Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types

Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated six differentially expressed genes (ATG16L2, ACSL5, MAP1LC3A, MAPKAPK3, PLXNB2, and SCFD1) within the significant pathways as relevant to ALS. We conclude that the disparate genetic etiologies of this fatal neurological disease converge on a smaller number of final common pathways and cell types

Nuevas rutas de síntesis de materiales porosos y su aplicación en procesos de separación

[ES] La presente tesis doctoral se centra en estudiar nuevas rutas de síntesis para la síntesis de materiales porosos tanto inorgánicos como orgánicos. En concreto está tesis está dividida en dos grandes capítulos. El primer capitulo se centra en el estudio de materiales inorgánicos porosos, las zeolitas. En el desarrollo de este capitulo se han sintetizado nuevos cationes orgánicos fosforados y arseniados, que han sido caracterizados y utilizados como agentes directores de estructura en la síntesis de zeolitas. El empleo de los cationes fosforados sintetizados ha permitido por primera vez, la síntesis de la zeolita ITQ-21 utilizando un catión orgánico fosforado. También utilizando el mismo catión orgánico fosforado se ha podido estudiar la transformación zeolítica entre la zeolita ITQ-33 e ITQ-34. Los cationes arseniados sintetizados han sido empleado como agentes directores de estructura en la síntesis de zeolitas ZSM-5. Se ha utilizado las mismas condiciones de síntesis que se habían empleado en la literatura para la síntesis de este material con los cationes análogos tanto nitrogenados como fosforados. El interés en utilizar cationes orgánicos como agentes directores de estructura basados en arsénico es debido a su elevado peso molecular y volumen. Esto permite localizar el arsénico del catión orgánico, y facilita la localización del resto de átomos de carbono que conforman el catión ocluido en el interior del material. En este sentido, el empleo de arsénico ha permitido localizar el catión orgánico en el interior de la zeolita mediante difracción de rayos X de polvo. Adicionalmente, también ha permitido el estudio del catión ocluido en la zeolita mediante la espectroscopía de absorción de rayos X (XAS). El segundo capítulo de esta tesis doctoral se centra en el estudio de materiales porosos orgánicos y su empleo en procesos de separación. En esta parte se ha sintetizado en primer lugar el COF (del inglés, Covalent Organic Framework) CC3-R que es un polímero orgánico poroso quiral descrito en la literatura. En este trabajo, se ha estudiado exhaustivamente por medio de 1H-MAS-NMR, observándose que el COF denominado CC3-R, selectivamente interacciona preferentemente con moléculas R-quirales, siendo por tanto un material prometedor para la resolución quiral mediante métodos de adsorción selectiva.[CA] La present tesi doctoral se centra a estudiar noves rutes de síntesis de materials porosos tant inorgànics com orgànics. En concret, aquesta tesi esta dividida en dos grans capítols. El primer capítol se centra en l'estudi de materials inorgànics porosos, les zeolites. En el desenvolupament d'aquest capítol s'han sintetitzat nous cations orgànics fosforats i arsenats, que han sigut caracteritzats i utilitzats com agents directors d'estructura en la síntesi de zeolites. L'ús de cations fosforats sintetitzats ha permés per primera vegada, la síntesi de la zeolita ITQ-21 utilitzant un catió orgànic fosforat. També utilitzant el mateix catió orgànic fosforat s'ha pogut estudiar la transformació zeolítica entre la zeolita ITQ-33 i ITQ-34. Els cations arsenats sintetitzats han sigut utilitzats com agents directors d'estructura en la síntesi de la zeolita ZSM-5. S'hi ha empleat les mateixes condicions de síntesis que s'havien utilitzat en la literatura per a la síntesi d'aquest material amb els cations anàlegs tant nitrogenats com fosforats. L'interés a utilitzar cations orgànics com agents d'estructura basats en arsènic és a causa del seu elevat pes molecular i volum. Açò permet localitzar l'arsènic del catió orgànic i facilita la localització de la resta d'àtoms de carboni que conformen el catió oclòs a l'interior del material. En aquest sentit, l'ús d'arsènic hi ha permés localitzar el catió orgànic en l'interior de la zeolita mitjançant la difracció de raig X de pols. Addicionalment, també hi ha permés l'estudi del catió oclòs a la zeolita mitjançant l'espectroscòpia d'absorció de raig X (XAS). El segon capítol d'aquesta tesi doctoral se centra en l'estudi de materials porosos orgànics i el seu ús en processos de separació. En aquesta part s'ha sintetitzat en primer lloc el COF ( de l'anglès, Covalent Organic Frameworks) CC3-R que és un polímer orgànic porós quiral descrit a la literatura. En aquest treball, s'ha estudiat exhaustivament per mitjà de 1H-MAS-NMR, observant-se que el COF denominat CC3-R, selectivament interacciona preferentment amb molècules R-quirals, sent per tant un material prometedor per a la resolució quiral mitjançant mètodes d'adsorció selectiva.[EN] The present doctoral thesis focuses on studying new synthesis routes for the synthesis of porous materials, both inorganic and organic. In particular, this thesis is divided into two major chapters. The first chapter focuses on the study of porous inorganic materials, zeolites. In the development of this chapter, new organophosphate and phosphorous organic cations have been synthesized, which have been characterized and used as structure directing agents in the synthesis of zeolites. The use of synthesized phosphorated cations has allowed, for the first time, the synthesis of the ITQ-21 zeolite using a phosphorous organic cation. Also using the same organic phosphorus cation, it has been possible to study the zeolitic transformation between ITQ-33 and ITQ-34 zeolite. Synthesized arsenized cations have been used as structure directing agents in the synthesis of ZSM-5 zeolites. The same synthesis conditions that had been used in the literature for the synthesis of this material with the analogous cations both nitrogen and phosphorus have been used. The interest in using organic cations as structure directing agents based on arsenic is due to its high molecular weight and volume. This allows locating both the arsenic of the organic cation and the location of the remaining carbon atoms that make up the cation occluded inside the material. In this sense, the use of arsenic has made it possible to locate the organic cation inside the zeolite by powder X-ray diffraction. Additionally, it has also allowed the study of the occluded cation in zeolite by X-ray absorption spectroscopy (XAS). The second chapter of this doctoral thesis focuses on the study of organic porous materials and their use in separation processes. In this part, the COF (Covalent Organic Framework) CC3-R, which is a chiral porous organic polymer described in the literature, has been synthesized in the first place. In this work, it has been studied exhaustively by means of 1H-MAS-NMR, observing that the COF denominated CC3-R, selectively interacts preferably with R-chiral molecules, being, therefore, a promising material for the chiral resolution by means of selective adsorption methods.Saez Ferre, S. (2019). Nuevas rutas de síntesis de materiales porosos y su aplicación en procesos de separación [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/119447TESI

