Caracterización energética de la unión de 1,3,6- naftalén trisulfonato al factor de crecimiento para fibroblastos ácido humano: implicaciones para su uso como agente anti-angiogénico

The equilibrium interaction of anti-cancer agent 1,3,6-naphatalene trisulfonate with human acidic fi broblast growthfactor has been studied by calorimetry. The affi nity decreases with increasing ionic strength. At pH 7.0 and 0.15 MNaCl concentration, a binding constant of the protein with the ligand was estimated in the 102 – 103 M-1 range, anaffi nity two orders of magnitude lower than that of aFGF with heparin. The interaction is enthalpically driven, andthe entropy change is unfavorable. A small heat capacity change with an unusual positive value of 90 cal K-1mol-1 wasdetermined from the temperature dependence of the enthalpies. Changes in accessible apolar and polar surface areasin the interaction were calculated from the thermodynamic data obtained and parametric equations in the literature.The results were compared with those measured from NMR data. The study includes structural bioenergetic considerationsabout the possible use of 1,3,6-naphatalene trisulfonate as an anti-angiogenic agent itself, or as a lead for thedevelopment of anti-angiogenic drugs.Se ha estudiado, mediante calorimetría isotérmica de reacción, la interacción del agente anticancerígeno 1,3,6-naftaléntrisulfonato con el factor de crecimiento para fi broblastos ácido humano. La afi nidad decrece con el aumento de lafuerza iónica. A pH 7,0 y NaCl 0,15 M, la constante de unión de la proteína con el ligando se encuentra en el rango102 – 103 M-1, una afi nidad dos órdenes de magnitud menor que la del FGFa por heparina. El cambio de entalpíafavorece la interacción, siendo el cambio de entropía desfavorable. De la dependencia del cambio de entalpía con latemperatura se calculó un pequeño cambio en la capacidad calorífi ca del proceso, con un valor excepcionalmentepositivo de 90 cal K-1mol-1. A partir de los datos termodinámicos medidos y de ecuaciones paramétricas establecidasen la literatura, se calcularon cambios en la superfi cie accesible al disolvente, tanto polar como apolar, que acompañana la interacción. Los resultados se compararon con los medidos mediante resonancia magnética nuclear. Elestudio incluye consideraciones de bioenergética estructural sobre el posible uso de 1,3,6-naftalén trisulfonato comoagente antiangiogénico o como molécula líder para el desarrollo de fármacos anti-angiogénicos

Proteasome Dysfunction Associated to Oxidative Stress and Proteotoxicity in Adipocytes Compromises Insulin Sensitivity in Human Obesity

AIMS: Obesity is characterized by a low-grade systemic inflammatory state and adipose tissue (AT) dysfunction, which predispose individuals to the development of insulin resistance (IR) and metabolic disease. However, a subset of obese individuals, referred to as metabolically healthy obese (MHO) individuals, are protected from obesity-associated metabolic abnormalities. Here, we aim at identifying molecular factors and pathways in adipocytes that are responsible for the progression from the insulin-sensitive to the insulin-resistant, metabolically unhealthy obese (MUHO) phenotype. RESULTS: Proteomic analysis of paired samples of adipocytes from subcutaneous (SC) and omental (OM) human AT revealed that both types of cells are altered in the MUHO state. Specifically, the glutathione redox cycle and other antioxidant defense systems as well as the protein-folding machinery were dysregulated and endoplasmic reticulum stress was increased in adipocytes from IR subjects. Moreover, proteasome activity was also compromised in adipocytes of MUHO individuals, which was associated with enhanced accumulation of oxidized and ubiquitinated proteins in these cells. Proteasome activity was also impaired in adipocytes of diet-induced obese mice and in 3T3-L1 adipocytes exposed to palmitate. In line with these data, proteasome inhibition significantly impaired insulin signaling in 3T3-L1 adipocytes. INNOVATION: This study provides the first evidence of the occurrence of protein homeostasis deregulation in adipocytes in human obesity, which, together with oxidative damage, interferes with insulin signaling in these cells. CONCLUSION: Our results suggest that proteasomal dysfunction and impaired proteostasis in adipocytes, resulting from protein oxidation and/or misfolding, constitute major pathogenic mechanisms in the development of IR in obesity.IMIBIC/Universidad de Córdoba-SCAI (ProteoRed, PRB2-ISCIII)MINECO/FEDERJunta de Andalucía/FEDERCIBERobn(Instituto de Salud Carlos III

