Publications by authors named "Cecilia Contreras-Cubas"

16 Publications

  • Page 1 of 1

Metabolic syndrome in indigenous communities in Mexico: a descriptive and cross-sectional study.

BMC Public Health 2020 Mar 17;20(1):339. Epub 2020 Mar 17.

Immunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Periférico Sur 4809, Colonia Arenal Tepepan, Delegación Tlalpan, C.P. 14610, Ciudad de México, Mexico.

Background: An Amerindian genetic background could play an important role in susceptibility to metabolic diseases, which have alarmingly increased in recent decades. Mexico has one of the highest prevalences of metabolic disease worldwide. The purpose of this study was to determine the prevalence of metabolic syndrome and its components in a population with high Amerindian ancestry.

Methods: We performed a descriptive, quantitative, and analytical cross-sectional study of 2596 adult indigenous volunteers from 60 different ethnic groups. Metabolic syndrome and its components were evaluated using the American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement criteria.

Results: The overall prevalence of metabolic syndrome in the indigenous Mexican population was 50.3%. Although females had a higher prevalence than males (55.6% vs. 38.2%), the males presented with combinations of metabolic syndrome components that confer a higher risk of cardiovascular disease. The most frequent metabolic syndrome component in both genders was low HDL-cholesterol levels (75.8%). Central obesity was the second most frequent component in females (61%), though it had a low prevalence in males (16.5%). The overall prevalence of elevated blood pressure was 42.7% and was higher in males than females (48.8 vs. 40%). We found no gender differences in the overall prevalence of elevated triglycerides (56.7%) or fasting glucose (27.9%).

Conclusions: We documented that individuals with Amerindian ancestry have a high prevalence of metabolic syndrome. Health policies are needed to control the development of metabolic disorders in a population with high genetic risk.
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http://dx.doi.org/10.1186/s12889-020-8378-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076922PMC
March 2020

Genetic variability of five ADRB2 polymorphisms among Mexican Amerindian ethnicities and the Mestizo population.

PLoS One 2019 2;14(12):e0225030. Epub 2019 Dec 2.

Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City, Mexico.

The Mexican population is characterized by high and particular admixture, and the picture of variants associated with disease remains unclear. Here we investigated the distribution of single nucleotide polymorphisms (SNPs) in the Mexican population. We focused on two non-synonymous and three synonymous SNPs in the beta-2 adrenergic receptor gene (ADRB2), which plays key roles in energy balance regulation. These SNPs were genotyped in 2,011 Mexican Amerindians (MAs) belonging to 62 ethnic groups and in 1,980 geographically matched Mexican Mestizos (MEZs). The frequency distribution of all five ADRB2 variants significantly differed between MAs, MEZs, and other continental populations (CPs) from the 1000 Genomes database. Allele frequencies of the three synonymous SNPs rs1042717A, rs1042718A, and rs1042719C were significantly higher in Mexican individuals, particularly among MAs, compared to in the other analyzed populations (P<0.05). The non-synonymous ADRB2 Glu27 allele (rs1042714G), which is associated with several common conditions, showed the lowest frequency in MAs (0.03) compared to other populations worldwide. Among MEZs, this allele showed a frequency of 0.15, intermediate between that in MAs and in Iberians (0.43). Moreover, Glu27 was the only SNP exhibiting a geographic gradient within the MEZ population (from 0.22 to 0.11), reflecting admixed mestizo ancestry across the country. Population differentiation analysis demonstrated that Glu27 had the highest FST value in MAs compared with Europeans (CEU) (0.71), and the lowest between MAs and Japanese (JPT) (0.01), even lower than that observed between MAs and MEZs (0.08). This analysis demonstrated the genetic diversity among Amerindian ethnicities, with the most extreme FST value (0.34) found between the Nahuatls from Morelos and the Seris. This is the first study of ADRB2 genetic variants among MA ethnicities. Our findings add to our understanding of the genetic contribution to variability in disease susceptibility in admixed populations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225030PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886845PMC
April 2020

Catalytically Impaired TYK2 Variants are Protective Against Childhood- and Adult-Onset Systemic Lupus Erythematosus in Mexicans.

