On the relevance of thrombomodulin variants in atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome; Genetic analysis; ThrombomodulinSíndrome hemolítica urèmica atípica; Anàlisi genètica; TrombomodulinaSíndrome hemolítico urémico atípico; Análisis genético; TrombomodulinaThis project was funded by the Instituto de Salud Carlos III: REDinREN (RD016/009/009) and Instituto de Investigacion Puerta de Hierro-Segovia Arana (IDIPHISA) to AH and by grants from the Spanish Ministerio de Economía y Competitividad–FEDER (European Regional Development Fund) (PID2019-104912RB-I00) and the Autonomous Region of Madrid (S2017/BMD-3673 and S2022/BMD-7278) to SRdC. TC was supported by a grant from National Health Institute Carlos III (RETIC ISCIII RD21/0005; RICORS), This work was developed under the supervision of the Spanish Registry of the Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy (aHUS/C3G) registry

Local variability of serotinous cones in a Canary Island pine (Pinus canariensis) stand

The endemic Canary Island pine (Pinus canariensis) has an effective strategy to counteract fire disturbance in the short term. It has a mixed strategy that combines the presence of serotinous cones and thick barks with the ability to re-sprout from the trunk after a fire, a rare trait in pine species. High frequency of fires in the Canary Islands is related to human action, as natural fires by lightning or vulcan activity have very low frequency; hence, the how and whys of the presence of serotinous cones in the species is still a topic of debate. Previous studies showed that the frequency of serotinous cones varies from stand to stand. Here, we analyzed the presence of serotinous cones at a local scale. We selected a Canary Island pine stand in the transition zone between dry and humid forests in the south of Tenerife. Branches were pruned from 20 trees in order to evaluate the presence of serotinous vs. non-serotinous cones by direct verticile counting on the branches. The opening temperature of serotinous cones was assessed in the laboratory. Percentages of serotinous vs. non-serotinous cones varied from 0 to 93 %, showing high variability between trees. Opening temperatures were very high (above 65 ºC) as compared to other Mediterranean pine species with serotinous cone

Single breath-hold saturation recovery 3D cardiac T1 mapping via compressed SENSE at 3T.

To propose and validate a novel imaging sequence that uses a single breath-hold whole-heart 3D T1 saturation recovery compressed SENSE rapid acquisition (SACORA) at 3T. The proposed sequence combines flexible saturation time sampling, compressed SENSE, and sharing of saturation pulses between two readouts acquired at different RR intervals. The sequence was compared with a 3D saturation recovery single-shot acquisition (SASHA) implementation with phantom and in vivo experiments (pre and post contrast; 7 pigs) and was validated against the reference inversion recovery spin echo (IR-SE) sequence in phantom experiments. Phantom experiments showed that the T1 maps acquired by 3D SACORA and 3D SASHA agree well with IR-SE. In vivo experiments showed that the pre-contrast and post-contrast T1 maps acquired by 3D SACORA are comparable to the corresponding 3D SASHA maps, despite the shorter acquisition time (15s vs. 188s, for a heart rate of 60 bpm). Mean septal pre-contrast T1 was 1453 ± 44 ms with 3D SACORA and 1460 ± 60 ms with 3D SASHA. Mean septal post-contrast T1 was 824 ± 66 ms and 824 ± 60 ms. 3D SACORA acquires 3D T1 maps in 15 heart beats (heart rate, 60 bpm) at 3T. In addition to its short acquisition time, the sequence achieves good T1 estimation precision and accuracy.TFdS has received funding from the European Union Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement N722427. CGA is a P-FIS fellow (Instituto deSalud Carlos III). This study was partially supported by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofunded with European structural and investment funds. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

La imagen y la narrativa como herramienta para el abordaje psicosocial en escenarios de violencia Departamento de Cundinamarca – Bogotá.

