Mechanism of Alkyl Migration in Diorganomagnesium 2,6-Bis(imino)pyridine Complexes: Formation of Grignard-Type Complexes with Square-Planar Mg(II) Centers

Dialkylmagnesium compounds [MgR2L2] (R = n-Bu, L = none or R = Bn, L = THF) react with 2,6-bis(imino)pyridines (BIP) to afford different types of Mg(II) alkyl complexes, depending on the nature of R. For R = n-Bu, thermally stable products resulting from selective alkyl transfer to the pyridine nitrogen (N1) atom are obtained. However, NMR studies showed that the reaction of [Mg(Bn)2THF2] with iPrBIP at −65 °C leads to a thermally unstable product arising from benzyl migration to position C2 in the pyridine ring. Above +5 °C, this compound rearranges, cleanly yielding a mixture of two isomeric complexes, in which the benzyl group has migrated to positions C3 or C4 of the central ring, respectively. Similar isomeric mixtures were obtained when [Mg(Bn)2THF2] was reacted with iPrBIP or MesBIP at room temperature. Such mixtures are thermally stable below 80 °C, but at this temperature, the 3-benzyl isomer converts into the thermodynamically favored 4-benzyl product, albeit not quantitatively. An alternate route was devised for the selective syntheses of the latter type of compounds. The X-ray diffraction structure of one of them provided an unusual example of a square-planar alkylmagnesium(II) center.Ministerio de Economía e Innovación CTQ2015-68978-

Oxygen-Induced Dimerization of Alkyl-Manganese(II) 2,6-Bisiminopyridine Complexes: Selective Synthesis of a New Ditopic NNN-Pincer Ligand

The outcome of the reaction of manganese(II) dialkyls with 2,6-bisiminopyridine (BIP) ligands is dramatically altered by the presence of very small amounts of oxygen (< 0.5 mol %), leading to binuclear species. These arise from the dimerization of the initial product, a Mn(II) 4-alkyl-2,6-bisiminodihydropyridinate alkyl complex. Cleavage of the binuclear Mn products with methanol affords the free dimeric bases, which can be regarded as a special type of ditopic NNN pincer ligand with an unusual tricyclic framework. The coordinative ability of the new ligands has been probed with the syntheses of Zn and Pd organometallic derivativesMinisterio de Economía e Innovación TQ2015- 68978-

External Validation in Northwest Spain of a Decision Support System for Grazing Dairy Cows (Grazemore)

A model to predict intake and milk production of cows on grazed grass (Grazemore) was developed (Mayne et al., 2004) for farmers to increase reliance on the grassland resources of the farm and reduce the tendency towards intensive dairy production in most countries of the Atlantic Arc of Europe (González, 2003). Climatic conditions and fertiliser use is the basis of the herbage growth model, but under practical conditions the estimation of the nutrient supply to cows is much affected by management, number of cows and the area of each paddock grazed. The intake capacity of the animal and the ingestibility of the feeds drive the herbage intake model, considering cow characteristics, pregnancy, body condition and stage of lactation, as well as supplementation (concentrates and forages) at grazing. The decision support system (DSS) fits both models to farm conditions and it is now at the farm validation phase in the six EU countries involved

Approaching In Vivo Models of Pneumococcus–Host Interaction: Insights into Surface Proteins, Capsule Production, and Extracellular Vesicles

Infections caused by the Gram-positive bacterium Streptococcus pneumoniae have become a major health problem worldwide because of their high morbidity and mortality rates, especially in developing countries. This microorganism colonizes the human upper respiratory tract and becomes pathogenic under certain circumstances, which are not well known. In the interaction with the host, bacterial surface structures and proteins play major roles. To gain knowledge into gradual changes and adaptive mechanisms that this pathogen undergoes from when it enters the host, we mimicked several in vivo situations representing interaction with epithelial and macrophage cells, as well as a condition of presence in blood. Then, we analyzed, in four pneumococcal strains, two major surface structures, the capsule and extracellular vesicles produced by the pneumococci, as well as surface proteins by proteomics, using the “shaving” approach, followed by LC-MS/MS. We found important differences in both surface ultrastructures and proteins among the culture conditions and strains used. Thus, this work provides insights into physiological adaptations of the pneumococcus when it interacts with the host, which may be useful for the design of strategies to combat infections caused by this pathogen

