their contribution is gender-dependent.


Asunto(s)
Receptores de Apelina/genética , Apelina/genética , Grupo de Ascendencia Continental Asiática/genética , Predisposición Genética a la Enfermedad/genética , Infarto del Miocardio/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Genotipo , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad
4.
Gene ; 766: 145132, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32911029

RESUMEN

Dysfunctions in mechanisms of gene regulation based on RNA interference are recognized as a common feature of the molecular basis of cancer pathogenesis. Therefore, as one of the crucial components of the machinery involved in the biogenesis of both siRNAs and microRNA molecules, DICER was recognized as one of the candidates for the research in the field of carcinogenesis. Due to their potential functional properties, several genetic variants located within DICER1 gene were analyzed for their possible association with the susceptibility to cancer through case-control studies. In order to elucidate their effect on the overall cancer risk, we conducted an updated meta-analysis of all eligible association studies. The publications were selected based on PubMed database search, while OpenMeta-analyst and MetaGenyo software were used for quantitative data synthesis. Statistically significant results were found for the association of rs1057035 with the overall cancer risk under multiple genetic models (PCT vs. TT < 0.001, ORCT vs. TT = 0.870, 95% CI = 0.812-0.933; Pallelic = 0.009, ORallelic = 0.896, 95% CI = 0.825-0.973; Pdom < 0.001, ORdom = 0.874, 95% CI = 0.817-0.934; Poverdom = 0.004, ORoverdom = 0.858, 95% CI = 0.773-0.953). Other selected genetic variants within DICER1, rs13078, rs1209904 and rs3742330, did not show the association with the overall susceptibility to malignant diseases. We conclude that rs1057035 may represent a potential biomarker associated with the risk of developing cancer, which requires a confirmation in a larger set of studies.


Asunto(s)
ARN Helicasas DEAD-box/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias/genética , Polimorfismo de Nucleótido Simple/genética , Ribonucleasa III/genética , Alelos , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Estudios de Asociación Genética , Genotipo , Humanos , MicroARNs/genética , Riesgo
5.
Gene ; 766: 145092, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32916247

RESUMEN

Cigarette smoking is a major lifestyle factor leading to different human diseases. The DNA repair gene, thymine DNA glycosylase, is important to cell survival because it stops cells from becoming cancerous protecting/preventing DNA. Exposure to CS may induce genetic changes such as single nucleotide polymorphisms in DNA repair genes. Therefore, the purpose of this study was to investigate the genotype and allele distributions of four TDG SNPs with only smoking behavior in normal patients. Four TDG SNPs-rs4135066 (C/T), rs3751209 (A/G), rs1866074 (C/T), and rs1882018 (C/T) were analyzed by genotyping 235 and 239 blood samples collected from cigarette smokers and non-smokers, among the Saudi population. The results showed that TDG rs4135066 has a significant susceptibility effect observed in long-term smokers (>5 years; OR = 4.53; P = 0.0347) but not in short-term smokers (≤5 years) in contrast with non-smokers. Also, in smokers aged less than 29 years, the "CT," "TT," and "CT + TT" alleles of rs1882018 increased the risk of developing all diseases related to smoking by approximately 6, 4, and 5 times, respectively, in contrast with the ancestral "CC" homozygous allele. A comparison of the allele distributions of TDG SNPs in a Saudi population with those in other populations represented in the HapMap project showed that the genetic makeup of the Saudi Arabian population appears to differ from that of other ethnicities. Exceptions include the Yoruba people in Ibadan, Nigeria; those of Mexican ancestry in Los Angeles, California; the Luhya population in Webuye, Kenya; Gujarati Indians in Houston, Texas; and the Tuscan population in Italy, which showed similar allelic frequencies for rs3751209 compared to our Saudi population. In this ethnic, we have found a high variation in the distribution of the alleles and genotype frequencies on TDG gene. This variation on TDG SNP's with smoking could lead to increase the susceptibility to many diseases related to smoking habits in this population.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Fumar/genética , Timina ADN Glicosilasa/genética , Adulto , Alelos , Grupos Étnicos/genética , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Masculino
6.
Gene ; 766: 145127, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32937184

