Poly-l/dl-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells

Limbal epithelial stem cells (LESCs) are responsible for the renewal of corneal epithelium. Cultivated limbal epithelial transplantation is the current treatment of choice for restoring the loss or dysfunction of LESCs. To perform this procedure, a substratum is necessary for in vitro culturing of limbal epithelial cells and their subsequent transplantation onto the ocular surface. In this work, we evaluated poly-L/DL-lactic acid 70:30 (PLA) films functionalized with type IV collagen (col IV) as potential in vitro carrier substrata for LESCs. We first demonstrated that PLA-col IV films were biocompatible and suitable for the proliferation of human corneal epithelial cells. Subsequently, limbal epithelial cell suspensions, isolated from human limbal rings, were cultivated using culture medium that did not contain animal components. The cells adhered significantly faster to PLA-col IV films than to tissue culture plastic (TCP). The mRNA expression levels for the LESC specific markers, K15, P63α and ABCG2 were similar or greater (significantly in the case of K15) in limbal epithelial cells cultured on PLA-col IV films than limbal epithelial cells cultured on TCP. The percentage of cells expressing the corneal (K3, K12) and the LESC (P63α, ABCG2) specific markers was similar for both substrata. These results suggest that the PLA-col IV films promoted LESC attachment and helped to maintain their undifferentiated stem cell phenotype. Consequently, these substrata offer an alternative for the transplantation of limbal cells onto the ocular surface.This work was supported by the Carlos III National Institute of Health, Spain (CIBER-BBN and Spanish Network on Cell Therapy, (TerCel RD12/0019/0036), MINECO/FEDER, EU), and the Castilla y León Regional Government, Spain (Regional Center for Regenerative Medicine and Cell Therapy, SAN673/VA/28/08 and SAN126/VA11/09)

Ruthenium molecular complexes immobilized on graphene as active catalysts for the synthesis of carboxylic acids from alcohol dehydrogenation

Ruthenium complexes containing N-heterocyclic carbene ligands functionalized with different polyaromatic groups (pentafluorophenyl, anthracene, and pyrene) are immobilized onto the surface of reduced graphene oxide. The hybrid materials composed of organometallic complexes and graphene are obtained in a single-step process. The hybrid materials are efficient catalysts for the synthesis of carboxylic acids from the dehydrogenation of alcohols in aqueous media. The catalytic materials can be recycled up to ten times without significant loss of activity. The catalytic activity of the pyrene derivative, Pyr-Ru (3) is enhanced when the ruthenium complex is anchored onto the surface of graphene. The carbonaceous material limits the degradation of the ruthenium complex resulting in increased activity and requiring lower catalyst loadings. The catalytic process of the pyrene hybrid material is heterogeneous in nature due to the strong interaction between the pyrene and graphene. The catalytic process of the anthracene and pentafluorophenyl hybrid materials is governed by the so-called ‘boomerang effect’. The ruthenium molecular complex is released from and returned to the graphene surface during the catalytic reaction. Mechanistic insight has been obtained experimentally and theoretically. The energy profile suggests that the rate-determining step is the water nucleophilic attack to a coordinated aldehyde complex to form a gem-diolate complex.The authors thank the financial support from MINECO (CTQ2015-69153-C2-2-R and CTQ2015- 67461-P), Generalitat Valenciana (AICO/2015/039), Universitat Jaume I (P1.1B2015-09) and Universidad de Zaragoza (UZ2014-CIE-01)

Efectos de muestras de tallas erróneas sobre los valores estimados del crecimiento individual y la condición de los stocks

