Primera versión española del NEPSY para la evaluación neuropsicológica del desarrollo en una muestra de niños españoles

All the subtests of the first Spanish language version of the NEPSY were administered to a sample of 415 children aged 3 to 12 years old: 193 boys and 222 girls. For statistical analysis, the sample was divided into two groups: one comprising 98 children aged 3-4, and the other 317 children aged 5-12. First, the adjustment of the distribution of the different items of this Spanish version of the NEPSY subtests to the normal curve was checked. The usefulness of these subtests to assess the level of children’s development according to their chronological age was then tested using regression analysis. Finally, we checked that the raw scores on the subtest items of this Spanish version ofthe NEPSY differed significantly between 3 and 4 year olds and between 5 and 6 year olds: in each age pair, the mean scores of the older group increased inaccuracy and decreased in runtime and errors.Se administran todos los subtests de la primera versión en castellano del NEPSY a una muestra de 415 niños de 3 a 12 años de edad: 193 varones y 222 niñas. Para las tareas estadísticas, se separan en dos grupos: uno de 98 niños de 3-4 años y otro de 317 de 4-12 años. En primer lugar, se comprueba el ajuste de las distribuciones de las distintas variables de los subtest de esta versión española del NEPSY a la curva normal. Posteriormente se comprueba la utilidad de estos para verificar el nivel de desarrollo de los niños por su edad cronológica, mediante un análisis de regresión. Finalmente, se verifica que las diferencias en las puntuaciones directas de las distintas variables de los subtestsde esta versión española del NEPSY, entre los niños de 3 y 4 años y entre losde 5 y 6 años, son estadísticamente significativas, de forma que ambos grupos de niños mayores aumentan las medias en exactitud y disminuyen las del tiempo de ejecución y los errores en las diferentes tareas

Long-range regulatory interactions at the 4q25 atrial fibrillation risk locus involve PITX2c and ENPEP

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Recent genome-wide association studies have uncovered genomic loci that underlie an increased risk for atrial fibrillation, the major cardiac arrhythmia in humans. The most significant locus is located in a gene desert at 4q25, approximately 170 kilobases upstream of PITX2, which codes for a transcription factor involved in embryonic left-right asymmetry and cardiac development. However, how this genomic region functionally and structurally relates to PITX2 and atrial fibrillation is unknown. [Results]: To characterise its function, we tested genomic fragments from 4q25 for transcriptional activity in a mouse atrial cardiomyocyte cell line and in transgenic mouse embryos, identifying a non-tissue-specific potentiator regulatory element. Chromosome conformation capture revealed that this region physically interacts with the promoter of the cardiac specific isoform of Pitx2. Surprisingly, this regulatory region also interacts with the promoter of the next neighbouring gene, Enpep, which we show to be expressed in regions of the developing mouse heart essential for cardiac electrical activity. [Conclusions]: Our data suggest that de-regulation of both PITX2 and ENPEP could contribute to an increased risk of atrial fibrillation in carriers of disease-associated variants, and show the challenges that we face in the functional analysis of genome-wide disease associations.This study was funded by the CNIC Translational Grant Programme (CNIC-08-2009 to MM and DF), the Spanish Ministerio de Economia y Competitividad (grants BFU2011-23083 to MM, BFU2013-41322-P to JLGS, BFU2012-38111 to AA, and CSD2007-00008 to JLGS and MM), the Comunidad Autónoma de Madrid (grant CELLDD-CM to MM), and the Andalusian Government (grant BIO-396 to JLGS). The CNIC is supported by the Spanish Ministerio de Economia y Competitividad and the Pro-CNIC Foundation.Peer Reviewe

An internal ribosome entry site element directs the synthesis of the 80 kDa isoforms of protein 4.1R

