Aluminium(iii) dialkyl 2,6-bisimino-4R-dihydropyridinates(−1): selective synthesis, structure and controlled dimerization

A family of stable and otherwise selectively unachievable 2,6-bisimino-4-R-1,4-dihydropyridinate aluminium (III) dialkyl complexes [AlR’2(4-R-i PrBIPH)] (R = Bn, Allyl; R’ = Me, Et, i Bu) have been synthesized, taking advantage of a method for the preparation of the corresponding 4-R-1,4-dihydropiridine precursors developed in our group. All the dihydropyrdinate(−1) dialkyl aluminium complexes have been fully characterized by 1 H- 13C-NMR, elemental analysis and in the case 2’a, also by X-ray diffraction studies. Upon heating in toluene solution at 110 °C, the dimethyl derivatives 2a and 2’a dimerize selectively through a double cycloaddition. This reaction leads to the formation of two new C–C bonds that involve the both meta positions of the two 4-R-1,4-dihydropyridinate fragments, resulting the binuclear aluminium species [Me2Al(4-R-i PrHBIP)]2 (R = Bn (3a); allyl (3’a)). Experimental kinetics showed that the dimerization of 2’a obeys second order rate with negative activation entropy, which is consistent with a bimolecular rate-determining step. Controlled methanolysis of both 3a and 3’a release the metalfree dimeric bases, (4-Bn-i PrHBIPH)2 and (4-allyl-i PrHBIPH)2, providing a convenient route to these potentially useful ditopic ligands. When the R’ groups are bulkier than Me (2b, 2’b and 2’c), the dimerization is hindered or fully disabled, favoring the formation of paramagnetic NMR-silent species, which have been identified on the basis of a controlled methanolysis of the final organometallic products. Thus, when a toluene solution of [AlEt2(4-Bn-i PrBIPH)] (2b) was heated at 110 °C, followed by the addition of methanol in excess, it yields a mixture of the dimer (4-Bn-i PrHBIPH)2 and the aromatized base 4-Bn-i PrBIP, in ca. 1 : 2 ratio, indicating that the dimerization of 2b competes with its spontaneous dehydrogenation, yielding a paramagnetic complex containing a AlEt2 unit and a non-innocent (4-Bn-i PrBIP)•− radicalanion ligand. Similar NMR monitoring experiments on the thermal behavior of [AlEt2(4-allyl-i PrBIPH)] (2’b) and [Ali Bu2(4-allyl-iPrBIPH)] (2’c) showed that these complexes do not dimerize, but afford exclusively NMR silent products. When such thermally treated samples were subjected to methanolysis, they resulted in mixtures of the alkylated 4-allyl-i PrBIP and non-alkylated i PrBIP ligand, suggesting that dehydrogenation and deallylation reactions take place competitivelyMinisterio de Economía y Competitividad de España (MINECO) y los Fondos europeos FEDER-CTQ2015-68978-P y PRX14/00339United States National Science Foundation-CHE-166491

Modeling photosynthetically active radiation from satellite-derived estimations over mainland Spain

A model based on the known high correlation between photosynthetically active radiation (PAR) and global horizontal irradiance (GHI) was implemented to estimate PAR from GHI measurements in this present study. The model has been developed using satellite-derived GHI and PAR estimations. Both variables can be estimated using Kato bands, provided by Satellite Application Facility on Climate Monitoring (CM-SAF), and its ratio may be used as the variable of interest in order to obtain the model. The study area, which was located in mainland Spain, has been split by cluster analysis into regions with similar behavior, according to this ratio. In each of these regions, a regression model estimating PAR from GHI has been developed. According to the analysis, two regions are distinguished in the study area. These regions belong to the two climates dominating the territory: an Oceanic climate on the northern edge; and a Mediterranean climate with hot summer in the rest of the study area. The models obtained for each region have been checked against the ground measurements, providing correlograms with determination coefficients higher than 0.99This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) [Project CGL2016-79284-P AEI/FEDER/UE]S

Subtidal macrozoobenthos communities from northern Chile during and post El Niño 1997–1998

Despite a large amount of climatic and oceanographic information dealing with the recurring climate phenomenon El Niño (EN) and its well known impact on diversity of marine benthic communities, most published data are rather descriptive and consequently our understanding of the underlying mechanisms and processes that drive community structure during EN are still very scarce. In this study, we address two questions on the effects of EN on macrozoobenthic communities: (1) how does EN affect species diversity of the communities in northern Chile? and (2) is EN a phenomenon that restarts community assembling processes by affecting species interactions in northern Chile? To answer these questions, we compared species diversity and co-occurrence patterns of soft-bottoms macrozoobenthos communities from the continental shelf off northern Chile during (March 1998) and after (September 1998) the strong EN event 1997–1998. The methods used varied from species diversity and species co-occurrence analyses to multivariate ordination methods. Our results indicate that EN positively affects diversity of macrozoobenthos communities in the study area, increasing the species richness and diversity and decreasing the species dominance. EN represents a strong disturbance that affects species interactions that rule the species assembling processes in shallow-water, sea-bottom environments

Segregation of Regulatory Polymorphisms with Effects on the Gluteus Medius Transcriptome in a Purebred Pig Population