La imagen y la narrativa como herramienta para el abordaje psicosocial en escenarios de violencia Departamento de Cundinamarca – Bogotá.El acompañamiento psicosocial en los contextos de violencia maneja diversos instrumentos, como el abordaje de contenidos desde el enfoque narrativo. Este suministra la agudeza de condiciones relacionadas con las víctimas, alcanzando a demostrar los contenidos psicosociales en los individuos y su identidad de supervivientes, a través de las diferentes situaciones contextuales y particulares desde la voz, la imagen y la edificación de relatos. También la narrativa, origina tácticas de auto comprensión e importancia de condiciones victimizantes, causantes del dolor y la consternación; por lo cual el sujeto y las colectividades desarrollan capacidades y destrezas resilientes; desplegando proyectos de vida ennoblecedores y eficaces, desde su escenario actual en reconocimiento a un pasado quebrantado por hechos violentos. Esta actuación académica plantea el análisis de las crónicas de vida extraídos del libro, Voces: Relatos de violencia y esperanza en Colombia, editado por el Banco mundial en el año 2009, sobre menciones históricas en el cuadro del conflicto armado, instaurando un contexto de análisis y reflexión de la mediación y la tarea psicosocial, introduciendo el arte de averiguar con el objetivo de la intensión terapéutica. Se plantean preguntas de tipo estratégica, circular y reflexiva que simbolizan la relevancia en el conocimiento del relato escogido, permitiendo una mayor obtención de información y a su vez un acompañamiento eficaz; por consiguiente, se desarrollan tres estrategias de abordaje psicosocial frente al caso de Cacarica, destacando así el impacto físico y psicológico que tuvieron dichas víctimas del conflicto armado, permitiendo fortalecer la comunidad a través de acciones dirigidas a su bienestar y empoderamiento. Con el presente trabajo académico, la UNAD fortifica a sus estudiantes de la facultad de psicología, en torno a afianzar aptitudes y capacidades personales como profesionales que admitan una mirada reflexiva frente a los cambios mutuos que ha generado el conflicto armado en Colombia, revelando la realidad socio histórica del país en el cuadro de post conflicto. De igual manera, ayuda a la alineación y cimentación de futuros profesionales competitivos con capacidad de afrontar, descifrar y proceder, a partir del enfoque narrativo en escenarios violentos con incomparables contenidos.The psychosocial accompaniment in violence context has different instruments like the approach of topics from the narrative approach. It supplies the acuteness of conditions related to victims, reaching to show the psychosocial contents in individuals, also their identity like surviving through different contextual situations and special use of the voice, image and the account building. Also, narrative origins self-understanding and the importance of victimizing conditions, the cause of pain and dismay; for this reason, people and community development capacities and resilient skills, unfolding life projects ennoble and effective, from their actual scene in ecognition to a broken past because violent situations. This academic space set out the analysis of the life chronicles extracted from the Book “Voices: Relates de violence and hope in olombia”, edited for the World Bank in 2009, about historical mentions in the armed conflict situation, establishing an analysis and reflection context of the mediation and the psychosocial work, introducing the art of discovering since therapeutic intensity. It is set out strategic, circular and reflexive questions, they symbolize relevance in the knowledge of selected account, allowing a better information and then an effective accompaniment; therefore, are developing three boarding psychosocial strategies around the Cacarica case, underlining then the physical and psychology impact experienced by the armed conflict victims, allowing to strengthen the community through actions directed to their welfare and empowerment. Through the present work, UNAD fortify their students from the psychology department, around to strengthen flairs and personal capacities like professionals who accept a reflexive view forehead to the mutual changes derived of the armed conflict in Colombia, revealing the socialhistorical reality in the country under the post conflict scene. In the same way, it helps to the alienation the foundation of future competitive professionals with the ability to confront, work out and proceed, starting at the narrative perspective in violent situations with incomparable contents

Induction of the calcineurin variant CnAβ1 after myocardial infarction reduces post-infarction ventricular remodelling by promoting infarct vascularization

AIMS: Ventricular remodelling following myocardial infarction progressively leads to loss of contractile capacity and heart failure. Although calcineurin promotes maladaptive cardiac hypertrophy, we recently showed that the calcineurin splicing variant, CnAβ1, has beneficial effects on the infarcted heart. However, whether this variant limits necrosis or improves remodelling is still unknown, precluding translation to the clinical arena. Here, we explored the effects and therapeutic potential of CnAβ1 overexpression post-infarction. METHODS AND RESULTS: Double transgenic mice with inducible cardiomyocyte-specific overexpression of CnAβ1 underwent left coronary artery ligation followed by reperfusion. Echocardiographic analysis showed depressed cardiac function in all infarcted mice 3 days post-infarction. Induction of CnAβ1 overexpression 1 week after infarction improved function and reduced ventricular dilatation. CnAβ1-overexpressing mice showed shorter, thicker scars, and reduced infarct expansion, accompanied by reduced myocardial remodelling. CnAβ1 induced vascular endothelial growth factor (VEGF) expression in cardiomyocytes, which resulted in increased infarct vascularization. This paracrine angiogenic effect of CnAβ1 was mediated by activation of the Akt/mammalian target of rapamycin pathway and VEGF. CONCLUSIONS: Our results indicate that CnAβ1 exerts beneficial effects on the infarcted heart by promoting infarct vascularization and preventing infarct expansion. These findings emphasize the translational potential of CnAβ1 for gene-based therapies.European Union [ERG-239158, CardioNeT-ITN-289600]; Spanish Ministry of Science and Innovation [BFU2009-10016, SAF2012-31451]; Regional Government of Madrid [2010-BMD-2321]; Fondo de Investigaciones Sanitarias [RD12/0042/0066]; Spanish Ministry of Economy and Competitiveness; Pro-CNIC FoundationS

Loss of SRSF3 in Cardiomyocytes Leads to Decapping of Contraction-Related mRNAs and Severe Systolic Dysfunction

