Human ISWI complexes are targeted by SMARCA5 ATPase and SLIDE domains to help resolve lesion-stalled transcription

Chromatin compaction of deoxyribonucleic acid (DNA) presents a major challenge to the detection and removal of DNA damage. Helix-distorting DNA lesions that block transcription are specifically repaired by transcription-coupled nucleotide excision repair, which is initiated by binding of the CSB protein to lesion-stalled RNA polymerase II. Using live cell imaging, we identify a novel

FICARAM-15 Cruise Report 20th March – 22nd May 2013 on board BIO Hespérides by the Group FICARAM

54 páginas, 19 figuras, 3 anexosThe FICARAM-15 is the fifteenth repetition of a section conducted in 1994. This section is part of the international program GOSHIP (http://www.go-ship.org/CruisePlans.html) to develop a globally coordinated network of sustained hydrographic sections as part of the global ocean/climate observing system. The objective of the FICARAM-15 cruise is to investigate the temporal evolution of the anthropogenic carbon and evaluate the CO2 absorption capacity of the South Atlantic region, the Equatorial zone, and the subtropical region of Azores-Gibraltar in the North Atlantic. This cruise is supported by the CATARINA project funded by the Ministry of Economy and Competitiveness (CTM2010-17141) and is part of the European Union FP7 project CARBOCHANGE (http://carbochange.b.uib.no/). The objective of FICARAM-15 cruise is framed in the CATARINA project conducted by the tasks I.2.1 (air-sea CO2 exchange) I.3 (ventilation of water masses), I.4.1 (zonal variability of N2O and CH4), I.4.2 (anthropogenic carbon storage), I.4.4 (saturation horizon of calcium carbonate along the section) and I.5.4 (evolution of the acidification rates). Another component of the FICARAM-15 cruise aims to examine the biological and biogeochemical mechanisms that hinder total dissolved organic carbon (DOC) remineralisation in marine systems, taking a multidisciplinary perspective and applying many different approaches. This is the global objective of the Spanish project DOREMI (CTM2012-34294) that joins this FICARAM-15 cruise.During the FICARAM cruise the physical oceanography group was responsible for collecting the following data sets: CTD and XBT data; vessel-mounted ADCP and lowered ADCP; continuous thermosalinograph. Physical oceanographers participated in the cruise financed through Project “Tipping Corners in the Meridional Overturning Circulation” (TIC-MOC), CTM2011-28867. The FICARAM-15 cruise was organized in two phases with a common sampling. LEG 1: From Punta Arenas (Chile) to Recife (Brazil): 62 stations. Chief Scientist: Aida F. Ríos, PI of CATARINA project LEG 2: From Recife (Brazil) to Cartagena (Spain): 46 stations Chief Scientist: Celia Marrasé, PI of DOREMI project This report contains the sampling of all the variables at each station along the FICARAM section, as well as the analysis of the biogeochemical variables and the preliminary results. The principal investigator of the DOREMI project produced another report with the common sampling section, showing the analysis and results of the experiments on dissolved organic matter carried out on board.This cruise is supported by the CATARINA project funded by the Ministry of Economy and Competitiveness (CTM2010-17141) and is part of the European Union FP7 project CARBOCHANGE (http://carbochange.b.uib.no/)Peer reviewe

Improving Scientific Knowledge of Mallorca Channel Seamounts (Western Mediterranean) within the Framework of Natura 2000 Network

The scientific exploration of Mallorca Channel seamounts (western Mediterranean) is improving the knowledge of the Ses Olives (SO), Ausias March (AM), and Emile Baudot (EB) seamounts for their inclusion in the Natura 2000 network. The aims are to map and characterize benthic species and habitats by means of a geological and biological multidisciplinary approach: high-resolution acoustics, sediment and rock dredges, beam trawl, bottom trawl, and underwater imagery. Among the seamounts, 15 different morphological features were differentiated, highlighting the presence of 4000 pockmarks, which are seafloor rounded depressions indicators of focused fluid flow escapes, usually gas and/or water, from beneath the seabed sediments. So far, a total of 547 species or taxa have been inventoried, with sponges, fishes, mollusks, and crustaceans the most diverse groups including new taxa and new geographical records. Up to 29 categories of benthic habitats have been found, highlighting those included in the Habitats Directive: maërl beds on the summits of AM and EB, pockmarks around the seamounts and coral reefs in their rocky escarpments as well as fields of Isidella elongata on sedimentary bathyal bottoms. Trawling is the main demersal fishery developed around SO and AM, which are targeted to deep water crustaceans: Parapenaeus longirostris, Nephrops norvegicus, and Aristeus antennatus. This study provides scientific information for the proposal of the Mallorca Channel seamounts as a Site of Community Importance and for its final declaration as a Special Area of Conservation

Agent Applications in Tourism

Agent technology has been applied in recent years to solve different problems that are common to many applications in Tourism, such as dynamic service discovery, automatic management of user profiles, personalisation of cultural information or planning of touristic activities. This chapter shows different contributions of Spanish research groups in the following areas: personalised access to cultural information from mobile devices, planning of complex touristic activities, service discovery in Tourism applications and dynamic location tracking

BCKDK deficiency: a treatable neurodevelopmental disease amenable to newborn screening

There are few causes of treatable neurodevelopmental diseases described to date. Branched-chain ketoacid dehydrogenase kinase (BCKDK) deficiency causes branched-chain amino acid (BCAA) depletion and is linked to a neurodevelopmental disorder characterized by autism, intellectual disability and microcephaly. We report the largest cohort of patients studied, broadening the phenotypic and genotypic spectrum. Moreover, this is the first study to present newborn screening findings and mid-term clinical outcome. In this cross-sectional study, patients with a diagnosis of BCKDK deficiency were recruited via investigators’ practices through a MetabERN initiative. Clinical, biochemical and genetic data were collected. Dried blood spot (DBS) newborn screening (NBS) amino acid profiles were retrieved from collaborating centres and compared to a healthy newborn reference population. Twenty-one patients with BCKDK mutations were included from 13 families. Patients were diagnosed between 8 months and 16 years (mean: 5.8 years, 43% female). At diagnosis, BCAA levels (leucine, valine and isoleucine) were below reference values in plasma and in CSF. All patients had global neurodevelopmental delay; 18/21 had gross motor function (GMF) impairment with GMF III or worse in 5/18, 16/16 intellectual disability, 17/17 language impairment, 12/17 autism spectrum disorder, 9/21 epilepsy, 12/15 clumsiness, 3/21 had sensorineural hearing loss and 4/20 feeding difficulties. No microcephaly was observed at birth, but 17/20 developed microcephaly during follow-up. Regression was reported in six patients. Movement disorder was observed in 3/21 patients: hyperkinetic movements (1), truncal ataxia (1) and dystonia (2). After treatment with a high-protein diet (≥ 2 g/kg/day) and BCAA supplementation (100–250 mg/kg/day), plasma BCAA increased significantly (P < 0.001), motor functions and head circumference stabilized/ improved in 13/13 and in 11/15 patients, respectively. Among cases with follow-up data, none of the three patients starting treatment before 2 years of age developed autism at follow-up. The patient with the earliest age of treatment initiation (8 months) showed normal development at 3 years of age. NBS in DBS identified BCAA levels significantly lower than those of the normal population. This work highlights the potential benefits of dietetic treatment, in particular early introduction of BCAA. Therefore, it is of utmost importance to increase awareness about this treatable disease and consider it as a candidate for early detection by NBS programmes.A.G.C. is supported by FIS P118/00111, FI21/0073 ‘Instituto de Salud Carlos III (ISCIII)’ and ‘Fondo Europeo de desarrollo regional (FEDER)’

Hyperkalemia in Heart Failure Patients in Spain and Its Impact on Guidelines and Recommendations: ESC-EORP-HFA Heart Failure Long-Term Registry

[Abstract] Introduction and objectives: Hyperkalemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction because it limits the use of effective drugs. We report estimates of the magnitude of this problem in routine clinical practice in Spain, as well as changes in potassium levels during follow-up and associated factors. Methods: This study included patients with acute (n=881) or chronic (n=3587) heart failure recruited in 28 Spanish hospitals of the European heart failure registry of the European Society of Cardiology and followed up for 1 year. Various outcomes were analyzed, including changes in serum potassium levels and their impact on treatment. Results: Hyperkalemia (K+> 5.4 mEq/L) was identified in 4.3% (95%CI, 3.7%-5.0%) and 8.2% (6.5%-10.2%) of patients with chronic and acute heart failure, respectively, and was responsible for 28.9% of all cases of contraindication to mineralocorticoid receptor antagonist use and for 10.8% of all cases of failure to reach the target dose. Serum potassium levels were not recorded in 291 (10.8%) of the 2693 chronic heart failure patients with reduced ejection fraction. During follow-up, potassium levels increased in 179 of 1431 patients (12.5%, 95%CI, 10.8%-14.3%). This increase was directly related to age, diabetes, and history of stroke and was inversely related to history of hyperkalemia. Conclusions: This study highlights the magnitude of the problem of hyperkalemia in patients with heart failure in everyday clinical practice and the need to improve monitoring of this factor in these patients due to its interference with the possibility of receiving optimal treatment.[Resumen] Introducción y objetivos. La hiperpotasemia es una preocupación creciente en el tratamiento de los pacientes con insuficiencia cardiaca y fracción de eyección reducida, pues limita el uso de fármacos eficaces. Este trabajo ofrece estimaciones de la magnitud de este problema en la práctica clínica habitual en España, los cambios en las concentraciones de potasio en el seguimiento y los factores asociados. Métodos. Pacientes con insuficiencia cardiaca aguda (n = 881) y crónica (n = 3.587) seleccionados en 28 hospitales españoles del registro europeo de insuficiencia cardiaca de la European Society of Cardiology y seguidos 1 año para diferentes desenlaces, incluidos cambios en las cifras de potasio y su impacto en el tratamiento. Resultados. La hiperpotasemia (K+ > 5,4 mEq/l) está presente en el 4,3% (IC95%, 3,7-5,0%) y el 8,2% (6,5-10,2%) de los pacientes con insuficiencia cardiaca crónica y aguda; causa el 28,9% de todos los casos en que se contraindica el uso de antagonistas del receptor de mineralocorticoides y el 10,8% de los que no alcanzan la dosis objetivo. Del total de 2.693 pacientes ambulatorios con fracción de eyección reducida, 291 (10,8%) no tenían registrada medición de potasio. Durante el seguimiento, 179 de 1.431 (12,5%, IC95%, 10,8-14,3%) aumentaron su concentración de potasio, aumento relacionado directamente con la edad, la diabetes mellitus y los antecedentes de ictus e inversamente con los antecedentes de hiperpotasemia. Conclusiones. Este trabajo destaca el problema de la hiperpotasemia en pacientes con insuficiencia cardiaca de la práctica clínica habitual y la necesidad de continuar y mejorar la vigilancia de este factor en estos pacientes por su interferencia en el tratamiento óptimo

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file