Highway construction in Wireless Sensor Networks

English: Wireless sensor networks are a rapidly growing field of study with many open research topics. The aim of this project is to build a hierarchy of clusters in wireless sensor networks and to communicate them through distinguished paths. Those paths are known as highways, and simplify higher level node inter-communication while reducing energy and memory requirements. To achieve this goal several distributed algorithms were designed and tested either in simulators or in real hardware. The message delivery rate, through highways, measured in hardware was close to 70\% and it effectively served as base for a higher level network module to make end to end communication between every node of the connected network. This opens a way for the development of more algorithms to make wireless sensor networks communications on large deployments effective and trouble less

VRK1 (Y213H) homozygous mutant impairs Cajal bodies in a hereditary case of distal motor neuropathy.

Background: Distal motor neuropathies with a genetic origin have a heterogeneous clinical presentation with overlapping features affecting distal nerves and including spinal muscular atrophies and amyotrophic lateral sclerosis. This indicates that their genetic background is heterogeneous. Patient and methods: In this work, we have identified and characterized the genetic and molecular base of a patient with a distal sensorimotor neuropathy of unknown origin. For this study, we performed whole-exome sequencing, molecular modelling, cloning and expression of mutant gene, and biochemical and cell biology analysis of the mutant protein. Results: A novel homozygous recessive mutation in the human VRK1 gene, coding for a chromatin kinase, causing a substitution (c.637T > C; p.Tyr213His) in exon 8, was detected in a patient presenting since childhood a progressive distal sensorimotor neuropathy and spinal muscular atrophy syndrome, with normal intellectual development. Molecular modelling predicted this mutant VRK1 has altered the kinase activation loop by disrupting its interaction with the C-terminal regulatory region. The p.Y213H mutant protein has a reduced kinase activity with different substrates, including histones H3 and H2AX, proteins involved in DNA damage responses, such as p53 and 53BP1, and coilin, the scaffold for Cajal bodies. The mutant VRK1(Y213H) protein is unable to rescue the formation of Cajal bodies assembled on coilin, in the absence of wild-type VRK1. Conclusion: The VRK1(Y213H) mutant protein alters the activation loop, impairs the kinase activity of VRK1 causing a functional insufficiency that impairs the formation of Cajal bodies assembled on coilin, a protein that regulates SMN1 and Cajal body formation.post-print2120 K

Heterozygous deletion of the Williams-Beuren syndrome critical interval in mice recapitulates most features of the human disorder

Williams-Beuren syndrome is a developmental multisystemic disorder caused by a recurrent 1.55-1.83 Mb heterozygous deletion on human chromosome band 7q11.23. Through chromosomal engineering with the cre-loxP system, we have generated mice with an almost complete deletion (CD) of the conserved syntenic region on chromosome 5G2. Heterozygous CD mice were viable, fertile and had a normal lifespan, while homozygotes were early embryonic lethal. Transcript levels of most deleted genes were reduced 50% in several tissues, consistent with gene dosage. Heterozygous mutant mice showed postnatal growth delay with reduced body weight and craniofacial abnormalities such as small mandible. The cardiovascular phenotype was only manifested with borderline hypertension, mildly increased arterial wall thickness and cardiac hypertrophy. The neurobehavioral phenotype revealed impairments in motor coordination, increased startle response to acoustic stimuli and hypersociability. Mutant mice showed a general reduction in brain weight. Cellular and histological abnormalities were present in the amygdala, cortex and hippocampus, including increased proportion of immature neurons. In summary, these mice recapitulate most crucial phenotypes of the human disorder, provide novel insights into the pathophysiological mechanisms of the disease such as the neural substrates of the behavioral manifestations, and will be valuable to evaluate novel therapeutic approaches.This work was supported by the Spanish Ministry of Ecomomy and Competitivity to V.C. (grant SAF2012-40036) and to L.P.J. (FIS PM002512 and SAF2004-06382), the European AnEuploidy project to L.P.J., M.D. and Y.H. The Rare Diseases CIBER (CIBERER) Fellowship supported M.S-P. and C.B

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Highway construction in Wireless Sensor Networks

English: Wireless sensor networks are a rapidly growing field of study with many open research topics. The aim of this project is to build a hierarchy of clusters in wireless sensor networks and to communicate them through distinguished paths. Those paths are known as highways, and simplify higher level node inter-communication while reducing energy and memory requirements. To achieve this goal several distributed algorithms were designed and tested either in simulators or in real hardware. The message delivery rate, through highways, measured in hardware was close to 70\% and it effectively served as base for a higher level network module to make end to end communication between every node of the connected network. This opens a way for the development of more algorithms to make wireless sensor networks communications on large deployments effective and trouble less

Use of mouse models to establish genotype-phenotype correlations in Williams-Beuren syndrome