Investigation of the strength of thermally conditioned basalt and e-glass fibres

It is projected that the total global production of composite materials will significantly exceed 10 million tons by 2015 of which over 90% will contain glass fibre reinforcement. Traditionally most of this composite material would be directed to landfill at end of life. Thus, recycling composites has started to gain great importance due to environmental and commercial aspects. The development of an efficient process to enable cost-effective regeneration of the mechanical properties of fibre for recycling, could result in a huge decrease of landfill disposal as well as the attenuation in CO2 emissions. There are several processes available for recycling composites but the most technologically advanced is thermal recycling. However, during the recycling process glass fibres that are treated at temperatures in a range between 300 up to 600 °C exhibit a huge drop in strength and as a result sometimes are considered as not reusable or unsuitable for reprocessing [1]. Although basalt fibre has been available for some time, recent development in the processing and production of basalt has resulted in the availability of continuous basalt fibre in similar form to traditional glass fibre. It is often stated that basalt has better high temperature resistance compared to E-glass fibre [2,3]. If this were true then basalt fibre may show better prospects to survive an end-of-life composite thermal recycling process as a useful reinforcement. The present work investigates and compares the changes in the mechanical properties of basalt fibres and E-Glass fibres when heat-treated to between 300 – 600 °C. Since the fibre surface plays an important role in the retained strength of brittle fibres, the investigation used fibre with similar epoxy compatible sizings in order to maximise the quality of the comparison. Results of single fibre testing of tensile strength and modulus are presented and discussed