<p>Abstract</p> <p>Background</p> <p>In red blood cells, protein 4.1 (4.1R) is an 80 kDa protein that stabilizes the spectrin-actin network and anchors it to the plasma membrane through its FERM domain. While the expression pattern of 4.1R in mature red cells is relatively simple, a rather complex array of 4.1R protein isoforms varying in N-terminal extensions, internal sequences and subcellular locations has been identified in nucleated cells. Among these, 135 kDa and 80 kDa isoforms have different N-terminal extensions and are expressed either from AUG1- or AUG2-containing mRNAs, respectively. These two types of mRNAs, varying solely by presence/absence of 17 nucleotides (nt) which contain the AUG1 codon, are produced by alternative splicing of the 4.1R pre-mRNA. It is unknown whether the 699 nt region comprised between AUG1 and AUG2, kept as a 5' untranslated region in AUG2-containing mRNAs, plays a role on 4.1R mRNA translation.</p> <p>Results</p> <p>By analyzing the <it>in vitro </it>expression of a panel of naturally occurring 4.1R cDNAs, we observed that all AUG1/AUG2-containing cDNAs gave rise to both long, 135 kDa, and short, 80 kDa, 4.1R isoforms. More importantly, similar results were also observed in cells transfected with this set of 4.1R cDNAs. Mutational studies indicated that the short isoforms were not proteolytic products of the long isoforms but products synthesized from AUG2. The presence of a cryptic promoter in the 4.1R cDNA sequence was also discounted. When a 583 nt sequence comprised between AUG1 and AUG2 was introduced into bicistronic vectors it directed protein expression from the second cistron. This was also the case when ribosome scanning was abolished by introduction of a stable hairpin at the 5' region of the first cistron. Deletion analysis of the 583 nt sequence indicated that nucleotides 170 to 368 are essential for expression of the second cistron. The polypyrimidine tract-binding protein bound to the 583 nt active sequence but not to an inactive 3'-fragment of 149 nucleotides.</p> <p>Conclusion</p> <p>Our study is the first demonstration of an internal ribosome entry site as a mechanism ensuring the production of 80 kDa isoforms of protein 4.1R. This mechanism might also account for the generation of 60 kDa isoforms of 4.1R from a downstream AUG3. Our results reveal an additional level of control to 4.1R gene expression pathways and will contribute to the understanding of the biology of proteins 4.1R and their homologues, comprising an ample family of proteins involved in cytoskeletal organization.</p

Spongionella secondary metabolites protect mitochondrial function in cortical neurons against oxidative stress

Accepted: 8 January 2014 This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Acknowledgments The research leading to these results has received funding from the following FEDER cofunded-grants: From Ministerio de Ciencia y Tecnología, Spain: AGL2009-13581-CO2-01, AGL2012-40485-CO2-01. From Xunta de Galicia, Spain: 10PXIB261254 PR. From the European Union’s Seventh Framework Programme managed by REA—Research Executive Agency (FP7/2007–2013) under grant agreement Nos. 265896 BAMMBO, 265409 µAQUA, and 262649 BEADS, 315285 CIGUATOOLS and 312184 PHARMASEA. From the Atlantic Area Programme (Interreg IVB Trans-national): 2009-1/117 Pharmatlantic. MER thanks the Government of the Arab Republic of Egypt for a PhD Scholarship. MJ thanks the Scottish University Life Science Alliance which provided funding to set up the compound library.Peer reviewedPublisher PD

Serum/plasma potassium monitoring using potentiometric point-of-care microanalyzers with improved ion selective electrodes

Different causes can trigger imbalances on homeostatic mechanisms between intracellular and extracellular compartments resulting in abnormal blood potassium concentrations (hypo or hyperkalemia). This can lead to serious consequences, even a life-threatening situation. Early diagnosis, treatment and follow-up are essential to minimize critical impacts in patients. Bedside determination of blood potassium is not accessible in all health care centers or in all emergency departments and far less common in this kind of centers in emerging countries. We have therefore proposed a portable, economic and long-lifetime potentiometric point-of-care (POC) analytical microsystem to deal with this question. It is a continuous flow microfluidic platform, made of cyclic olefin copolymer (COC), which combines microfluidics and a detection system based on the potentiometric technique containing a potassium selective electrode with a novel composition of polymeric membrane, which improves lifetime. Its size is smaller than a credit card and shows a linear range of Nernst calibration equation from 1 to 26 mM K+, a detection limit of 0.16 mM K+, a satisfactory repeatability and reproducibility, and an analysis frequency of 20 samples h−1, requiring only 25 μL as sample volume. Moreover, lifetime is as long as 9 months by intensive use. All these features comply with medical requirements. Human serum samples were analyzed with the developed device and the obtained results were compared with those provided by two methods: ICP-OES and another using ion selective electrodes. No significant differences were observed, demonstrating the suitability of the developed POC microanalyzer for bedside health applications

Aportaciones al conocimiento de la orquidoflora palentina (España)