RESUMEN

Telomeres are duplex tandem repeats of DNA sequence 5'-TTAGGG-3' at chromosomal ends synthesized by telomerase enzyme (TE). Telomeres length (TL) shortening is associated with age and age-related disorders. Recently, we demonstrated marked leukocytes TL (LTL) shortening in T2DM. To set the relationship between the TE, LTL and T2DM, we analyzed samples from 212 Kuwaiti subjects, 112 patients withT2DM and 100 non-diabetic subjects. The plasma TE and fasting insulin were measured by ELISA, the LTL was estimated by qPCR and three SNPs of genes related to TL; TERC rs12696304 (C/G), TERT rs2736100 (C/A) and ACYP2 rs6713088 (C/G) were genotyped by rtPCR. Results revealed comparable TE levels and alleles/genotypes between the cases and controls with no influence of either on the LTL. Interestingly, although the plasma concentration of the TE was generally low, it was significantly influenced by the TERT and ACYP2 but not TERC polymorphisms. The CC genotype carriers of rs2736100 (C/A) had significantly higher plasma TE levels compared to CA and AA carriers, p 0.009 and p 0.047, respectively, and the A-allele was associated with low TE, p 0.018. Similarly, significantly higher TE levels were detected in CC carriers of ACYP2 rs6713088 (C/G) compared with GC carriers, p 0.002, and the G-allele was associated with low TE, p 0.009. Finally, the TERT and ACYP2 polymorphisms had an influence on blood glucose levels. In conclusion, the telomeres shortening in T2DM was not due to TE deficiency or gene polymorphisms, while the TE levels were significantly associated with the TERT and ACYP2 but not TERC polymorphisms.


Asunto(s)
Ácido Anhídrido Hidrolasas/genética , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleótido Simple/genética , ARN/genética , Telomerasa/genética , Acortamiento del Telómero/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Telomerasa/sangre
7.
Gene ; 766: 145158, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32949694

RESUMEN

The reproductive performance (e.g. fertility) of dairy cows, which declined over past few decades due to the intense and intensive selection, needs to be improved. Previous genome-wide association study (GWAS) of female Holstein screened the Adenylate cyclase 5 (ADCY5) as the candidate gene for cow fertility. As a member of the adenylyl cyclases family, adenylate cyclase 5 (ADCY5) is famous for regulating extrapyramidal motor system related various neuropsychiatric diseases, and its genetic variant is reported to associate with lower birth and placenta weight which leads to asymmetric fetal growth restriction. It was hypothesized that ADCY5 may affect the fertility of cows by regulating the processes of ovarian development. Herein, genomic DNA from 768 ovaries samples of healthy unrelated Holstein cow were used to screen potential insertion/deletion (indel) mutations using eight pairs of primers, and we found three novel polymorphic indel variants, namely, rs385624978 (P3-D11-bp), rs433028962 (P5-I19-bp) and rs382393457 (P8-D19-bp). The minor allelic frequencies (MAF) of P3-D11-bp, P5-I19-bp and P8-D19-bp loci were 0.188, 0.365 and 0.06, respectively, and there were 7 different haplotypes. Additionally, linkage disequilibrium analysis demonstrated no linkage among them. Importantly, P3-D11-bp locus was significantly related to both ovarian width (P = 1.0E-6) and corpus luteum diameter (P = 0.015); P5-I19-bp locus had a significant relation with corpus albicans diameter (P = 0.030) and ovaries with mutational homozygous genotype produced a superior corpus albicans diameter than those with other genotypes. Briefly, three novel indel mutations of bovine ADCY5 gene were identified and two of them were uncovered to be significantly correlated with ovarian phenotypic traits or corpus luteum or albicans traits. These findings contributed to the application of molecular marker-assisted selection (MAS) in improving female fertility in cattle, which could accelerate the development of the cattle industry.


