Metabolic Effects of Oral Phenelzine Treatment on High-Sucrose-Drinking Mice

Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models.This study was partly supported by the DIOMED project (INTERREG IVB SUDOE 1/P1/E178)

Oral Administration of Semicarbazide Limits Weight Gain together with Inhibition of Fat Deposition and of Primary Amine Oxidase Activity in Adipose Tissue

An enzyme hitherto named semicarbazide-sensitive amine oxidase (SSAO), involved in the oxidation of primary amines, is abundantly expressed in adipocytes. Although SSAO physiological functions remain unclear, several molecules inhibiting its activity have been described to limit fat accumulation in preadipocyte cultures or to reduce body weight gain in obese rodents. Here, we studied whether oral administration of semicarbazide, a prototypical SSAO inhibitor, limits fat deposition in mice. Prolonged treatment with semicarbazide at 0.125% in drinking water limited food and water consumption, hampered weight gain, and deeply impaired fat deposition. The adiposomatic index was reduced by 31%, while body mass was reduced by 15%. Such treatment completely inhibited SSAO, but did not alter MAO activity in white adipose tissue. Consequently, the insulin-like action of the SSAO substrate benzylamine on glucose transport was abolished in adipocytes from semicarbazide-drinking mice, while their insulin sensitivity was not altered. Although semicarbazide is currently considered as a food contaminant with deleterious effects, the SSAO inhibition it induces appears as a novel concept to modulate adipose tissue development, which is promising for antiobesity drug discovery

Haptenos, conjugados y anticuerpos para el fungicida ciprodinil

La presente invención se refiere a haptenos, conjugados, derivados marcados y anticuerpos para ciprodinil. Así mismo, la presente invención también se refiere al uso de conjugados de ciprodinil como antígenos de ensayo o inmunógenos para obtener anticuerpos de este fungicida; y al uso de los derivados marcados de ciprodinil como antígenos de ensayo. Además, la presente invención también se refiere a un método de análisis de ciprodinil utilizando los anticuerpos obtenidos, en ocasiones junto con antígenos de ensayo que son conjugados o derivados marcados. Esta invención también proporciona un kit para analizar ciprodinil que comprende anticuerpos de este fungicida, en ocasiones junto con antígenos de ensayo que son conjugados o derivados marcados.Peer reviewedConsejo Superior de Investigaciones Científicas (España), Universitata de ValenciaA1 Solicitud de patente con informe sobre el estado de la técnic

Scalability of a multi-physics system for forest fire spread prediction in multi-core platforms

Advances in high-performance computing have led to an improvement in modeling multi-physics systems because of the capacity to solve complex numerical systems in a reasonable time. WRF-SFIRE is a multi-physics system that couples the atmospheric model WRF and the forest fire spread model called SFIRE with the objective of considering the atmosphere-fire interactions. In systems like WRF-SFIRE, the trade-off between result accuracy and time required to deliver that result is crucial. So, in this work, we analyze the influence of WRF-SFIRE settings (grid resolutions) into the forecasts accuracy and into the execution times on multi-core platforms using OpenMP and MPI parallel programming paradigms

The Genetic Basis of Type 2 Diabetes in Hispanics and Latin Americans: Challenges and Opportunities

Type 2 diabetes (T2D) affects 415 million people worldwide, and has a much higher prevalence in Hispanics (16.9%), compared to non-Hispanic whites (10.2%). Genome-wide association studies and whole-genome and whole-exome sequencing studies have discovered more than 100 genetic regions associated with modified risk for T2D. However, the identified genetic factors explain a very small fraction of the estimated heritability. Until recently, little attention has been put in studying other non European populations that suffer from a higher burden of T2D, such as Hispanics/Latinos. In the past few years, genetic studies in Hispanic populations have started to provide new insights into the genetic architecture of T2D in this ancestry group. Of note, several genetic variants that are absent or very rare in non-Hispanic populations but more common in Hispanics have shown from moderate to strong association with T2D and have provided new insights into the biology of T2D, which may be ultimately useful for developing novel therapeutic strategies applicable to all populations. Studying diverse populations can also improve the ability to find the causal variants in known T2D loci by a multi-ancestry fine-mapping approach, which leverages the different patterns of linkage disequilibrium between the causal and the ascertained genetic variants. In this mini-review, we summarize the main genetic findings discovered in Hispanics and discuss the limitations and challenges of performing genetic studies in these populations. Finally, we present possible next steps to make studies in Latino populations more valuable in providing a deeper understanding of T2D and anticipate their future application to the development of predictive and preventive medicine and personalized therapies