Sci Rep 2019 08 21;9(1):12165. Epub 2019 Aug 21.

Immunogenomics and Metabolic Diseases Laboratory, National Institute of Genomic Medicine, SS, Mexico City, Mexico.

Type I interferon (IFN-I) pathway plays a central role in the systemic lupus erythematosus (SLE) pathogenesis. Recent data suggest that SLE is associated with variants in IFN-I genes, such as tyrosine kinase 2 (TYK2), which is crucial in anti-viral immunity. Here, five TYK2 single nucleotide polymorphisms (SNPs) were genotyped in 368 childhood-onset SLE Mexican patients and 516 sex-matched healthy controls. Allele frequencies were also estimated in four indigenous groups. SLE protection was associated with TYK2 risk infection variants affecting residually its catalytic domain, rs12720356 (OR = 0.308; p = 0.041) and rs34536443 (OR = 0.370; p = 0.034), but not with rs2304256, rs12720270, and rs280500. This association was replicated in a 506 adult-onset SLE patients sample (OR = 0.250; p = 0.005, and OR = 0.277; p = 0.008, respectively). The minor alleles of both associated SNPs had a lower frequency in Mestizos than in Spaniards and were absent or rare in indigenous, suggesting that the presence of these alleles in the Mexican Mestizo population was derived from the Spaniards. For the first time, we report genetic variants with a protective effect in childhood- and adult-onset SLE Mexican population. Our results suggest that the frequency of IFN-I alleles associated with SLE, may have been shaped in populations exposed to infectious diseases for long periods, and this could be an explanation why Native American ancestry is associated with a higher SLE prevalence and an earlier onset.
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http://dx.doi.org/10.1038/s41598-019-48451-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704113PMC
August 2019

Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls.

Nature 2019 06 22;570(7759):71-76. Epub 2019 May 22.

Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea.

Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10) and candidate genes from knockout mice (P = 5.2 × 10). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.
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http://dx.doi.org/10.1038/s41586-019-1231-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699738PMC
June 2019

Next-generation sequencing for identifying a novel/de novo pathogenic variant in a Mexican patient with cystic fibrosis: a case report.

BMC Med Genomics 2019 05 22;12(1):68. Epub 2019 May 22.

Laboratorio de Inmunogenómica y enfermedades metabólicas, Instituto Nacional de Medicina Genómica,SS, Periférico Sur No. 4809, Arenal Tepepan,Tlalpan, 14610. CDMX, Mexico City, Mexico.

Background: Mexico is among the countries showing the highest heterogeneity of CFTR variants. However, no de novo variants have previously been reported in Mexican patients with cystic fibrosis (CF).

Case Presentation: Here, we report the first case of a novel/de novo variant in a Mexican patient with CF. Our patient was an 8-year-old male who had exhibited the clinical onset of CF at one month of age, with steatorrhea, malabsorption, poor weight gain, anemia, and recurrent respiratory tract infections. Complete sequencing of the CFTR gene by next generation sequencing (NGS) revealed two different variants in trans, including the previously reported CF-causing variant c.3266G > A (p.Trp1089*, W1089*), that was inherited from the mother, and the novel/de novo CFTR variant c.1762G > T (p.Glu588*).

Conclusion: Our results demonstrate the efficiency of targeted NGS for making a rapid and precise diagnosis in patients with clinically suspected CF. This method can enable the provision of accurate genetic counselling, and improve our understanding of the molecular basis of genetic diseases.
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http://dx.doi.org/10.1186/s12920-019-0528-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532186PMC
May 2019

Gene variants in AKT1, GCKR and SOCS3 are differentially associated with metabolic traits in Mexican Amerindians and Mestizos.

Gene 2018 Dec 31;679:160-171. Epub 2018 Aug 31.

Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, CDMX, Mexico. Electronic address:

Amerindian ancestry appears to be a risk factor for metabolic diseases (MetD), making Mexicans an ideal population to better understand the genetic architecture of metabolic health. In this study, we determine the association of genetic variants previously reported with metabolic entities, in two Mexican populations, including the largest sample of Amerindians reported to date. We investigated the association of eigth single-nucleotide polymorphisms (SNPs) in AKT1, GCKR, and SOCS3 genes with different metabolic traits in 1923 Mexican Amerindians (MAs) belonging to 57 ethnic groups, and 855 Mestizos (MEZs). The allele frequency of 7/8 SNPs showed significant differences between MAs and MEZs. Interestingly, some alleles were monomorphic in particular ethnic groups, and highly frequent in other ones. With the exception of GCKR rs1260326T, as expected, all SNP frequencies in the MEZ population had intermediate values between its two main ancestral populations (MAs and Iberian populations in Spain [IBS]). We detected ethnic differences in linkage disequilibrium patterns and haplotype structure between MAs and MEZs, possibly due to the high genetic heterogeneity in these populations. Remarkably, AKT1 was associated with hypertension in MEZs, but not in MAs. GCKR was associated with protection against type 2 diabetes (T2D) in MAs, and with hypertriglyceridemia and protection against low HDL Cholesterol (HDL-C) levels in MEZs. The CAT haplotype in SOCS3 was associated with metabolic syndrome (MetS) in MEZs, and correlated with protection against high blood pressure (HBP) and risk for high waist circumference and T2D in MAs. Our results show differential genetic associations with metabolic traits between MAs and MEZs, possibly due to the differences in genetic structure between these Mexican populations.
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http://dx.doi.org/10.1016/j.gene.2018.08.076DOI Listing
December 2018

A Loss-of-Function Splice Acceptor Variant in Is Protective for Type 2 Diabetes.

Diabetes 2017 11 24;66(11):2903-2914. Epub 2017 Aug 24.

Department of Genetics, Harvard Medical School, Boston, MA.

Type 2 diabetes (T2D) affects more than 415 million people worldwide, and its costs to the health care system continue to rise. To identify common or rare genetic variation with potential therapeutic implications for T2D, we analyzed and replicated genome-wide protein coding variation in a total of 8,227 individuals with T2D and 12,966 individuals without T2D of Latino descent. We identified a novel genetic variant in the gene associated with ∼20% reduced risk for T2D. This variant, which has an allele frequency of 17% in the Mexican population but is rare in Europe, prevents splicing between exons 1 and 2. We show in vitro and in human liver and adipose tissue that the variant is associated with a specific, allele-dosage-dependent reduction in the expression of isoform 2. In individuals who do not carry the protective allele, expression of isoform 2 in adipose is positively correlated with both incidence of T2D and increased plasma glycated hemoglobin in individuals without T2D, providing support that the protective effects are mediated by reductions in isoform 2. Broad phenotypic examination of carriers of the protective variant revealed no association with other disease states or impaired reproductive health. These findings suggest that reducing isoform 2 expression in relevant tissues has potential as a new therapeutic strategy for T2D, even beyond the Latin American population, with no major adverse effects on health or reproduction.
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http://dx.doi.org/10.2337/db17-0187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652606PMC
November 2017

The Class II Trehalose 6-phosphate Synthase Gene Modulates Trehalose Metabolism in Nodules.

Front Plant Sci 2016 1;7:1589. Epub 2016 Nov 1.

Departamento de Biología Molecular de Plantas, Instituto de Biotecnología/Universidad Nacional Autónoma de México Cuernavaca, Mexico.

Legumes form symbioses with rhizobia, producing nitrogen-fixing nodules on the roots of the plant host. The network of plant signaling pathways affecting carbon metabolism may determine the final number of nodules. The trehalose biosynthetic pathway regulates carbon metabolism and plays a fundamental role in plant growth and development, as well as in plant-microbe interactions. The expression of genes for trehalose synthesis during nodule development suggests that this metabolite may play a role in legume-rhizobia symbiosis. In this work, , which encodes a Class II trehalose-6-phosphate synthase (TPS) of common bean (), was silenced by RNA interference in transgenic nodules. The silencing of in root nodules resulted in a reduction of 85% (± 1%) of its transcript, which correlated with a 30% decrease in trehalose contents of transgenic nodules and in untransformed leaves. Composite transgenic plants with silenced in the roots showed no changes in nodule number and nitrogen fixation, but a severe reduction in plant biomass and altered transcript profiles of all Class II genes. Our data suggest that plays a key role in modulating trehalose metabolism in the symbiotic nodule and, therefore, in the whole plant.
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http://dx.doi.org/10.3389/fpls.2016.01589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5088437PMC
November 2016

Heterogenous Distribution of MTHFR Gene Variants among Mestizos and Diverse Amerindian Groups from Mexico.