Asunto(s)
Adenilil Ciclasas/genética , Ovario/fisiología , Polimorfismo de Nucleótido Simple/genética , Animales , Bovinos , Femenino , Fertilidad/genética , Frecuencia de los Genes/genética , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Haplotipos/genética , Mutación INDEL/genética , Desequilibrio de Ligamiento/genética , Fenotipo , Reproducción/genética
8.
Food Chem ; 334: 127519, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32721832

RESUMEN

We aimed to characterize and quantify glucosinolate compounds and contents in broccoli, and a total of 80 genotypes and eight developmental organs were analyzed with UHPLC-Triple-TOF-MS. The method was validated in terms of performance, and the coefficients of determination (R2) were 0.97 and 0.99 for glucoraphanin and gluconapin, respectively. In 80 genotypes, twelve glucosinolates were found in broccoli florets ranging from 0.467 to 57.156 µmol/g DW, with the highest glucosinolate content being approximately 122-fold higher than the lowest value. The principal component of glucobrassicin, neoglucobrassicin and glucoraphanin explained 60.53% of the total variance. There were positive correlations among hydroxyglucobrassicin, methoxyglucobrassicin, glucobrassicin, glucoerucin, gluconasturtiin, glucoraphanin, and glucotropaeolin (P < 0.05). The root contained 43% of total glucosinolates in 80 genotypes, and glucoraphanin represented 29% of the total glucosinolate content in different organs. The mutant broccoli genotypes were found by analysis of gluconapin contents in different organs.


Asunto(s)
Brassica/metabolismo , Glucosinolatos/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Brassica/genética , Cromatografía Líquida de Alta Presión , Genotipo , Glucosinolatos/análisis , Imidoésteres/análisis , Indoles/análisis
9.
Food Chem ; 334: 127550, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32693335

RESUMEN

Potato accumulates large amounts of soluble sugar during cold storage periods. However, a system based understanding of this process is still largely unknown. Here, we compared the dynamic cold-responded transcriptome of genotypes between cold-induced sweetening resistant (CIS-R) and cold-induced sweetening sensitive (CIS-S) in tubers. Comparative transcriptome revealed that activating the pathways of starch degradation, sucrose synthesis and hydrolysis could be common strategies in response to cold in both genotypes. Moreover, the variation in sugar accumulation between genotypes may be due to genetic differences in cold response, which could be mainly explained: CIS-R genotype was active in starch synthesis and attenuated in sucrose hydrolysis by promoting the coordinate expression of aseries ofgenes involved in starch-sugar interconversion. Additionally, transcription factors, the candidate master regulators of starch-sugar interconversion, were discussed. Taken together, this work has provided an avenue for studying the mechanism involved in the regulation of the CIS resistance.


Asunto(s)
Solanum tuberosum/genética , Almidón/metabolismo , Azúcares/metabolismo , Edulcorantes/metabolismo , Transcriptoma , Frío , Regulación hacia Abajo , Genotipo , Hidrólisis , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tubérculos de la Planta/metabolismo , Análisis de Componente Principal , Solanum tuberosum/metabolismo , Regulación hacia Arriba
10.
Georgian Med News ; (306): 76-81, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33130651

RESUMEN

HCV infection and its complications, especially hepatocellular carcinoma, is a substantial public health burden. In 2015 "Nationwide hepatitis C elimination program" was launched in Georgia. According to the protocol, patients with HCC also receive DAA antiviral treatment. We study the effect of the different DAA therapy regiments on the incidence or recurrence of HCC and its prognosis. Overall, 408 patients were recruited in Georgian-French Joint Hepatology Clinic HEPA between April 2015-March 2016. The selection criteria were as follows: 1 - age 50-65 years; 2. Liver fibrosis level F3-F4 or cirrhosis at least 15 years of disease history; 3. HCV positive diagnosed by PCR method, whatever the level of viral load and genotype; 4. absence of previous complications of cirrhosis (ascites, gastrointestinal bleeding or HCC; 5. Child-Pugh class A or B; and 6. absence of severe extrahepatic disease. Essential clinical and biological parameters were recorded. Clinical monitoring and management of adverse events were performed on a regular base. HCV All patients included in the study received anti-HCV treatment with direct-acting antivirals (DAAs) within the national hepatitis C elimination program in accordance with national protocols. During April 2015-March 2016 treatment was provided with sofosbuvir (SOF) in combination with ribavirin (RBV), with or without pegylated interferon (IFN). Since March 2016, ledipasvir/sofosbuvir (LDV/SOF) was prescribed to all patients with or without RBV depending on the HCV genotype, level of fibrosis, and previous treatment experience. In conclusion, we find that neither different DAA regimens nor different treatment duration affects HCC risk after antiviral treatment. Moreover, there are no significant changes in mortality rate due to HCC in these groups. Therefore, it can be concluded, that HCC status is not a contraindication for DAA treatment, especially at the early stages of cancer, when a tumor is curative.


