Reactividad de 2-acetilhidrazonometil-1-arilimidazol frente a agentes reductores

Catalytic hydrogenation of compounds 1 led mainly to the products resulting of the hydrogenolysis of the bond C=N, while the hydrazides 2 were obtained in small yields using Pd(C) as catalyst. Reduction of la with AlLiH4 yielded the hydrazide 2a for the Z stereoisomer and the products 4a and 5a for the E stereoisomer by hydrogenolysis.La hidrogenación catalítica de los compuestos 1 origina mayoritariamente el producto resultante de la hidrogenolisis del enlace C=N y sólo se obtienen bajos rendimientos de las hidracidas 2 al utilizar Pd(C) como catalizador. La reducción con AlLiH4 de la rinde, para el estereoisómero Z, la hidracida 2a; mientras que el estereoisómero E conduce por hidrogenolisis a los compuestos 4a y 5a

Reactivity of 2-acetylhydrazonemethyl-l -arylimidazole with reducing agents

La hidrogenación catalítica de los compuestos 1 origina mayoritariamente el producto resultante de la hidrogenolisis del enlace C=N y sólo se obtienen bajos rendimientos de las hidracidas 2 al utilizar Pd(C) como catalizador. La reducción con AILiH4 de la rinde, para el estereoisómero Z, la hidracida 2a; mientras que el estereoisómero E conduce por hidrogenolisis a los compuestos 4a y 5a.Catalytic hydrogenation of compounds 1 led mainly to the products resulting of the hydrogenolysis of the bond C=N, while the hydrazides 2 were obtained in small yields using Pd(C) as catalyst. Reduction of la with AILiH. yielded the hydrazide 2a for the Z stereoisomer and the products 4a and 5a for the E stereoisomer by hydrogenolysis

Cumarinas en especies del género seseli (fam. umbelliferae)

A survey of the coumarins from species of the genus Seseli (Fam. Umbelliferae) is reported.Se presenta una revisión de cumarinas en especies del género Seseli (Fam. Umbelliferae)

Inhibidores selectivos de la monoamino oxidasa. 1. Hidracinas de formilimidazoles 1-sustitudos

A series of hydrazinomethylimidazole 1-sustituted was prepared and evaluated for their monoamine oxidase (MAO) inhibitory activity. In vitro testing revealed that the 1-arylimidazole derivatives were selectively inhibitors of MAO A at low concentrations.Se ha preparado una serie de hidracinometilimidazoles 1-sustituidos y estudiado su actividad IMAO. Los ensayos in vitro revelan que los 1-arilimidazoles son inhibidores selectivos de la MAO A a bajas concentraciones

Sampling design variance estimation of small area estimators in the Spanish Labour Force Survey

The main goal of this paper is to investigate how to estimate sampling design variances of modelbased and model-assisted small area estimators in a complex survey sampling setup. For this purpose the Spanish Labour Force Survey is considered. Sample and aggregated data are taken from the Canary Islands in the second trimester of 2003 in order to obtain some small area estimators of ILO unemployment totals. Several problems arising from the application of standard small area estimation procedures to the survey are described. It is shown that standard variance estimators based on explicit formulas are not applicable in the strict sense, since the assumptions under which they are derived do not hold. In addition two resampling techniques, bootstrap and jackknife, are considered. These methods treat all the considered estimators in the same manner and therefore they can be used as performance measures to compare them. From the analysis of the obtained results, some recommendations are given