PLoS One 2016 20;11(9):e0163248. Epub 2016 Sep 20.

Inmunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Folate deficiency has been related to several conditions, including neural tube defects (NTDs) and cardiovascular diseases. Hence, MTHFR genetic variants have been studied worldwide, particularly the C677T and A1298C. We genotyped the C677T and A1298C MTHFR polymorphisms in Mexican Amerindians (MAs), from the largest sample included in a genetic study (n = 2026, from 62 ethnic groups), and in a geographically-matched Mexican Mestizo population (MEZ, n = 638). The 677T allele was most frequent in Mexican individuals, particularly in MAs. The frequency of this allele in both MAs and MEZs was clearly enriched in the South region of the country, followed by the Central East and South East regions. In contrast, the frequency of the 1298C risk allele in Mexicans was one of the lowest in the world. Both in MAs and MEZs the variants 677T and 1298C displayed opposite allele frequency gradients from southern to northern Mexico. Our findings suggest that in Mestizos the 677T allele was derived from Amerindians while the 1298C allele was a European contribution. Some subgroups showed an allele frequency distribution that highlighted their genetic diversity. Notably, the distribution of the frequency of the 677T allele was consistent with that of the high incidence of NTDs reported in MEZ.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5029802PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163248PLOS
August 2017

Gender-Dependent Association of FTO Polymorphisms with Body Mass Index in Mexicans.

PLoS One 2016 4;11(1):e0145984. Epub 2016 Jan 4.

Laboratorio de Immunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaría de Salud, Mexico City, Mexico.

To evaluate the associations between six single-nucleotide polymorphisms (SNPs) in intron 1 of FTO and body mass index (BMI), a case-control association study of 2314 unrelated Mexican-Mestizo adult subjects was performed. The association between each SNP and BMI was tested using logistic and linear regression adjusted for age, gender, and ancestry and assuming additive, recessive, and dominant effects of the minor allele. Association analysis after BMI stratification showed that all five FTO SNPs (rs1121980, rs17817449, rs3751812, rs9930506, and rs17817449), were significantly associated with obesity class II/III under an additive model (P<0.05). Interestingly, we also documented a genetic model-dependent influence of gender on the effect of FTO variants on increased BMI. Two SNPs were specifically associated in males under a dominant model, while the remainder were associated with females under additive and recessive models (P<0.05). The SNP rs9930506 showed the highest increased in obesity risk in females (odds ratio = 4.4). Linear regression using BMI as a continuous trait also revealed differential FTO SNP contributions. Homozygous individuals for the risk alleles of rs17817449, rs3751812, and rs9930506 were on average 2.18 kg/m(2) heavier than homozygous for the wild-type alleles; rs1121980 and rs8044769 showed significant but less-strong effects on BMI (1.54 kg/m(2) and 0.9 kg/m(2), respectively). Remarkably, rs9930506 also exhibited positive interactions with age and BMI in a gender-dependent manner. Women carrying the minor allele of this variant have a significant increase in BMI by year (0.42 kg/m(2), P = 1.17 x 10(-10)). Linear regression haplotype analysis under an additive model, confirmed that the TGTGC haplotype harboring all five minor alleles, increased the BMI of carriers by 2.36 kg/m(2) (P = 1.15 x 10(-5)). Our data suggest that FTO SNPs make differential contributions to obesity risk and support the hypothesis that gender differences in the mechanisms involving these variants may contribute to disease development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145984PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703196PMC
July 2016

Association of HMOX1 and NQO1 Polymorphisms with Metabolic Syndrome Components.

PLoS One 2015 1;10(5):e0123313. Epub 2015 May 1.

Immunogenomics and Metabolic Disease Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City, Mexico.