Asunto(s)
Antivirales , Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Niño , Quimioterapia Combinada , Genotipo , Georgia , Georgia (República) , Hepacivirus/genética , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Resultado del Tratamiento
11.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(11): 1275-1282, 2020 Nov 06.
Artículo en Chino | MEDLINE | ID: mdl-33147929

RESUMEN

Objective: To reveal the relationship between G6PD genotypes and the G6PD enzyme activities in dried blood spots of newborn screening. Methods: Simple random sampling procedure was used in this study. The fluorescence PCR melting curve analysis was performed to classify G6PD gene variants in 635 neonates coming from Guangzhou Newborn Screening Center during October 1 to 20, 2016, including 15 reported variants. Those samples consisted of 377 cases with screening positive results (261 from males and 116 from females) and 258 cases with screening negative results (32 from males and 226 from females). The cut-off value of G6PD was less than 2.6 U/g Hb in dry blood spots. Sanger sequencing for G6PD gene was used in 7 cases with screening negative results under simple random sampling. One-way ANOVA and least significant difference method (LSD) test were performed to compare the difference of G6PD activity among genotypes. Results: The top 6 frequency of G6PD gene variants were c.1388G>A(35.07%), c.1376G>T(32.13%), c.95A>G(12.72%), c.871G>A(8.32%), c.1024C>T(4.08%) and c.392G>T(2.28%), accounting for 94.62% of all variant alleles (580/613). A total of 253 males positive for enzyme activity were detected to have gene mutations. The positive rate of G6PD enzyme activity was 98.06%(253/258). The mean values of G6PD activities for c.1376G>T,c.95A>G and c.1388G>A were 0.85, 1.10 and 1.28 U/g Hb, respectively. There were significant differences among the three groups (F=28.7, P<0.01). A total of 105 females positive for enzyme activity were detected to have gene mutations. The positive rate of G6PD enzyme activity was 90.52%(105/116). The positive rate of G6PD enzyme activity was 26.95% among 256 females with one point mutation while it was 83.72% in females with multi-allele variants. The G6PD activity of heterozygous females was (2.9±0.8) U/g Hb, which was significant higher than that of females with multi-allele variants (1.5±1.0) U/g Hb (t=8.6,P<0.01). Conclusions: G6PD activities in dried blood spots were related to G6PD genotypes in males. They were also associated with the numbers of allele variants in females. Newborn screening for G6PD deficiency can be used to detect most of G6PD-deficient hemizygotes and female patients with multi-allele variants, which is helpful for preventing neonatal jaundice and medicine application.


Asunto(s)
Deficiencia de Glucosafosfato Deshidrogenasa , Glucosafosfato Deshidrogenasa , Femenino , Genotipo , Glucosafosfato Deshidrogenasa/genética , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Heterocigoto , Humanos , Recién Nacido , Masculino , Mutación , Tamizaje Neonatal
12.
BMC Bioinformatics ; 21(1): 491, 2020 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-33129253

RESUMEN

BACKGROUND: Advances in genotyping and phenotyping techniques have enabled the acquisition of a great amount of data. Consequently, there is an interest in multivariate statistical analyses that identify genomic regions likely to contain causal mutations affecting multiple traits (i.e., pleiotropy). As the demand for multivariate analyses increases, it is imperative that optimal tools are available to assess their performance. To facilitate the testing and validation of these multivariate approaches, we developed simplePHENOTYPES, an R/CRAN package that simulates pleiotropy, partial pleiotropy, and spurious pleiotropy in a wide range of genetic architectures, including additive, dominance and epistatic models. RESULTS: We illustrate simplePHENOTYPES' ability to simulate thousands of phenotypes in less than one minute. We then provide two vignettes illustrating how to simulate sets of correlated traits in simplePHENOTYPES. Finally, we demonstrate the use of results from simplePHENOTYPES in a standard GWAS software, as well as the equivalence of simulated phenotypes from simplePHENOTYPES and other packages with similar capabilities. CONCLUSIONS: simplePHENOTYPES is a R/CRAN package that makes it possible to simulate multiple traits controlled by loci with varying degrees of pleiotropy. Its ability to interface with both commonly-used marker data formats and downstream quantitative genetics software and packages should facilitate a rigorous assessment of both existing and emerging statistical GWAS and GS approaches. simplePHENOTYPES is also available at https://github.com/samuelbfernandes/simplePHENOTYPES .


