Bases genéticas y moleculares de la preeclampsia

La preeclampsia es una enfermedad compleja, exclusiva de la gestación humana y responsables de una alta morbimortalidad perinatal. Ha sido denominada la enfermedad de las múltiples teorÍas, en la cual tanto factores medioambientales como genéticos se han asociado al desarrollo de la misma. para la identificación de los genes candidatos asociados con la PE, se han empleado dos tipos de metodologÍa, los estudios de asociación y los estudios de ligamiento.[Serrano NC, Páes MC, MartÍnez MP, Casas JP, Gil L, Nvarro AA. Bases genéticas y moleculares de la preeclampsia. MedUNAB 2002; 5(15):185-94].Palabras clave: Genética, preeclampsia, polimorfismos, estudios de ligamiento, estudios de asociación, metileneterahidrofolato reductasa, lipoprotein lipasa, óxidonitrico sintasa endotelial, factor V de Leiden, angiotesinógeno, HLA-G, y factor denecrosis tumoral alfa.Preeclampsia is a complex disease, exclusive of human pregnancy and responsible for high perinatal morbidity and mortality. It has been called the disease of multiple theories, in which both environmental and genetic factors have been associated with its development. For the identification of candidate genes associated with PE, two types of methodology have been used, association studies and linkage studies. This article explains the rationale for both studies and reviews the main candidate genes within the pathophysiology of the disease, including those that code for the enzymes methylene tetrahydrofolate reductase, lipoprotein lipase and endothelial nitric oxide synthase; factor V Leiden, angiotensinogen, HLA-G, and necrotumor factor alph

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1(3 release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1(3 release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers

Detection of kinase domain mutations in BCR::ABL1 leukemia by ultra-deep sequencing of genomic DNA

The screening of the BCR::ABL1 kinase domain (KD) mutation has become a routine analysis in case of warning/failure for chronic myeloid leukemia (CML) and B-cell precursor acute lymphoblastic leukemia (ALL) Philadelphia (Ph)-positive patients. In this study, we present a novel DNA-based next-generation sequencing (NGS) methodology for KD ABL1 mutation detection and monitoring with a 1.0E-4 sensitivity. This approach was validated with a well-stablished RNA-based nested NGS method. The correlation of both techniques for the quantification of ABL1 mutations was high (Pearson r = 0.858, p < 0.001), offering DNA-DeepNGS a sensitivity of 92% and specificity of 82%. The clinical impact was studied in a cohort of 129 patients (n = 67 for CML and n = 62 for B-ALL patients). A total of 162 samples (n = 86 CML and n = 76 B-ALL) were studied. Of them, 27 out of 86 harbored mutations (6 in warning and 21 in failure) for CML, and 13 out of 76 (2 diagnostic and 11 relapse samples) did in B-ALL patients. In addition, in four cases were detected mutation despite BCR::ABL1 < 1%. In conclusion, we were able to detect KD ABL1 mutations with a 1.0E-4 sensitivity by NGS using DNA as starting material even in patients with low levels of disease

Museos y exposiciones en Madrid como oportunidad de trabajar conceptos-clave de las Ciencias Sociales con estudiantes Erasmus+ Incoming en colaboración con estudiantes UCM, asociaciones de estudiantes, oficina de relaciones internacionales y PDI

Proyecto de Innovación que pone en contacto los recursos museísticos y expositivos de Madrid con los estudiantes internacionales para trabajar conceptos-clave en las ciencias sociales, como vulnerabilidad y comunicació

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

Search for anomalous production of events with three or more leptons in pp collisions at √s = 8TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.A search for physics beyond the standard model in events with at least three leptons is presented. The data sample, corresponding to an integrated luminosity of 19.5fb-1 of proton-proton collisions with center-of-mass energy s=8TeV, was collected by the CMS experiment at the LHC during 2012. The data are divided into exclusive categories based on the number of leptons and their flavor, the presence or absence of an opposite-sign, same-flavor lepton pair (OSSF), the invariant mass of the OSSF pair, the presence or absence of a tagged bottom-quark jet, the number of identified hadronically decaying τ leptons, and the magnitude of the missing transverse energy and of the scalar sum of jet transverse momenta. The numbers of observed events are found to be consistent with the expected numbers from standard model processes, and limits are placed on new-physics scenarios that yield multilepton final states. In particular, scenarios that predict Higgs boson production in the context of supersymmetric decay chains are examined. We also place a 95% confidence level upper limit of 1.3% on the branching fraction for the decay of a top quark to a charm quark and a Higgs boson (t→cH), which translates to a bound on the left- and right-handed top-charm flavor-violating Higgs Yukawa couplings, λtcH and λctH, respectively, of |λtcH|2+|λctH|2<0.21

Hypertriglyceridemia and preeclampsia: Its physiological role and up-to-date evidence

Preeclampsia is a disease with a highincidence for maternal and fetal morbidity and mortality, mainly indeveloping countries. Although its etiology remains unclear, severalstudies have shown that endothelial cell dysfunction plays an important role in the genesis, development and complications relatedto this disease. Among the different processes, lipid per oxidation is involved in what could be an increase in serum lipid concentrations in pregnant women, especially triglycerides. The aim of this review is to describe the role of lipids in the pathophysiology of preeclampsia and the current evidence about the finding of hypertriglyceridemia and its development