Biphasic effect of insulin on beta cell apoptosis depending on glucose deprivation

AbstractInsulin resistant states are associated with an increase in the beta cell mass and also high levels of circulating insulin. Ultimately the beta cells undergo a failure that leads to diabetes. At this stage, a question arises if those persistent high levels of circulating insulin may contribute to beta cell damage. To address this important issue, we submitted beta cells to a prolonged effect of increasing concentrations of insulin. We observed that a prolonged effect of high levels of insulin on the presence of serum (15–24h) in glucose-deprived beta cells induced apoptosis. This apoptotic effect was both dose- and cycloheximide-dependent

Mercury and selenium binding biomolecules in terrestrial mammals (Cervus elaphus and Sus scrofa) from a mercury exposed area

Acknowledgements The authors are grateful to Junta de Comunidades de Castilla-La Mancha (PCC-05-004-2, PAI06-0094, PCI-08-0096, PEII09-0032-5329) and the Ministerio de Economía y Competitividad (CTQ2013-48411-P) for financial support. M.J. Patiño Ropero acknowledges the Junta de Comunidades de Castilla-La Mancha for her PhD. fellowship.Peer reviewedPostprin

Water-level fluctuations and metapopulation dynamics as drivers of genetic diversity in populations of three Tanganyikan cichlid fish species

Altres ajuts: Most specimens used in this study were collected during different expeditions to Lake Tanganyika that were financed by the Belgian Science Policy (1992, 1995, 2001, 2006, and 2007), the two last in the context of MOLARCH-a EuroDIVERSITY Funded Collaborative Research Project, with additional support of the Leopold III Foundation for Nature Research and Nature Conservation to EV. CS was supported by grants I-48-B06 and P20994-B03 from the Austrian Science Foundation. During his stay at the RBINS, BN was supported by PhD grant SFRH ⁄ BD ⁄ 17704 ⁄ 2004 from the Fundaçao para a Ciência e Tecnologia.Understanding how genetic variation is generated and maintained in natural populations, and how this process unfolds in a changing environment, remains a central issue in biological research. In this work, we analysed patterns of genetic diversity from several populations of three cichlid species from Lake Tanganyika in parallel, using the mitochondrial DNA control region. We sampled populations inhabiting the littoral rocky habitats in both very deep and very shallow areas of the lake. We hypothesized that the former would constitute relatively older, more stable and genetically more diverse populations, because they should have been less severely affected by the well-documented episodes of dramatic water-level fluctuations. In agreement with our predictions, populations of all three species sampled in very shallow shorelines showed traces of stronger population growth than populations of the same species inhabiting deep shorelines. However, contrary to our working hypothesis, we found a significant trend towards increased genetic diversity in the younger, demographically less stable populations inhabiting shallow areas, in comparison with the older and more stable populations inhabiting the deep shorelines. We interpret this finding as the result of the establishment of metapopulation dynamics in the former shorelines, by the frequent perturbation and reshuffling of individuals between populations due to the lake-level fluctuations. The repeated succession of periods of allopatric separation and secondary contact is likely to have further increased the rapid pace of speciation in lacustrine cichlids

A versatile protocol for Stille−Migita cross coupling reactions

The combination of catalytic amounts of [Pd(PPh3)4], copper thiophene-2-carboxylate (CuTC) and [Ph2PO2][NBu4] allowed a series of exigent Stille–Migita reactions to be performed with high yields; as the protocol is fluoride free, a variety of O-silyl and C-silyl groups remained intact

Total Synthesis of Iejimalide A-D and Assessment of the Remarkable Actin-Depolymerizing Capacity of These Polyene Macrolides

A concise and convergent total synthesis of the highly cytotoxic marine natural products iejimalide A−D (1−4) is reported, which relies on an effective ring-closing metathesis (RCM) reaction of a cyclization precursor containing no less than 10 double bonds. Because of the exceptional sensitivity of this polyunsaturated intermediate and its immediate precursors toward acid, base, and even gentle warming, the assembly process hinged upon the judicious choice of protecting groups and the careful optimization of all individual transformations. As a consequence, particularly mild protocols for Stille as well as Suzuki reactions of elaborate coupling partners have been developed that hold considerable promise for applications in other complex settings. Moreover, a series of non-natural “iejimalide-like” compounds has been prepared, differing from the natural lead in the polar head groups linked to the macrolide's N-terminus. With the aid of these compounds it was possible to uncover the hitherto unknown effect of iejimalide and analogues on the actin cytoskeleton. Their capacity to depolymerize this microfilament network rivals that of the latrunculins which constitute the standard in the field. Structural modifications of the peptidic terminus in 2 are thereby well accommodated, without compromising the biological effects. The iejimalides hence constitute an important new class of probe molecules for chemical biology in addition to their role as promising lead structures for the development of novel anticancer agents

Estado de conservación y características demográficas de Patella ferruginea Gmelin, 1791 (Mollusca, Gastropoda) en la Isla de Alborán (Mediterráneo occidental)

Due to the high risk of the global extinction in which Patella ferruginea Gmelin, 1791 is found, it is considered of great interest to describe and quantify its demographic characteristics in those sites where it still persists, as well as to evaluate the reasons which have led this limpet to be one of the most threatened marine species in the Mediterranean Sea. Over the study period (2000–2002), systematic census were made on the perimeter of the Alboran Island (Alboran Sea, westernmost area of the Mediterranean Sea) with the object to quantify the abundance of the species in the locality, as well as their external biometry and spatial distribution. As a result, the presence of a probable reproductive population of P. ferruginea was found on the island. The negative effect provoked by the continuous presence of man was proved, prejudicing the population in those zones which were more accessible for their harvesting. For this reason, it is necessary to regulate the use of the natural resources of the island to favour the conservation and spontaneous recolonisation of the zone by P. ferruginea.Dado el peligro de extinción global en el que actualmente se encuentra Patella ferruginea Gmelin, 1791, se considera de gran interés describir y cuantificar las características poblacionales de la especie en aquellas localidades donde aún persiste, así como evaluar las razones que han llevado a considerar a esta lapa como una de las especies marinas más amenazadas de extinción del Mediterráneo. Durante el período de estudio (2000–2002) fueron realizados muestreos sistemáticos en el perímetro de la Isla de Alborán (Mar de Alborán, extremo occidental del Mediterráneo) con objeto de cuantificar la abundancia de la especie en la localidad, así como su biometría externa y distribución espacial. Como resultado, se ha constatado la presencia en la isla de una población de P. ferruginea probablemente reproductora. Se ha comprobado el efecto negativo provocado por la continua presencia humana en la isla, perjudicando a la población en aquellas zonas más accesibles para la recolección de ejemplares. Es por ello que se considera necesario regular el uso de los recursos naturales en la isla con objeto de favorecer la conservación y recolonización espontánea de la localidad por P. ferruginea

Changes in the human peritoneal mesothelial cells during aging

The number of older patients admitted to peritoneal dialysis (PD) programmes is growing. At the same time, there is increasing data about the role of mesothelial cells in determining the functional alteration of the peritoneum during PD. However, little is known about the functional changes accompanying the ageing process in mesothelial cells. We aimed to evaluate whether the aging process is accompanied by changes in some functional characteristic of the human peritoneal mesothelial cells (HPMC), which could account for the poor prognosis observed in old patients with PD. HPMCs were isolated from patients undergoing a nonurgent, nonseptic abdominal surgical procedure, without renal, vascular or inflammatory disease. Cytokine levels (by enzyme-linked immunosorbent assay (ELISA)), nitrates+nitrites, and cyclooxygenase (COX) activity (by a chemiluminescence assay), cytokines, COX, nitric oxide synthase (NOS), and nuclear factor (NF)-κB1, two messenger ribonucleic acid (mRNA) gene expressions (by reverse transcriptase (RT)-Multiplex PCR), COX, and NOS promoter gene activities, and NF-κB-dependent transcription (by transient transfection assays) were determined. Our data show a significant increase in cytokines, COX, and NOS activities, and mRNA expression of cytokines, COX-2, inducible nitric oxide synthase (iNOS) and precursors of NF-κB in HPMCs from old people. This was also the case for COX-2 and iNOS promoter gene activities and NF-κB-dependent transcription. There was a positive correlation between the age of the donor's cell and the proinflammatory profile of the HPMCs. Such age-dependent increase (around two–three times) is partially abolished by different antioxidant or free-radical scavengers. Thus, aging is accompanied by the presence of an inflammatory state in HPMCs, which involves the participation of different reactive oxygen species

Studies on Iejimalide B: Preparation of the Seco Acid and Identification of the Molecule's "Achilles Heel"

Limitations of models in total synthesis are illustrated by a study towards the potent cytotoxic macrolide iejimalide B. Although the Yamaguchi protocol allowed for the esterification of elaborate segments, attempted macrolactonization of the seco acid met with failure (see scheme, Boc= tert-butyloxycarbonyl). The assembly of the seco acid involves some of the most advanced applications of the Julia olefination known to date

Factores relevantes para convertirse en una Ciudad Inteligente Sostenible: un estudio empírico en Europa

El interés en las Ciudades Inteligentes o Smart Cities no deja de crecer y extenderse en todo el mundo. En las últimas décadas, las organizaciones nacionales e internacionales han realizado estudios centrados en la definición, creación y uso de indicadores para medir y evaluar las Smart Cities. La mayor parte de la literatura revela que estas ciudades muestran altos valores en los indicadores creados para medir y clasificar Ciudades Inteligentes. En este contexto, el objetivo de este trabajo es, en primer lugar, identificar las posibles similitudes o diferencias existentes entre las ciudades con respecto a sus niveles de desarrollo de Smart Cities y, por otro, identificar sus factores relevantes. Más específicamente, presentamos evidencia descriptiva y estilizada sobre algunos factores que confirman las diferencias entre Ciudades Inteligentes en Europa utilizando diferentes técnicas estadísticas, sobre una muestra de 73 ciudades europeas. Los resultados muestran, por un lado, que existen clusters robustos alrededor de las Smart Cities europeas y, por otro, que las ciudades que se localizan geográficamente en la región del oeste y las gobernadas por mujeres presentan los niveles más altos de Smart Cities.info:eu-repo/semantics/acceptedVersio