En este trabajo se comentan hallazgos de orquídeas poco conocidas en el territorio palentino, se aportan algunas novedades para la provincia y se comentan algunos datos de provincias limítrofes. Puesto que el grupo de orquidáceas ha suscitado un especial interés en los estudios concernientes a flora rara y amenazada, se detalla el estatus de conservación de aquellos táxones incluidos en documentos técnicos y listados ofi ciales de protección de flora

Spongionella Secondary Metabolites Regulate Store Operated Calcium Entry Modulating Mitochondrial Functioning in SH-SY5Y Neuroblastoma Cells

cknowledgements The research leading to these results has received funding from the following FEDER cofounded-grants. From CDTI and Technological Funds, supported by Ministerio de Economía y Competitividad, AGL2012-40185-CO2-01, AGL2014-58210-R, and Consellería de Cultura, Educación e OrdenaciónUniversitaria, GRC2013-016, and through AxenciaGalega de Innovación, Spain, ITC-20133020 SINTOX. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD. From the European Union's Seventh Framework Programme managed by REA - Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA. Jon Andoni Sánchez is supported by a fellowship from Plan Galego de Investigación e Crecemento, Xunta de Galicia, Spain.Peer reviewedPublisher PD

EphrinA4 plays a critical role in α4 and αL mediated survival ofhuman CLL cells during extravasation

A role of endothelial cells in the survival of CLL cells during extravasation is presently unknown. Herein we show that CLL cells but not normal B cells can receive apoptotic signals through physical contact with TNF-α activated endothelium impairing survival in transendothelial migration (TEM) assays. In addition, the CLL cells of patients having lymphadenopathy (LApos) show a survival advantage during TEM that can be linked to increased expression of α4 and αL integrin chains. Within this context, ephrinA4 expressed on the surface of CLL cells sequestrates integrins and inactivates them resulting in reduced adhesion and inhibition of apoptotic/survival signals through them. In agreement, ephrinA4 silencing resulted in increased survival of CLL cells of LApos patients but not LA neg patients. Similarly was observed when a soluble ephrinA4 isoform was added to TEM assays strongly suggesting that accumulation of this isoform in the serum of LApos patients could contribute to CLL cells dissemination and survival in vivo. In supporting, CLL lymphadenopathies showed a preferential accumulation of apoptotic CLL cells around high endothelial venules lacking ephrinA4. Moreover, soluble ephrinA4 isolated from sera of patients increased the number and viability of CLL cells recovered from the lymph nodes of adoptively transferred mice. Finally, we present evidence suggesting that soluble ephrinA4 mediated survival during TEM could enhance a transcellular TEM route of the CLL cells. Together these findings point to an important role of ephrinA4 in the nodal dissemination of CLL cells governing extravasation and survival

Viability study of machine learning-based prediction of COVID-19 pandemic impact in obsessive-compulsive disorder patients

Background: Machine learning modeling can provide valuable support in different areas of mental health, because it enables to make rapid predictions and therefore support the decision making, based on valuable data. However, few studies have applied this method to predict symptoms’ worsening, based on sociodemographic, contextual, and clinical data. Thus, we applied machine learning techniques to identify predictors of symptomatologic changes in a Spanish cohort of OCD patients during the initial phase of the COVID-19 pandemic. Methods: 127 OCD patients were assessed using the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS) and a structured clinical interview during the COVID-19 pandemic. Machine learning models for classification (LDA and SVM) and regression (linear regression and SVR) were constructed to predict each symptom based on patient’s sociodemographic, clinical and contextual information. Results: A Y-BOCS score prediction model was generated with 100% reliability at a score threshold of ± 6. Reliability of 100% was reached for obsessions and/or compulsions related to COVID-19. Symptoms of anxiety and depression were predicted with less reliability (correlation R of 0.58 and 0.68, respectively). The suicidal thoughts are predicted with a sensitivity of 79% and specificity of 88%. The best results are achieved by SVM and SVR. Conclusion: Our findings reveal that sociodemographic and clinical data can be used to predict changes in OCD symptomatology. Machine learning may be valuable tool for helping clinicians to rapidly identify patients at higher risk and therefore provide optimized care, especially in future pandemics. However, further validation of these models is required to ensure greater reliability of the algorithms for clinical implementation to specific objectives of interest.Sandra Carvalho receives scholarship and support from the Portuguese Foundation for Science and Technology (FCT), co-funded through COMPETE 2020 – PO Competitividade e Internacionalização/Portugal 2020/European Union, FEDER (Fundos Europeus Estruturais e de Investimento – FEEI) under the number:PTDC/PSI-ESP/29701/2017.publishe