The End-Organ Impairment in Liver Cirrhosis: Appointments for Critical Care

Liver cirrhosis (LC) can lead to a clinical state of liver failure, which can exacerbate through the course of the disease. New therapies aimed to control the diverse etiologies are now more effective, although the disease may result in advanced stages of liver failure, where liver transplantation (LT) remains the most effective treatment. The extended lifespan of these patients and the extended possibilities of liver support devices make their admission to an intensive care unit (ICU) more probable. In this paper the LC is approached from the point of view of the pathophysiological alterations present in LC patients previous to ICU admission, particularly cardiovascular, but also renal, coagulopathic, and encephalopathic. Infections and available liver detoxifications devices also deserve mentioning. We intend to contribute towards ICU physician readiness to the care for this particular type of patients, possibly in dedicated ICUs

Regulation of Calcium Signaling by STIM1 and ORAI1

STIM1 and ORAI1 proteins are regulators of intracellular Ca2+ mobilization. This Ca2+ mobilization is essential to shape Ca2+ signaling in eukaryotic cells. STIM1 is a transmembrane protein located at the endoplasmic reticulum, where it acts as an intraluminal Ca2+ sensor. The transient drop of intraluminal Ca2+ concentration triggers STIM1 activation, which relocates to plasma membrane-endoplasmic reticulum junctions to bind and activate ORAI1, a plasma membrane Ca2+ channel. Thus, the Ca2+ influx pathway mediated by STIM1/ORAI1 is termed store-operated Ca2+ entry (SOCE). STIM and ORAI proteins are also involved in non-SOCE Ca2+ influx pathways, as we discuss here. In this chapter, we review the current knowledge regarding the role of SOCE, STIM1, and ORAI1 in cell signaling, with special focus on the modulation of the activity of kinases, phosphatases, and transcription factors that are strongly influenced by the extracellular Ca2+ influx mediated by these regulators

Characterization of multiple SPS knockout mutants reveals redundant functions of the four Arabidopsis sucrose phosphate synthase isoforms in plant viability, and strongly indicates that enhanced respiration and accelerated starch turnover can alleviate the blockage of sucrose biosynthesis

We characterized multiple knock-out mutants of the four Arabidopsis sucrose phosphate synthase (SPSA1, SPSA2, SPSB and SPSC) isoforms. Despite their reduced SPS activity, spsa1/spsa2, spsa1/spsb, spsa2/spsb, spsa2/spsc, spsb/spsc, spsa1/spsa2/spsb and spsa2/spsb/spsc mutants displayed wild type (WT) vegetative and reproductive morphology, and showed WT photosynthetic capacity and respiration. In contrast, growth of rosettes, flowers and siliques of the spsa1/spsc and spsa1/spsa2/spsc mutants was reduced compared with WT plants. Furthermore, these plants displayed a high dark respiration phenotype. spsa1/spsb/spsc and spsa1/spsa2/spsb/spsc seeds poorly germinated and produced aberrant and sterile plants. Leaves of all viable sps mutants, except spsa1/spsc and spsa1/spsa2/spsc, accumulated WT levels of nonstructural carbohydrates. spsa1/spsc leaves possessed high levels of metabolic intermediates and activities of enzymes of the glycolytic and tricarboxylic acid cycle pathways, and accumulated high levels of metabolic intermediates of the nocturnal starch-to-sucrose conversion process, even under continuous light conditions. Results presented in this work show that SPS is essential for plant viability, reveal redundant functions of the four SPS isoforms in processes that are important for plant growth and nonstructural carbohydrate metabolism, and strongly indicate that accelerated starch turnover and enhanced respiration can alleviate the blockage of sucrose biosynthesis in spsa1/spsc leaves.This work was partially supported by the Comisión Interministerial de Ciencia y Tecnología and Fondo Europeo de Desarrollo Regional (Spain) [grant numbers BIO2010-18239, BIO2013-49125-C2-1-P, BIO2008-02292 and BIO2011-28847-C02-02]. A.M.S-L. acknowledges a predoctoral fellowship from the Spanish Ministry of Science and Innovation. M.B. acknowledges a post-doctoral fellowship from the Public University of Navarra.Peer Reviewe

Volatile compounds emitted by diverse phytopathogenic microorganisms promote plant growth and flowering through cytokinin action