Agroecosystem energy transitions in the old and new worlds: trajectories and determinants at the regional scale

Energy efficiency in biomass production is a major challenge for a future transition to sustainable food and energy provision. This study uses methodologically consistent data on agroecosystem energy flows and different metrics of energetic efficiency from seven regional case studies in North America (USA and Canada) and Europe (Spain and Austria) to investigate energy transitions in Western agroecosystems from the late nineteenth to the late twentieth centuries. We quantify indicators such as external final energy return on investment (EFEROI, i.e., final produce per unit of external energy input), internal final EROI (IFEROI, final produce per unit of biomass reused locally), and final EROI (FEROI, final produce per unit of total inputs consumed). The transition is characterized by increasing final produce accompanied by increasing external energy inputs and stable local biomass reused. External inputs did not replace internal biomass reinvestments, but added to them. The results were declining EFEROI, stable or increasing IFEROI, and diverging trends in FEROI. The factors shaping agroecosystem energy profiles changed in the course of the transition: Under advanced organic and frontier agriculture of the late nineteenth and early twentieth centuries, population density and biogeographic conditions explained both agroecosystem productivity and energy inputs. In industrialized agroecosystems, biogeographic conditions and specific socio-economic factors influenced trends towards increased agroecosystem specialization. The share of livestock products in a region's final produce was the most important factor determining energy returns on investment

A Biradical Balancing Act: Redox Amphoterism in a Diindenoanthracene Derivative Results from Quinoidal Acceptor and Aromatic Donor Motifs

The reduced and oxidized states of an open-shell diindeno­[<i>b,i</i>]­anthracene (<b>DIAn</b>) derivative have been investigated by experimental and theoretical techniques. As a result of moderate biradical character and the ability of cyclopenta-fused scaffolds to stabilize both positive and negative charges, <b>DIAn</b> exhibits rich redox chemistry with four observable and isolable charged states. Structural and electronic properties of the <b>DIAn</b> system are brought to light by UV–vis–NIR and Raman spectroelectrochemical measurements. Aromatization of the diindeno-fused anthracene core upon successive single-electron injections is revealed through single-crystal X-ray diffraction of radical anion and dianion salts. We present a rare case where the pseudoaromatic/quinoidal ground state of a neutral biradical polycyclic hydrocarbon leads to a stable cascade of five redox states. Our detailed investigation of the transformation of molecular structure along all four redox events provides a clearer understanding of the nature of charge carriers in ambipolar organic field-effect transistors

Acceptance of near-natural greenspace management relates to ecological and socio-cultural assigned values among European urbanites

Grasslands are widespread elements of urban greenspace providing recreational, psychological and aesthetic benefits to city residents. Two urban grassland types of contrasting management dominate urban greenspaces: frequently mown, species-poor short-cut lawns and less intensively managed, near-natural tall-grass meadows. The higher conservation value of tall-grass meadows makes management interventions such as converting short-cut lawns into tall-grass meadows a promising tool for urban biodiversity conservation. The societal success of such interventions, however, depends on identifying the values urban residents assign to different types of urban grasslands, and how these values translate to attitudes towards greenspace management. Using 2027 questionnaires across 19 European cities, we identify the assigned values that correlate with people's personal greenspace use and their preferences for different types of urban grasslands to determine how these values relate to the agreement with a scenario of converting 50 of their cities� short-cut lawns into tall-grass meadows. We found that most people assigned nature-related values, such as wildness, to tall-grass meadows and utility-related values, such as recreation, to short-cut lawns. Positive value associations of wildness and species richness with tall-grass meadows, and social and nature-related greenspace activities, positively correlated with agreeing to convert short-cut lawns into tall-grass meadows. Conversely, disapproval of lawn conversion correlated with positive value associations of cleanliness and recreation potential with short-cut lawns. Here, people using greenspaces for nature-related activities were outstandingly positive about lawn conversion. The results show that the plurality of values assigned to different types of urban grasslands should be considered in urban greenspace planning. For example, tall-grass meadows could be managed to also accommodate the values associated with short-cut lawns, such as tidiness and recreation potential, to support their societal acceptance

