The fasciculation and elongation protein 1 (FEZ1) is a mammalian orthologue of the Caenorhabditis elegans protein UNC-76, which is necessary for axon growth in that nematode. In previous studies FEZ1 has been found to interact with protein kinase C, DISC1, the agnoprotein of the human polyomavirus JC virus, and E4B, a U-box-type ubiquitin-protein isopeptide ligase. We reported previously that FEZ1 and its paralogue FEZ2 are proteins that interact with NEK1, a protein kinase involved in polycystic kidney disease and DNA repair mechanisms at the G 2 /M phase of the cell cycle. Here we report the identification of 16 proteins that interact with human FEZ1-(221-396) in a yeast two-hybrid assay of a human fetal brain cDNA library. The 13 interacting proteins of known functions take part either in transcription regulation and chromatin remodeling (6 proteins), the regulation of neuronal cell development (2 proteins) and cellular transport mechanisms (3 proteins) or participate in apoptosis (2 proteins). We were able to confirm eight of the observed interactions by in vitro pull-down assays with recombinant fusion proteins. The confirmed interacting proteins include FEZ1 itself and three transcription controlling proteins (SAP30L, DRAP1, and BAF60a). In mapping studies we found that the C-terminal regions of FEZ1, and especially its coiled-coil region, are involved in its dimerization, its heterodimerization with FEZ2, and in the interaction with 10 of the identified interacting proteins. Our results give further support to the previous speculation of the functional involvement of FEZ1 in neuronal development but suggest further that FEZ1 may also be involved in transcriptional control.FEZ1 (fasciculation and elongation protein -1) was initially identified as a mammalian orthologue of the Caenorhabditis elegans UNC-76 protein, which is necessary for normal axonal outgrowth, bundling, and elongation in this nematode (1). FEZ1 mRNA is expressed abundantly in the rat adult brain and throughout all developmental stages of the brain in mouse embryos (2, 3). The human FEZ1 includes 392 amino acid residues, and its predicted structural organization shows that the protein possesses three glutamine-rich regions and a coiled-coil region (4) (Fig. 3). A mammalian homologue of FEZ1, the protein FEZ2, which shows ubiquitous tissue expression, was described in rat and human and has 48% amino acid sequence identity to FEZ1 (3).Interestingly, FEZ1 was identified as an interacting protein partner in several yeast two-hybrid screens with independent protein baits. The first bait shown to interact with FEZ1 was the regulatory domain of the protein kinase C (PKC) 4 (2). It was further found that FEZ1 is a cellular substrate for phosphorylation through PKC and that phosphorylated FEZ1 promotes neurite extension of PC12 cells in the absence of nerve growth factor. In a second study, using the C terminus of DISC1 (disrupted-in-schizophenia 1) as bait, FEZ1 was also identified as an interacting protein. The DISC1 gene has been implicated as a...
Objective: The global burden of diabetes mellitus will impact strongly American countries in the coming decades. Type 2 diabetes mellitus (T2DM) is a multifactorial disease and the basis for its genetic susceptibility remains not fully understood. Different population studies have demonstrated that variants of the TCF7L2 gene are strongly associated with an increased risk of T2DM. Moreover, institutions or countries with limited budget to conduct genetic research need cost effective methods for detecting DNA variants. Subjects and methods: We standardized a rapid and simple allele-specific PCR method for genotyping the rs12255372 single nucleotide polymorphism (SNP) in a pilot study exploring the association of three TCF7L2 polymorphisms (rs7903146, rs12255372 and DG10S478) with T2DM in 70 patients and 73 controls from Venezuela. Results: The performance of the designed allele-specific PCR reaction for rs12255372 genotyping was reliable and accurate. Patients carrying the TCF7L2 rs7903146 T allele (CT + TT genotypes) and heterozygous CT genotype had a significantly higher risk for T2DM (OR = 2.9 and 2.3, respectively). Although rs12255372 and DG10S478 risk alleles predominated in T2DM group no statistical significance was found. Conclusions: We developed a novel allele-specific PCR method for easier and rapid detection of rs12255372 polymorphism without the use of expensive instrumentation and reagents. Our study in a relatively small sample of the Venezuelan population replicated the association of the rs7903146 SNP with T2DM. Further studies with larger sample size and more biochemical data should be conducted to explore the genetic basis of T2DM susceptibility in Venezuela. Arch Endocrinol Metab. 2016;60(3):246-51
El municipio Maneiro del Estado Nueva Esparta - Venezuela, corresponde con un territorio insular localiza-do en el Caribe venezolano, en este municipio se han registrado a lo largo de los últimos años recurrente inundaciones, que afectan directamente a la población, con pérdidas humanas y materiales. Para enfrentar esta problemática, se plantea una propuesta hidráulica sostenible, que busca mitigar las consecuencias que se generan debido a crecidas, a través del diseño y aplicación de técnicas innovadoras, conocidas como Sistemas Urbanos de Drenajes Sostenibles (SuDS). A través de esta, se plantea el prediseño de un sistema de captación de escorrentía para el amortiguamiento de la posible inundación y que, a su vez, en épocas de sequía, funcione como parque recreacional, complementado con infraestructuras de almacenamiento de agua para consumo humano y riego urbano. Por último, se realiza una comparación del impacto de las soluciones hidráulicas a través del tránsito de avenidas, para determinar su efectividad y sostenibilidad.
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