Despite its importance in fisheries studies, there is insufficient understanding on the effect of sampling error or bias on individual growth and other stock indicators. We show the influence of sample length distributions on parameter estimates, illustrating with an example. For the brown swimming crab, we simulated length samples in five configurations and estimated parameters of von Bertalanffy (k, L∞L∞ , t0), asymptotic weight ( W∞W∞ ), weight-length relationship (a, b), growth performance (ϕ’) and condition factor (Kn). Parameter estimates were compared with baseline values using relative bias, standard error and root mean square error. The results show that the accuracy and bias of parameter estimates depend on the lengths sampled. For example, the bias and accuracy of L∞L∞ and W∞W∞ vary inversely with sampled length, whereas combining length segments yields smaller biases of k and t0 than those of L∞L∞ and W∞W∞ . In general, the accuracy of parameter estimates does not always depend on sampling the entire length range, and errors are not the same for all parameters. These results are useful to guide sampling when resources are scarce. We discuss potential reasons for incomplete length sample structure and offer recommendations to obtain best estimates for parameters of interest.A pesar de su importancia en los estudios de pesquerías, aún no se comprende lo suficiente el efecto del error o del sesgo del muestreo en los parámetros de crecimiento individual y otros indicadores poblacionales. Utilizando un ejemplo, aquí se muestra la influencia de las distribuciones muestrales de longitud en las estimaciones de parámetros poblacionales. Para la jaiba café, simulamos muestreo de longitud en cinco configuraciones y estimamos parámetros de von Bertalanffy (k, L∞L∞ , t0), peso asintótico ( W∞W∞ ), relación peso-longitud (a, b), eficiencia de crecimiento (ϕ’), y factor de condición (Kn). Las estimaciones de los parámetros se compararon con valores de referencia utilizando el sesgo relativo, el error estándar y el error cuadrático medio. Los resultados muestran cómo la precisión y el sesgo de las estimaciones de parámetros dependen de las longitudes muestreadas. Por ejemplo, el sesgo y la precisión de L∞L∞ y W∞W∞ , varían inversamente con la longitud muestreada, mientras que la combinación de segmentos de longitud produce sesgos de k y t0 más pequeños que los de L∞L∞ y W∞W∞ . En general, la precisión de las estimaciones de los parámetros no siempre depende del muestreo de todo el rango de tallas disponible, y los errores no son los mismos para todos los parámetros. Estos resultados son útiles para guiar el muestreo cuando los recursos son escasos. Discutimos las posibles razones de la estructura de la muestra de longitud incompleta y ofrecemos recomendaciones para obtener las mejores estimaciones para los parámetros de interés

Iridium complexes catalysed the selective dehydrogenation of glucose to gluconic acid in water

[EN] We describe an unprecedented catalytic dehydrogenation of glucose by homogeneous catalysts. Iridium(iii) complexes containing the fragment [Cp*Ir(NHC)](2+) (NHC = N-heterocyclic carbene ligand) are shown to be very active and highly selective catalysts for the dehydrogenation of glucose to gluconic acid and molecular hydrogen. Glucose is converted to gluconic acid at a catalyst loading of 2 mol%, at reflux in water, without additives and with a selectivity of over 95%. Experimental evidence obtained by H-1 NMR spectroscopy and mass spectrometry (ESI/MS) reveals the formation of iridium coordinated to glucose and gluconic acid species. A plausible mechanism is proposed, based on the experimental evidence and supported by DFT calculations.The authors thank the MINECO (Severo Ochoa, CTQ2015-69153-C2-1-R, CTQ2015-69153-C2-2-R and CTQ2015-67461-P), Diputacion General de Aragon (Grupo Consolidado E21) and Universitat Jaume I (P1.1B2015-09) for financial support. P. Borja thanks the Universitat Jaume I for a postdoctoral grant. The authors are very grateful to the 'Serveis Centrals d'Instrumentacio Cientifica (SCIC)' of the Universitat Jaume I, S. Fuertes (Universidad of Zaragoza) for data collection of the X-ray structure of 4 and to the Instituto de Biocomputacion y Fisica de Sistemas Complejos (BIFI) and the Centro de Supercomputacion de Galicia (CESGA) for the generous allocation of computational resources.Borja, P.; Vicent, C.; Baya, M.; García Gómez, H.; Mata, JA. (2018). Iridium complexes catalysed the selective dehydrogenation of glucose to gluconic acid in water. Green Chemistry. 20(17):4094-4101. https://doi.org/10.1039/c8gc01933aS409441012017Corma, A., Iborra, S., & Velty, A. (2007). Chemical Routes for the Transformation of Biomass into Chemicals. Chemical Reviews, 107(6), 2411-2502. doi:10.1021/cr050989dBesson, M., Gallezot, P., & Pinel, C. (2013). Conversion of Biomass into Chemicals over Metal Catalysts. 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E., Greeves, N., & Lopez‐Sanchez, J. A. (2016). Visible‐Light‐Controlled Oxidation of Glucose using Titania‐Supported Silver Photocatalysts. ChemCatChem, 8(22), 3475-3483. doi:10.1002/cctc.201600775Da Vià, L., Recchi, C., Gonzalez-Yañez, E. O., Davies, T. E., & Lopez-Sanchez, J. A. (2017). Visible light selective photocatalytic conversion of glucose by TiO2. Applied Catalysis B: Environmental, 202, 281-288. doi:10.1016/j.apcatb.2016.08.035Monge, M. E., Pérez, J. J., Dwivedi, P., Zhou, M., McCarty, N. A., Stecenko, A. A., & Fernández, F. M. (2013). Ion mobility and liquid chromatography/mass spectrometry strategies for exhaled breath condensate glucose quantitation in cystic fibrosis studies. Rapid Communications in Mass Spectrometry, 27(20), 2263-2271. doi:10.1002/rcm.6683Sandín-España, P., Mateo-Miranda, M., López-Goti, C., De Cal, A., & Alonso-Prados, J. L. (2016). Development of a rapid and direct method for the determination of organic acids in peach fruit using LC–ESI-MS. 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Trapping and Characterization of a Reaction Intermediate in Carbapenem Hydrolysis by \u3cem\u3eB. cereus\u3c/em\u3e Metallo-β-lactamase

