The addition of liguid fructose to a Western-type diet in LDL-R-/- mice induces liver inflammation and fibrogenesis markers without disrupting insulin receptor signalling after an insulin challenge

A high consumption of fat and simple sugars, especially fructose, has been related to the development of insulin resistance, but the mechanisms involved in the effects of these nutrients are not fully understood. This study investigates the effects of a Western-type diet and liquid fructose supplementation, alone and combined, on insulin signalling and inflammation in low-density lipoprotein (LDL) receptor-deficient mice (LDL-R−/−). LDL-R−/− mice were fed chow or Western diet ±15% fructose solution for 12 weeks. Plasma glucose and insulin, and the expression of genes related to inflammation in the liver and visceral white adipose tissue (vWAT), were analysed. V-akt murine thymoma viral oncogene homolog-2 (Akt) activation was measured in the liver of the mice after a single injection of saline or insulin. None of the dietary interventions caused inflammation in vWAT, whereas the Western diet induced hepatic inflammation, which was further enhanced by liquid fructose, leading also to a significant increase in fibrogenesis markers. However, there was no change in plasma glucose or insulin, or insulin-induced Akt phosphorylation. In conclusion, hepatic inflammation and fibrogenesis markers induced by a Western diet supplemented with liquid fructose in LDL-R−/− mice are not associated with a significant impairment of hepatic insulin signalling

Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues

Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake

Selective suppression of α-Synuclein in monoaminergic neurons of mice by intranasal delivery of targeted small interfering RNA or antisense oligonucleotides: Potential therapy for Parkinson's disease

Póster presentado en: ACNP (American College of Neuropsychopharmacology) 52nd Annual Conference, celebrada del 8 al 12 de diciembre de 2013 en Hollywood, Florida (Estados Unidos)Abstract publicado en: Neuropsychopharmacology 38:S419-S420 (2013). ISSN: 0893-133X. eISSN: 1740-634X. DOI:10.1038/npp.2013.280α-Synuclein (α-Syn) appears to play a crucial role in the pathogenesis of several neurodegenerative disorders including Parkinson's disease (PD). The brains of Parkinson patients typically contain insoluble intracellular protein inclusions called Lewy bodies. Increased neuronal α-Syn levels represent a major component of Lewy bodies and therefore, the suppression of α-Syn expression provides a valid therapeutic target for PD. The goal of this study was to assess the ability of various small interfering RNA (siRNA) and antisense oligonucleotide (ASO) sequences directed against α-Syn to downregulate endogenous or overexpressed α-Syn mRNA levels in BE-M17 neuroblastoma cells. Moreover, we evaluated the feasibility of reducing α-Syn expression selectively in PD-vulnerable brain areas including substantia nigra pars compacta (SNc), ventral tegmental area (VTA), locus coeruleus (LC) and dorsal raphe nucleus (DR) of mice after the internalization of conjugated siRNA/ASO molecules into monoamine neurons following intranasal administration. Conclusions: These results set the stage for the testing of these molecules as potential disease-modifying agents in neurotoxin-based and genetic models of PD linked to pathogenic increases in α-Syn. In this study we have characterized conjugated siRNA and ASO molecules that actively reduce endogenous α-Syn expression in vivo using the intranasal route to deliver directly siRNA/ASO into the brainPeer Reviewe

Genetic Variants at the 9p21.3 Locus Are Associated with Risk for Non-Compressible Artery Disease: Results from the ARTPER Study

Peripheral artery disease (PAD) and non-compressible artery disease (NCAD) constitute predictors of subclinical atherosclerosis easily assessed through the ankle brachial index (ABI). Although both diseases show substantial genetic influences, few genetic association studies have focused on the ABI and PAD, and none have focused on NCAD. To overcome these limitations, we assessed the role of several candidate genes on the ABI, both in its continuous distribution and in the clinical manifestations associated to its extreme values: PAD and NCAD. We examined 13 candidate genomic regions in 1606 participants from the ARTPER study, a prospective population-based cohort, with the ABI assessed through ultrasonography. Association analyses were conducted independently for individuals with PAD (ABI 1.4) vs. healthy participants. After including potential covariates and correction for multiple testing, minor alleles in the genetic markers rs10757278 and rs1333049, both in the 9p21.3 region, were significantly associated with a decreased risk of NCAD. Associations with the ABI showed limited support to these results. No significant associations were detected for PAD. The locus 9p21.3 constitutes the first genetic locus associated with NCAD, an assessment of subclinical atherosclerosis feasible for implementation in primary healthcare settings that has been systematically neglected from genetic studies

