An alternative mechanistic paradigm for the β-Z hydrosilylation of terminal alkynes: The role of acetone as a silane shuttle

The β-Z selectivity in the hydrosilylation of terminal alkynes has been hitherto explained by introduction of isomerisation steps in classical mechanisms. DFT calculations and experimental observations on the system [M(I)2{κ-C,C,O,O-(bis-NHC)}]BF4 (M=Ir (3 a), Rh (3 b); bis-NHC=methylenebis(N-2-methoxyethyl)imidazole-2-ylidene) support a new mechanism, alternative to classical postulations, based on an outer-sphere model. Heterolytic splitting of the silane molecule by the metal centre and acetone (solvent) affords a metal hydride and the oxocarbenium ion [R 3Si - O(CH3)2]+, which reacts with the corresponding alkyne in solution to give the silylation product [R 3Si - CHï£C - R]+. Thus, acetone acts as a silane shuttle by transferring the silyl moiety from the silane to the alkyne. Finally, nucleophilic attack of the hydrido ligand over [R3Si - CHï£C - R]+ affords selectively the β-(Z)- vinylsilane. The β-Z selectivity is explained on the grounds of the steric interaction between the silyl moiety and the ligand system resulting from the geometry of the approach that leads to β-(E)-vinylsilanes. Silanes catch the shuttle: An outer-sphere mechanism that explains the β-Z hydrosilylation of terminal alkynes based on the role of acetone as a silane shuttle is disclosed. Heterolytic splitting of the silane molecule by the metal centre and acetone affords a metal hydride and the oxocarbenium ion [R 3Si - O(CH3)2]+, which reacts with the alkyne in solution to give the silylation product [R3Si - CHï£C - R]+ (see figure). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO/FEDER) (CONSOLIDER INGENIO-2010, CTQ2011-27593 projects, and “Ramón y Cajal” (P.J.S.M.) and “Juan de la Cierva” (M.I.) programmes) and the DGA/FSE (E07).Peer Reviewe

A decade of left atrial appendage closure: from procedural data to long-term clinical benefit

Introducción y objetivos: Conocer el beneficio clínico del cierre percutáneo de la orejuela izquierda (OI) en nuestro medio; en concreto, la reducción de eventos tromboembólicos y hemorrágicos, que permitiría un mejor posicionamiento de esta intervención. Métodos: Estudio retrospectivo que recoge la actividad del cierre de OI en un centro durante 9 años. Se registraron la tasa de éxito del dispositivo y del procedimiento, así como las tasas de eventos tromboembólicos y de hemorragia mayor. Resultados: Se evaluaron 260 procedimientos de cierre de OI en una población con fibrilación auricular no valvular y puntuación en las escalas CHA 2 DS 2 -VASc de 4,3 ± 1,6 y HAS-BLED de 3,7 ± 1,2. El éxito del procedimiento fue del 98,8%, y la tasa de eventos adversos graves en los primeros 7 días fue del 2,3%. Con un seguimiento medio de 2,5 ± 1,9 años y una población de 637,9 pacientes-año, la tasa de eventos tromboembólicos fue de 1,4 por 100 pacientes-año (75,5% de reducción del riesgo) y la de hemorragia mayor fue de 3,0 por 100 pacientes-año (58,5% de reducción del riesgo), ambas significativamente menores que las predichas. Las tasas de eventos por 100 pacientes-año en los pacientes con seguimiento muy largo (más de 4 años) mostraron tendencia a ser menores que en el resto de la población (0,7 frente a 2,0, con p = 0,17, para evento tromboembólico, y 1,7 frente a 4,0, con p = 0,09, para hemorragia mayor). Conclusiones: En nuestra población, el cierre de la OI mostró un elevado éxito del procedimiento y una baja tasa de eventos inmediatos. El cierre de la OI indujo una significativa reducción en la tasa prevista de eventos tromboembólicos y hemorrágicos, y dicha reducción se mantuvo a muy largo plazo.Introduction and objectives: A better positioning of left atrial appendage closure (LAAC) requires assessment of its clinical benefits to reduce thromboembolic and bleeding events in a real-word population. Methods: Single-center retrospective study of our consecutive LAAC activity for 9 years. Both the device success and procedural success were registered as well as the reduction of the expected rates of thromboembolic and major bleeding events. Results: A total of 260 LAAC procedures were performed in a population with nonvalvular atrial fibrillation with CHA2 DS 2 -VASc and HAS-BLED scores of 4.3 ± 1.6 and 3.7 ± 1.2, respectively. Procedural success was 98.8%, and the rate of serious adverse events within the first 7 days was 2.3%. At a median follow-up of 2.5 ± 1.9 years and an estimated population of 637.9 patients-year, the thromboembolic event rate was 1.4 per 100 patients-year (75.5% risk reduction) and the rate of major bleeding was 3.0 per 100 patients-year (58.5% risk reduction), which was significantly lower than anticipated. The thromboembolic and major bleeding events per 100 patients-year showed a lower tendency for patients with very long follow-up (over 4 years) compared to the remaining of the population (0.7 vs 2.0 with P = .17, and 1.7 vs 4.0 with P = .09, respectively)