Metabolic syndrome (MetS) is among the most important public health problems worldwide, and is recognized as a major risk factor for various illnesses, including type 2 diabetes mellitus, obesity, and cardiovascular diseases. Recently, oxidative stress has been suggested as part of MetS aetiology. The heme oxygenase 1 (HMOX1) and NADH:quinone oxidoreductase 1 (NQO1) genes are crucial mediators of cellular defence against oxidative stress. In the present study, we analysed the associations of HMOX1 (GT)n and NQO1 C609T polymorphisms with MetS and its components. Our study population comprised 735 Mexican Mestizos unrelated volunteers recruited from different tertiary health institutions from Mexico City. In order to know the HMOX1 (GT)n and NQO1 C609T allele frequencies in Amerindians, we included a population of 241 Amerindian native speakers. Their clinical and demographic data were recorded. The HMOX1 (GT)n polymorphism was genotyped using PCR and fluorescence technology. NQO1 C609T polymorphism genotyping was performed using TaqMan probes. Short allele (<25 GT repeats) of the HMOX1 polymorphism was associated with high systolic and diastolic blood pressure, and the T allele of the NQO1 C609T polymorphism was associated with increased triglyceride levels and decreased HDL-c levels, but only in individuals with MetS. This is the first study to analyse the association between MetS and genes involved in oxidative stress among Mexican Mestizos. Our data suggest that polymorphisms of HMOX1 and NQO1 genes are associated with a high risk of metabolic disorders, including high systolic and diastolic blood pressure, hypertriglyceridemia, and low HDL-c levels in Mexican Mestizo individuals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123313PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416764PMC
January 2016

Determining abundance of microRNAs and other small RNAs in legumes.

Methods Mol Biol 2013 ;1069:81-92

Departamento de Biología Molecular de Plantas, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico.

High-throughput sequencing techniques have been applied to the discovery of several different regulatory small RNAs, including siRNAs and microRNAs in different plant species. Their subsequent characterization demands the use of sensitive and quantitative methods for their detection. Here we describe the use of northern blot and quantitative PCR for these purposes. We highlight the advantages and shortcomings of each method and offer a detailed description of those techniques that best work in our hands, in particular having in mind their use for the study of several small RNAs in a given sample. We enumerate relevant alternatives as well as cautionary comments in cases where we have detected potential difficulties.
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http://dx.doi.org/10.1007/978-1-62703-613-9_7DOI Listing
March 2014

Non-coding RNAs in the plant response to abiotic stress.

Planta 2012 Oct 4;236(4):943-58. Epub 2012 Jul 4.

Departamento de Biología Molecular de Plantas, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apdo Postal 510-3, 62250 Cuernavaca, Mor, Mexico.

As sessile organisms, plants have to cope with the ever-changing environment as well as with numerous forms of stress. To react to these external cues, plants have evolved a suite of response mechanisms operating at many different levels, ranging from physiological to molecular processes that provide the organism with a wide phenotypic plasticity, allowing for fine tuning of the reactions to these adverse circumstances. During the past decade, non-coding RNAs (ncRNAs) have emerged as key regulatory molecules, which contribute to a significant portion of the transcriptome in eukaryotes and are involved in the control of transcriptional and post-transcriptional gene regulatory pathways. Although accumulated evidence supports an important role for ncRNAs in plant response and adaptation to abiotic stress, their mechanism(s) of action still remains obscure and a functional characterization of the ncRNA repertoire in plants is still needed. Moreover, common features in the biogenesis of different small ncRNAs, and in some cases, cross talk between different gene regulatory pathways may add to the complexity of these pathways and could play important roles in modulating stress responses. Here we review the various ncRNAs that have been reported to participate in the response to abiotic stress in plants, focusing on their importance in plant adaptation and evolution. Understanding how ncRNAs work may reveal novel mechanisms involved in the plant responses to the environment.
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http://dx.doi.org/10.1007/s00425-012-1693-zDOI Listing
October 2012

The Phaseolus vulgaris miR159a precursor encodes a second differentially expressed microRNA.