Background: The main goal of the present study was to analyse the genetic architecture of mRNA expression in muscle, a tissue with an outmost economic importance for pig breeders. Previous studies have used F2 crosses to detect porcine expression QTL (eQTL), so they contributed with data that mostly represents the between-breed component of eQTL variation. Herewith, we have analysed eQTL segregation in an outbred Duroc population using two groups of animals with divergent fatness profiles. This approach is particularly suitable to analyse the within-breed component of eQTL variation, with a special emphasis on loci involved in lipid metabolism. Methodology/Principal Findings: GeneChip Porcine Genome arrays (Affymetrix) were used to determine the mRNA expression levels of gluteus medius samples from 105 Duroc barrows. A whole-genome eQTL scan was carried out with a panel of 116 microsatellites. Results allowed us to detect 613 genome-wide significant eQTL unevenly distributed across the pig genome. A clear predominance of trans- over cis-eQTL, was observed. Moreover, 11 trans-regulatory hotspots affecting the expression levels of four to 16 genes were identified. A Gene Ontology study showed that regulatory polymorphisms affected the expression of muscle development and lipid metabolism genes. A number of positional concordances between eQTL and lipid trait QTL were also found, whereas limited evidence of a linear relationship between muscle fat deposition and mRNA levels of eQTL regulated genes was obtained. Conclusions/Significance: Our data provide substantial evidence that there is a remarkable amount of within-breed genetic variation affecting muscle mRNA expression. Most of this variation acts in trans and influences biological processes related with muscle development, lipid deposition and energy balance. The identification of the underlying causal mutations and the ascertainment of their effects on phenotypes would allow gaining a fundamental perspective about how complex traits are built at the molecular level

SEOM clinical guideline for treatment of kidney cancer (2017)

The goal of this article is to provide recommendations about the management of kidney cancer. Based on pathologic and molecular features, several kidney cancer variants were described. Nephron-sparing techniques are the gold standard of localized disease. After a randomized trial, sunitinib could be considered in adjuvant treatment in high-risk patients. Patients with advanced disease constitute a heterogeneous population. Prognostic classification should be considered. Both sunitinib and pazopanib are the standard options for first-line systemic therapy in advanced renal cell carcinoma. Based on the results of two randomized trials, both nivolumab and cabozantinib should be considered the standard for second and further lines of therapy. Response evaluation for present therapies is a challenge

Estudio numérico de las fluctuaciones de los modos del campo EM en un sistema de percolación 3D

En este trabajo se estudia la radiación del campo producido por nano-emisores desordenados en un clúster de percolación tridimensional (3D). En este trabajo hemos utilizado el conjunto de ecuaciones que acopla a las ecuaciones de Maxwell con los nano-emisores de 4 niveles. Como parámetro de cuantificación de la localización del campo, calculamos la relación de participación inversa (IPR). Se estudia el comportamiento dinámico de la amplitud de campo, generada por emisores incorporados en un clúster con probabilidad de ocupación p en los poros. La simulación numérica se realiza mediante el algoritmo de las diferencias finitas en el dominio del tiempo (FDTD). Los resultados numéricos muestran tiempos específicos donde el campo localizado tiene gran amplitud y una fuerte relación con los niveles alto y bajo de los emisores. El efecto estudiado abre nuevas perspectivas para controlar la localización de campos ópticos en nanotecnologías ópticas modernas

In Vivo Assessment of Parenteral Formulations of Oligo(3-Hydroxybutyric Acid) Conjugates with the Model Compound Ibuprofen

Polymer-drug conjugates have gained significant attention as pro-drugs releasing an active substance as a result of enzymatic hydrolysis in physiological environment. In this study, a conjugate of 3-hydroxybutyric acid oligomers with a carboxylic acid group-bearing model drug (ibuprofen) was evaluated in vivo as a potential pro-drug for parenteral administration. Two different formulations, an oily solution and an o/w emulsion were prepared and administered intramuscularly (IM) to rabbits in a dose corresponding to 40 mg of ibuprofen/kilogramme. The concentration of ibuprofen in blood plasma was analysed by HPLC, following solid–phase extraction and using indometacin as internal standard (detection limit, 0.05 μg/ml). No significant differences in the pharmacokinetic parameters (Cmax, Tmax, AUC) were observed between the two tested formulations of the 3-hydroxybutyric acid conjugate. In comparison to the non-conjugated drug in oily solution, the relative bioavailability of ibuprofen conjugates from oily solution, and o/w emulsion was reduced to 17% and 10%, respectively. The 3-hydroxybutyric acid formulations released the active substance over a significantly extended period of time with ibuprofen still being detectable 24 h post-injection, whereas the free compound was almost completely eliminated as early as 6 h after administration. The conjugates remained in a muscle tissue for a prolonged time and can hence be considered as sustained release systems for carboxylic acid derivatives

Isolation of human fibroadipogenic progenitors and satellite cells from frozen muscle biopsies

Altres ajuts: Association Française contre les Myopathies (22525)Altres ajuts: Fundación Isabel GemioSkeletal muscle contains multiple cell types that work together to maintain tissue homeostasis. Among these, satellite cells (SC) and fibroadipogenic progenitors cells (FAPs) are the two main stem cell pools. Studies of these cells using animal models have shown the importance of interactions between these cells in repair of healthy muscle, and degeneration of dystrophic muscle. Due to the unavailability of fresh patient muscle biopsies, similar analysis of interactions between human FAPs and SCs is limited especially among the muscular dystrophy patients. To address this issue here we describe a method that allows the use of frozen human skeletal muscle biopsies to simultaneously isolate and grow SCs and FAPs from healthy or dystrophic patients. We show that while the purified SCs differentiate into mature myotubes, purified FAPs can differentiate into adipocytes or fibroblasts demonstrating their multipotency. We find that these FAPs can be immortalized and the immortalized FAPs (iFAPs) retain their multipotency. These approaches open the door for carrying out personalized analysis of patient FAPs and interactions with the SCs that lead to muscle loss