Elucidation of the Interaction Mechanism between Organic Chiral Cages with Biomolecules through Nuclear Magnetic Resonance and Theoretical Studies

[EN] A multinuclear NMR has been carried out to elucidate the mechanism of action of CC3-R box-type chiral materials for the separation of enantiomers, supported by theoretical calculations. The potential of these materials to be used as chiral resolution agents through NMR is evidence in this study.Program Severo Ochoa SEV-2016-0683 is gratefully acknowledged. S.S-F. thanks MEC for his Severo Ochoa Grant SPV-2013-067884, P.O.-B. thanks MEC for his Ramon y Cajal contract RYC-2014-16620. M.B. and F.R. thank the financial support by the Spanish Government (MAT2017-82288-C2-1-P and MAT2015-71842-P). The authors thank the MULTY2-HYCAT (EU-Horizon 2020 funded project under grant agreement no. 720783). The Electron Microscopy Service of the UPV is acknowledged for their help in sample characterization.Saez-Ferre, S.; Boronat Zaragoza, M.; Cantin Sanz, A.; Rey Garcia, F.; Oña-Burgos, P. (2018). Elucidation of the Interaction Mechanism between Organic Chiral Cages with Biomolecules through Nuclear Magnetic Resonance and Theoretical Studies. The Journal of Physical Chemistry C. 122(29):16821-16829. https://doi.org/10.1021/acs.jpcc.8b05069S16821168291222

Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis : a genome-wide association study

Myasthenia gravis is a chronic autoimmune disease characterized by autoantibody-mediated interference of signal transmission across the neuromuscular junction. We performed a genome-wide association study (GWAS) involving 1,873 patients diagnosed with acetylcholine receptor antibody-positive myasthenia gravis and 36,370 healthy individuals to identify disease-associated genetic risk loci. Replication of the discovered loci was attempted in an independent cohort from the UK Biobank. We also performed a transcriptome-wide association study (TWAS) using expression data from skeletal muscle, whole blood, and tibial nerve to test the effects of disease-associated polymorphisms on gene expression. We discovered two signals in the genes encoding acetylcholine receptor subunits that are the most common antigenic target of the autoantibodies: a GWAS signal within the cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) gene and a TWAS association with the cholinergic receptor nicotinic beta 1 subunit (CHRNB1) gene in normal skeletal muscle. Two other loci were discovered on 10p14 and 11q21, and the previous association signals at PTPN22, HLA-DQA1/HLA-B, and TNFRSF11A were confirmed. Subgroup analyses demonstrate that early-and late-onset cases have different genetic risk factors. Genetic correlation analysis confirmed a genetic link between myasthenia gravis and other autoimmune diseases, such as hypothyroidism, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. Finally, we applied Priority Index analysis to identify potentially druggable genes/proteins and pathways. This study provides insight into the genetic architecture underlying myasthenia gravis and demonstrates that genetic factors within the loci encoding acetylcholine receptor subunits contribute to its pathogenesis.Peer reviewe

