Role of COQ4 on mitochondrial DNA maintenance

Resumen del póster presentado en Mitochondrial Medicine, celebrado en Hinxton (Inglaterra) del 09 al 11 de mayo de 2018.Coenzyme Q (CoQ) is a lipidic molecule composed by a hydroquinone head and an isoprenoid chain. Since its discovery, several functions have been assigned to CoQ, being the transfer of electrons from complexes I and II to complex III in the mitochondrial respiratory chain the best known. CoQ also receives electrons from other dehydrogenases involved in different cellular processes and it is a potent membrane antioxidant. CoQ is endogenously synthesized by a set of enzymes forming a biosynthetic complex in the mitochondrial inner membrane, which has been mostly studied in yeast models. Defects in any of the genes coding for these proteins result in reduced levels of CoQ and, consequently, defects in energy production. COQ4 is one of the proteins involved in CoQ biosynthesis, but its exact enzymatic activity is still unknown. COQ4 KO HEK 293T-Rex/Flp-In cells generated by CRISPR/Cas9, as well as patient fibroblasts carrying mutations in COQ4 show the accumulation of a yet uncharacterised biosynthetic intermediate that lacks redox activity. Two candidate molecules have emerged from mass spectrometry analysis performed to identify this intermediate. On the other hand, the KO cells show a surprising phenotype related to mtDNA metabolism which may be due either to the lack of de novo synthesis of CoQ, to the biosynthetic complex instability itself, to the presence of the intermediate, or to a different and yet not characterized role of COQ4. Altogether, these results indicate a possible double function of the COQ4 protein

Essential Physiological Differences Characterize Short- and Long-Lived Strains of Drosophila melanogaster

Aging is a multifactorial process which affects all animals. Aging as a result of damage accumulation is the most accepted explanation but the proximal causes remain to be elucidated. There is also evidence indicating that aging has an important genetic component. Animal species age at different rates and specific signaling pathways, such as insulin/insulin-like growth factor, can regulate life span of individuals within a species by reprogramming cells in response to environmental changes. Here, we use an unbiased approach to identify novel factors that regulate life span in Drosophila melanogaster. We compare the transcriptome and metabolome of two wild-type strains used widely in aging research: short-lived Dahomey and long-lived Oregon R flies. We found that Dahomey flies carry several traits associated with short-lived individuals and species such as increased lipoxidative stress, decreased mitochondrial gene expression, and increased Target of Rapamycin signaling. Dahomey flies also have upregulated octopamine signaling known to stimulate foraging behavior. Accordingly, we present evidence that increased foraging behavior, under laboratory conditions where nutrients are in excess increases damage generation and accelerates aging. In summary, we have identified several new pathways, which influence longevity highlighting the contribution and importance of the genetic component of aging.This work was supported by the European Research Council (260632 - ComplexI&Aging to A.S.); the Academy of Finland (252048 to A.S); the Biotechnology and Biological Sciences Research Council ( BB/M023311/1 to A.S.); the Centre for International Mobility (CIMO) (TM-12- 8391 and TM-13-8919 to N.G.); the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (PI14/00328 to R.P. and PI17/01286 to P.N.); the Autonomous Government of Catalonia (2017SGR696 and SLT002/16/00250 to R.P.); the Ministry of Education and Science of Ukraine (grant number 0117U006426 to O.L.); FEDER funds from the European Union (“A way to build Europe” to R.P.); and the Doctoral Programme in Medicine and Life Sciences of University of Tampere (to T.R). R.S is a Sir Henry Wellcome Postdoctoral Fellow funded by Wellcome (204715/Z/16/Z

Four decades of geophysical research on Iberia and adjacent margins

The dimensions, the geographical position and the complex geological history of the Iberian Peninsula makes it a unique and singular target to study its crustal and upper mantle structure and geodynamical evolution using geophysical methods. The lithospheric structure beneath Iberia has been investigated since the 1970’s using deep multichannel seismic reflection and refraction/wide-angle reflection profiling. Gravimetric and magnetic data were acquired following the deployment of permanent and temporary stations, mostly during the 1990’s. Beginning in the late 1990’s, the progressive use of Global Navigation Satellite Systems (GNSS) instruments contributed to monitor the present-day motions. During the last decades, numerous geological and geophysical surveys have investigated the Iberian lithosphere and upper mantle in the onshore and offshore regions, the most recent ones related to the TopoIberia project. The approach developed in this contribution is twofold. Firstly, we summarize the available geophysical information over Iberia, from focusing on the upper crust to the lithosphere-asthenosphere boundary and the transition zone marking the bottom of the upper mantle. Results of GNSS data, potential fields, controlled source seismic profiles, magnetotelluric data, body and surface wave tomography, receiver functions and 2D and 3D lithospheric modeling are reviewed and compared. Secondly, we focus on the areas of greater geodynamic interest and the regions where inconsistencies within the geophysical results, or contradictions in their tectonic interpretation exist, identifying the major questions that are still under debate. Besides shedding light to the state of knowledge and pointing out present-day research challenges, this review provides a tool for the integration of the diverse geophysical datasets with the surface geology and geodynamical processes that are interpreted to have built the complex geology of the Iberian Peninsula.The authors acknowledge funding from the Generalitat de Catalunya, grant/awards number AGAUR 2017SGR1022, and AGAUR 2017SGR847, the Spanish Ministry of Science, Innovation, and Universities grant numbers RTI2018-095594-B-I00, PGC2018-095154-B-100 and PGC2018-094227-B-I00 and the Spanish Ministry of Economy and Competitiveness grant numbers CGL2017-84901-C2 and PIE-CSIC-201830E039. IP is funded by the Spanish Ministry of Science, Innovation, and Universities and University of Salamanca grant BEAGAL18/00090. AV acknowledges funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S).Peer reviewe

