Irisin, Two Years Later

In January 2012, Boström and colleagues identified a new muscle tissue secreted peptide, which they named irisin, to highlight its role as a messenger that comes from skeletal muscle to other parts of the body. Irisin is a cleaved and secreted fragment of FNDC5 (also known as FRCP2 and PeP), a member of fibronectin type III repeat containing gene family. Major interest in this protein arose because of its great therapeutic potential in diabetes and perhaps also therapy for obesity. Here we review the most important aspects of irisin's action and discuss its involvement in energy and metabolic homeostasis and whether the beneficial effects of exercise in these disease states could be mediated by this protein. In addition the effects of irisin at the central nervous system (CNS) are highlighted. It is concluded that although current and upcoming research on irisin is very promising it is still necessary to deepen in several aspects in order to clarify its full potential as a meaningful drug target in human disease states

Hypothalamic mTOR signaling mediates the orexigenic action of ghrelin

Current evidence suggests that ghrelin, a stomach derived peptide, exerts its orexigenic action through specific modulation of Sirtuin1 (SIRT1)/p53 and AMP-activated protein kinase (AMPK) pathways, which ultimately increase the expression of agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARC). However, there is a paucity of data about the possible action of ghrelin on alternative metabolic pathways at this level. Here, we demonstrate that ghrelin elicits a marked upregulation of the hypothalamic mammalian target of rapamycin (mTOR) signaling pathway. Of note, central inhibition of mTOR signaling with rapamycin decreased ghrelin's orexigenic action and normalized the mRNA expression of AgRP and NPY, as well as their key downstream transcription factors, namely cAMP response-element binding protein (pCREB) and forkhead box O1 (FoxO1, total and phosphorylated). Taken together, these data indicate that, in addition to previous reported mechanisms, ghrelin also promotes feeding through modulation of hypothalamic mTOR pathway

Microbiological and Physicochemical Changes in Natural Green Heat-Shocked Aloreña de Málaga Table Olives

11 Páginas; 5 Tablas; 6 FigurasPreserving the highly appreciated natural freshness of Aloreña de Málaga table olives and preventing their progressive darkening during processing is a major challenge. In this work, heat-shocked (60°C, 5 min) fruits were processed according to the three denominations referred to in the Protected Designation of Origen (cured, fresh green, and traditional) and their characteristics compared with those that followed the habitual industrial process (controls). The results revealed that the effects of the heat treatment on the evolution of pH, titratable acidity, salt, sugar, organic acid, ethanol content, texture, and color of fruits as well as on microbial populations (yeasts and lactic acid bacteria) were slight in the case of the fresh green and cured presentations. However, the differences between heat-shocked and its control were remarkable in the traditional process. Notably, the heat treatment favored lactic acid fermentation, retention of the green appearance of the fruits, stability during packaging, and led to the highest sensory evaluation. The metagenomic analysis carried out at the end of the fermentation revealed the presence in all samples of three genera (Lactobacillus, Pediococcus, and Celerinatantimonas) which encompassed most of the sequences. The number of Lactobacillus sequences was statistically higher (p ≥ 0.05) in the case of traditional heat-shocked fruits than in its control.The research leading to these results has received funding from Junta de Andalucía Government through the PrediAlo project (AGR-7755: www.predialo.science.com.es) and FEDER European funds. FA-L wishes to express thanks to the Spanish government for his RyC postdoctoral research contract while VR-G would like to thank ceiA3, Spanish Government, Bank of Santander, IG-CSIC and ‘Aloreña de Málaga’ Olive Manufacturing Association for her predoctoral fellowship. Authors express their gratitude to Dr. Borja Sánchez (IPLA-CSIC) for his invaluable help in the metagenomic analysis.Peer reviewe

IAA : Información y actualidad astronómica (15)

Sumario : INVESTIGACIÓN. Aerosoles atmosféricos: sus efectos en el clima de las atmósferas del sistema solar.-- El gas molecular en las galaxias.-- VENTANA ABIERTA. Todo un privilegio.-- CHARLAS CON...Vicent Martínez.-- ACTUALIDAD CIENTÍFICA. Un sistema planetario joven en torno a Beta Pictores.-- Una nueva visita a Canis Major .-- ACTIVIDADES IAA.-- AGENDA.Esta revista se publica con la ayuda de la Accion Especial DIF 2001-4284-E del Programa Nacional de Difusión de la Ciencia y la Tecnología, del Ministerio de Ciencia y Tecnología.N

Confined Pt11+ Water Clusters in a MOF Catalyze the Low‐Temperature Water–Gas Shift Reaction with both CO2 Oxygen Atoms Coming from Water