Sánchez-López, Ángela María et al.It is known that volatile emissions from some beneficial rhizosphere microorganisms promote plant growth. Here we show that volatile compounds (VCs) emitted by phylogenetically diverse rhizosphere and non-rhizhosphere bacteria and fungi (including plant pathogens and microbes that do not normally interact mutualistically with plants) promote growth and flowering of various plant species, including crops. In Arabidopsis plants exposed to VCs emitted by the phytopathogen Alternaria alternata, changes included enhancement of photosynthesis and accumulation of high levels of cytokinins (CKs) and sugars. Evidence obtained using transgenic Arabidopsis plants with altered CK status show that CKs play essential roles in this phenomenon, because growth and flowering responses to the VCs were reduced in mutants with CK-deficiency (35S:AtCKX1) or low receptor sensitivity (ahk2/3). Further, we demonstrate that the plant responses to fungal VCs are light-dependent. Transcriptomic analyses of Arabidopsis leaves exposed to A. alternata VCs revealed changes in the expression of light- and CK-responsive genes involved in photosynthesis, growth and flowering. Notably, many genes differentially expressed in plants treated with fungal VCs were also differentially expressed in plants exposed to VCs emitted by the plant growth promoting rhizobacterium Bacillus subtilis GB03, suggesting that plants react to microbial VCs through highly conserved regulatory mechanisms.This work was partially supported by the Comisión Interministerial de Ciencia y Tecnología and Fondo Europeo de Desarrollo Regional (Spain) (grant numbers BIO2010-18239 and BIO2013- 49125-C2-1-P), the Government of Navarra (grant number IIM010491.RI1), the I-Link0939 project from the Ministerio de Economía y Competitividad, the Ministry of Education, Youth and Sports of the Czech Republic (Grant L01204 from the National Program of Sustainability) and Palacky University institutional support. AM S-L and P G-G gratefully acknowledge predoctoral fellowships from the Spanish Ministry of Science and Innovation. M B and G A acknowledge post-doctoral fellowships awarded by the Public University of Navarra.Peer reviewe

Solving Inaccuracies in Anatomical Models for Electrocardiographic Inverse Problem Resolution by Maximizing Reconstruction Quality

[EN] Electrocardiographic Imaging has become an increasingly used technique for non-invasive diagnosis of cardiac arrhythmias, although the need for medical imaging technology to determine the anatomy hinders its introduction in the clinical practice. This paper explores the ability of a new metric based on the inverse reconstruction quality for the location and orientation of the atrial surface inside the torso. Body surface electrical signals from 31 realistic mathematical models and four AF patients were used to estimate the optimal position of the atria inside the torso. The curvature of the L-curve from the Tikhonov method, which was found to be related to the inverse reconstruction quality, was measured after application of deviations in atrial position and orientation. Independent deviations in the atrial position were solved by finding the maximal L-curve curvature with an error of 1.7 +/- 2.4 mm in mathematical models and 9.1 +/- 11.5 mm in patients. For the case of independent angular deviations, the error in location by using the L-curve was 5.8 +/- 7.1 degrees in mathematical models and 12.4 degrees +/- 13.2 degrees in patients. The ability of the L-curve curvature was tested also under superimposed uncertainties in the three axis of translation and in the three axis of rotation, and the error in location was of 2.3 +/- 3.2 mm and 6.4 degrees +/- 7.1 degrees in mathematical models, and 7.9 +/- 10.7 mm and 12.1 degrees +/- 15.5 degrees in patients. The curvature of L-curve is a useful marker for the atrial position and would allow emending the inaccuracies in its location.This work was supported in part by Generalitat Valenciana under Grant ACIF/2013/021, in part by the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain, under Grant PI13-01882, Grant PI13-00903, Grant PI14/00857, Grant TEC2013-46067-R, and Grant DTS16/00160, in part by the Spanish Society of Cardiology (Grant for Clinical Research in Cardiology 2015), and in part by the Spanish Ministry of Science and Innovation (Red RIC) under Grant PLE2009-0152.Rodrigo Bort, M.; Climent, AM.; Liberos Mascarell, A.; Hernández-Romero, I.; Arenal, A.; Bermejo, J.; Fernández-Avilés, F.... (2018). Solving Inaccuracies in Anatomical Models for Electrocardiographic Inverse Problem Resolution by Maximizing Reconstruction Quality. IEEE Transactions on Medical Imaging. 37(3):733-740. https://doi.org/10.1109/TMI.2017.2707413S73374037