COVID-19 outbreaks in a transmission control scenario: challenges posed by social and leisure activities, and for workers in vulnerable conditions, Spain, early summer 2020

Severe acute respiratory syndrome coronavirus 2 community-wide transmission declined in Spain by early May 2020, being replaced by outbreaks and sporadic cases. From mid-June to 2 August, excluding single household outbreaks, 673 outbreaks were notified nationally, 551 active (>6,200 cases) at the time. More than half of these outbreaks and cases coincided with: (i) social (family/friends’ gatherings or leisure venues) and (ii) occupational (mainly involving workers in vulnerable conditions) settings. Control measures were accordingly applied

patrimonio intelectual

Actas de congresoLas VI Jornadas se realizaron con la exposición de ponencias que se incluyeron en cuatro ejes temáticos, que se desarrollaron de modo sucesivo para facilitar la asistencia, el intercambio y el debate, distribuidos en tres jornadas. Los ejes temáticos abordados fueron: 1. La enseñanza como proyecto de investigación. Recursos de enseñanza-aprendizaje como mejoras de la calidad educativa. 2. La experimentación como proyecto de investigación. Del ensayo a la aplicabilidad territorial, urbana, arquitectónica y de diseño industrial. 3. Tiempo y espacio como proyecto de investigación. Sentido, destino y usos del patrimonio construido y simbólico. 4. Idea constructiva, formulación y ejecución como proyecto de investigación. Búsqueda y elaboración de resultados que conforman los proyectos de la arquitectura y el diseño

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Participatory research in agroecology: a tool for sustainable development

La agricultura, tanto a escala mundial como de la Unión Europea, está sumida en una grave crisis, que tiene su origen en una compleja trama de problemas sociales (desempleo, envejecimiento de la población rural...), económicos (incremento de los costes de producción, pérdida de renta agraria...) y ecológicos (contaminación de agua, polución del aire, erosión del suelo...). En este contexto, la Agroecología se postula como un paradigma científico que puede de forma efectiva mejorar la sustentabilidad agraria. Para ello, los investigadores necesitan herramientas metodológicas de carácter sistémico que logren movilizar a la población rural en la resolución de tales problemas. En este sentido, dos metodologías complementarias, se han destacado en el ámbito de la investigación en Agroecología, una de ellas es el MESMIS, que se puede enmarcar dentro del Análisis de Sistemas Agrarios, y la otra es la Investigación Acción Participativa. Los aportes de la primera se materializan sobre todo a escala de finca o unidad de manejo, mientras que la segunda se postula como un marco metodológico que articula diferentes niveles jerárquicos (finca, sociedad local y sociedad mayor) en un proceso de cambio que introduce en el análisis la dimensión temporal. Este artículo presenta y discute brevemente los orígenes, aportes y limitaciones de ambas propuestas metodológicas, ofreciendo numerosas referencias bibliográficas para facilitar a los lectores interesados una mayor profundización en la temática tratada.Agriculture is in crisis in the European Union and worldwide. This crisis stems from a complex plot of social (unemployment, rural population ageing...), economic (increasing production costs, agrarian income losses...), and ecological (water and air pollution, soil erosion...) problems. In this context, Agroecology is presented as a scientific paradigm that effectively improves agricultural sustainability. Therefore, researchers need methodological tools of systemic nature to mobilise rural population in order to solve such problems. In this respect, two complementary methodologies stand out within the researching realm of Agroecology: the MESMIS methodology, framed within the Analysis of Agrarian Systems, and the Participatory Action Research. The contributions of the first one mainly materialize at farm or management unit scale, whereas the second one is a methodological framework that articulates different hierarchical levels –farm, local society and major society– within a process of change that introduces time dimension in the analysis. In this article, we present and discuss the origin, contributions and limitations of both methodological proposals, offering numerous bibliographical references to study these themes in depth