CAMBIOS EN LAS VARIABLES DE RIESGO CARDIOVASCULAR EN UNA COHORTE DE ESTUDIANTES UNIVERSITARIOS DE LA CIUDAD DE MÉXICO

Las enfermedades cardiovasculares ocupan actualmente los primeros lugares de mortalidad  y en países desarrollados y  de acuerdo a las tendencias actuales  lo serán también en los países en desarrollo. No se han realizado estudios de cohorte relacionados a conocer el comportamiento de las variables cardiovasculares en población de América Latina, por ello, el propósito del presente estudio fue determinar el comportamiento a tres años y medio de las variables de riesgo cardiovascular en estudiantes universitarios de la ciudad de México. (Universidad Autónoma Metropolitana-Iztapalapa).El diseño del  estudio fue  de cohorte prospectiva. Ingresaron 73 estudiantes, se autoaplicó un cuestionario para obtener información demográfica, de antecedentes patológicos heredofamiliares y factores de riesgo. Se medió, peso, talla, Índice de Masa Corporal (IMC), Circunferencia de Cintura (CC) % de grasa corporal y presión arterial. Se tomó muestra sanguínea en ayunas para medir colesterol total (CT), triglicéridos (Tg), Lípidos de Baja densidad (LDL) y de alta densidad (HDL)  y glucosa. Se calculó el Índice Aterogénico (IA). Resultados. El total de alumnos que terminaron el seguimiento fue de 50.  35 mujeres y 15 hombres.  El 70% de los estudiantes tenía antecedentes familiares de diabetes, 38% de hipertensión, 12% era fumador  y 58% ingería alcohol por lo menos una vez al mes. De acuerdo al IMC el 34% de las mujeres tenía sobrepeso y 5.7 eran obesas. Durante el periodo de seguimiento, los hombres incrementaron significativamente (0,00) el peso, la CC, y la glucosa. Las mujeres solo el LDL, la sístole y diástole disminuye de manera significativa ( 0.23, 0.18) respectivamente. Ningún estudiante fue diabético o hipertenso durante el periodo de estudio. Los hallazgos de este estudio no tienen relevancia clínica aún, sin embargo se debe enfatizar en la prevención primaria dentro de las universidades. Abstract Cardiovascular diseases are one of the main causes of death and disability in developed countries and it is currently increasing in developing countries too. Given that there are scarce cohort studies in -Latin America regarding cardiovascular risk factors, particularly in young population groups, the purpose of the this study was to follow up the behaviour of cardiovascular variables during a period of three and a half years. The study was conducted in a university student population ages 18 to 25 years old. Methodology.  A prospective cohort study of 73 university students from Mexico City was performed. A self-assessment questionnaire was used to obtain demographic characteristics and cardiovascular risk factors. Anthropometric, clinical, and biochemical variables were measured every three months. In addition, weight, height, Body Mass Index (BMI), waist circumference (WC), percentage body fat, and blood pressure were measured. From blood samples, cholesterol, triglycerides, High Density Lipoproteins and glucose were measured. Low Density Lipoproteins were calculated using the Friedewald formula. Paired Student’s t-tests were performed in order to compare means and cases  were expressed in graphical formats for lipid results. Results. Only 35 women and 15 men completed the three and a half years follow up. Of this total, 70% of students had diabetes background, 38% had hypertension, 12% had smoked and 58% had drank alcohol at least once a month. According to BMI measurements, 34% of women were overweight and 5.7% were obese compared with men where 27.7% were overweight. Men presented no cases of obesity. Conclusions. The behavior of cardiovascular variables over the three and a half- year period were different - between women and men. During this period, men increased significantly (0 .000) their weight, WC, BMI, and glucose levels.  Women, only LDL levels  increased significantly (0.18) while systole and diastole measures decrease significantly ( 0.23, 0.18). No subjects reported suffering from diabetes or hypertension during the period of study. The difference over the follow up did not have clinical relevance. Palabras clave: Variables cardiovasculares, cohorte, estudiantes universitarios

Spectroscopy of 32Ne and the Island of Inversion

We report on the first spectroscopic study of the N=22 nucleus 32Ne at the newly completed RIKEN Radioactive Ion Beam Factory. A single gamma-ray line with an energy of 722(9) keV was observed in both inelastic scattering of a 226 MeV/u 32Ne beam on a Carbon target and proton removal from 33Na at 245 MeV/u. This transition is assigned to the de-excitation of the first J^pi = 2+ state in 32Ne to the 0+ ground state. Interpreted through comparison with state-of-the-art shell model calculations, the low excitation energy demonstrates that the Island of Inversion extends to at least N=22 for the Ne isotopes.Comment: Accepted for publication in Phys. Rev. Lett. 11 pages, 3 figure