Metallo-β-lactamases hydrolyze most β-lactam antibiotics. The lack of a successful inhibitor for them is related to the previous failure to characterize a reaction intermediate with a clinically useful substrate. Stopped-flow experiments together with rapid freeze−quench EPR and Raman spectroscopies were used to characterize the reaction of Co(II)−BcII with imipenem. These studies show that Co(II)−BcII is able to hydrolyze imipenem in both the mono- and dinuclear forms. In contrast to the situation met for penicillin, the species that accumulates during turnover is an enzyme−intermediate adduct in which the β-lactam bond has already been cleaved. This intermediate is a metal-bound anionic species with a novel resonant structure that is stabilized by the metal ion at the DCH or Zn2 site. This species has been characterized based on its spectroscopic features. This represents a novel, previously unforeseen intermediate that is related to the chemical nature of carbapenems, as confirmed by the finding of a similar intermediate for meropenem. Since carbapenems are the only substrates cleaved by B1, B2, and B3 lactamases, identification of this intermediate could be exploited as a first step toward the design of transition-state-based inhibitors for all three classes of metallo-β-lactamases

Catalytic Dehydrogenative Coupling of Hydrosilanes with Alcohols for the Production of Hydrogen On-demand: Application of a Silane/Alcohol Pair as a Liquid Organic Hydrogen Carrier

The compound [Ru(p-cym)(Cl)2(NHC)] is an effective catalyst for the room-temperature coupling of silanes and alcohols with the concomitant formation of molecular hydrogen. High catalyst activity is observed for a variety of substrates affording quantitative yields in minutes at room temperature and with a catalyst loading as low as 0.1 mol %. The coupling reaction is thermodynamically and, in the presence of a Ru complex, kinetically favourable and allows rapid molecular hydrogen generation on-demand at room temperature, under air, and without any additive. The pair silane/alcohol is a potential liquid organic hydrogen carrier (LOHC) for energy storage over long periods in a safe and secure way. Silanes and alcohols are non-toxic compounds and do not require special handling precautions such as high pressure or an inert atmosphere. These properties enhance the practical applications of the pair silane/alcohol as a good LOHC in the automotive industry. The variety and availability of silanes and alcohols permits a pair combination that fulfils the requirements for developing an efficient LOHC