Carbapenemase-producing enterobacteriaceae in Spain in 2012

We report the epidemiological impact of carbapenemase-producing Enterobacteriaceae (CPE) in Spain in 2012. Of the 237 carbapenemases detected, 163 were from the OXA-48 group, 60 were from VIM-1, 8 were from KPC-2, 5 were from IMP, and 1 was from NDM-1. Interhospital spread of carbapenemase-producing Klebsiella pneumoniae was due to a limited number of multilocus sequence types (MLST) and carbapenemase types, including ST15-VIM-1, ST11-OXA-48, ST405-OXA-48, ST101-KPC-2, and ST11-VIM-1. The number of CPE cases in Spain has increased sharply in recent years, due mainly to the emergence of OXA-48.This study was supported by the Antibiotic Resistance Surveillance Program of the Spanish Centro Nacional de Microbiología of the Instituto de Salud Carlos III. Verónica Bautista was supported by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund “A way to achieve Europe” ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015).S

Conocimientos y prevalencia de consumo de tabaco de los estudiantes del Grado en Enfermería.

OBJETIVOS: Conocer la información sobre tabaquismo y la prevalencia de consumo de tabaco en la población de estudiantes del Grado de Enfermería de la Universidad de Zaragoza y de la Universidad San Jorge, además de evaluar las diferencias en la prevalencia según sexo, curso académico y centro universitario. METODOLOGÍA: Estudio descriptivo transversal. La población a estudio son los estudiantes de los cursos de primero y tercero del Grado en Enfermería de las Facultades de Ciencias de la Salud de UNIZAR y de USJ en el curso 2016-2017. El cuestionario elegido fue el utilizado en el estudio ECTEC. RESULTADOS: El 57,3% de los estudiantes no han fumado nunca, el 9,6% fuman ocasionalmente y el 22% fuman a diario. La edad media en la que fumaron por primera vez es de 15,5 años. No existen diferencias en la prevalencia según sexo y según el curso. La prevalencia de estudiantes de USJ que fuman a diario es más del doble (38,2%) que la de los estudiantes de UNIZAR (15,8%). CONCLUSIONES: La prevalencia de tabaquismo entre el alumnado de enfermería es similar a la de la población general, sin diferencias según sexo ni curso, pero con diferencias según la universidad. Se debe mejorar la formación que los estudiantes de enfermería reciben sobre tabaquismo en todos los aspectos, ya que estos profesionales son personal clave en la prevención y tratamiento del tabaquismo

Field quality of 1.5 m long conduction cooled superconducting undulator coils with 20 mm period length

The Institute for Beam Physics and Technology (IBPT) at the Karlsruhe Institute of Technology (KIT) and the industrial partner Babcock Noell GmbH (BNG) are collaborating since 2007 on the development of superconducting undulators both for ANKA and low emittance light sources. The first full length device with 15 mm period length has been successfully tested in the ANKA storage ring for one year. The next superconducting undulator has 20 mm period length (SCU20) and is also planned to be installed in the accelerator test facility and synchrotron light source ANKA. The SCU20 1.5 m long coils have been characterized in a conduction cooled horizontal test facility developed at KIT IBPT. Here we present the local magnetic field and field integral measurements, as well as their analysis including the expected photon spectrum

ECIU position paper on living labs and experimentation spaces:Recommendations and insights about the potential of Living Labs as innovation and learning platforms in the ECIU University

To accelerate transformations towards just and sustainable future cities across Europe, local and regional projects need to scale up and share sustainability pathways and planning efforts. In this context, Living Labs, and innovation and experimentation spaces in general, have demonstrated great potential in serving as platforms for connecting universities with societal stakeholder, facilitating transdisciplinary collaboration in the innovation process but also as tools for cross-case learning and upscaling innovative solutions. At the same time there is an ever increasing emergence and diversification of these spaces, even within ECIU, that can often create a certain confusion and at the same time reluctance to engage and make use of them or explore their full potential

Progress of the Development of a Superconducting Undulator as a THz Source for FELs

To produce radiation in the THz frequency range at X-ray Free Electron Lasers, undulators with large period length, high fields, and large gaps are required. These demands can be fulfilled by superconducting undulators. In this contribution, the actual requirements on the main parameters of such a superconducting undulator will be discussed and the progress of the design will be discussed. In addition, beam impedance and heat load results obtained analytically as well as by large-scale wakefield simulations will be presented