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by the common deletion of 26-28 contiguous genes in the 7q11.23 region, which poses difficulties to the establishment of genotype-phenotype correlations. The use of mouse models would broader the knowledge of the syndrome, the role of deleted genes, affected pathways and possible treatments. In this thesis project, several mouse models, tissues and cells have been used to define the phenotypes at different levels, the deregulated genes and pathways and to discover modifying elements and novel treatments for the cardiovascular phenotype. In addition, a new binding motif has been described for Gtf2i, a deleted gene encoding a transcription factor with a major role in WB, providing new target genes from deregulated pathways. The obtained results reveal the essential role of mouse models for the study of Williams-Beuren syndrome and provide new treatments options and affected pathways and genes which could be future treatment targets.La síndrome de Williams-Beuren és una malaltia del neurodesenvolupament causada per una deleció comú d’entre 26 i 28 gens contigus a la regió 7q11.23, dificultant l’establiment de relacions genotip-fenotip. L’ús de models de ratolí pot augmentar el coneixement sobre la malaltia, el paper dels gens delecionats, les vies moleculars afectades i els futurs tractaments. En aquesta tesi s’han usat diversos models de ratolí, les seves cèl·lules i teixits per tal de descriure i definir fenotips, gens i vies moleculars desregulades i per descobrir elements modificadors i nous tractaments. Per últim, s’ha definit un nou motiu d’unió per Gtf2i, uns dels gens delecionats que codifica per un factor de transcripció amb un rol central en la síndrome, proporcionats possible nous gens diana de vies moleculars desregulades. Els resultats obtinguts revelen el paper essencial dels models de ratolí per a l’estudi de la síndrome de Williams-Beuren, proporcionen noves opcions terapèutiques i defineixen nous gens i vies moleculars afectades que podrien suposar noves dianes terapèutiques

Highway construction in Wireless Sensor Networks

English: Wireless sensor networks are a rapidly growing field of study with many open research topics. The aim of this project is to build a hierarchy of clusters in wireless sensor networks and to communicate them through distinguished paths. Those paths are known as highways, and simplify higher level node inter-communication while reducing energy and memory requirements. To achieve this goal several distributed algorithms were designed and tested either in simulators or in real hardware. The message delivery rate, through highways, measured in hardware was close to 70\% and it effectively served as base for a higher level network module to make end to end communication between every node of the connected network. This opens a way for the development of more algorithms to make wireless sensor networks communications on large deployments effective and trouble less

Secuenciación masiva como prueba de segundo nivel en programas de cribado neonatal

Resumen del trabajo presentado al I Congreso Interdisciplinar en Genética Humana, celebrado en Madrid del 25 al 28 de abril de 2017.-- et al.[Objetivos]: Los programas de cribado neonatal son programas de salud pública para el diagnóstico e intervención de enfermedades genéticas que, de no ser tratadas, pueden llegar a tener consecuencias clínicas graves. Con el objetivo de reducir falsos positivos, falsos negativos y tiempos de diagnóstico, y facilitar el asesoramiento genético, se ha evaluado el uso de secuenciación masiva como prueba de segundo nivel en estos programas. [Material y Método]: Se han usado muestras de papel de filtro de recién nacidos positivos para el cribado para elaborar librarías de secuenciación masiva. Se ha desarrollado un panel de 71 genes que incluye las enfermedades detectadas por los programas de cribado neonatal y se han identificado variantes raras que pueder ser causantes de enfermedad. Se han analizado 214 muestras de forma retrospectiva para establecer la sensibilidad y especificidad y 362 muestras prospectivas en tiempo real para determinar la utilidad clínica. [Resultados]: Retrospectivamente se han identificado mutaciones bialélicas en un 65,8% de las muestras y mutaciones en un sólo alelo en el 14,4%. De las muestras sin mutaciones identificadas (19,6%), el 76% corresponden a hipotiroidismo. En muestras con diagnóstico genético previo (n=99), la sensibilidad al final del proceso de mejora de los algoritmos de detección fue del 100%. En la fase prospectiva se han detectado mutaciones bialélicas en un 21,8%, únicas en 31,2% y en el 47% de las muestras no se detectaron mutaciones, siendo el 68.8% de estas muestras positivas para fibrosis quística. En esta fase, se ha obtenido una sensibilidad del 100% en muestras de fibrosis quística (n=131) que contaban con diagnóstico genético paralelo. [Conclusiones]: Hemos desarrollado con éxito un panel secuenciación masiva que puede permitir omitir o redirigir las pruebas de confirmación bioquímicas y proporcionar asesoramiento genético temprano en los programas de cribado neonatalPeer reviewe

Reduction of NADPH-oxidase activity ameliorates the cardiovascular phenotype in a mouse model of Williams-Beuren Syndrome

A hallmark feature of Williams-Beuren Syndrome (WBS) is a generalized arteriopathy due to elastin deficiency, presenting as stenoses of medium and large arteries and leading to hypertension and other cardiovascular complications. Deletion of a functional NCF1 gene copy has been shown to protect a proportion of WBS patients against hypertension, likely through reduced NADPH-oxidase (NOX)–mediated oxidative stress. DD mice, carrying a 0.67 Mb heterozygous deletion including the Eln gene, presented with a generalized arteriopathy, hypertension, and cardiac hypertrophy, associated with elevated angiotensin II (angII), oxidative stress parameters, and Ncf1 expression. Genetic (by crossing with Ncf1 mutant) and/or pharmacological (with ang II type 1 receptor blocker, losartan, or NOX inhibitor apocynin) reduction of NOX activity controlled hormonal and biochemical parameters in DD mice, resulting in normalized blood pressure and improved cardiovascular histology. We provide strong evidence for implication of the redox system in the pathophysiology of the cardiovascular disease in a mouse model of WBS. The phenotype of these mice can be ameliorated by either genetic or pharmacological intervention reducing NOX activity, likely through reduced angII–mediated oxidative stress. Therefore, anti-NOX therapy merits evaluation to prevent the potentially serious cardiovascular complications of WBS, as well as in other cardiovascular disorders mediated by similar pathogenic mechanism.This work was supported by grants from the Spanish Ministry of Science and Innovation of Health (FIS 07/0059 to VC, FIS 10/2512 to LAP-J, RD06/0020/0001 to XRB) and the VI Framework Programme of the European Union (LSHG-CT-2006-037627 to LAP-J). VC is a Miguel Servet FIS Investigator (CP04/00068). MS-P is supported by a CIBERER Fellowship. MM-M is supported by the CSIC JAE-Doc program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip