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

Biological Versus Chronological Aging: JACC Focus Seminar

Aging is the main risk factor for vascular disease and ensuing cardiovascular and cerebrovascular events, the leading causes of death worldwide. In a progressively aging population, it is essential to develop early-life biomarkers that efficiently identify individuals who are at high risk of developing accelerated vascular damage, with the ultimate goal of improving primary prevention and reducing the health care and socioeconomic impact of age-related cardiovascular disease. Studies in experimental models and humans have identified 9 highly interconnected hallmark processes driving mammalian aging. However, strategies to extend health span and life span require understanding of interindividual differences in age-dependent functional decline, known as biological aging. This review summarizes the current knowledge on biological age biomarkers, factors influencing biological aging, and antiaging interventions, with a focus on vascular aspects of the aging process and its cardiovascular disease related manifestations.The CNIC is supported by the MCNU, the ISCIII, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Work in Dr. Andrés’ laboratory is supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (MCNU) (SAF2016-79490-R) and the Instituto de Salud Carlos III (ISCIII) (AC16/00091, AC17/00067, and CB16/11/00405) with cofunding from the European Regional Development Fund (ERDF/FEDER, “Una manera de hacer Europa”) and the Fundació Marató TV3 (122/C/2015). Dr. Hamczyk is supported by the MCNU (post-doctoral contract FJCI-2017-33299). Ms. Nevado is supported by the Ministerio de Educación, Cultura y Deporte (pre-doctoral contract FPU16/05027). Ms. Barettino is supported by the MCNU (pre-doctoral contract BES-2017-079705).S

Testing procedures for selection of new pinewood preservation products

In this work we compare the results of three experimental series of tests used as a first approach on selection of natural products for wood preservation

Headache and type 2 diabetes association: a US national ambulatory case-control study

Objective We investigate the joint observation between type 2 diabetes and headache using a case-control study of a US ambulatory dataset. Background Recent whole-population cohort studies propose that type 2 diabetes may have a protective effect against headache prevalence. With headaches ranked as a leading cause of disability, headache-associated comorbidities could help identify shared molecular mechanisms. Methods We performed a case-control study using the US National Ambulatory Medical Care Survey, 2009, on the joint observation between headache and specific comorbidities, namely type 2 diabetes, hypertension and anxiety, for all patients between 18 and 65 years of age. The odds ratio of having a headache and a comorbidity were calculated using conditional logistic regression, controlling for gender and age over a study population of 3,327,947 electronic health records in the absence of prescription medication data. Results We observed estimated odds ratio of 0.89 (95% CI: 0.83-0.95) of having a headache and a record of type 2 diabetes over the population, and 0.83 (95% CI: 2.02-2.57) and 0.89 (95% CI: 3.00-3.49) for male and female, respectively. Conclusions We find that patients with type 2 diabetes are less likely to present a recorded headache indication. Patients with hypertension are almost twice as likely of having a headache indication and patients with an anxiety disorder are almost three times as likely. Given the possibility of confounding indications and prescribed medications, additional studies are recommended

PTP1B deficiency increases glucose uptake in neonatal hepatocytes: involvement of IRA/GLUT2 complexes

11 pages, 5 figures, 1 table.The contribution of the liver to glucose utilization is essential to maintain glucose homeostasis. Previous data from protein tyrosine phosphatase (PTP) 1B-deficient mice demonstrated that the liver is a major site for PTP1B action in the periphery. In this study, we have investigated the consequences of PTP1B deficiency in glucose uptake in hepatocytes from neonatal and adult mice. The lack of PTP1B increased basal glucose uptake in hepatocytes from neonatal (3-5 days old) but not adult (10-12 wk old) mice. This occurs without changes in hexokinase, glucokinase, and glucose 6-phosphatase enzymatic activities. By contrast, the glucose transporter GLUT2 was upregulated at the protein level in neonatal hepatocytes and livers from PTP1B-deficient neonates. These results were accompanied by a significant increase in the net free intrahepatic glucose levels in the livers of PTP1B(-/-) neonates. The association between GLUT2 and insulin receptor (IR) A isoform was increased in PTP1B(-/-) neonatal hepatocytes compared with the wild-type. Indeed, PTP1B deficiency in neonatal hepatocytes shifted the ratio of isoforms A and B of the IR by increasing the amount of IRA and decreasing IRB. Moreover, overexpression of IRA in PTP1B(-/-) neonatal hepatocytes increased the amount of IRA/GLUT2 complexes. Conversely, hepatocytes from adult mice only expressed IRB. Since IRA plays a direct role in the regulation of glucose uptake in neonatal hepatocytes through its specific association with GLUT2, we propose the increase in IRA/GLUT2 complexes due to PTP1B deficiency as the molecular mechanism of the increased glucose uptake in the neonatal stage.This work was supported by grants BFU2005-1615 (A. M. Valverde), SAF 2004-5545 (M. Benito), and CIBER de Diabetes y Enfermedades Metabólicas Asociadas (ISCIII, Spain). A. González-Rodríguez and C. Nevado were recipients of fellowships from Ministerio de Educación y Ciencia (Spain).Peer reviewe

