Visible-light-promoted iridium(III)-catalyzed acceptorless dehydrogenation of N-Heterocycles at room temperature

An effective visible-light-promoted iridium(III)catalyzed hydrogen production from N-heterocycles is described. A single iridium complex constitutes the photocatalytic system playing a dual task, harvesting visible-light and facilitating C-H cleavage and H-2 formation at room temperature and without additives. The presence of a chelating C-N ligand combining a mesoionic carbene ligand along with an amido functionality in the Ir-III complex is essential to attain the photocatalytic transformation. Furthermore, the le l complex is also an efficient catalyst for the thermal reverse process under mild conditions, positioning itself as a proficient candidate for liquid organic hydrogen carrier technologies (LOHCs). Mechanistic studies support a light-induced formation of H-2 from the Ir-H intermediate as the operating mode of the iridium complex

Lean mass explains the association between muscular fitness and bone outcomes in 13-year-old boys

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record AIM: This study investigated the associations between fitness indices and bone outcomes in young males. METHODS: Data were collected between autumn and winter 2014-2015 on 121 males with a mean age of 13.1 ± 0.1 years: 41 swimmers, 37 footballers, 29 cyclists and 14 nonathletes. Participants were recruited from athletic clubs and schools across South West England. Lean mass, areal bone mineral density and hip structural estimates were measured using dual-energy X-ray absorptiometry. The relationships between bone outcomes and the vertical jump, standing long jump and the 20-m shuttle run test were analysed using three regression models: model 1 was adjusted by age and stature, model 2 added vigorous physical activity and model 3 then added lean mass. RESULTS: The boys' performance in the vertical jump and standing long jump was positively associated with the majority of bone outcomes in models 1 and 2, but most of these disappeared in model 3. The 20-m shuttle run test was positively associated with most bone outcomes in all three models. Lean mass played a key role in the association between muscular fitness and bone outcomes. CONCLUSION: Vigorous physical activity did not explain the associations between fitness and bone outcomes, but lean mass did.European Union Seventh Framework Programme (FP7/2007–2013

Acidosis: The Prime Determinant of Depressed Sensorium in Diabetic Ketoacidosis

OBJECTIVE — The etiology of altered sensorium in diabetic ketoacidosis (DKA) remains unclear. Therefore, we sought to determine the origin of depressed consciousness in DKA. RESEARCH DESIGN AND METHODS — We analyzed retrospectively clinical and biochemical data of DKA patients admitted in a community teaching hospital. RESULTS — We recorded 216 cases, 21 % of which occurred in subjects with type 2 diabetes. Mean serum osmolality and pH were 304 31.6 mOsm/kg and 7.14 0.15, respectively. Acidosis emerged as the prime determinant of altered sensorium, but hyperosmolarity played a synergistic role in patients with severe acidosis to precipitate depressed sensorium (odds ratio 2.87). Combination of severe acidosis and hyperosmolarity predicted altered consciousness with 61 % sensitivity and 87 % specificity. Mortality occurred in 0.9 % of the cases. CONCLUSIONS — Acidosis was independently associated with altered sensorium, but hy-perosmolarity and serum “ketone ” levels were not. Combination of hyperosmolarity and acidosis predicted altered sensorium with good sensitivity and specificity. Diabetes Care 33:1837–1839, 2010 D iabetic ketoacidosis (DKA) is fre-quently associated with alteredmental status, which is correlated with the severity of the disease and prog-nosis (1). However, the etiology of de-pressed sensorium in DKA remains uncertain and controversial (2,3). Puta-tive factors in the pathogenesis of diabetic ketoacidotic coma include cerebral hypo-perfusion due to circulatory collapse and cerebral thrombosis (4), reduced cerebral glucose and oxygen utilization (1,5), aci-dosis (6,7), hyperosmolarity (8,9), and direct toxic effect of ketone bodies (2). Cerebral edema remains an important precipitant of altered consciousness in DKA, especially in children. Different studies have yielded con-flicting results regarding the role of these etiologic factors in the pathogenesis of al-tered mentation in patients with DKA. Hence, the origin of clouded sensorium in DKA remains to be fully elucidated. We undertook to study the etiology of de-pressed consciousness in patients admit-ted with DKA at the Regional Medica

Regulation of membrane ruffling by polarized STIM1 and ORAI1in cortactin-rich domains