Estudio de carcinoma medular de tiroides a partir de un caso índice

El carcinoma de tiroides es un tumor infrecuente; constituye menos del 1% de las neoplasias malignas en la población general y el 0, 5%-3% en la edad pediátrica. Existen cuatro tipos: papilar (80%-90% de los casos), folicular (5%-10%), medular (5%) y anaplásico (2%-3%). En el tipo medular, el 80% son esporádicos, y un 20% se asocia a un síndrome hereditario que se divide, fundamentalmente, en tres grupos: neoplasia endócrina múltiple 1, neoplasia endócrina múltiple 2 y carcinoma medular de tiroides familiar. Las formas hereditarias se producen por una mutación en el protooncogén RET, localizado en el brazo largo del cromosoma 10. Se presenta un caso de carcinoma medular de tiroides detectado a raíz de un estudio genético familiar con el propósito de resaltar la importancia del diagnóstico precoz y la intervención de equipos multidisciplinares expertos en esta patología para su manejo y seguimiento. Thyroid cancer is an uncommon type of cancer, accounting less than 1% of all cancers in adults, and 0.5-3% of all cancers in children. There are four different types: papillary carcinoma (80-90% of cases), follicular (5-10%), medullary (5%) and anaplastic cell (2-3%). Eighty per cent of cases of medullary thyroid cancer are sporadic, but 20% are associated with an inherited syndrome that is divided into three groups: multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma. The inherited forms are caused by a disruption in the RET oncogene, which is located in the long arm of chromosome 10. A hereditary case of medullary thyroid carcinoma is presented. It was detected because of a familial genetic study. The purpose of the paper is emphasize the importance of the early diagnosis and the intervention of multidisciplinary teams of experts

Characterization of microsatellite loci in Erysimum mediohispanicum (Brassicaceae) and cross-amplification in related species

• Premise of the study : We have developed and optimized microsatellite loci from a genomic library of Erysimum mediohispanicum. Microsatellites were also tested for cross-amplifi cation in 31 other Erysimum species. • Methods and Results : A total of 10 microsatellite loci were successfully amplifi ed. They were polymorphic for 81 E. mediohispanicum individuals from two locations in Sierra Nevada (southeastern Spain), which showed similar patterns of genetic diversity. On average, microsatellites had 8.6 alleles per locus and an expected heterozygosity of 0.69. Only one locus signifi cantly departed from Hardy – Weinberg equilibrium in both locations. Most of the markers successfully amplifi ed in other Erysimum species. • Conclusions : The genetic attributes of microsatellite loci will allow their application to population genetic studies in Erysimum , such as genetic differentiation and structure, gene fl ow, pollinator-mediated speciation, and hybridization studies.&nbsp

Relaciones filogenéticas en Erysimun (Brassicaceae) de las Cordilleras Béticas (SE Península Ibérica)

The Baetic mountains, located in the southern Iberian Peninsula, is a major hotspot of biodiversity in the Mediterranean Basin, constituting one of the most important glacial refugia for vascular plants in Europe. Despite their relatively limited extension, the Baetic Mountains contain almost 50% of the total endemic Erysimum species in the Iberian Peninsula. The broadly distributed Erysimum genus has diversified profusely in the Mediterranean region, with more than a hundred species described in the area, out of a total of c. 200 species included in the genus. We used two plastid DNA regions (ndhF and trnT-L) and one nuclear DNA region (ITS1-5.8S rDNA-ITS2), with 3,556 bp total length, to carry out phylogenetic analysis by Bayesian inference, maximum likelihood and maximum parsimony, in order to explore the evolutionary relationships between the Erysimum species inhabiting these ranges. Analyses of concatenated sequences from the two genomes identified two main clades with no overlap in species composition so that samples from the same species fell within the same major clade. The phylogenetic relationships depicted by those two clades do not give support to the E. nevadense group, previously proposed on taxonomic grounds. In addition, our results indicated recurrent changes in flower colour in the Baetic Erysimum species although, alternatively, reticulate evolution, which is suggested by incongruent position of taxa in the different trees, may have also affected this trait.Las cordilleras Béticas, localizadas en el sudeste de la Península Ibérica, representan una importante zona para la biodiversidad de la cuenca mediterránea, constituyendo uno de los refugios glaciares más destacados de plantas vasculares en Europa. A pesar de su extensión relativamente limitada, las cordilleras Béticas albergan casi el 50% del total de las especies endémicas de Erysimum de la Península Ibérica. Erysimum es un género ampliamente distribuido, que se ha diversificado profusamente en la región mediterránea, con más de un centenar de especies descritas en dicha área, del total de las alrededor de 200 especies incluidas en el género. Usamos dos regiones de ADN plastidial (ndhF y trnT-L) y una región de ADN nuclear (ITS1-5.8S rDNA-ITS2), con una longitud total de 3.556 pb, para llevar a cabo análisis filogenéticos mediante inferencia bayesiana, máxima verosimilitud y máxima parsimonia, con el fin de explorar las relaciones evolutivas entre las especies de Erysimum que habitan en éstas cordilleras. El análisis de secuencias concatenadas de los dos genomas identifica dos clados principales y las muestras de la misma especie aparecen siempre en un clado o en el otro pero no en ambos. Las relaciones filogenéticas que indican esos dos clados no apoyan la circunscripción del grupo taxonómico E. nevadense, previamente definido en dicho género. Además, los análisis indican cambios recurrentes en el color floral de las especies de Erysimum que habitan los Sistemas Béticos aunque la evolución reticulada, que sugiere la posición de algunos taxones en uno y otro árbol, puede haber también afectado a este rasgo, lo que sería una hipótesis alternativa.This study has been supported by MARM (078/2007), Junta de Andalucía (P07-RNM-02869 and P11-RNM-7676), MONTES Consolider-Ingenio (CSD2008-00040), and Spanish MCyT (CGL2009-07015, and CGL2012-34736) grants. AJMP and MA were supported by Spanish Education and Science grants AP-2006- 00685 and BES-2007-14206, respectively