Editorial: Role of Nrf2 in disease: Novel molecular mechanisms and therapeutic approaches

This is supported by FIS/FEDER CP14/00008, CP16/00014, CP16/00017, PI15/00448, PI16/00735, PI16/02057, PI17/00130, Spanish Ministry of Economy and Competitiveness (RYC-2017- 22369), Sociedad Española de Nefrología, Fundacion Renal Iñigo Álvarez de Toledo (FRIAT). Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)

Shards: An optical spectro-photometric survey of distant galaxies

Pérez-González et al.We present the Survey for High-z Absorption Red and Dead Sources (SHARDS), an ESO/GTC Large Program carried out using the OSIRIS instrument on the 10.4 m Gran Telescopio Canarias (GTC). SHARDS is an ultra-deep optical spectro-photometric survey of the GOODS-N field covering 130 arcmin2 at wavelengths between 500 and 950 nm with 24 contiguous medium-band filters (providing a spectral resolution R ∿ 50). The data reach an AB magnitude of 26.5 (at least at a 3σ level) with sub-arcsec seeing in all bands. SHARDS' main goal is to obtain accurate physical properties of intermediate- and high-z galaxies using well-sampled optical spectral energy distributions (SEDs) with sufficient spectral resolution to measure absorption and emission features, whose analysis will provide reliable stellar population and active galactic nucleus (AGN) parameters. Among the different populations of high-z galaxies, SHARDS' principal targets are massive quiescent galaxies at z > 1, whose existence is one of the major challenges facing current hierarchical models of galaxy formation. In this paper, we outline the observational strategy and include a detailed discussion of the special reduction and calibration procedures which should be applied to the GTC/OSIRIS data. An assessment of the SHARDS data quality is also performed. We present science demonstration results on the detection and study of emission-line galaxies (star-forming objects and AGNs) at z = 0-5. We also analyze the SEDs for a sample of 27 quiescent massive galaxies with spectroscopic redshifts in the range 1.0 < z ≲ 1.4. We discuss the improvements introduced by the SHARDS data set in the analysis of their star formation history and stellar properties. We discuss the systematics arising from the use of different stellar population libraries, typical in this kind of study. Averaging the results from the different libraries, we find that the UV-to-MIR SEDs of the massive quiescent galaxies at z = 1.0-1.4 are well described by an exponentially decaying star formation history with scale Ï„ = 100-200 Myr, age around 1.5-2.0 Gyr, solar or slightly sub-solar metallicity, and moderate extinction, A(V) ∿ 0.5 mag. We also find that galaxies with masses above M* are typically older than lighter galaxies, as expected in a downsizing scenario of galaxy formation. This trend is, however, model dependent, i.e., it is significantly more evident in the results obtained with some stellar population synthesis libraries, and almost absent in others. © 2013. The American Astronomical Society. All rights reserved.We acknowledge support from the Spanish Programa Nacional de Astronomía y Astrofísica under grants AYA2009-07723-E and AYA2009-10368. SHARDS has been funded by the Spanish MICINN/MINECO under the Consolider-Ingenio 2010 Program grant CSD2006-00070: First Science with the GTC. O.G.-M., C.M.-T., J.M.R.-E., and J.R.-Z. wish to acknowledge support from grant AYA2010-21887-C04-04. A.A.-H. and A.H.-C. acknowledge financial support from the Universidad de Cantabria through the Augusto G. Linares Program.Peer Reviewe