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

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

Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas

Multiple osteochondromas is an autosomal dominant skeletal disorder characterized by the formation of multiple cartilage-capped tumours. Two causal genes have been identified, EXT1 and EXT2, which account for 65% and 30% of cases, respectively. We have undertaken a mutation analysis of the EXT1 and EXT2 genes in 39 unrelated Spanish patients, most of them with moderate phenotype, and looked for genotype-phenotype correlations. We found the mutant allele in 37 patients, 29 in EXT1 and 8 in EXT2. Five of the EXT1 mutations were deletions identified by MLPA. Two cases of mosaicism were documented. We detected a lower number of exostoses in patients with missense mutation versus other kinds of mutations. In conclusion, we found a mutation in EXT1 or in EXT2 in 95% of the Spanish patients. Eighteen of the mutations were novel.Fil: Sarrión, P.. Universidad de Barcelona; EspañaFil: Sangorrin, A.. Hospital Sant Joan de Déu; EspañaFil: Urreizti, R.. Universidad de Barcelona; EspañaFil: Delgado, María Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Artuch, R.. Hospital Sant Joan de Déu; EspañaFil: Martorell, L.. Hospital Sant Joan de Déu; EspañaFil: Armstrong, J.. Hospital Sant Joan de Déu; EspañaFil: Anton, J.. Hospital Sant Joan de Déu; EspañaFil: Torner, F.. Hospital Sant Joan de Déu; EspañaFil: Vilaseca, M. A.. Hospital Sant Joan de Déu; EspañaFil: Nevado, J.. Hospital Universitario La Paz; EspañaFil: Lapunzina, P.. Hospital Universitario La Paz; EspañaFil: Asteggiano, Carla Gabriela. Universidad Nacional de Córdoba; Argentina. Universidad Católica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Balcells, S.. Universidad de Barcelona; EspañaFil: Grinberg, D.. Universidad de Barcelona; Españ

The western Mediterranean region provided the founder population of domesticated narrow-leafed lupin

Key message: This study revealed that the western Mediterranean provided the founder population for domesticated narrow-leafed lupin and that genetic diversity decreased significantly during narrow-leafed lupin domestication. Abstract: The evolutionary history of plants during domestication profoundly shaped the genome structure and genetic diversity of today’s crops. Advances in next-generation sequencing technologies allow unprecedented opportunities to understand genome evolution in minor crops, which constitute the majority of plant domestications. A diverse set of 231 wild and domesticated narrow-leafed lupin (Lupinus angustifolius L.) accessions were subjected to genotyping-by-sequencing using diversity arrays technology. Phylogenetic, genome-wide divergence and linkage disequilibrium analyses were applied to identify the founder population of domesticated narrow-leafed lupin and the genome-wide effect of domestication on its genome. We found wild western Mediterranean population as the founder of domesticated narrow-leafed lupin. Domestication was associated with an almost threefold reduction in genome diversity in domesticated accessions compared to their wild relatives. Selective sweep analysis identified no significant footprints of selection around domestication loci. A genome-wide association study identified single nucleotide polymorphism markers associated with pod dehiscence. This new understanding of the genomic consequences of narrow-leafed lupin domestication along with molecular marker tools developed here will assist plant breeders more effectively access wild genetic diversity for crop improvement