Diabetic and dyslipidaemic morbidly obese exhibit more liver alterations compared with healthy morbidly obese

Background & aims: To study the origin of fat excess in the livers of morbidly obese (MO) individuals, we analysed lipids and lipases in both plasma and liver and genes involved in lipid transport, or related with, in that organ. Methods: Thirty-two MO patients were grouped according to the absence (healthy: DM−DL−) or presence of comorbidities (dyslipidemic: DM−DL+; or dyslipidemic with type 2 diabetes: DM+DL+) before and one year after gastric bypass. Results: The livers of healthy, DL and DM patients contained more lipids (9.8, 9.5 and 13.7 times, respectively) than those of control subjects. The genes implicated in liver lipid uptake, including HL, LPL, VLDLr, and FAT/CD36, showed increased expression compared with the controls. The expression of genes involved in lipid-related processes outside of the liver, such as apoB, PPARα and PGC1α, CYP7a1 and HMGCR, was reduced in these patients compared with the controls. PAI1 and TNFα gene expression in the diabetic livers was increased compared with the other obese groups and control group. Increased steatosis and fibrosis were also noted in the MO individuals. Conclusions: Hepatic lipid parameters in MO patients change based on their comorbidities. The gene expression and lipid levels after bariatric surgery were less prominent in the diabetic patients. Lipid receptor overexpression could enable the liver to capture circulating lipids, thus favouring the steatosis typically observed in diabetic and dyslipidaemic MO individuals.This research has received funding from the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III of the Spanish Ministry for Health and Consumer Affairs (PI030024, PI030042, PI070079 and PI11/01159

Quaternary fossil horses within the Prados-Guatén Depression (Pantoja de La Sagra, Toledo)