Late Holocene archaeobotanical evolution of the Canale di Imbocco (Roman imperial port of Portus, Central Italy)

The Roman port of Portus was the most important in the Mediterranean during the imperial period (27 BC–476 AD). It wasmade up of an outer port or Claudius basin and an inner hexagon or Trajan's port, joined by the Canale di Imbocco. The archaeobotanical record obtained in a continuos sediment core taken in this channel ismade up of 19 types of plant macroremains, with a predominance of fibers of the seagrass Posidonia oceanica L., replaced by fluvial sediments in the upper part of the core. Seeds, fruits and thorns of aquatic species frommarine or brackish waters, halophyte species, edible species, freshwater riparian vegetation and remains of charcoal and wood also appear regularly. According to the inferred palaeoenviromental evolution of this core, Portus was an area of fluvial-marine interaction during the Roman Empire, with brackish water conditions interrupted by stormy periods deduced from the record of P. oceanica. The archaeobotanical and sedimentary evolution points to a restriction of marine contributions and a final implantation of a fluvial environment. In this evolution, a specific interval with abundant charcoal and caryopses of Triticum could correspond to a fire, which was followed by a possible period of greater construction activity linked with large fragments of wood.This paper was jointly supported by the following projects: a) project DGYCIT CTM2006-06722/MAR; b) DGYCIT project CGL2006-01412; c) “From the Atlantic to the Mediterranean (DEATLANTIR): Research in the infrastructures of Portus-Ostia Antica: the Lanterna wharf” (Programme of Archeology Projects Abroad, Ministry of Culture and Sports); d) From the Atlantic to the Tyrrhenian. Hispanic ports and their commercial relations with Ostia Antica (DEATLANTIR II - HAR2017-89154-P - (National R&D Plan)); and e) FEDER project 2014-2020 UHU-1260298. Other funds come from the research groups HUM-132, RNM-238 and RNM-293 (P.A.I.D.I). It is a contribution to the Center for Research in Historical, Cultural and Natural Heritage of the University of Huelva. The archaeobotanical record is deposited in the Laboratory of Paleontology and Applied Ecology of the University of Huelva

A new roman fish-salting workshop in the Saltes Island (Tinto-Odiel Estuary, SW Spain): La Cascajera and its archaeological and geological context

The southwestern Atlantic coast of the Iberian Peninsula presents an important Roman heritage that includes numerous fish-salting workshops, with an industrial activity that went on for almost a millennium (1st century BC-7th century AD). Nevertheless, a future broad research is still necessary to determine the geologic substratum on which they are based, their palaeoenvironmental evolution, their main economic objectives and the byproducts derived from their activities. This paper is focused on the geology, dating and the archaeological record of La Cascajera, a new site located in the Tinto-Odiel estuary (SW Spain). This new cetaria occupied the northwestern end of La Cascajera ridge (Saltés Island), constituted by sandy, bioclastic deposits of previous washover fans (1st-2th centuries AD). During the main period of activity (middle of 4th century AD-5th century AD), the existence of a certain typology of amphorae as well as the documentation of a shell deposit formed mostly by Glycymeris suggest that this factory was oriented to the production of mixed fish sauces and the handling of edible bivalves. The main features of this deposit (texture, paleontology, taphonomy) could be used to differentiate middens from natural shelly ridges.La costa suratlántica de la Península Ibérica posee un importante legado romano que incluye numerosos talleres halieúticos, con una actividad que se desarrolló durante casi un milenio (siglo I a.C.-siglo VII d.C.). Sin embargo, se precisan nuevas investigaciones que determinen el contexto geológico en el que se desarrollaron, su evolución paleoambiental, sus principales objetivos económicos y los subproductos derivados de sus actividades. Este trabajo se centra en la geología, datación y registro arqueológico de La Cascajera, un nuevo yacimiento localizado en el estuario de los ríos Tinto y Odiel (S.O. de España). Esta nueva cetaria ocupaba el extremo noroccidental de la cresta de La Cascajera (Isla de Saltés), constituida por depósitos bioclásticos arenosos de abanicos de derrame previos (siglos I-II d.C.). Durante su principal periodo de actividad (mitad del siglo IV d.C.-siglo V d.C.), la existencia de una cierta tipología de ánforas así como la existencia de un conchero formado principalmente por Glycymeris sugieren que esta factoría estaba dedicada a la producción de salsas mixtas de pescado y la extracción de bivalvos comestibles. Las principales características de este conchero (textura, paleontología, tafonomía) podrían ser usadas para diferenciar concheros de acumulaciones naturales de conchas.Ministerio de Innovación, Ciencia y Empresa de España. Plan Nacional de I+D+i DEATLANTIR II-HAR2017-89154-PJunta de Andalucía-HUM-132, RNM-238 y RNM-29

