DYRK1A genetic variants are not linked to Alzheimer's disease in a Spanish case-control cohort

<p>Abstract</p> <p>Background</p> <p>As dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has been implicated in the abnormal hyperphosphorylation of tau in Alzheimer's disease (AD) brain, and the development of neurofibrillary tangles, we examined the contribution of this gene to the susceptibility for AD.</p> <p>Methods</p> <p>We examined genetic variations of DYRK1A by genotyping haplotype tagging SNPs (htSNPs) (rs11701483, rs2835740, rs1137600, rs2835761, rs2835762, rs2154545 and rs8132976) in a group of 634 Spanish AD cases and 733 controls.</p> <p>Results</p> <p>There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by APOE ε4 allele.</p> <p>Conclusion</p> <p>Our negative findings in the Spanish population argue against the hypothesis that DYRK1A genetic variations are causally related to AD risk. Still, additional studies using different sets of patients and control subjects deserve further attention, since supporting evidence for association between DYRK1A gene and AD risk in the Japanese population exists.</p

HoxA-11 and FOXO1A Cooperate to Regulate Decidual Prolactin Expression: Towards Inferring the Core Transcriptional Regulators of Decidual Genes

During the menstrual cycle, the ovarian steroid hormones estrogen and progesterone control a dramatic transcriptional reprogramming of endometrial stromal cells (ESCs) leading to a receptive state for blastocyst implantation and the establishment of pregnancy. A key marker gene of this decidualization process is the prolactin gene. Several transcriptional regulators have been identified that are essential for decidualization of ESCs, including the Hox genes HoxA-10 and HoxA-11, and the forkhead box gene FOXO1A. While previous studies have identified downstream target genes for HoxA-10 and FOXO1A, the role of HoxA-11 in decidualization has not been investigated. Here, we show that HoxA-11 is required for prolactin expression in decidualized ESC. While HoxA-11 alone is a repressor on the decidual prolactin promoter, it turns into an activator when combined with FOXO1A. Conversely, HoxA-10, which has been previously shown to associate with FOXO1A to upregulate decidual IGFBP-1 expression, is unable to upregulate PRL expression when co-expressed with FOXO1A. By co-immunoprecipitation and chromatin immunoprecipitation, we demonstrate physical association of HoxA-11 and FOXO1A, and binding of both factors to an enhancer region (−395 to −148 relative to the PRL transcriptional start site) of the decidual prolactin promoter. Because FOXO1A is induced upon decidualization, it serves to assemble a decidual-specific transcriptional complex including HoxA-11. These data highlight cooperativity between numerous transcription factors to upregulate PRL in differentiating ESC, and suggest that this core set of transcription factors physically and functionally interact to drive the expression of a gene battery upregulated in differentiated ESC. In addition, the functional non-equivalence of HoxA-11 and HoxA-10 with respect to PRL regulation suggests that these transcription factors regulate distinct sets of target genes during decidualization

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

Preparation and Application of Electrodes in Capacitive Deionization (CDI): a State-of-Art Review

As a promising desalination technology, capacitive deionization (CDI) have shown practicality and cost-effectiveness in brackish water treatment. Developing more efficient electrode materials is the key to improving salt removal performance. This work reviewed current progress on electrode fabrication in application of CDI. Fundamental principal (e.g. EDL theory and adsorption isotherms) and process factors (e.g. pore distribution, potential, salt type and concentration) of CDI performance were presented first. It was then followed by in-depth discussion and comparison on properties and fabrication technique of different electrodes, including carbon aerogel, activated carbon, carbon nanotubes, graphene and ordered mesoporous carbon. Finally, polyaniline as conductive polymer and its potential application as CDI electrode-enhancing materials were also discussed

An integrated FE process model for precision analysis of thermo-mechanical behaviors of rolls and strip in hot strip rolling

A finite element (FE)-based approach is presented for the precision analysis of the thermo-mechanical behavior of the rolls and strip in hot strip rolling. Basic FE models for the analysis of the thermal behavior as well as those for the analysis of the mechanical behavior of each object-roll or strip, are described in detail. Also described are various numerical schemes, including those for the treatment of the thermal as well as mechanical interactions among the objects. A series of numerical tests are conducted to assess the validity of the basic FE models and also of the numerical schemes proposed. Then, illustrated is how to combine the basic FE models into an integrated process model for the precision analysis of the thermo-mechanical behavior. (C) 2002 Elsevier Science B.V. All rights reserved.X1135sciescopu

Prediction of residual stresses in a plate subject to accelerated cooling - A 3-D finite element model and an approximate model

In this paper, we present finite element (FE) models for the analysis of heat transfer and for the analysis of 3-D elastic-viscoplastic deformation of steel at elevated temperatures. Then, it is shown that, in conjunction with the models for the prediction of phase fraction, and thermal and mechanical properties, an integrated FE model can be obtained which is capable of predicting the detailed aspects of the thermal and mechanical behavior of the plate subject to accelerated cooling in a plate mill. Also, we present an approximate model for on-line prediction. The prediction accuracy of the approximate model is examined through comparison with the predictions from the integrated FE model. Then, using the model, the effect of some selected process variables on the residual stress distributions is investigated.X115sciescopu