All-trans retinoic acid inhibits migration and invasiveness of rheumatoid fibroblast-like synoviocytes

[Abstract] Fibroblast-like synoviocytes (FLSs) are pivotal in inflammation and joint damage of rheumatoid arthritis (RA). They acquire an active and aggressive phenotype, displaying increased migration and invasiveness and contributing to perpetuate synovial inflammation and destruction of cartilage and bone. The main current therapies of RA are focused against inflammatory factors and immune cells; however, a significant percentage of patients do not successfully respond. Combined treatments with drugs that control inflammation and that reverse the pathogenic phenotype of FLS could improve the prognosis of these patients. An unexplored area includes the retinoic acid, the main biologic retinoid, which is a candidate drug for many diseases but has reached clinical use only for a few. Here, we explored the effect of all-trans retinoic acid (ATRA) on the aggressive phenotype of FLS from patients with RA. RA FLSs were treated with ATRA, tumor necrosis factor (TNF), or TNF+ATRA, and cell migration and invasion were analyzed. In addition, a microarray analysis of expression, followed by gene-set analysis and quantitative polymerase chain reaction validation, was performed. We showed that ATRA induced a notable decrease in FLS migration and invasion that was accompanied by complex changes in gene expression. At supraphysiological doses, many of these effects were overridden or reverted by the concomitant presence of TNF. In conclusion, these results have demonstrated the therapeutic potential of retinoic acid on RA FLS provided TNF could be counterbalanced, either with high ATRA doses or with TNF inhibitors. SIGNIFICANCE STATEMENT All-trans retinoic acid (ATRA) reduced the rheumatoid arthritis (RA) fibroblast-like synoviocyte migration and invasiveness and down-regulated gene expression of cell motility and migration genes. At supraphysiological doses, some of these effects were reverted by tumor necrosis factor. Therefore, ATRA could be an RA drug candidate that would require high doses or combined treatment with anti-inflammatory drugs.Instituto de Salud Carlos III; PI1701660Instituto de Salud Carlos III; PI1401153Instituto de Salud Carlos III (RETICS); RD16/0012/001

Energy-based monitoring and correction to enhance the accuracy and stability of explicit co-simulation

[Abstract] The simulation of complex engineering applications often requires the consideration of component-level dynamics whose nature and time-scale differ across the elements of which the system is composed. Co-simulation offers an effective approach to deal with the modelling and numerical integration of such assemblies by assigning adequate description and solution methods to each component. Explicit co-simulation, in particular, is frequently used when efficient code execution is a requirement, for instance in real-time setups. Using explicit schemes, however, can lead to the introduction of energy artifacts at the discrete-time interface between subsystems. The resulting energy errors deteriorate the accuracy of the co-simulation results and may in some cases develop into the instability of the numerical integration process. This paper discusses the factors that influence the severity of the energy errors generated at the interface in explicit co-simulation applications, and presents a monitoring and correction methodology to detect and remove them. The method uses only the information carried by the variables exchanged between the subsystems and the co-simulation manager. The performance of this energy-correction technique was evaluated in multi-rate co-simulation of mechanical and multiphysics benchmark examples.Xunta de Galicia; ED431B2016/031Xunta de Galicia; ED431F2021/04Ministerio de Economía, Industria y Competitividad; RYC-2016-20222Ministerio de Economía, Industria y Competitividad; TRA2017-86488-

Utjecaj prinosa pašnjaka i pašnog obroka na kvalitetu travnjaka, unos paše i proizvodnju mlijeka.