Body composition changes after a weight loss intervention: A 3-year follow-up study

Studies comparing different types of exercise-based interventions have not shown a consistent effect of training on long-term weight maintenance. The aim of this study was to compare the effects of exercise modalities combined with diet intervention on body composition immediately after intervention and at 3 years’ follow-up in overweight and obese adults. Two-hundred thirty-nine people (107 men) participated in a 6-month diet and exercise-based intervention, split into four randomly assigned groups: strength group (S), endurance group (E), combined strength and endurance group (SE), and control group (C). The body composition measurements took place on the first week before the start of training and after 22 weeks of training. In addition, a third measurement took place 3 years after the intervention period. A significant interaction effect (group × time) (p = 0.017) was observed for the fat mass percentage. It significantly decreased by 5.48 ± 0.65%, 5.30 ± 0.65%, 7.04 ± 0.72%, and 4.86 ± 0.65% at post-intervention for S, E, SE, and C, respectively. Three years after the intervention, the fat mass percentage returned to values similar to the baseline, except for the combined strength and endurance group, where it remained lower than the value at pre-intervention (p < 0.05). However, no significant interaction was discovered for the rest of the studied outcomes, neither at post-intervention nor 3 years later. The combined strength and endurance group was the only group that achieved lower levels of fat mass (%) at both post-intervention and 3 years after intervention, in comparison with the other groups.This work received financial support from the Ministerio de Ciencia e Innovación, Convocatoria de Ayudas I+D 2008, Proyectos de Investigación Fundamental No Orientada, del VI Plan de Investigación Nacional 2008–2011 (Contract: DEP2008-06354-C04-01). This study is registered at www.clinicaltrials.gov (ID: NCT0111685

Arabidopsis responds to Alternaria alternata volatiles by triggering plastid phosphoglucose isomerase-independent mechanisms

Sánchez-López, Ángela María et al.Volatile compounds (VCs) emitted by phylogenetically diverse microorganisms (including plant pathogens and microbes that do not normally interact mutualistically with plants) promote photosynthesis, growth, and the accumulation of high levels of starch in leaves through cytokinin (CK)-regulated processes. In Arabidopsis (Arabidopsis thaliana) plants not exposed to VCs, plastidic phosphoglucose isomerase (pPGI) acts as an important determinant of photosynthesis and growth, likely as a consequence of its involvement in the synthesis of plastidic CKs in roots. Moreover, this enzyme plays an important role in connecting the Calvin-Benson cycle with the starch biosynthetic pathway in leaves. To elucidate the mechanisms involved in the responses of plants to microbial VCs and to investigate the extent of pPGI involvement, we characterized pPGI-null pgi1-2 Arabidopsis plants cultured in the presence or absence of VCs emitted by Alternaria alternata. We found that volatile emissions from this fungal phytopathogen promote growth, photosynthesis, and the accumulation of plastidic CKs in pgi1-2 leaves. Notably, the mesophyll cells of pgi1-2 leaves accumulated exceptionally high levels of starch following VC exposure. Proteomic analyses revealed that VCs promote global changes in the expression of proteins involved in photosynthesis, starch metabolism, and growth that can account for the observed responses in pgi1-2 plants. The overall data show that Arabidopsis plants can respond to VCs emitted by phytopathogenic microorganisms by triggering pPGI-independent mechanisms.This work was supported by the Comisión Interministerial de Ciencia y Tecnología and Fondo Europeo de Desarrollo Regional, Spain (grant nos. BIO2010–18239 and BIO2013–49125–C2–1–P), by the Government of Navarra (grant no. IIM010491.RI1), by the I-Link0939 project from the Ministerio de Economía y Competitividad, by the Ministry of Education, Youth, and Sports of the Czech Republic (grant no. LO1204 from the National Program of Sustainability), by Palacky University institutional support, by predoctoral fellowships from the Spanish Ministry of Science and Innovation (to A.M.S.-L. and P.G.-G.), and by postdoctoral fellowships from the Public University of Navarra (to M.B. and G.A.).Peer Reviewe