Asunto(s)
Simulación por Computador , Epistasis Genética , Ligamiento Genético , Pleiotropía Genética , Programas Informáticos , Frecuencia de los Genes/genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Desequilibrio de Ligamiento/genética , Análisis Multivariante , Fenotipo , Carácter Cuantitativo Heredable , Flujo de Trabajo
13.
Nat Commun ; 11(1): 5540, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-33139712

RESUMEN

APOE4 is the strongest genetic risk factor associated with late-onset Alzheimer's disease (AD). To address the underlying mechanism, we develop cerebral organoid models using induced pluripotent stem cells (iPSCs) with APOE ε3/ε3 or ε4/ε4 genotype from individuals with either normal cognition or AD dementia. Cerebral organoids from AD patients carrying APOE ε4/ε4 show greater apoptosis and decreased synaptic integrity. While AD patient-derived cerebral organoids have increased levels of Aß and phosphorylated tau compared to healthy subject-derived cerebral organoids, APOE4 exacerbates tau pathology in both healthy subject-derived and AD patient-derived organoids. Transcriptomics analysis by RNA-sequencing reveals that cerebral organoids from AD patients are associated with an enhancement of stress granules and disrupted RNA metabolism. Importantly, isogenic conversion of APOE4 to APOE3 attenuates the APOE4-related phenotypes in cerebral organoids from AD patients. Together, our study using human iPSC-organoids recapitulates APOE4-related phenotypes and suggests APOE4-related degenerative pathways contributing to AD pathogenesis.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Apolipoproteína E3/genética , Apolipoproteína E3/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Organoides/metabolismo , Sinapsis/metabolismo , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Regulación de la Expresión Génica , Genotipo , Humanos , Organoides/patología , ARN/metabolismo , Transcriptoma
14.
BMC Infect Dis ; 20(1): 815, 2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-33167892

RESUMEN

BACKGROUND: The availability of effective, oral direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has put elimination of HCV as a public health challenge within reach. However, little is known about the characteristics of transmission networks of people who inject drugs (PWID). METHODS: Sequencing of a segment of the HCV genome was performed on samples collected from a community-based cohort of PWID between August 2005 and December 2016. Phylogenetic trees were inferred, and clusters were identified (70% bootstrap threshold; 0.04 maximum genetic distance threshold). We describe sex, race, age difference, and HIV infection status of potential transmission partners. Logistic regression was used to assess factors associated with being in an HCV cluster. RESULTS: Of 508 HCV genotype 1 viremic PWID, 8% (n = 41) were grouped into 20 clusters, consisting of 19 pairs and 1 triad. In adjusted analyses, female sex (odds ratio [OR] 2.3 [95% confidence interval (CI) 1.2-4.5]) and HIV infection (OR 5.7 [CI 2.7-11.9]) remained independently associated with being in an HCV infection cluster. CONCLUSIONS: Molecular epidemiological analysis reveals that, in this cohort of PWID in Baltimore, HIV infection and female sex were associated with HCV clustering. Combination HCV prevention interventions targeting HIV infected PWID and addressing HCV infection prevention needs of women have potential to advance HCV elimination efforts.