Sixty-four Holstein-Friesian cows were randomly assigned to one of four treatments (M15, M20, H15 and H20) in a 2x2 factorial design, by considering: two pre-grazing pasture mass levels (PM, kg DM/ha): medium (M-1,600) vs. high (H-2,400); and two pasture allowance levels (PA, kg DM/cow/day): low (15) vs. high (20). Two periods (PI vs. PII) were studied. Sward density and pre-grazing sward height were higher in high compared to medium pre-grazing PM swards in PI (P<0.001, 255 vs. 235 kg DM/cm/ha and P<0.001, 14.8 vs. 10.9 cm, respectively) and PII (P<0.001, 216 vs. 196 kg DM/cm/ha and P<0.001, 14.3 vs. 13.0 cm, respectively). Lower post-grazing sward height and higher pasture utilization were obtained in low compared to high PA swards in PI (P<0.001, 4.1 vs. 4.9 cm and P<0.001, 98.8 vs. 89.9 %, respectively) and PII (P<0.001, 4.3 vs. 5.0 cm and P<0.001, 97.1 vs. 89.9 %, respectively). Pasture crude protein content and pasture organic matter digestibility were higher in medium compared to high pre-grazing PM swards in PI (P<0.001, 210 vs. 176 g/kg DM and P<0.05, 846 vs. 836 g/kg DM, respectively) and PII (P<0.05, 212 vs. 192 g/kg DM and P<0.05, 828 vs. 821 g/kg DM, respectively). This was due to higher leaf and lower dead proportions in medium than in high pre-grazing PM swards. Pasture dry matter intake (PDMI) (P<0.001, 16.5 vs. 14.7 kg DM/cow/day), milk yield (MY) (P<0.01, 23.8 vs. 22.7 kg/day) and milk solids yield (MSY) (P<0.05, 1.69 vs. 1.61 kg/cow) were higher in high compared to low PA swards in PI. Higher PDMI (P<0.001, 15.7 vs. 14.1 kg DM/cow/day), MY (P<0.001, 15.4 vs. 13.6 kg/day) and MSY (P<0.01, 1.19 vs. 1.08 kg/cow) were also found in high than in low PA swards in PII. The highest (P<0.001) milk output per ha (16,983 kg/ha) and milk solids per ha (1,268 kg/ha) were found in the group of dairy cows grazing in the M20 swards.Šezdeset četiri holštaj-frizijske krave nasumično su razvrstane u četiri skupine (M15, M20, H15 i H20), uzevši u obzir 2x2 faktorijalni dizajn s obzirom na: dvije razine prinosa pašnjaka prije napasivanja (PM, kg DM/ha) - srednja (M-1600) naprema visoka (H-2400), te dvije razine pašnog obroka (PA, kg DM / krava /dan) - niski (15) naprema visoki (20). Istražena su dva razdoblja (PI naprema PII). Između travnjaka s visokim i srednjim prinosom prije napasivanja (PM), u prvom razdoblju utvrđene su razlike s obzirom na gustoću travnjaka (P<0,001; H = 255 naprema M = 235 kg DM/cm/ha) i visinu trave (P<0,001; H = 14,8 naprema M = 10,9 cm). U drugom razdoblju, statistička značajnost i razlike između navedenih skupina iznosili su P<0,001; H = 216 naprema M = 196 kg DM/cm/ha i P<0,001; H = 14,3 naprema M = 13,0 cm. Najniža visina trave i najviša iskoristivost pašnjaka nakon napasivanja utvrđene su usporedbom niskog i visokog pašnog obroka tijekom prvog razdoblja (P<0,001; niski = 4,1 naprema visoki = 4,9 cm te P<0,001; niski = 98,8 naprema visoki = 89,9%) kao i tijekom drugog razdoblja (P<0,001; niski = 4,3 naprema visoki = 5,0 cm te P<0,001; niski = 97,1 naprema visoki = 89,9%). Sadržaj sirovih proteina i probavljivost organske tvari tijekom prvog razdoblja bili su viši kod pašnjaka sa srednjim prinosom pašnjaka prije napasivanja u odnosu na pašnjake s visokom razinom prinosa prije napasivanja (P<0,001; M = 210 naprema H = 176 g/kg DM i P<0,05; M = 846 naprema H = 836 g/kg DM. Tijekom drugog razdoblja, statistička značajnost i vrijednosti navedenih pokazatelja iznosili su (P<0,05; M = 212 naprema H = 192 g/kg DM i P<0,05; M = 828 naprema H = 821 g/kg DM). Navedeno se može pripisati većem udjelu lišća i manjem udjelu uvenule mase na pašnjacima sa srednjim prinosom prije napasivanja u odnosu na pašnjake s visokim prinosom prije napasivanja. Usporedba niskog i visokog pašnog obroka tijekom prvog razdoblja, pokazala je statistički značajne razlike za unos suhe tvari pašom (P<0,001; niski = 16,5 naprema visoki = 14,7 kg DM/krava/dnevno), proizvodnju mlijeka (P<0,01; niski = 23,8 naprema. visoki = 22,7 kg/day) te proizvodnju krute tvari mlijeka (P<0,05; niski = 1,69 naprema. visoki = 1,61 kg/krava). Tijekom drugog razdoblja, viši unos suhe tvari pašom utvrđen kod visokoga pašnog obroka u odnosu na niski pašni obrok (P<0,001; visoki = 15,7 naprema niski = 14,1 kg DM/krava/dnevno), viša je bila i proizvodnja mlijeka (P<0,001; visoki = 15,4 naprema niski = 13,6 kg/day) te proizvodnja krute tvari mlijeka (P<0,01; visoki = 1,19 naprema niski = 1,08 kg/krava). Najviša proizvodnja mlijeka po hektaru (P<0,001; 16,983 kg/ha) i krute tvari mlijeka po hektaru (1,268 kg/ha) utvrđena je kod krava koje su napasivane u skupini M20 travnjaka

Utjecaj prinosa pašnjaka i pašnog obroka na kvalitetu travnjaka, unos paše i proizvodnju mlijeka.

Sixty-four Holstein-Friesian cows were randomly assigned to one of four treatments (M15, M20, H15 and H20) in a 2x2 factorial design, by considering: two pre-grazing pasture mass levels (PM, kg DM/ha): medium (M-1,600) vs. high (H-2,400); and two pasture allowance levels (PA, kg DM/cow/day): low (15) vs. high (20). Two periods (PI vs. PII) were studied. Sward density and pre-grazing sward height were higher in high compared to medium pre-grazing PM swards in PI (P<0.001, 255 vs. 235 kg DM/cm/ha and P<0.001, 14.8 vs. 10.9 cm, respectively) and PII (P<0.001, 216 vs. 196 kg DM/cm/ha and P<0.001, 14.3 vs. 13.0 cm, respectively). Lower post-grazing sward height and higher pasture utilization were obtained in low compared to high PA swards in PI (P<0.001, 4.1 vs. 4.9 cm and P<0.001, 98.8 vs. 89.9 %, respectively) and PII (P<0.001, 4.3 vs. 5.0 cm and P<0.001, 97.1 vs. 89.9 %, respectively). Pasture crude protein content and pasture organic matter digestibility were higher in medium compared to high pre-grazing PM swards in PI (P<0.001, 210 vs. 176 g/kg DM and P<0.05, 846 vs. 836 g/kg DM, respectively) and PII (P<0.05, 212 vs. 192 g/kg DM and P<0.05, 828 vs. 821 g/kg DM, respectively). This was due to higher leaf and lower dead proportions in medium than in high pre-grazing PM swards. Pasture dry matter intake (PDMI) (P<0.001, 16.5 vs. 14.7 kg DM/cow/day), milk yield (MY) (P<0.01, 23.8 vs. 22.7 kg/day) and milk solids yield (MSY) (P<0.05, 1.69 vs. 1.61 kg/cow) were higher in high compared to low PA swards in PI. Higher PDMI (P<0.001, 15.7 vs. 14.1 kg DM/cow/day), MY (P<0.001, 15.4 vs. 13.6 kg/day) and MSY (P<0.01, 1.19 vs. 1.08 kg/cow) were also found in high than in low PA swards in PII. The highest (P<0.001) milk output per ha (16,983 kg/ha) and milk solids per ha (1,268 kg/ha) were found in the group of dairy cows grazing in the M20 swards.Šezdeset četiri holštaj-frizijske krave nasumično su razvrstane u četiri skupine (M15, M20, H15 i H20), uzevši u obzir 2x2 faktorijalni dizajn s obzirom na: dvije razine prinosa pašnjaka prije napasivanja (PM, kg DM/ha) - srednja (M-1600) naprema visoka (H-2400), te dvije razine pašnog obroka (PA, kg DM / krava /dan) - niski (15) naprema visoki (20). Istražena su dva razdoblja (PI naprema