Iridium-(K2-NSi) catalyzed dehydrogenation of formic acid: effect of auxiliary ligands on the catalytic performance

IThe iridium(III) complexes [Ir(H)(Cl)(κ2-NSitBu2)(κ2-bipyMe2)] (2) and [Ir(H)(OTf)(κ2-NSitBu2)(κ2-bipyMe2)] (3) (NSitBu2 = {4-methylpyridine-2-yloxy}ditertbutylsilyl) have been synthesized and characterized including X-ray studies of 3. A comparative study of the catalytic activity of complexes 2, 3, [Ir(H)(OTf)(κ2-NSitBu2)(coe)] (4), and [Ir(H)(OTf)(κ2-NSitBu2)(PCy3)] (5) (0.1 mol%) as catalysts precursors for the solventless formic acid dehydrogenation (FADH) in the presence of Et3N (40 mol%) at 353 K has been performed. The highest activity (TOF5 min ≈ 3260 h−1) has been obtained with 3 at 373 K. However, at that temperature the FTIR spectra show traces of CO together with the desired products (H2 and CO2). Thus, the best performance was achieved at 353 K (TOF5 min ≈ 1210 h−1 and no observable CO). Kinetic studies at variable temperature show that the activation energy of the 3-catalyzed FADH process is 16.76 kcal mol−1. Kinetic isotopic effect (5 min) values of 1.6, 4.5, and 4.2 were obtained for the 3-catalyzed dehydrogenation of HCOOD, DCOOH, and DCOOD, respectively, at 353 K. The strong KIE found for DCOOH and DCOOD evidenced that the hydride transfer from the C–H bond of formic acid to the metal is the rate-determining step of the process

Hydrolysis and methanolysis of silanes catalyzed by iridium(III) bis-N-heterocyclic carbene complexes: Influence of the wingtip groups

New [Ir(CH3CN)2(I)2{κC,C′-bis(NHC)}]BF4 complexes featuring bis-NHC ligands with a methylene bridge and different N substitution (−CH2CH2CH2CH3 and −CH2CH2OPh) were synthesized. NMR studies and X-ray diffraction structures evidenced that the wingtip group −CH2CH2OPh presents a hemilabile behavior in solution, with the oxygen atom coordinating and dissociating at room temperature, which contrasts with the strong coordination of the ether functions in the complex [Ir(I)2{κC,C′,O,O′-bis(NHCOMe)}]BF4 (bis(NHCOMe) = methylenebis(N,N′-bis(2-methoxyethyl)imidazol-2-ylidene)), previously reported by us. These complexes proved to be efficient catalysts for the hydrolysis and methanolysis of silanes, affording molecular hydrogen and silyl alcohols or silyl ethers as the main reaction products in excellent yields. The hydrogen generation rates were very much dependent on the nature of the hydrosilane and the coordination ability of the wingtip group. The latter also played a key role in the recyclability of the catalytic system.This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO/FEDER) (CONSOLIDER INGENIO CSD2009-0050, CTQ2011-27593 projects, and “Juan de la Cierva” (M.I.) and Ramón y Cajal (P.J.S.M.) programs) and the DGA/FSE-E07. The authors express their appreciation to the support from the Ministry of Higher Education, Saudi Arabia, in establishment of the Center of Research Excellence in Petroleum Refining & Petrochemicals at King Fahd University of Petroleum & Minerals (KFUPM) and the support from KFUPM-University of Zaragoza research agreement.Peer Reviewe