Durante la primera reunión de campo del Grupo Madrileño de Cuaternario (GQM-AEQUA) se localizaron restos fragmentarios de dentición de caballos fósiles en los antiguos areneros de Pantoja de La Sagra (Toledo), actualmente en proceso de desmantelamiento y relleno. Ante la posibilidad de deterioro y pérdida los restos fueron recolectados y trasladados al Museo Nacional de Ciencias Naturales (CSIC, Madrid) donde se ha procedido a su análisis. Las piezas fósiles analizadas responden a un maxilar izquierdo con tres piezas dentales in situ (molares y premolares), y otras siete más aisladas. Todos los dientes aislados, junto con el fragmento de maxilar existente, corresponden a un adulto joven. Los restos fósiles se encontraban asociados a un nivel de arenas fluviales situado unos cuatro metros por debajo de la superficie de la Terraza de +15 m de la Depresión Prados-Guatén definida como un nivel perteneciente al tránsito Pleistoceno inferior-medio, del antiguo Sistema fluvial Manzanares-Guatén por Silva (1988). En concreto los niveles superiores de esta terraza han sido interpretados como resultado de la superposición de los últimos depósitos del antiguo sistema fluvial y los primeros asociados al relleno de la Depresión por tributarios de área fuente más local tras su abandono como consecuencia del proceso de captura del valle inferior del Manzanares por parte del Río Jarama al SW de la Ciudad de Madrid (Silva et al., 1988). Los caracteres morfológicos y morfométricos de las piezas dentarias permiten identificarlos como Equus ferus cf. mosbachensis cuya distribución bioestratigráfica abarca la parte final del Pleistoceno Medio (c.a. 500-200 ka B.P.). Junto a los restos fósiles aparecieron también escasos fragmentos líticos correspondientes a productos de lascado en sílex de difícil atribución tecnológica. Los restos fósiles analizados, indican que el depósito extensivo de arenas fluviales en el eje de la Depresión, culminó durante el final del Pleistoceno medio, y que la dinámica fluvial de la Depresión tras su proceso de abandono fue de hecho más activa de lo que se pensaba con la instalación de sistemas de arroyos relevantes alimentados por cabeceras locales antes del encajamiento definitivo actual de los arroyos Prados y Guatén.During the first field-meeting of the Madrid Quaternary Research Group (GQM-AEQUA) several fossil teeth remnants of horses were localised at the ancient sand-quarries of Pantoja de La Sagra (Toledo), which presently are abandoned and refilling in progress. The possibility of deterioration and loss of the localised fossils remnants induced by the quarry works, they were collected and taken away to the Museo Nacional de Ciencias Naturales (CSIC, Madrid) for their preservation and analysis. Fossil remains correspond to a left maxilla with two in situ molars, another one inset on its alveolar cavity, fragments of premolar cavities, as well as other seven more isolated teeth. These fossils were outcropping in a sandy level at four meters below the +15 m fluvial terrace surface of the axial sector of de Prados-Guatén Depression, which is considered the last fluvial level belonging to the ancient Manzanares-Guatén fluvial system during the Lower-Middle Pleistocene transit (Silva, 1988). In detail, the upper fluvial sediments of this particular terrace level were interpreted as the result of the overlapping between the last materials deposited by the ancient Manzanares-Guatén fluvial system and the first ones resulting from the readjustment of former tributaries after the abandonment of the Depression caused by fluvial capture of the Lower Manzanares Valley SW Madrid City. The morphological features of the oclusal surface of the horse teeth and morphometric comparative analyses indicate that they belong to the specie Equus ferus, and probably to the subspecie mosbachensis. However due to the bad definition of this group in Europe and the few individuals analysed the better classification is Equus ferus cf. mosbachensis. The bioestratigraphic distribution of this fossil horse group in Europe extends on the upper part of the Middle Pleistocene (c.a. 500-200 ka B.P.). Few lithic artefacts outcropped also associated to the fossil remains, constituted by laminar flakes of hard technological classification. Fossil remains analysed in this work joint to the unique previous quaternary fossil mammal described for the Prados-Guatén Depression constituted by Mammuthus meridionalis NESTI of the former quarry of Esquivias adjacent to the AVE railway line (Silva et al., 1988b; 1999). The chronostratigraphic attribution of the fossil horses (Upper Middle Pleistocene) described here indicate that fluvial sedimentary activity within the Depression was relevant after its abandonment. Ancient tributaries of the former Manzanares-Guatén fluvial system, feed by local-intrabasinal headwaters, reworked the previous sandy sediments triggering multiepisodic deposition during the upper part of the Middle Pleistocene, before the more recent eventual incision of present streams dissecting the Depression

The Peripheral Arterial disease study (PERART/ARTPER): prevalence and risk factors in the general population

<p>Abstract</p> <p>Background</p> <p>The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the study is to know the prevalence and associated risk factors of peripheral arterial disease in the general population.</p> <p>Methods</p> <p>We performed a cross-sectional, multicentre, population-based study in 3786 individuals >49 years, randomly selected in 28 primary care centres in Barcelona (Spain). Peripheral arterial disease was evaluated using the ankle-arm index. Values < 0.9 were considered as peripheral arterial disease.</p> <p>Results</p> <p>The prevalence (95% confidence interval) of peripheral arterial disease was 7.6% (6.7-8.4), (males 10.2% (9.2-11.2), females 5.3% (4.6-6.0); <it>p </it>< 0.001).</p> <p>Multivariate analysis showed the following risk factors: male sex [odds ratio (OR) 1.62; 95% confidence interval 1.01-2.59]; age OR 2.00 per 10 years (1.64-2.44); inability to perform physical activity [OR 1.77 (1.17-2.68) for mild limitation to OR 7.08 (2.61-19.16) for breathless performing any activity]; smoking [OR 2.19 (1.34-3.58) for former smokers and OR 3.83 (2.23-6.58) for current smokers]; hypertension OR 1.85 (1.29-2.65); diabetes OR 2.01 (1.42-2.83); previous cardiovascular disease OR 2.19 (1.52-3.15); hypercholesterolemia OR 1.55 (1.11-2.18); hypertriglyceridemia OR 1.55 (1.10-2.19). Body mass index ≥25 Kg/m²OR 0.57 (0.38-0.87) and walking >7 hours/week OR 0.67 (0.49-0.94) were found as protector factors.</p> <p>Conclusions</p> <p>The prevalence of peripheral arterial disease is low, higher in males and increases with age in both sexes. In addition to previously described risk factors we found a protector effect in physical exercise and overweight.</p