PII). Između travnjaka s visokim i srednjim prinosom prije napasivanja (PM), u prvom razdoblju utvrđene su razlike s obzirom na gustoću travnjaka (P<0,001; H = 255 naprema M = 235 kg DM/cm/ha) i visinu trave (P<0,001; H = 14,8 naprema M = 10,9 cm). U drugom razdoblju, statistička značajnost i razlike između navedenih skupina iznosili su P<0,001; H = 216 naprema M = 196 kg DM/cm/ha i P<0,001; H = 14,3 naprema M = 13,0 cm. Najniža visina trave i najviša iskoristivost pašnjaka nakon napasivanja utvrđene su usporedbom niskog i visokog pašnog obroka tijekom prvog razdoblja (P<0,001; niski = 4,1 naprema visoki = 4,9 cm te P<0,001; niski = 98,8 naprema visoki = 89,9%) kao i tijekom drugog razdoblja (P<0,001; niski = 4,3 naprema visoki = 5,0 cm te P<0,001; niski = 97,1 naprema visoki = 89,9%). Sadržaj sirovih proteina i probavljivost organske tvari tijekom prvog razdoblja bili su viši kod pašnjaka sa srednjim prinosom pašnjaka prije napasivanja u odnosu na pašnjake s visokom razinom prinosa prije napasivanja (P<0,001; M = 210 naprema H = 176 g/kg DM i P<0,05; M = 846 naprema H = 836 g/kg DM. Tijekom drugog razdoblja, statistička značajnost i vrijednosti navedenih pokazatelja iznosili su (P<0,05; M = 212 naprema H = 192 g/kg DM i P<0,05; M = 828 naprema H = 821 g/kg DM). Navedeno se može pripisati većem udjelu lišća i manjem udjelu uvenule mase na pašnjacima sa srednjim prinosom prije napasivanja u odnosu na pašnjake s visokim prinosom prije napasivanja. Usporedba niskog i visokog pašnog obroka tijekom prvog razdoblja, pokazala je statistički značajne razlike za unos suhe tvari pašom (P<0,001; niski = 16,5 naprema visoki = 14,7 kg DM/krava/dnevno), proizvodnju mlijeka (P<0,01; niski = 23,8 naprema. visoki = 22,7 kg/day) te proizvodnju krute tvari mlijeka (P<0,05; niski = 1,69 naprema. visoki = 1,61 kg/krava). Tijekom drugog razdoblja, viši unos suhe tvari pašom utvrđen kod visokoga pašnog obroka u odnosu na niski pašni obrok (P<0,001; visoki = 15,7 naprema niski = 14,1 kg DM/krava/dnevno), viša je bila i proizvodnja mlijeka (P<0,001; visoki = 15,4 naprema niski = 13,6 kg/day) te proizvodnja krute tvari mlijeka (P<0,01; visoki = 1,19 naprema niski = 1,08 kg/krava). Najviša proizvodnja mlijeka po hektaru (P<0,001; 16,983 kg/ha) i krute tvari mlijeka po hektaru (1,268 kg/ha) utvrđena je kod krava koje su napasivane u skupini M20 travnjaka