Fisheries and Biodiversity in the Upper Gulf of California, Mexico

The Upper Gulf of California (UGC) has been recognized by its high primary productivity and abundant fishing (Aragon-Noriega & Calderon-Aguilera, 2000). Sediments and nutrients from the Colorado River, and complex hydrodynamics render this as an Important site for spawning, mating and nursing for numerous species of commercial and ecological importance (Cudney & Turk, 1998; Ramirez-Rojo & Aragón-Noriega 2006). Temperature, salinity and abundance of nutrients in this region vary depending on fresh water runoff from the Colorado River (Alvarez-Borrego et al., 1975; Hernández-Ayón et al., 1993; Lavín & Sánchez, 1999). Commercial fishing of high market value resources such as shrimp takes place in the UGC by artisanal or small scale, and industrial fishing. Artisanal fishing is done on relatively small (30 feet) fiber glass boats or artisanal boats with outboard motors, usually operated by two fishers; their primary fishing gear is drift gillnets, which they use to catch croakers, Spanish mackerel and even shrimp. This type of fishing is carried out by cooperatives and individual fishers from the three ports of the UGC: Puerto Peñasco and El Golfo de Santa Clara, in the State of Sonora, and San Felipe, in Baja California. Because marine resources in the region are migratory, fisheries are seasonal generating bursts of accumulated fishing effort over a few months depending on availability of species (see Cudney & Turk 1998). Increasing demand of economically important species has motivated a steady rise in fishing effort and use of gear and fishing practices jeopardizing critical species such as totoaba, Totoaba macdonaldi, an endemic croaker declared under risk of extinction (Cisneros-Mata et al., 1995), and the rare vaquita, Phocoena sinus. Vaquita are accidentally caught in all kinds of gillnets used in the Upper Gulf (D’Agrosa et al., 1995; Blanco 2002)

Enhanced quantum tunneling in quantum Zeno dynamics freezing the momentum direction

Quantum tunneling is a fundamental quantum-mechanical effect involved in plenty of physical phenomena. Its control would impact these phenomena and the technologies based on them. We show that the quantum tunneling probability through a potential barrier can be increased to approach unity in a quantum Zeno dynamics undergone by the tunneling particle in which the direction of the momentum is frequently monitored. We first model the measurements of the momentum direction as selective von Neumann projections, and then as nonselective, direction-sensitive interactions of the particle with probe particles. Nonselective measurements are more efficient than selective measurements in enhancing the quantum tunneling probability

Genomic analyses of microdissected Hodgkin and Reed-Sternberg cells: mutations in epigenetic regulators and p53 are frequent in refractory classic Hodgkin lymphoma

This work was supported by grants from the Plan Nacional de I + D + I cofinanced by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), PI12/1832, the Spanish Association for Cancer Research (AECC), and Programas para Grupos de Investigación de la Comunidad Autónoma de Madrid (Biomedicina 2017)

Influenza virus differentially activates mTORC1 and mTORC2 signaling to maximize late stage replication

<div><p>Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during influenza virus infection have not been established. In addition, the role of mTORC2 during influenza virus infection remains unknown. Here we show that mTORC2 and PDPK1 differentially phosphorylate AKT upon influenza virus infection. PDPK1-mediated phoshorylation of AKT at a distinct site is required for mTORC1 activation by influenza virus. On the other hand, the viral NS1 protein promotes phosphorylation of AKT at a different site via mTORC2, which is an activity dispensable for mTORC1 stimulation but known to regulate apoptosis. Influenza virus HA protein and down-regulation of the mTORC1 inhibitor REDD1 by the virus M2 protein promote mTORC1 activity. Systematic phosphoproteomics analysis performed in cells lacking the mTORC2 component Rictor in the absence or presence of Torin, an inhibitor of both mTORC1 and mTORC2, revealed mTORC1-dependent substrates regulated during infection. Members of pathways that regulate mTORC1 or are regulated by mTORC1 were identified, including constituents of the translation machinery that once activated can promote translation. mTORC1 activation supports viral protein expression and replication. As mTORC1 activation is optimal midway through the virus life cycle, the observed effects on viral protein expression likely support the late stages of influenza virus replication when infected cells undergo significant stress.</p></div