Cold-blooded vertebrates evolved organized germinal center-like structures

Germinal centers (GCs) or analogous secondary lymphoid microstructures (SLMs) are thought to have evolved in endothermic species. However, living representatives of their ectothermic ancestors can mount potent secondary antibody responses upon infection or immunization, despite the apparent lack of SLMs in these cold-blooded vertebrates. How and where adaptive immune responses are induced in ectothermic species in the absence of GCs or analogous SLMs remain poorly understood. Here, we infected a teleost fish (trout) with the parasite Ichthyophthirius multifiliis (Ich) and identified the formation of large aggregates of highly proliferating IgM+ B cells and CD4+ T cells, contiguous to splenic melanomacrophage centers (MMCs). Most of these MMC-associated lymphoid aggregates (M-LAs) contained numerous antigen (Ag)–specific B cells. Analysis of the IgM heavy chain CDR3 repertoire of microdissected splenic M-LAs and non–M-LA areas revealed that the most frequent B cell clones induced after Ich infection were highly shared only within the M-LAs of infected animals. These M-LAs represented highly polyclonal SLMs in which Ag-specific B cell clonal expansion occurred. M-LA–associated B cells expressed high levels of activation-induced cytidine deaminase and underwent significant apoptosis, and somatic hypermutation of Igμ genes occurred prevalently in these cells. Our findings demonstrate that ectotherms evolved organized SLMs with GC-like roles. Moreover, our results also point to primordially conserved mechanisms by which M-LAs and mammalian polyclonal GCs develop and function.publishedVersio

In-hospital postoperative infection after heart transplantation: risk factors and development of a novel predictive score

[Abstract] Introduction: Infection is one of the most significant complications following heart transplantation (HT). The aim of this study was to identify specific risk factors for early postoperative infections in HT recipients, and to develop a multivariable predictive model to identify HT recipients at high risk. Methods: A single-center, observational, and retrospective study was conducted. The dependent variable was in-hospital postoperative infection. We examined demographic and epidemiological data from donors and recipients, surgical features, and adverse postoperative events as independent variables. Backwards, stepwise multivariable logistic regression with a P-value < 0.05 was used to identify clinical factors independently associated with the risk of in-hospital postoperative infections following HT. Results: Six hundred seventy-seven patients were included in this study. During the in-hospital postoperative period, 348 episodes of infection were diagnosed in 239 (35.9%) patients. Seven variables were identified as independent clinical predictors of early postoperative infection after HT: history of diabetes mellitus, previous sternotomy, preoperative mechanical ventilation, primary graft failure, major surgical bleeding, use of mycophenolate mofetil, and use of itraconazole. Based on the results of multivariable models, we constructed a 7-variable (8-point) score to predict the risk of in-hospital postoperative infection in HT recipients, which showed a reasonable ability to predict the risk of in-hospital postoperative infection in this population. Prospective external validation of this new score is warranted to confirm its clinical applicability. Conclusions: In-hospital postoperative infection is a common complication after HT, affecting 35% of patients who underwent this procedure at our institution. Diabetes mellitus, previous sternotomy, preoperative mechanical ventilation, primary graft failure, major surgical bleeding, use of mycophenolate mofetil, and itraconazole were all independent clinical predictors of early postoperative infection after HT

Non-conventional yeasts as hosts for heterologous protein production

Yeasts are an attractive group of lower eukaryotic microorganisms, some of which are used in several industrial processes that include brewing, baking and the production of a variety of biochemical compounds. More recently, yeasts have been developed as host organisms for the production of foreign (heterologous) proteins. Saccharomyces cerevisiae has usually been the yeast of choice, but an increasing number of alternative non-Saccharomyces yeasts has now become accessible for modern molecular genetics techniques. Some of them exhibit certain favourable traits such as high-level secretion or very strong and tightly regulated promoters, offering significant advantages over traditional bakers’ yeast. In the present work, the current status of Kluyveromyces lactis, Yarrowia lipolytica, Hansenula polymorpha and Pichia pastoris (the best-known alternative yeast systems) is reviewed. The advantages and limitations of these systems are discussed in relation to S. cerevisiae

Non-conventional yeasts as hosts for heterologous protein production.