Forchlorfenuron-mimicking haptens: From immunogen design to antibody characterization by hierarchical clustering analysis

To obtain highly-specific and selective forchlorfenuron binders, a collection of functionalized derivatives with different spacer arm locations and lengths was prepared. By immunization with target-mimicking haptens, a large battery of monoclonal and polyclonal antibodies against this synthetic cell regulator was produced and exhaustively characterized in two immunoassay formats using homologous and heterologous conjugates. Antibodies with IC50 values lower than 0.3 nM were successfully raised from the prepared immunogens, thus evidencing the efficacy of the explored strategies. In order to identify significant epitopes in the antibody-antigen interaction, a series of new chemical forchlorfenuron analogues, with slight modifications at both rings of the target molecule, were synthesized and evaluated in competitive assays. As a novel approach in hapten recognition studies, data processing was performed by computational classification methods based on hierarchical clustering. This strategy was shown to be highly valuable for a straightforward profiling of antibodies according to analogue recognition patterns. A relationship could be established between the antigen binding properties of antibodies and the structure of the immunogen. Whereas antibodies with equivalent affinities had been obtained from all of the derivatives, their specificity was found to be largely influenced by the differential exposition of the molecule to the immune system.This work was supported by Ministerio de Educación y Ciencia (AGL2009-12940-C02/01/02/ALI), and cofinanced by FEDER Funds. C.S.P. and J.V.M. were hired by the CSIC, the former under a predoctoral I3P contract and the latter under a Ramón y Cajal postdoctoral contract.Peer Reviewe

Derivados funcionalizados e inmunorreactivos para el fungicida fludioxonil

La presente invención se refiere a haptenos, conjugados, derivados marcados y anticuerpos para fludioxonil. Asímismo, la presente invención también se refiere al uso de conjugados de fludioxonil como antígenos de ensayo o inmunógenos para obtener anticuerpos de este fungicida; y al uso de los derivados marcados de fludioxonil como antígenos de ensayo. Además, la presente invención también se refiere a un método de análisis de fludioxonil utilizando los anticuerpos obtenidos, en ocasiones junto con antígenos de ensayo que son conjugados o derivados marcados. Esta invención también proporciona un kit para analizar fludioxonil que comprende anticuerpos de este fungicida, en ocasiones junto con antígenos de ensayo que son conjugados o derivados marcadosPeer reviewedConsejo Superior de Investigaciones Científicas, Universitat de ValènciaA1 Solicitud de patente con informe sobre el estado de la técnic

Derivados funcionalizados e inmunorreactivos para el fungicida fludioxonil

La presente invención se refiere a haptenos, conjugados, derivados marcados y anticuerpos para fludioxonil. Asímismo, la presente invención también se refiere al uso de conjugados de fludioxonil como antígenos de ensayo o inmunógenos para obtener anticuerpos de este fungicida; y al uso de los derivados marcados de fludioxonil como antígenos de ensayo. Además, la presente invención también se refiere a un método de análisis de fludioxonil utilizando los anticuerpos obtenidos, en ocasiones junto con antígenos de ensayo que son conjugados o derivados marcados. Esta invención también proporciona un kit para analizar fludioxonil que comprende anticuerpos de este fungicida, en ocasiones junto con antígenos de ensayo que son conjugados o derivados marcadosPeer reviewedConsejo Superior de Investigaciones Científicas, Universitat de ValènciaB1 Patente sin examen previ