Epigenetic regulation of S100 protein expression

S100 proteins are small, calcium-binding proteins whose genes are localized in a cluster on human chromosome 1. Through their ability to interact with various protein partners in a calcium-dependent manner, the S100 proteins exert their influence on many vital cellular processes such as cell cycle, cytoskeleton activity and cell motility, differentiation, etc. The characteristic feature of S100 proteins is their cell-specific expression, which is frequently up- or downregulated in various pathological states, including cancer. Changes in S100 protein expression are usually characteristic for a given type of cancer and are therefore often considered as markers of a malignant state. Recent results indicate that changes in S100 protein expression may depend on the extent of DNA methylation in the S100 gene regulatory regions. The range of epigenetic changes occurring within the S100 gene cluster has not been defined. This article reviews published data on the involvement of epigenetic factors in the control of S100 protein expression in development and cancer

Epigenetic deregulation of multiple S100 gene family members by differential hypomethylation and hypermethylation events in medulloblastoma

Deregulated expression of genes encoding members of the S100 family of calcium-binding proteins has been associated with the malignant progression of multiple tumour types. Using a pharmacological expression reactivation approach, we screened 16 S100 genes for evidence of epigenetic regulation in medulloblastoma, the most common malignant brain tumour of childhood. Four family members (S100A2, S100A4, S100A6 and S100A10) demonstrated evidence of upregulated expression in multiple medulloblastoma cell lines, following treatment with the DNA methyltransferase inhibitor, 5′-aza-2′-deoxycytidine. Subsequent analysis revealed methylation of critical CpG sites located within these four genes in an extended cell line panel. Assessment of these genes in the non-neoplastic cerebellum (from which medulloblastomas develop) revealed strong somatic methylation affecting S100A2 and S100A4, whereas S100A6 and S100A10 were unmethylated. Assessed against these normal tissue-specific methylation states, S100A6 and S100A10 demonstrated tumour-specific hypermethylation in medulloblastoma primary tumours (5 out of 40 and 4 out of 35, respectively, both 12%) and cell lines (both 7 out of 9, 78%), which was associated with their transcriptional silencing. Moreover, S100A6 hypermethylation was significantly associated with the aggressive large cell/anaplastic morphophenotype (P=0.026). In contrast, pro-metastatic S100A4 displayed evidence of hypomethylation relative to the normal cerebellum in a significant proportion primary tumours (7 out of 41, 17%) and cell lines (3 out of 9, 33%), which was associated with its elevated expression. In summary, these data characterise complex patterns of somatic methylation affecting S100 genes in the normal cerebellum and demonstrate their disruption causing epigenetic deregulation of multiple S100 family members in medulloblastoma development. Epigenetic events affecting S100 genes have potential clinical utility and merit further investigation as molecular biomarkers for this disease

Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells

Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA–binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3β. Dysregulation of GSK3β led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis

Global Mapping of Cell Type–Specific Open Chromatin by FAIRE-seq Reveals the Regulatory Role of the NFI Family in Adipocyte Differentiation

Identification of regulatory elements within the genome is crucial for understanding the mechanisms that govern cell type–specific gene expression. We generated genome-wide maps of open chromatin sites in 3T3-L1 adipocytes (on day 0 and day 8 of differentiation) and NIH-3T3 fibroblasts using formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq). FAIRE peaks at the promoter were associated with active transcription and histone modifications of H3K4me3 and H3K27ac. Non-promoter FAIRE peaks were characterized by H3K4me1+/me3-, the signature of enhancers, and were largely located in distal regions. The non-promoter FAIRE peaks showed dynamic change during differentiation, while the promoter FAIRE peaks were relatively constant. Functionally, the adipocyte- and preadipocyte-specific non-promoter FAIRE peaks were, respectively, associated with genes up-regulated and down-regulated by differentiation. Genes highly up-regulated during differentiation were associated with multiple clustered adipocyte-specific FAIRE peaks. Among the adipocyte-specific FAIRE peaks, 45.3% and 11.7% overlapped binding sites for, respectively, PPARγ and C/EBPα, the master regulators of adipocyte differentiation. Computational motif analyses of the adipocyte-specific FAIRE peaks revealed enrichment of a binding motif for nuclear family I (NFI) transcription factors. Indeed, ChIP assay showed that NFI occupy the adipocyte-specific FAIRE peaks and/or the PPARγ binding sites near PPARγ, C/EBPα, and aP2 genes. Overexpression of NFIA in 3T3-L1 cells resulted in robust induction of these genes and lipid droplet formation without differentiation stimulus. Overexpression of dominant-negative NFIA or siRNA–mediated knockdown of NFIA or NFIB significantly suppressed both induction of genes and lipid accumulation during differentiation, suggesting a physiological function of these factors in the adipogenic program. Together, our study demonstrates the utility of FAIRE-seq in providing a global view of cell type–specific regulatory elements in the genome and in identifying transcriptional regulators of adipocyte differentiation

Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states