BioBlitz Serra Llarga-Secans de la Noguera 2021: desenvolupament i espècies presents

En aquest article es fa la descripció de la tasca duta a terme durant el BioBlitz Serra Llarga-Secans de la Noguera dels dies 21 i 22 de maig de 2021 i es presenta el llistat despècies observades amb lobjectiu de facilitar que aquestes observacions es puguin integrar en les bases de dades públiques de biodiversitat.This paper lists the work carried out during the BioBlitz Serra Llarga-Secans de la Noguera on 21-22 May 2021. We present the list of observed species with the aim of facilitating that these observation could be integrated into public biodiversity databases

Epidemiology of human papillomavirus-related oropharyngeal cancer in a classically low-burden region of southern Europe

The incidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing in some regions. Nevertheless, the epidemiology of this disease has not been extensively investigated in southern Europe. We conducted a retrospective cohort study of patients diagnosed with primary oropharyngeal cancer from 1991 to 2016. Cancer tissues underwent histopathological evaluation, DNA quality control, HPV-DNA detection and p16 immunohistochemistry. Data were collected from medical records. Factors associated with HPV positivity and time trends were evaluated with multivariable Bayesian models. The adjusted prevalence of HPV-related cases in 864 patients with a valid HPV-DNA result was 9.7%, with HPV-DNA/p16 double positivity being considered. HPV-related oropharyngeal cancer was likely to occur in non-smokers and non-drinkers, to be located in the tonsil or diagnosed at advanced stages. Time-trend analysis showed an increasing risk of HPV-related oropharyngeal cancer in the most recent periods (5-year period increase of 30%). This increase was highest and with a clear increasing trend only in the most recent years (2012-2016). The prevalence of HPV-related oropharyngeal cancer started to sharply increase in the most recent years in our setting, as occurred two decades ago in areas where most oropharyngeal cancer cases are currently HPV-related. Our results provide a comprehensive assessment of the epidemiological landscape of HPV-related oropharyngeal cancer in a region of southern Europe

MAPPING COMMUNITY INTEREST HABITATS IN THE COLUMBRETES ARCHIPELAGO, AN EXTRAORDINARY HOT SPOT OF BIODIVERSITY

The Columbretes Archipelago and their submerged surroundings are part of an unusual, Pleistocene volcanic field located in the Western Mediterranean designated as a Site of Community Importance (SCI) of the Natura 2000 Network. In the present study, 4 benthic habitats of community interest (1110, 1170, 1180 and 8330) have been identified by analyzing several sources of information. Generalized additive models (GAMs) have been used to model the potential distribution of reefs (1170) and maërl beds (1110). Our results highlight the diversity and extent of these habitats and allow comparisons to other marine SCIs of Spain. This can be attributed to the variability of the environment of this site. The Columbretes Islands combine a relatively shallow environment with volcanic structures, hydrothermalism with active degassing, current-driven sedimentary lobes and the influence of inland flows. Understanding high biodiversity spots is crucial as they offer natural laboratories to describe how ecosystems respond to the effects of global change. The knowledge obtained will be of paramount importance for the conservation of species and habitats. Furthermore, it will establish a baseline for future monitoring and assist in the development of effective management plans