Yeasts are an attractive group of lower eukaryotic microorganisms, some of which are used in several industrial processes that include brewing, baking and the production of a variety of biochemical compounds. More recently, yeasts have been developed as host organisms for the production of foreign (heterologous) proteins. Saccharomyces cerevisiae has usually been the yeast of choice, but an increasing number of alternative non-Saccharomyces yeasts has now become accessible for modern molecular genetics techniques. Some of them exhibit certain favourable traits such as high-level secretion or very strong and tightly regulated promoters, offering significant advantages over traditional bakers' yeast. In the present work, the current status of Kluyveromyces lactis, Yarrowia lipolytica, Hansenula polymorpha and Pichia pastoris (the best-known alternative yeast systems) is reviewed. The advantages and limitations of these systems are discussed in relation to S. cerevisiae.Spanish Society for Microbiolog

CALIFA, the Calar Alto Legacy Integral Field Area survey: IV. Third public data release

This paper describes the third public data release (DR3) of the Calar Alto Legacy Integral Field Area (CALIFA) survey. Science-grade quality data for 667 galaxies are made public, including the 200 galaxies of the second public data release (DR2). Data were obtained with the integral-field spectrograph PMAS/PPak mounted on the 3.5 m telescope at the Calar Alto Observatory. Three different spectral setups are available: i) a low-resolution V500 setup covering the wavelength range 3745-7500 Å (4240-7140 Å unvignetted) with a spectral resolution of 6.0 Å (FWHM) for 646 galaxies, ii) a medium-resolution V1200 setup covering the wavelength range 3650-4840 Å (3650-4620 Å unvignetted) with a spectral resolution of 2.3 Å (FWHM) for 484 galaxies, and iii) the combination of the cubes from both setups (called COMBO) with a spectral resolution of 6.0 Å and a wavelength range between 3700-7500 Å (3700-7140 Å unvignetted) for 446 galaxies. The Main Sample, selected and observed according to the CALIFA survey strategy covers a redshift range between 0.005 and 0.03, spans the color-magnitude diagram and probes a wide range of stellar masses, ionization conditions, and morphological types. The Extension Sample covers several types of galaxies that are rare in the overall galaxy population and are therefore not numerous or absent in the CALIFA Main Sample. All the cubes in the data release were processed using the latest pipeline, which includes improved versions of the calibration frames and an even further improved image reconstruction quality. In total, the third data release contains 1576 datacubes, including ~1.5 million independent spectra. © 2016 ESO.SFS thanks the CONACYT-125180 and DGAPA-IA100815 projects for providing him support in this study. R.G.B., R.G.D., and E.P. are supported by grants AYA2014-57490-P and JA-FQM-2828. SZ is supported by the EU Marie Curie Integration Grant >SteMaGE> No. PCIG12-GA-2012-326466 (Call Identifier: FP7-PEOPLE-2012 CIG). J. F.-B. from grant AYA2013-48226-C3-1-P from the Spanish Ministry of Economy and Competitiveness (MINECO), as well as from the FP7 Marie Curie Actions of the European Commission, via the Initial Training Network DAGAL under REA grant agreement 289313 B.G-L- acknowledges financial support by the Spanish MINECO under grants AYA2013-41656-P and AYA2015-68217-P Support for L.G. is provided by the Ministry of Economy, Development, and Tourism's Millennium Science Initiative through grant IC12009, awarded to The Millennium Institute of Astrophysics, MAS. L.G. also acknowledges support by CONICYT through FONDECYT grant 3140566, and AYA2013-42227-P from the Spanish Ministerio de Ciencia e Innovacion and TIC 114 and PO08-TIC-3531 from Junta de Andalucia. AG acknowledges support from the FP7/2007-2013 under grant agreement no. 267251 (AstroFIt). RAM was funded by the Spanish programme of International Campus of Excellence Moncloa (CEI). JMA acknowledges support from the European Research Council Starting Grant (SEDmorph; P.I. V. Wild). I.M. and A.d.O. acknowledge the support by the projects AYA2010-15196 from the Spanish Ministerio de Ciencia e Innovacion and TIC 114 and PO08-TIC-3531 from Junta de Andalucia. AMI acknowledges support from Agence Nationale de la Recherche through the STILISM project (ANR-12-BS05-0016-02). M.M. acknowledges financial support from AYA2010-21887-004-02 from the Ministerio de Economia y Competitividad. PSB acknowledges support from the Ramon y Cajal program, grant ATA2010-21322-C03-02 from the Spanish Ministry of Economy and Competitiveness (MINECO). C.J.W. acknowledges support through the Marie Curie Career Integration Grant 303912. V.W. acknowledges support from the European Research Council Starting Grant (SEDMorph P.I. V. Wild) and European Career Re-integration Grant (Phiz-Ev P.I. V. Wild). YA acknowledges financial support from the Ramon y Cajal programme (RyC-2011-09461) and project AYA2013-47742-C4-3-P, both managed by the Ministerio de Economia y Competitividad, as well as the >Study of Emission-Line Galaxies with Integral Field Spectroscopy> (SELGIFS) programme, funded by the EU (FP7-PEOPLE-2013-IRSES-612701) within the Marie-Sklodowska-Curie Actions scheme. ROM acknowledges support from CAPES (Brazil) through a PDJ fellowship from project 88881.030413/2013-01, program CSF-PVE.Peer Reviewe

Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer

[Abstract] Background. MicroRNAs are aberrantly expressed and correlate with tumourigenesis and the progression of solid tumours. The miR-200 family determines the epithelial phenotype of cancer cells and regulates invasiveness and migration. Thus, we hypothesised that the quantitative detection of the miR-200 family as epithelial-specific microRNAs in the blood could be a useful clinical biomarker for gastric cancer (GC). Methods. We initially validated the expression levels of miR-200a, 200b, 200c and 141 in GC cell lines (n = 2) and blood from healthy controls (n = 19) using real-time quantitative reverse transcription PCR (qRT-PCR). The microarray expression profiles of the miR-200 family in 160 paired samples of non-tumour gastric mucosae and GC were downloaded through ArrayExpress and analysed. MiR-200c was selected for clinical validation. The qRT-PCR prospective assessment of miR-200c was performed using 67 blood samples (52 stage I-IV GC patients and 15 controls); the area under the receiver operating characteristic curve (AUC-ROC) was estimated. The Kaplan-Meier and Breslow-Wilcoxon tests were used to assess the correlation of miR-200c with overall and progression-free survival (OS and PFS). Multivariate analyses were performed using the Cox model. Results. The miR-200c blood expression levels in GC patients were significantly higher than in normal controls (p = 0.018). The AUC-ROC was 0.715 (p = 0.012). The sensitivity, specificity and accuracy rates of 65.4%, 100% and 73.1%, respectively, were observed. The levels of miR-200c in the blood above the cutoff defined by the ROC curve was found in 17.6% of stage I-II GC patients, 20.6% of stage III patients and 67.7% of stage IV patients (p < 0.001). The miR-200c expression levels were not associated with clinical or pathological characteristics or recent surgical procedures. There was a correlation (p = 0.016) with the number of lymph node metastases and the increased expression levels of miR-200c in blood were significantly associated with a poor OS (median OS, 9 vs 24 months; p = 0.016) and PFS (median PFS, 4 vs 11 months; p = 0.044). Multivariate analyses confirmed that the upregulation of miR-200c in the blood was associated with OS (HR = 2.24; p = 0.028) and PFS (HR = 2.27; p = 0.028), independent of clinical covariates. Conclusions. These data suggest that increased miR-200c levels are detected in the blood of gastric cancer patients. MiR-200c has the potential to be a predictor of progression and survival.Instituto de Salud Carlos III; PI061541Xunta de Galicia; PS08/7