Plant Mol Biol 2012 Sep 15;80(1):103-15. Epub 2011 Nov 15.

Depto. Biología Molecular de Plantas, Instituto de Biotecnología, Universidad Nacional Autónoma de México, AP 62210, Cuernavaca, Morelos, Mexico.

Plant microRNAs originate from a stem-loop structured single-stranded RNA precursor. Each stem-loop is processed to generate a mature microRNA that is recruited to an ARGONAUTE-containing multi-protein complex to direct silencing of its target mRNA. Here we report that the conserved plant miR159a precursor produces a second 21-nt long RNA with the properties of a microRNA. Its presence in different plant species is supported by its conservation in the stem-loop position and expression as determined by northern blot analysis. We show that successive processing by DCL1 produces this novel microRNA from the same precursor as miR159a. In contrast to the low levels observed in other plant models for the equivalent of miR159.2, in P. vulgaris, the accumulation of miR159.2 is easily detectable and when compared to miR159a, their expression patterns are distinct in different organs and growth conditions. Further evidence of the functionality of miR159.2 comes from its association with silencing complexes as demonstrated by co-immunoprecipitation experiments using an AGO1-specific antibody and processing of an artificial GFP reporter construct containing a complementary target sequence. These results indicate that the second small RNA corresponds to a microRNA, at least partially independent of miR159 activity, and that in plants a miRNA precursor may encode multiple regulatory small RNAs.
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http://dx.doi.org/10.1007/s11103-011-9847-0DOI Listing
September 2012

First step in pre-miRNAs processing by human Dicer.

Acta Pharmacol Sin 2009 Aug;30(8):1177-85

Departamento de Biología Celular, Instituto de Fisiología Celular, UNAM Apartado Postal 70-600, Circuito exterior s/n Ciudad Universitaria, Delegación Coyoacan, CP 04510, México DF.

Aim: To investigate the strand preference of the initial cleavage of human pre-miRNAs by human Dicer in vitro.

Methods: We used a series of in vitro transcribed pre-miRNAs that were radioactively labeled at their 5' or 3' ends in cleavage reactions with recombinant human Dicer or HeLa cytoplasmic S100 extracts. Pre-miRNAs samples were purified by denaturing and native PAGE and only the stem-loop structures were used in the experiments. Products of cleavage reactions were resolved by denaturing PAGE, and scanned by phosphor-imaging.

Results: Recombinant hDicer performs a biased first-cleavage in the pre-let-7b and hsa-pre-miR-17 3' strand. This result is recapitulated in HeLa S100 cytoplasmic extracts.

Conclusion: The differential first-nick is observed in cleavage reactions only when stem-loops are substrates for hDicer.
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http://dx.doi.org/10.1038/aps.2009.108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006688PMC
August 2009

Ascorbate uptake in normal and diabetic rat retina and retinal pigment epithelium.

Comp Biochem Physiol C Toxicol Pharmacol 2007 Jul-Aug;146(1-2):175-179. Epub 2007 Mar 3.

Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F., México.

Oxidative stress is an important causative factor in the pathogenesis of diabetic retinopathy. Therefore, it becomes important to understand the mechanisms that help maintain appropriate levels of a small molecule antioxidant such as ascorbate in the retina. The outer blood-barrier which results from the tight junctions between the retinal pigment epithelial cells (RPE) restricts the flow of nutrients reaching the retina. In this study, we characterized the transport properties of carboxyl-(14)C ascorbate (AA) in normal rat retina and RPE, and compared them with those in streptozotocin-diabetic rats. Retina and RPE accumulated AA by a temperature-sensitive and energy-dependent kinetic mechanism with an apparent K(M) of 380 and 420 microM, respectively. Accumulation of AA was significantly reduced in a sodium-free medium. Although high glucose concentrations reduced AA uptake by 40%, this was not affected by cytochalasin B. The RPE and retina of diabetic rats presented lower levels of AA accumulation. These findings suggest the presence of the specific vitamin C transporter SVCT in retina and RPE, which may be involved in the manifestation of diabetic retinopathy.
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http://dx.doi.org/10.1016/j.cbpc.2007.02.015DOI Listing
October 2007