Local delivery of optimized nanobodies targeting the PD-1/PD-L1 axis with a self-amplifying RNA viral vector induces potent antitumor responses

Despite the success of immune checkpoint blockade for cancer therapy, many patients do not respond adequately. We aimed to improve this therapy by optimizing both the antibodies and their delivery route, using small monodomain antibodies (nanobodies) delivered locally with a self-amplifying RNA (saRNA) vector based on Semliki Forest virus (SFV). We generated nanobodies against PD-1 and PD-L1 able to inhibit both human and mouse interactions. Incorporation of a dimerization domain reduced PD-1/PD-L1 IC50 by 8- and 40-fold for antiPD-L1 and anti-PD-1 nanobodies, respectively. SFV viral particles expressing dimeric nanobodies showed a potent antitumor response in the MC38 model, resulting in >50% complete regressions, and showed better therapeutic efficacy compared to vectors expressing conventional antibodies. These effects were also observed in the B16 melanoma model. Although a short-term expression of nanobodies was observed due to the cytopathic nature of the saRNA vector, it was enough to generate a strong proinflammatory response in tumors, increasing infiltration of NK and CD8+ T cells. Delivery of the SFV vector expressing dimeric nanobodies by local plasmid electroporation, which could be more easily translated to the clinic, also showed a potent antitumor effect

Imported cysticercosis in Spain: A retrospective case series from the +REDIVI Collaborative Network

Neurocysticercosis (NCC) is the most common parasitic neurological disease worldwide and a major cause of epilepsy. Spain is the country reporting the highest number of NCC imported cases in Europe. Retrospective case series of NCC patients registered in the +REDIVI Network from October 1, 2009 to July 2018. A specific questionnaire, including clinical and diagnostic characteristics, was created and sent to the collaborator centers. 46 cases were included in the analysis. 55% were male, mean age of 40 years. 95.6% were migrants. The median duration since migration from an endemic area was 10 years. Predominant nationalities were Ecuadorians (50%) and Bolivians (30.4%). Frequent locations were parenchymal (87%), subarachnoid (26.1%) and intraventricular cysts (10.9%). Serological analysis was performed in 91.3%, being 54.8% positive. Most prevalent clinical manifestations were persistent headache (60.9%), epilepsy (43.5%) and visual changes (13%). Patients were mainly treated with albendazole (76.1%), corticosteroids (67.4%), and anticonvulsionants (52.2%). 82.5% had a favorable clinical outcome. Most NCC cases were long-standing migrants. Few clinical differences were observed depending on the cysticerci location. The treatment was often not according to current recommendations, and no uniform criteria were followed when it came to the therapeutic regimen. NCC case management in Spain (including clinician awareness and laboratory capacity improvements) needs to be strengthened.We would thanks María Jesús Perteguer from the National Center of Microbiology for the information and update on NCC lab techniques currently performed in Spain. The corresponding author’s affiliation centre belongs to the ISCIII-Sub. Gral. Redes- Network Biomedical Research on Tropical Diseases (RICET in Spanish) grant RD16CIII/0003/0001, RD16/0027/0020, RD16CIII/0003/0001 and the European Regional Development Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S