RATIONALE: RBPs (RNA binding proteins) play critical roles in the cell by regulating mRNA transport, splicing, editing, and stability. The RBP SRSF3 (serine/arginine-rich splicing factor 3) is essential for blastocyst formation and for proper liver development and function. However, its role in the heart has not been explored. OBJECTIVE: To investigate the role of SRSF3 in cardiac function. METHODS AND RESULTS: Cardiac SRSF3 expression was high at mid gestation and decreased during late embryonic development. Mice lacking SRSF3 in the embryonic heart showed impaired cardiomyocyte proliferation and died in utero. In the adult heart, SRSF3 expression was reduced after myocardial infarction, suggesting a possible role in cardiac homeostasis. To determine the role of this RBP in the adult heart, we used an inducible, cardiomyocyte-specific SRSF3 knockout mouse model. After SRSF3 depletion in cardiomyocytes, mice developed severe systolic dysfunction that resulted in death within 8 days. RNA-Seq analysis revealed downregulation of mRNAs encoding sarcomeric and calcium handling proteins. Cardiomyocyte-specific SRSF3 knockout mice also showed evidence of alternative splicing of mTOR (mammalian target of rapamycin) mRNA, generating a shorter protein isoform lacking catalytic activity. This was associated with decreased phosphorylation of 4E-BP1 (eIF4E-binding protein 1), a protein that binds to eIF4E (eukaryotic translation initiation factor 4E) and prevents mRNA decapping. Consequently, we found increased decapping of mRNAs encoding proteins involved in cardiac contraction. Decapping was partially reversed by mTOR activation. CONCLUSIONS: We show that cardiomyocyte-specific loss of SRSF3 expression results in decapping of critical mRNAs involved in cardiac contraction. The molecular mechanism underlying this effect likely involves the generation of a short mTOR isoform by alternative splicing, resulting in reduced 4E-BP1 phosphorylation. The identification of mRNA decapping as a mechanism of systolic heart failure may open the way to the development of urgently needed therapeutic tools.This study was supported by grants from the European Union (CardioNeT-ITN-289600 and CardioNext-ITN-608027 to E.L-P.), from the Spanish Ministerio de Economía y Competitividad (RTI2018-096961-BI00, SAF2015-65722-R and SAF2012-31451 to E.L-P.; BIO2015-67580-P and PGC2018-097019-B-I00 to J.V.), the Spanish Carlos III Institute of Health (CPII14/00027 to E.L-P, RD12/0042/066 to P.G.-P. and E.L-P, and RD12/0042/0056, PRB2-IPT13/0001-ISCIII-SGEFI/FEDER, ProteoRed to J.V.), the Madrid Regional Government (2010-BMD-2321 “Fibroteam” to E.L-P.). This study was also supported by the Plan Estatal de I+D+I 2013-2016 – European Regional Development Fund (ERDF) “A way of making Europe”, Spain. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

Activation of Serine One-Carbon Metabolism by Calcineurin A beta 1 Reduces Myocardial Hypertrophy and Improves Ventricular Function

BACKGROUND In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria. OBJECTIVES The authors aimed to determine the role of the calcineurin splicing variant CnA beta 1 in the context of cardiac hypertrophy and its mechanism of action. METHODS Transgenic mice overexpressing CnAb1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnA beta 1 (CnA beta 1(Delta i12) mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses. RESULTS In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnA beta 1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAb1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnA beta 1. CnA beta 1(Delta i12) mice show increased cardiac hypertrophy and declined contractility. CONCLUSIONS The metabolic reprogramming induced by CnAb1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches. (J Am Coll Cardiol 2018; 71: 654-67) (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).This work was supported by grants from the European Union (CardioNeT-ITN-289600 and CardioNext-608027 to Dr. Lara-Pezzi; Meet-ITN-317433 to Dr. Enriquez; UE0/MCA1108 to Dr. Acin-Perez), from the Spanish Ministry of Economy and Competitiveness (SAF2015-65722-R and SAF2012-31451 to Dr. Lara-Pezzi; SAF2015-71521-REDC, BFU2013-50448, and SAF2012-32776 to Dr. Enriquez; RyC-2011-07826 to Dr. Acin-Perez; BIO2012-37926 and BIO2015-67580-P to Dr. Vazquez), from the Spanish Carlos III Institute of Health (CPII14/00027 to Dr. Lara-Pezzi; RD12/0042/066 to Drs. Garcia-Pavia and Lara-Pezzi), from the Regional Government of Madrid (2010-BMD-2321 ``Fibroteam´´ to Dr. Lara-Pezzi; 2011-BMD-2402 ``Mitolab´´ to Dr. Enriquez) and the FIS-ISCIII (PRB2-IPT13/0001 and RD12/0042/0056-RIC-RETICS to Dr. Vazquez). This work was also supported by the Plan Estatal de IthornDthornI 2013-2016-European Regional Development Fund (FEDER) ``A way of making Europe,´´ Spain. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness and by the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Drs. Vazquez and Garcia-Pavia have served as consultants for VL39. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Padron-Barthe, Villalba-Orero, and Gomez-Salinero contributed equally to this work and are joint first authors. Robyn Shaw, MD, PhD, served as Guest Editor for this paper.S