La movilidad celular y la migración requieren la reorganización del citoesqueleto cortical en el borde principal de las células y la entrada de Ca2 + extracelular es esencial para esta reorganización. Sin embargo, la naturaleza molecular de los reguladores de esta vía es desconocida. Este trabajo contribuye a comprender el papel de STIM1 y ORAI1 en la promoción de la ondulación de la membrana al mostrar que la fosfo-STIM1 se localiza en el borde principal de las células, y que tanto phospho-STIM1 como ORAI1 se localizan conjuntamente con la cortactina (CTTN), un regulador del citoesqueleto en las zonas de rizo de la membrana. Las líneas celulares STIM1-KO y ORAI1-KO se generaron mediante la edición del genoma CRISPR / Cas9 en células U2OS. En ambos casos, las células KO presentaron una reducción notable de la entrada de Ca2 + operada por el almacén (SOCE) que se rescató mediante la expresión de STIM1-mCherry y ORAI1-mCherry. Estos resultados demostraron que SOCE regula la deformación de la membrana en el borde anterior de las células. Por otra parte, ORAI1 endógeno y ORAI1-GFP sobreexpresado coinmuno precipitado con CTTN endógeno. Este último resultado, además del fenotipo de las células KO, la preservación de la co-localización de ORAI1-CTTN durante el fruncido, y la inhibición de la rizo de la membrana por parte del inhibidor del canal de Ca2 + SKF96365, apoya aún más un vínculo funcional entre el SOCE y el fruncido de la membrana.Cell motility and migration requires the reorganization of the cortical cytoskeleton at the leading edge of cells and extracellular Ca2+ entry is essential for this reorganization. However the molecular nature of the regulators of this pathway is unknown. This work contributes to understanding the role of STIM1 and ORAI1 in the promotion of membrane ruffling by showing that phospho-STIM1 localizes at the leading edge of cells, and that both phospho-STIM1 and ORAI1 co-localize with cortactin (CTTN), a regulator of the cytoskeleton at membrane ruffling areas. STIM1-KO and ORAI1-KO cell lines were generated by CRISPR/Cas9 genome editing in U2OS cells. In both cases, KO cells presented a notable reduction of store-operated Ca2+ entry (SOCE) that was rescued by expression of STIM1-mCherry and ORAI1-mCherry. These results demonstrated that SOCE regulates membrane ruffling at the leading edge of cells. Moreover, endogenous ORAI1 and overexpressed ORAI1-GFP co-immuno precipitated with endogenous CTTN. This latter result, in addition to the KO cells’ phenotype, the preservation of ORAI1-CTTN co-localization during ruffling, and the inhibition of membrane ruffling g by the Ca2+- channel inhibitor SKF96365, further supports a functional link between SOCE and membrane ruffling.• Ministerio de Economía y Competitividad y Fondo Social Europeo. Becas BFU2011-22798 y BFU2014-52401-P, para Francisco Javier Martín Romero • Consejo de Investigación Médica. Beca MC_UU_12016 / 2, para Darío R. Alessi • Ministerio de Economía y Competitividad. Beca BES-2012-052061, para Aida María López Guerrero • Gobierno de Extremadura. Ayuda PD10081, para Patricia Tomás Martín • Ministerio de Educación, Cultura y Deporte. Beca FPU13 / 03430, para Carlos Pascual Caro • Consejo de Investigación Médica. Ayuda MR / K015869 / 1, para Graeme Ball • EMBO. Beca ASTF-311-2014, para Eulalia Pozo Guisado • Ministerio de Educación, Cultura Española y Deporte. Beca PRX14 / 00176, para Francisco Javier Martín RomeropeerReviewe

Economic values for ecosystem services:A global synthesis and way forward

This paper presents a global synthesis of economic values for ecosystem services provided by 15 terrestrial and marine biomes. Information from over 1,300 studies, yielding over 9,400 value estimates in monetary units, has been collected and organised in the Ecosystem Services Valuation Database (ESVD). This is a substantial expansion of data since the de Groot et al. (2012) description of the ESVD and provides an important juncture to explore developments in the use of valuation methods and the contexts in which valuations are conducted. In this paper we provide summary values for 23 ecosystem services from 15 biomes to represent the magnitude, variation and gaps in economic values. To enable the comparison and synthesis of values, estimates in the ESVD are standardised to a common set of units (Int$/ha/year at 2020 price levels). This data provides a basis for value transfers to inform decision-making in current policy contexts but requires due consideration and adjustment for context specific determinants of value. Although the coverage of the ESVD is global, the geographic distribution of data is not even. There is a particularly high representation of European ecosystems and relatively little information for Russia, Central Asia and North Africa. Therefore, the data are not globally representative of biophysical and socio-economic contexts. The distribution of data across ecosystem services is also far from even, with some services very well represented (e.g. recreation, wild fish and wild animals, ecosystem and species appreciation, air filtration and global climate regulation) and others with almost no value estimates (e.g. disease control, water baseflow maintenance, rainfall pattern regulation). In the past decade, there has been a notable increase in demand for information on the economic value of ecosystem services from both public and private institutions to improve the conservation and management of natural capital. The literature is developing to meet this demand but there is a need for targeted and refined valuation research to ensure sufficient certainty, comparability, and representativeness of the data, and to enable transferability and fill knowledge gaps. This paper concludes by identifying avenues for future development to further increase the amount, quality, representativeness and application of data on economic values for ecosystem services.</p

2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart

2-Deoxy-D-glucose (2DG) has recently received emergency approval for the treatment of COVID-19 in India, after a successful clinical trial. SARS-CoV-2 infection of cultured cells is accompanied by elevated glycolysis and decreased mitochondrial function, whereas 2DG represses glycolysis and stimulates respiration, and restricts viral replication. While 2DG has pleiotropic effects on cell metabolism in cultured cells it is not known which of these manifests in vivo. On the other hand, it is known that 2DG given continuously can have severe detrimental effects on the rodent heart. Here, we show that the principal effect of an extended, intermittent 2DG treatment on mice is to augment the mitochondrial respiratory chain proteome in the heart; importantly, this occurs without vacuolization, hypertrophy or fibrosis. The increase in the heart respiratory chain proteome suggests an increase in mitochondrial oxidative capacity, which could compensate for the energy deficit caused by the inhibition of glycolysis. Thus, 2DG in the murine heart appears to induce a metabolic configuration that is the opposite of SARS-CoV-2 infected cells, which could explain the compound's ability to restrict the propagation of the virus to the benefit of patients with COVID-19 disease

Renal (Uremic) Encephalopathy in a Goat

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72407/1/j.1439-0442.2005.00752.x.pd

Factors associated with the development of septic shock in patients with candidemia: A post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms