A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme Cystathionine β -Synthase: Increased CO Reactivity as a Novel Molecular Mechanism of Pathogenicity?

The human disease classical homocystinuria results from mutations in the gene encoding the pyridoxal 5′-phosphate- (PLP-) dependent cystathionine β-synthase (CBS), a key enzyme in the transsulfuration pathway that controls homocysteine levels, and is a major source of the signaling molecule hydrogen sulfide (H2S). CBS activity, contributing to cellular redox homeostasis, is positively regulated by S-adenosyl-L-methionine (AdoMet) but fully inhibited upon CO or NO• binding to a noncatalytic heme moiety. Despite extensive studies, the molecular basis of several pathogenic CBS mutations is not yet fully understood. Here we found that the ferrous heme of the reportedly mild p.P49L CBS variant has altered spectral properties and markedly increased affinity for CO, making the protein much more prone than wild type (WT) CBS to inactivation at physiological CO levels. The higher CO affinity could result from the slightly higher flexibility in the heme surroundings revealed by solving at 2.80-Å resolution the crystallographic structure of a truncated p.P49L. Additionally, we report that p.P49L displays impaired H2S-generating activity, fully rescued by PLP supplementation along the purification, despite a minor responsiveness to AdoMet. Altogether, the results highlight how increased propensity to CO inactivation of an otherwise WT-like variant may represent a novel pathogenic mechanism in classical homocystinuria

Computational Modelling of Tissue-Engineered Cartilage Constructs

Cartilage is a fundamental tissue to ensure proper motion between bones and damping of mechanical loads. This tissue often suffers damage and has limited healing capacity due to its avascularity. In order to replace surgery and replacement of joints by metal implants, tissue engineered cartilage is seen as an attractive alternative. These tissues are obtained by seeding chondrocytes or mesenchymal stem cells in scaffolds and are given certain stimuli to improve establishment of mechanical properties similar to the native cartilage. However, tissues with ideal mechanical properties were not obtained yet. Computational models of tissue engineered cartilage growth and remodelling are invaluable to interpret and predict the effects of experimental designs. The current model contribution in the field will be presented in this chapter, with a focus on the response to mechanical stimulation, and the development of fully coupled modelling approaches incorporating simultaneously solute transport and uptake, cell growth, production of extracellular matrix and remodelling of mechanical properties.publishe

Innovative sea surface monitoring with GNSS-REflectometry aboard ISS: overview and recent results from GEROS-ISS

GEROS-ISS (GEROS hereafter) stands for GNSS REflectometry, Radio Occultation and Scatterometry onboard the International Space Station. It is a scientific experiment, proposed to the European Space Agency (ESA) in 2011 for installation aboard the ISS. The main focus of GEROS is the dedicated use of signals from the currently available Global Navigation Satellite Systems (GNSS) for remote sensing of the System Earth with focus to Climate Change characterisation. The GEROS mission idea and the current status are briefly reviewed.Peer ReviewedPostprint (author's final draft

Impacto de un programa intervención em alunos del segundo ciclo

O objetivo do presente estudo consistiuem avaliar um programa de intervenção junto a alunos do 2º ciclo de escolaridade nas seguintes dimensões: tomada de decisão, conhecimentos sobre sexualidade, competências sociais, assertividade e autoconceito. Metodologia: Participaram 145 alunos, distribuídos pelos grupos controle e experimental. Os instrumentos utilizados foram: TCU Decision-Making; Questionário de Conhecimentos sobre Sexualidade; Assertion Self-Statement Test- Revised; Questionário de Competências Sociais; Piers-Harris Children’s Self-Concept Scale. Os resultados revelaram diferenças no pós-teste entre os grupos ao nível da sexualidade. Verificaram-se diferenças do pré-teste para o pós-teste no grupo experimental nos níveis da sexualidade, da assertividade e das competências sociais. No grupo experimental encontraram-se associações positivas entre tomada de decisão, competências sociais e assertividade, bem como entre sexualidade, competências sociais e autoconceito, no pós-teste. Os preditores da assertividade no pós-teste foram tomada de decisão, sexualidade e competências sociais. Como conclusão, os resultados enfatizam a importância de intervenção junto a adolescentes, particularmente na tomada de decisão, na sexualidade e nas competências sociais. Palavras-chave: Habilidades sociais, sexualidade, autoconceito.In this study we evaluate an intervention program in the following dimensions: Decision Making, Knowledge on Sexuality, Social Skills, Assertiveness and Self-Concept with students in 5th and 6th grade. Methodology: 145 students participated in the study divided by control and experimental group. The instruments used were: Decision-Making TCU, Knowledge on Sexuality Questionnaire; Assertion Self-Statement Test-Revised;Social Skills Questionnaire, and Piers-Harris Children's Self- Concept Scale. The results indicate differences at post-test between the groups on knowledge regarding sexuality. There were also differences from pre-test to post-test in the experimental group on knowledge on sexuality, assertiveness and social skills. Positive associations among decision making, social skills and assertiveness were found as well as among knowledge on sexuality, social skills and self-concept, in the experimental group, in the pos-test. Finally, the predictors of assertiveness regarding health behaviors, in the pos-test were: decision making, knowledge regarding sexuality and social skills. The results emphasize the importance of intervention for adolescents in terms of health promotion particularly in decision making, sexuality and social skills.El objetivo del presente estudio fue evaluar un programa de intervención con alumnos del 2º ciclo de escolaridad en las siguientes dimensiones: Toma de Decisión, Conocimientos sobre Sexualidad, Habilidades Sociales, Asertividad y Autoconcepto. Metodología: Participaron 145 alumnos, distribuidos en grupo control y experimental. Los instrumentos utilizados fueron: TCU Decision-Making; Cuestionario de Conocimientos sobre Sexualidad; AssertionSelf-Statement Test-Revised; Cuestionario de Habilidades Sociais; Piers-Harris Children'sSelf-Concept Scale. Los resultados mostraron diferencias en el post-test entre los grupos en cuanto a la sexualidad. Se verificaron diferencias del pre-test para el post-teste en el grupo experimental, cuanto a sexualidad, asertividad y habilidades sociales. Se encontraron asociaciones positivas entre toma de decisión, habilidades sociales y asertividad, así como entre sexualidad,habilidades sociales yautoconcepto, en el post-test en el grupo experimental. Los predictores de la asertividad en el post-test fueron toma de decisión, sexualidad y habilidades sociales. Los resultados destacan la importancia de la intervención con adolescentes particularmente en la toma de decisiones, sexualidad y habilidades sociales.(undefined

The Complete Genome Sequence of Thermoproteus tenax: A Physiologically Versatile Member of the Crenarchaeota

Here, we report on the complete genome sequence of the hyperthermophilic Crenarchaeum Thermoproteus tenax (strain Kra 1, DSM 2078(T)) a type strain of the crenarchaeotal order Thermoproteales. Its circular 1.84-megabase genome harbors no extrachromosomal elements and 2,051 open reading frames are identified, covering 90.6% of the complete sequence, which represents a high coding density. Derived from the gene content, T. tenax is a representative member of the Crenarchaeota. The organism is strictly anaerobic and sulfur-dependent with optimal growth at 86 degrees C and pH 5.6. One particular feature is the great metabolic versatility, which is not accompanied by a distinct increase of genome size or information density as compared to other Crenarchaeota. T. tenax is able to grow chemolithoautotrophically (CO2/H-2) as well as chemoorganoheterotrophically in presence of various organic substrates. All pathways for synthesizing the 20 proteinogenic amino acids are present. In addition, two presumably complete gene sets for NADH:quinone oxidoreductase (complex I) were identified in the genome and there is evidence that either NADH or reduced ferredoxin might serve as electron donor. Beside the typical archaeal A(0)A(1)-ATP synthase, a membrane-bound pyrophosphatase is found, which might contribute to energy conservation. Surprisingly, all genes required for dissimilatory sulfate reduction are present, which is confirmed by growth experiments. Mentionable is furthermore, the presence of two proteins (ParA family ATPase, actin-like protein) that might be involved in cell division in Thermoproteales, where the ESCRT system is absent, and of genes involved in genetic competence (DprA, ComF) that is so far unique within Archaea

A generic simulator for aperture synthesis radiometers

ESA's SMOS mission has demonstrated that Synthetic Aperture Interferometric Radiometers can be a useful tool for Earth observation. Today, the NASA's GeoStar instrument (USA), ESA's GAS instrument (Europe), or CSSAR's GIMS instrument (China) are just three examples of planned geostationary millimeter-wave sounders using synthetic aperture interferometric radiometry for continuous atmospheric monitoring with a much improved spatial resolution. The study of the performance in terms of angular resolution and radiometric performance, and the optimization of this new type of instruments is a complex task that requires dedicated ad-hoc simulators. The SAIPRS (Synthetic Aperture Interferometric Radiometer Performance Simulator) is an ESA project aiming at the development of a generic simulator in terms of receiver architecture and array configuration, including moving antennas (and eventually changing polarization reference frames). This work summarizes the key aspects of the architecture of this simulator.Peer Reviewe

A generic simulator for aperture synthesis radiometers

ESA's SMOS mission has demonstrated that Synthetic Aperture Interferometric Radiometers can be a useful tool for Earth observation. Today, the NASA's GeoStar instrument (USA), ESA's GAS instrument (Europe), or CSSAR's GIMS instrument (China) are just three examples of planned geostationary millimeter-wave sounders using synthetic aperture interferometric radiometry for continuous atmospheric monitoring with a much improved spatial resolution. The study of the performance in terms of angular resolution and radiometric performance, and the optimization of this new type of instruments is a complex task that requires dedicated ad-hoc simulators. The SAIPRS (Synthetic Aperture Interferometric Radiometer Performance Simulator) is an ESA project aiming at the development of a generic simulator in terms of receiver architecture and array configuration, including moving antennas (and eventually changing polarization reference frames). This work summarizes the key aspects of the architecture of this simulator.Peer Reviewe

Integrity Aspects of Hybrid EGNOS-based Navigation on Support of Search And-Rescue Missions with UAVs

This paper describes the goals, concept and overall approach of the European 7th Framework Programme´s project named CLOSE-SEARCH, which stands for ´Accurate and safe EGNOS-SoL Navigation for UAV-based low-cost SAR operations´ and is being conducted by a consortium of a research centre (Institute of Geomatics, IG), a private non-profit technology centre (Asociaci¢n de la Industria Navarra, AIN), the Geodetic Engineering Laboratory (TOPO) of the Ecole Polytechnique F‚d‚rale of Lausanne (EPFL), an aerospace engineering company (DEIMOS Engenharia, DME), a public research agency and geospatial data provider (Institute of Cartography of Catalonia, ICC) and an end user, the Direcci¢ General de Protecci¢ Civil (DGPC, the Catalan civil protection authority). The goal of CLOSE-SEARCH is to integrate in a small Unmanned Aerial Vehicle (UAV) (helicopter type, for reasons of maneuverability), a thermal imaging sensor and a multi-sensor navigation system (based on the use of a Barometric Altimeter (BA), a Magnetometer (MAGN), a Redundant Inertial Navigation System (RINS) and an SBAS-enabled GNSS receiver) with an Autonomous Integrity Monitoring (AIM) capability, to support the search component of Search-And-Rescue (SAR) operations in remote, difficult-to-access areas and/or in time critical situations. The proposed integration will result in a Hardware and Software prototype that will demonstrate an end-to-end functionality: by systematically flying over a region (during day or night, under adverse weather conditions and in rather inaccessible areas) and it will identify disaster survivors or lost people through the detection of the body heat. In other words, CLOSE-SEARCH strives to be a low-cost and robust system that searches for distressed people in situations where only an approximate knowledge of their whereabouts is available. Finally, it is also the goal of CLOSE-SEARCH to demonstrate the added value of a future multi-constellation augmented GNSS configuration (Galileo/GPS-EGNOS or Galileo/GPS-SoL)

Microwave imaging radiometers by aperture synthesis— performance simulator (part 1): radiative transfer module

The Synthetic Aperture Interferometric Radiometer Performance Simulator (SAIRPS) is a three-year project sponsored by the European Space Agency (ESA) to develop a completely generic end-to-end performance simulator of arbitrary synthetic aperture interferometric radiometers. This means, on one side, a generic radiative transfer module from 1 to 100 GHz, including land and ocean covers, as well as a fully 3D atmosphere and Faraday ionospheric rotation based on variable TEC. On the other hand, the instrument can have an arbitrary array topology (number of antenna elements, and their time-dependent position and orientation). Receivers’ topology can also be modified, starting from a very generic one to connecting and disconnecting subsystems, whose parameters can be individually configured. These parameters can be defined either by mathematical functions or by input data files, including the frequency and temperature dependence. Generic calibration and image reconstruction algorithms that are suitable for arbitrary array topologies have also been implemented, as well as tools to compute the instrument performance metrics, i.e., radiometric accuracy, sensitivity, angular resolution, etc. This manuscript presents the generic architecture of the SAIRPS, the algorithms implemented in the Radiative Transfer Module, and simulation results showing its performance. A companion manuscript (Part II) describes the instrument and calibration modelling, the image reconstruction algorithms, and the validation tests that were performed.Peer ReviewedPostprint (published version