Asunto(s)
Infecciones por VIH/epidemiología , VIH/genética , Hepacivirus/genética , Hepatitis C/epidemiología , Filogenia , Abuso de Sustancias por Vía Intravenosa/epidemiología , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Baltimore/epidemiología , Análisis por Conglomerados , Femenino , Estudios de Seguimiento , Genotipo , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Hepatitis C/transmisión , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Factores Sexuales , Parejas Sexuales , Viremia/epidemiología
15.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(10. Vyp. 2): 31-38, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-33205928

RESUMEN

OBJECTIVE: To assess the delayed effect of course therapy with cerebrolysin on the cognitive functioning of the first degree relatives of patients with Alzheimer's disease (AD), including, depending on the ApoE4 genotype. MATERIAL AND METHODS: A cohort of 72 blood relatives of patients with AD, including 46 with objectively confirmed clinical and neuropsychological examination signs of mild cognitive dysfunction (group 1) and 26 (group 2) with cognitive impairment that meets the diagnostic criteria of mild cognitive impairment (ICD-10 F06.7), was studied. The dynamics of the initial (0 day) indicators of cognitive functioning was compared immediately after a four-week course of treatment with cerebrolysin infusions, as well as 1 and 2 months after its completion, depending on the presence of ApoE4(+) or ApoE4(-) genotype. Clinical, psychopathological, psychometric, follow-up, molecular-genetic and statistical methods were used. RESULTS: A positive prolonged effect of course therapy with cerebrolysin on cognitive functioning of the first degree relatives of patients with AD was established in both groups. A significant negative effect of the ApoE4(+) genotype on the immediate and delayed effects of cerebrolysin treatment has been proven. CONCLUSION: The results can form the basis for the development of therapeutic measures aimed at preventing the progression of cognitive impairment and the development of dementia in the first degree relatives of patients with AD as those with the highest risk of dementia.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/prevención & control , Aminoácidos , Apolipoproteínas E/genética , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/genética , Disfunción Cognitiva/prevención & control , Progresión de la Enfermedad , Genotipo , Humanos , Pruebas Neuropsicológicas
16.
An Acad Bras Cienc ; 92(3): e20181251, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33206796

RESUMEN

Ilex paraguariensis (yerba mate) is a native species from South America and is a rich source of bioactive compounds. There is a lack of research efforts on the phytochemical investigation of callus culture from this species. In the present study, an effort was made to optimize callus culture conditions and to identify secondary compounds. Calli were induced from 10 genotypes using leaf explants and the best genotype was selected to evaluate the effects of cytokinin types and concentrations on callus induction and biomass accumulation. The best genotype and cytokinin treatment were used to conduct one last experiment with sucrose concentrations in culture media and its effects on calli biomass, antioxidant activity and secondary compounds accumulation. Callus initiation was genotype dependent, and the 6-156-6 line had the best response. Zeatin supplemented medium showed higher callus induction rate (82%) and higher biomass accumulation after 120 days (328.2 mg). Higher biomass and secondary compounds accumulation were observed for calli on 3% sucrose medium. Antioxidant activity was not affected by sucrose concentrations. Yerba mate callus culture allowed the accumulation of chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, theobromine and caffeine.


Asunto(s)
Ilex paraguariensis , Genotipo , Extractos Vegetales , Hojas de la Planta , América del Sur
17.
Mem Inst Oswaldo Cruz ; 115: e200110, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33146244

RESUMEN

We aimed to investigate the association of CD14 -260C/T (rs2569190) polymorphism and Chagas cardiomyopathy and the functional characteristics of CD14+ and CD14- monocytes upon infection with Trypanosoma cruzi. We observed an association between the T- genotype (absence of allele -260T) related to low CD14 expression and the dilated cardiomyopathy type of Chagas disease. Furthermore, we observed that CD14- monocytes showed a more activated profile upon in vitro infection with T. cruzi than CD14+ monocytes. Our findings suggest that T- genotype is associated with susceptibility to develop Chagas dilated cardiomyopathy, likely linked to the T. cruzi-induced inflammatory profile of CD14- monocytes.