Search for a singly produced third-generation scalar leptoquark decaying to a tau lepton and a bottom quark in proton-proton collisions at root s=13 TeV

A search is presented for a singly produced third-generation scalar leptoquark decaying to a tau lepton and a bottom quark. Associated production of a leptoquark and a tau lepton is considered, leading to a final state with a bottom quark and two tau leptons. The search uses proton-proton collision data at a center-of-mass energy of 13 TeV recorded with the CMS detector, corresponding to an integrated luminosity of 35.9 fb(-1). Upper limits are set at 95% confidence level on the production cross section of the third-generation scalar leptoquarks as a function of their mass. From a comparison of the results with the theoretical predictions, a third-generation scalar leptoquark decaying to a tau lepton and a bottom quark, assuming unit Yukawa coupling (lambda), is excluded for masses below 740 GeV. Limits are also set on lambda of the hypothesized leptoquark as a function of its mass. Above lambda = 1.4, this result provides the best upper limit on the mass of a third-generation scalar leptoquark decaying to a tau lepton and a bottom quark.Peer reviewe

Constraints on models of scalar and vector leptoquarks decaying to a quark and a neutrino at root s=13 TeV

The results of a previous search by the CMS Collaboration for squarks and gluinos are reinterpreted to constrain models of leptoquark (LQ) production. The search considers jets in association with a transverse momentum imbalance, using the M-T2 variable. The analysis uses proton-proton collision data at root s = 13 TeV, recorded with the CMS detector at the LHC in 2016 and corresponding to an integrated luminosity of 35.9 fb(-1). Leptoquark pair production is considered with LQ decays to a neutrino and a top, bottom, or light quark. This reinterpretation considers higher mass values than the original CMS search to constrain both scalar and vector LQs. Limits on the cross section for LQ pair production are derived at the 95% confidence level depending on the LQ decay mode. A vector LQ decaying with a 50% branching fraction to t nu, and 50% to b tau, has been proposed as part of an explanation of anomalous flavor physics results. In such a model, using only the decays to t nu, LQ masses below 1530 GeV are excluded assuming the Yang-Mills case with coupling kappa = 1, or 1115 GeV in the minimal coupling case kappa = 0, placing the most stringent constraint to date from pair production of vector LQs.Peer reviewe

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Ciencias Sociales: Economía y Humanidades HANDBOOK T-I

Se presenta un breve examen de la producción y comercialización de rosa en México; un estudio en México sobre el ingreso mínimo de las familias que identifica la línea de pobreza alimentaria en el área rural del sur de México, 2012; un pequeño estudio donde hablará sobre el análisis comparado del Sector Gubernamental y la Economía Mexicana desde la perspectiva de los eslabonamientos productivos Hirshman-Rasmuss; un estudio sobre los canales de comercialización de limón persa en el municipio de Martínez de la Torre, Veracruz; una análisis del comercio estratégico en el TLCAN: El Estado en la política agrícola de biocombustibles; también se expresan acerca de la importancia de la comercialización del café en México; un diagnóstico, retos del comercio electrónico en el Sector Agroindustrial Mexicano; trabajo nos muestra y habla sobre la inversión extranjera directa y su impacto en crecimiento de México, un análisis en prospectiva: 1999-2010; un estudio acerca sobre la importancia de la Banca en México; un trabajo acerca de la competitividad de la producción agrícola en México, un análisis regional; se analizan todo acerca de el SIAL productor de quesos en Poxtla, competividad y territorio; se habla acerca de la intermediación financiera al servicio de la comunidad indígena: el fondo regional indígena Tarhiata Keri; ademas un estudio acerca de la demanda de Importaciones de durazno (Prunus pérsica L. Batsch) en México procedentes de Estados Unidos de América (1982-2011); Loera y Sepúlveda analizan los parámetros de la productividad forestal en la producción de madera en rollo; un análisis de factores sociales, ambientales y económicos del territorio rural cercano a la ciudad de México; un estudio acerca de la crisis económica mundial y su efecto sobre los flujos migratorios de América Latina; Magadán, Hernández y Escalona presentan la tipología de los sujetos sociales que intervienen en el mercado campesino de Ocotlán Oaxaca; la normalización del proceso de compostaje: una opción para desarrollar el mercado de la composta; acerca de la reestructuración del capitalismo y crisis política en México; la rentabilidad de la producción de miel en el municipio de León, Guanjuato; la economía del maíz en la región metropolitana, Chiapas, 2014; análisis de los centros de educación y cultura ambiental, necesidad de profesionalización Pedagógica de facilitadores ambientales; los Costos y competitividad de la producción del limón persa en el municipio de Martínez de la Torre, Veracruz

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe