1,843,020 research outputs found
Evaluation and intercomparison of global atmospheric transport models using Rn-222 and other short-lived tracers
Full text linkSimulations of Rn-222 and other short-lived tracers are used to evaluate and intercompare the representations of convective and synoptic processes in 20 global atmospheric transport models. Results show that most established three-dimensional models simulate vertical mixing in the troposphere to within the constraints offered by the observed mean Rn-222 concentrations and that subgrid parameterization of convection is essential for this purpose. However, none of the models captures the observed variability of Rn-222 concentrations in the upper troposphere, and none reproduces the high Rn-222 concentrations measured at 200 hPa over Hawaii. The established three-dimensional models reproduce the frequency and magnitude of high- Rn-222 episodes observed at Crozet Island in the Indian Ocean, demonstrating that they can resolve the synoptic-scale transport of continental plumes with no significant numerical diffusion. Large differences between models are found in the rates of meridional transport in the upper troposphere (interhemispheric exchange, exchange between tropics and high latitudes). The four two-dimensional models which participated in the intercomparison tend to underestimate the rate of vertical transport from the lower to the upper troposphere but show concentrations of Rn-222 in the lower troposphere that are comparable to the zonal mean values in the three-dimensional models
A Regulatory “miRcircuitry” Involving miR221&222 and ERα Determines ERα Status of Breast Cancer Cells
No full textEstrogen Receptor α (ERα) is the most important diagnostic and prognostic factor in breast
cancer. Several lines of evidence have suggested that ERα-negative breast tumors, highly
aggressive and non-responsive to hormonal therapy, arise from ERα-positive precursors
through different molecular pathways. microRNAs (miRs) are small non-coding RNAs that
regulate gene expression at post-transcriptional level and are aberrantly expressed in breast
cancer. We hypothesized that microRNAs may have a pivotal role in ERα suppression and
ERα-negative tumors formation. MicroRNAs microarray, quantitative real-time PCR,
immunohistochemistry and in-situ hybridization analyses of breast cancer cell lines and
primary tumors with different ERα-status indicated that miR221&222 are exclusively
expressed in ERα-negative breast tumors. Overexpression of both microRNAs in ERα-
positive cell lines strongly reduces the levels of ERα protein and, using luciferase reporter
assays, we clearly demonstrated that ERα is a bona fide target of miR221&222. Gene
expression profiles were analyzed after miR221 or miR222 over-expression in ERα-positive
cells: up-regulation of anti-apoptotic genes, growth factors and down modulation of adhesion
molecules indicated that miR221&222 may not only increase the ability to suppress
apoptosis and accelerate tumor formation but also promote remodeling of the tumor
microenvironment and escape of tumor cells through the basement membrane, all
characteristics of ERα-negative cells. To gain more insights into the inverse correlation
between miR221&222 and ERα in breast cancer, by computational analyses and reporter
assay, we characterized the transcriptional unit of miR221&222. We identified several
estrogen-responsive elements (ERE) at the genomic locus of miR221&222 and, by using
different approaches, we demonstrated that ERα suppresses miR221&222 expression.
Overexpression of exogenous or endogenous ERα protein in ERα-negative cells markedly
repressed miR221&222; conversely, knockdown of ERα in ERα-positive cells increased
their expression. Finally, chromatin immunoprecipitation (ChIP) on ERα-positive cells
showed that ligand-bound ERα and its co-repressor proteins, NcoR and SMRT, were highly
enriched at miR221&222 genomic locus. Notably, ChIP experiments after estradiol (E2)
stimulation or ERα-knockdown revealed that ERα recruitment is essential for the corepressor
enrichment and miR221&222 repression. These findings suggest that the negative regulatory loop involving miR221&222 and ERα may confer proliferative advantage and
migratory activity to breast cancer cells and promote the transition from ERα-positive to
ERα-negative tumors. Therefore, the elucidation of this pathway could be an important step
in the development of the next generation of breast cancer therapeutics agents that may
prevent hormone-resistance that frequently occurs during treatment
C-222 INSTALA IPN SERVICIO MÉDICO DE HOMEOPATÍA Y ACUPUNTURA EN EL CENTRO DEL DISTRITO FEDERAL
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C-222 INSTALA IPN SERVICIO MÉDICO DE HOMEOPATÍA Y ACUPUNTURA EN EL CENTRO DEL DISTRITO FEDERAL
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C-222 INSTALA IPN SERVICIO MÉDICO DE HOMEOPATÍA Y ACUPUNTURA EN EL CENTRO DEL DISTRITO FEDERAL
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C-222 INSTALA IPN SERVICIO MÉDICO DE HOMEOPATÍA Y ACUPUNTURA EN EL CENTRO DEL DISTRITO FEDERAL
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C-222 INSTALA IPN SERVICIO MÉDICO DE HOMEOPATÍA Y ACUPUNTURA EN EL CENTRO DEL DISTRITO FEDERAL
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C-222 INSTALA IPN SERVICIO MÉDICO DE HOMEOPATÍA Y ACUPUNTURA EN EL CENTRO DEL DISTRITO FEDERAL
No full textC-222 INSTALA IPN SERVICIO MÉDICO DE HOMEOPATÍA Y ACUPUNTURA EN EL CENTRO DEL DISTRITO FEDERALC-222 INSTALA IPN SERVICIO MÉDICO DE HOMEOPATÍA Y ACUPUNTURA EN EL CENTRO DEL DISTRITO FEDERALjp
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