Asunto(s)
Cardiomiopatía Dilatada/genética , Cardiomiopatía Chagásica/genética , Receptores de Lipopolisacáridos/genética , Enfermedad de Chagas , Genotipo , Insuficiencia Cardíaca , Humanos , Trypanosoma cruzi , Disfunción Ventricular Izquierda
19.
BMC Infect Dis ; 20(1): 750, 2020 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-33050903

RESUMEN

BACKGROUND: Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC). Mapping the genetic diversity of MTBC in high TB burden country like Ethiopia is important to understand principles of the disease transmission and to strengthen the regional TB control program. The aim of this study was to investigate the genetic diversity of Mycobacterium tuberculosis complex (MTBC) isolates circulating in the South Omo, southern Ethiopia. METHODS: MTBC isolates (N = 156) were genetically analyzed using spacer oligotyping (spoligotyping) and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing. Major lineages and lineages were identified using MTBC databases. Logistic regression was used to correlate patient characteristics with strain clustering. RESULTS: The study identified Euro-American (EA), East-African-Indian (EAI), Indo-Oceanic (IO), Lineage_7/Aethiops vertus, Mycobacterium bovis and Mycobacterium africanum major lineages in proportions of 67.3% (105/156), 22.4% (35/156), 6.4% (10/156), 1.9% (3/156), 1.3% (2/156) and 0.6% (1/156), respectively. Lineages identified were Delhi/CAS 23.9% (37/155), Ethiopia_2 20.6% (32/155), Haarlem 14.2% (22/155), URAL 14.2%(22/155), Ethiopia_3 8.4% (13/155), TUR 6.5% (10/155), Lineage_7/Aethiops vertus 1.9% (3/155), Bovis 1.3% (2/155), LAM 1.3% (2/155), EAI 0.6% (1/155), X 0.6% (1/155) and Ethiopia H37Rv-like strain 0.6% (1/155). Of the genotyped isolates 5.8% (9/155) remained unassigned. The recent transmission index (RTI) was 3.9%. Orphan strains compared to shared types (AOR: 0.09, 95% CI: 0.04-0.25) were associated with reduced odds of clustering. The dominant TB lineage in pastoral areas was EAI and in non-pastoral areas was EA. CONCLUSION: The epidemiological data, highly diverse MTBC strains and a low RTI in South Omo, provide information contributing to the TB Control Program of the country.


Asunto(s)
Variación Genética , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Etiopía/epidemiología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite/genética , Epidemiología Molecular , Reacción en Cadena de la Polimerasa Multiplex , Mycobacterium bovis/aislamiento & purificación , Mycobacterium tuberculosis/aislamiento & purificación , Esputo/microbiología , Tuberculosis Pulmonar/microbiología , Adulto Joven
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1757-1761, 2020 Oct.
Artículo en Chino | MEDLINE | ID: mdl-33067986

RESUMEN

OBJECTIVE: To explore the clinical significance of G6PD gene mutation detection in female heterozygote with G6PD deficiency. METHODS: G6PD activity and fourteen common G6PD gene mutations in female blood samples were detected by biochemical phenotype detection and PCR-reverse dot blotting, respectively. Unidentified genotype of G6PD positive samples was further ascertained by direct DNA sequencing. The results from two methods were compared and analyzed. RESULTS: A total of 493 unrelated females were enrolled, and the G6PD activity and G6PD mutations was detected. Among them, 473 females were found to be normal in G6PD activity and 20 females with G6PD deficiency, and the detection rate by G6PD activity method was 4.06%. In all enrolled females, G6PD gene mutations, including the mutation of c.1311 C>T, were identified in 130 females, and the detection rate was 26.3%. Detection rate of the mutations that can lead to G6PD deficiency was 8.11%. The detection rates between the two methods were significantly different (P<0.01). The misdiagnosis rate of the G6PD activity detection reached 49. 94% for the female heterozygotes. Eight G6PD mutations and 13 mutation patterns were identified in the research, and most of mutation patterns were single nucleotide missense mutation. In addition to c.1311C>T mutation, the most common mutations were c.1376G>T, c.1388G>A and c.95 A>G. G6PD mutations were identified in 19 of 20 females with G6PD deficiency, and were also detected in 21 of 473 females with normal G6PD activity, of which the rate of heterozygous mutation was 90.88%. CONCLUSION: The phenotype detection based on G6PD enzyme activity alone is not sufficient for the diagnosis of female heterozygotes. The detection of G6PD mutations that covers the common mutations in specified region can effectively identify the female heterozygotes with normal G6PD activity.


Asunto(s)
Deficiencia de Glucosafosfato Deshidrogenasa , Femenino , Genotipo , Glucosafosfato Deshidrogenasa/genética , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Heterocigoto , Humanos , Mutación
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