Transition metal catalysis in the mitochondria of living cells

The development of transition metal catalysts capable of promoting non-natural transformations within living cells can open significant new avenues in chemical and cell biology. Unfortunately, the complexity of the cell makes it extremely difficult to translate standard organometallic chemistry to living environments. Therefore, progress in this field has been very slow, and many challenges, including the possibility of localizing active metal catalysts into specific subcellular sites or organelles, remain to be addressed. Herein, we report a designed ruthenium complex that accumulates preferentially inside the mitochondria of mammalian cells, while keeping its ability to react with exogenous substrates in a bioorthogonal way. Importantly, we show that the subcellular catalytic activity can be used for the confined release of fluorophores, and even allows selective functional alterations in the mitochondria by the localized transformation of inert precursors into uncouplers of the membrane potentialWe are thankful for the support given by the Spanish grant SAF2013-41943-R, the Xunta de Galicia (GRC2013-041 and 2015-CP082), the ERDF and the European Research Council (Advanced Grant No. 340055). M.T.G. thanks the Ministerio de Economía y Competitividad for the Postdoctoral fellowship. M.M.C. thanks Ministerio de Economía y Competitividad for the Juan de la Cierva-Incorporacio´n fellowship (IJCI-2014-19326).S

Competitividad de un puerto y su relación actual con el sistema portuario español

Los puertos comerciales tienen una labor fundamental en el tráfico mundial de mercancías y no son ajenos a la competencia entre éstos para atraer el mayor número de clientes que les reporten los beneficios económicos necesarios para seguir invirtiendo en su desarrollo y ser, de esta forma, cada vez más atractivos para realizar en ellos las actividades logísticas necesarias. Este fenómeno responde a la gestión empresarial de los puestos, que pretenden captar mayores cantidades de tráfico entrando en competencia unos con otros, lo cual se ve impulsado por el modelo de gestión portuaria existente en España, donde se promueve la competencia entre terminales portuarias que deben ser lo más competitivas posibles

Energy efficiency: comparison between the CALENER certificate and real consumptions

Modelización de una vivienda sostenible y comparación con los resultados obtenidos con los programas reconocidos en España de certificación

The C-terminal SH3 domain contributes to the intramolecular inhibition of Vav family proteins

Vav proteins are phosphorylation-dependent guanine nucleotide exchange factors (GEFs) that catalyze the activation of members of the Rho family of guanosine triphosphatases (GTPases). The current regulatory model holds that the nonphosphorylated, catalytically inactive state of these GEFs is maintained by intramolecular interactions among the amino-terminal domains and the central catalytic core, which block the binding of Vav proteins to GTPases. We showed that this autoinhibition is mechanistically more complex, also involving the bivalent association of the carboxyl-terminal Src homology 3 (SH3) region of Vav with its catalytic and pleckstrin homology (PH) domains. Such interactions occurred through proline-rich region-independent mechanisms. Full release from this double-locked state required synergistic weakening effects from multiple phosphorylated tyrosine residues, thus providing an optimized system to generate gradients of Vav GEF activity depending on upstream signaling inputs. This mechanism is shared by mammalian and Drosophila melanogaster Vav proteins, suggesting that it may be a common regulatory feature for this protein family.Work in the laboratory of X.R.B. has been funded by grants from the Spanish Ministry of Economy and Competitiveness (SAF2009-07172, SAF2012-3171, RD06/0020/0001, and RD12/0036/0002), the Castilla-León Autonomous Government (CSI039A12-1), and the Asociación Española Contra el Cáncer (AECC). O.L. has been supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2011-22988 and RD06/0020/1001). The salary of M.B. has been partially supported by a JAE-Predoc contract (CSIC), the AECC, and grant RD06/0020/0001. S.F. is supported by a graduate student FPI contract from the Spanish Ministry of Economy and Competitiveness (BES-2010-031386). Spanish funding is cosponsored by the European Regional Development Fund.Peer Reviewe

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Genetic diversity and population genetic analysis of Donax vittatus (Mollusca: Bivalvia) and phylogeny of the genus with mitochondrial and nuclear markers

In this study, the genetic diversity of Donax vittatus across the Iberian Peninsula was investigated using four mitochondrial (COI, Cytb, 16S F and M types) and three nuclear (H8, 18S and 285) genes. These same molecular markers were also sequenced in D. semistriatus and D variegatus to address the phylogenetic relationships of the species of the genus Donax common along the European coasts. Our results showed high haplotype diversity in combination with a low nucleotide diversity and a star-shaped network with a predominant haplotype, indicating a recent population expansion for the examined sampling sites of D. vittatus. Furthermore, analyses of population differentiation performed with COI mitochondrial marker, including global Far estimation and pairwise Far values, indicated the non-existence of significant genetic structure in D. vittatus of Northwest Iberian populations. Because these localities show a high genetic similarity, we suggest that D. vittatus could be a potentially alternative exploitable resource, as complement to the D. trunculus fisheries, whose natural stocks have decreased dramatically in some areas. Furthermore, we present for the first time, evidence of DUI in the clams D. vittatus and D. semistriatus. (C) 2017 Elsevier Ltd. All rights reservd.Ministerio de Economia y Competitividad [AGL2016-75288-R AEI/FEDER]Northern Regional Operational Programme (NORTE), through the European Regional Development FundINDITEX-UDCPortuguese Foundation for Science and Technology (FCT) [SFRH/BPD/108445/2015][NORTE-01-0145-FEDER-000035]info:eu-repo/semantics/publishedVersio