The synthesis and reactivity of single metal atoms in a low‐valence state bound to just water, rather than to organic ligands or surfaces, is a major experimental challenge. Herein, we show a gram‐scale wet synthesis of Pt11+ stabilized in a confined space by a crystallographically well‐defined first water sphere, and with a second coordination sphere linked to a metal–organic framework (MOF) through electrostatic and H‐bonding interactions. The role of the water cluster is not only isolating and stabilizing the Pt atoms, but also regulating the charge of the metal and the adsorption of reactants. This is shown for the low‐temperature water–gas shift reaction (WGSR: CO + H2O → CO2 + H2), where both metal coordinated and H‐bonded water molecules trigger a double water attack mechanism to CO and give CO2 with both oxygen atoms coming from water. The stabilized Pt1+ single sites allow performing the WGSR at temperatures as low as 50 °C.This work was supported by the MINECO (Spain) (Projects CTQ2016–75671–P, MAT2013 40823–R, MAT2016–81732–ERC, CTQ2017–86735–P, MAT2017–86992–R, MAT2017–82288–C2–1–P and Excellence Units “Severo Ochoa” and “Maria de Maeztu” SEV–2016–0683 and MDM–2015–0538) the Generalitat Valenciana (PROMETEOII/2014/004) and the Ministero dell’Istruzione, dell’Università e della Ricerca (Italy) and the Junta de Andalucía (FQM–195). M. M. and M.–A. R. C. thanks the MINECO for a predoctoral contract. Thanks are also extended to the Ramón y Cajal Program (E. V. R.–F., E. P. and J.–C. H.–G.) and the “Subprograma atracció de talent–contractes postdoctorals de la Universitat de Valencia” (J. F.–S.). M. L.–H. acknowledges the financial support from the Juan de la Cierva Fellowships Program of MINECO (IJCI–2014–19367)

Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease

This is an open access article distributed under the terms of the Creative Commons Attribution License.[Introduction]: Fibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. However, it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in fibromyalgia. Furthermore, the role of mitochondria in the redox imbalance reported in fibromyalgia also is controversial. We undertook this study to investigate the role of mitochondrial dysfunction, oxidative stress, and mitophagy in fibromyalgia. [Methods]: We studied 20 patients (2 male, 18 female patients) from the database of the Sevillian Fibromyalgia Association and 10 healthy controls. We evaluated mitochondrial function in blood mononuclear cells from fibromyalgia patients measuring, coenzyme Q10 levels with high-performance liquid chromatography (HPLC), and mitochondrial membrane potential with flow cytometry. Oxidative stress was determined by measuring mitochondrial superoxide production with MitoSOX™ and lipid peroxidation in blood mononuclear cells and plasma from fibromyalgia patients. Autophagy activation was evaluated by quantifying the fluorescence intensity of LysoTracker™ Red staining of blood mononuclear cells. Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells. [Results]: We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy. [Conclusions]: These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.This work was supported by grants FIS PI080500 and FIS EC08/00076, Ministerio de Sanidad, Spain. The authors dedicate this manuscript to FM patients and AFIBROSE (Asociación de Fibromialgia de Sevilla) for their unconditional help.Peer Reviewe

Direct oral anticoagulants in patients with hypertrophic cardiomyopathy and atrial fibrillation.

Background: Chronic anticoagulation with vitamin K antagonists (VKAs) is recommended in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF). Direct oral anticoagulants (NOACs) are an alternative to VKAs but there are limited data to support their use in HCM. We sought to describe the pattern of use, thromboembolic events, bleeding and quality of life in patients with HCM and AF treated with NOACs. Methods: Data from patients treated with NOACs (n=99) and VKA (n=433) at 9 inherited cardiac diseases units were retrospectively collected. Annual rates of embolic events, serious bleeding and death were analysed and compared. Quality of life and treatment satisfaction were evaluated with SF-36 and SAFUCA questionnaires in 80 NOAC-treated and 57 VKA-treated patients. Results: After median follow-up of 63 months (IQR:26–109), thromboembolic events (TIA/stroke and peripheral embolism) occurred in 10% of patients on oral anticoagulation. Major/clinically relevant bleeding occurred in 3.8% and the global mortality rate was 23.3%. Thromboembolic event rate was 0.62 per 100 patient-years in the NOAC group vs. 1.59 in the VKA group [subhazard ratio (SHR) 0.32;95%CI:0.04– 2.45;p=0.27]. Major/clinically relevant bleeding occurred in 0.62 per 100 person-years in the NOAC group vs. 0.60 in the VKA group (SHR 1.28;95%CI 0.18–9.30;p=0.85). Quality of life scores were similar in both groups; however, NOAC-treated patients achieved higher scores in the SAFUCA. Conclusions: HCM patients with AF on NOACs showed similar embolic and bleeding rates to those on VKA. Although quality of life was similar in both groups, the NOAC group reported higher treatment satisfaction.pre-print929 K

10 Myr evolution of sedimentation rates in a deep marine to non-marine foreland basin system: Tectonic and sedimentary controls (Eocene, Tremp–Jaca Basin, Southern Pyrenees, NE Spain)

The propagation of the deformation front in foreland systems is typically accompanied by the incorporation of parts of the basin into wedge-top piggy-back basins, this process is likely producing considerable changes to sedimentation rates (SR). Here we investigate the spatial-temporal evolution of SR for the Tremp–Jaca Basin in the Southern Pyrenees during its evolution from a wedge-top, foreredeep, forebulge configuration to a wedge-top stage. SR were controlled by a series of tectonic structures that influenced subsidence distribution and modified the sediment dispersal patterns. We compare the decompacted SR calculated from 12 magnetostratigraphic sections located throughout the Tremp–Jaca Basin represent the full range of depositional environment and times. While the derived long-term SR range between 9.0 and 84.5 cm/kyr, compiled data at the scale of magnetozones (0.1–2.5 Myr) yield SR that range from 3.0 to 170 cm/kyr. From this analysis, three main types of depocenter are recognized: a regional depocenter in the foredeep depozone; depocenters related to both regional subsidence and salt tectonics in the wedge-top depozone; and a depocenter related to clastic shelf building showing transgressive and regressive trends with graded and non-graded episodes. From the evolution of SR we distinguish two stages. The Lutetian Stage (from 49.1–41.2 Ma) portrays a compartmentalized basin characterized by variable SR in dominantly underfilled accommodation areas. The markedly different advance of the deformation front between the Central and Western Pyrenees resulted in a complex distribution of the foreland depozones during this stage. The Bartonian–Priabonian Stage (41.2–36.9 Ma) represents the integration of the whole basin into the wedge-top, showing a generalized reduction of SR in a mostly overfilled relatively uniform basin. The stacking of basement units in the hinterland during the whole period produced unusually high SR in the wedge-top depozoneAgència de Gestió d'Ajuts Universitaris i de Recerca, Grant/Award Number: 2017SGR596; Secretaría de Estado de Investigación, Desarrollo e Innovación, Grant/Award Number: BES-2015-073302 and CGL2014-55900-P; Swiss National Science Foundation, Grant/Award Number: 200020_18201

Cellular and humoral functional responses after BNT162b2 mRNA vaccination differ longitudinally between naive and subjects recovered from COVID-19

We have analyzed BNT162b2 vaccine-induced immune responses in naive subjects and individuals recovered from coronavirus disease 2019 (COVID-19), both soon after (14 days) and later after (almost 8 months) vaccination. Plasma spike (S)-specific immunoglobulins peak after one vaccine shot in individuals recovered from COVID-19, while a second dose is needed in naive subjects, although the latter group shows reduced levels all along the analyzed period. Despite how the neutralization capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mirrors this behavior early after vaccination, both groups show comparable neutralizing antibodies and S-specific B cell levels late post-vaccination. When studying cellular responses, naive individuals exhibit higher SARS-CoV-2-specific cytokine production, CD4+ T cell activation, and proliferation than do individuals recovered from COVID-19, with patent inverse correlations between humoral and cellular variables early post-vaccination. However, almost 8 months post-vaccination, SARS-CoV-2-specific responses are comparable between both groups. Our data indicate that a previous history of COVID-19 differentially determines the functional T and B cell-mediated responses to BNT162b2 vaccination over time.C.d.F., J.G.-P., and J.A. are supported by Instituto de Salud Carlos III (ISCII). We thank JM Ligos and Cytek Biosciences for their technical support. Research in E.L.-C.’s lab was supported by Fundación Familia Alonso, Santander Bank, Real Seguros, Fundación Mutua Madrileña, Fundación Uria, Fundación La Caixa, and Ayuntamiento de Madrid.S

Experimental validation of Lyot stop apodization in ground-based coronagraphy

ABSTRACT We show that the use of apodizing functions at the coronagraph Lyot plane may be useful for improving the image contrast of ground-based coronagraphs. An experimental set-up consisting of a tip–tilt mirror, a coronagraph and a low-noiseEMCCDcamerawas implemented at theWilliam Herschel Telescope. Images were taken in the I band, which meant that the D/r0 value was around 10. Experimental results confirm that, for moderately aberrated wavefronts, our instrument works as theoretically expected, and that the contrast value attained is high enough to provide direct detection of faint companions.This research was supported by the Ministerio de Economía y Competitividad under project FIS2012-31079 and the Fundación Séneca of Murcia under projects 15419/PI/10 and 15345/PI/10