Bases moleculares de la hemocromatosis hereditaria

La hemocromatosis hereditaria es la enfermedad más relevante dentro de las enfermedades hereditarias debido a su alta prevalencia. Se trata de una enfermedad del metabolismo del hierro que está afectada una correcta eliminación de este por el organismo y que es regulada, principalmente, por la hormona hepcidina y la proteína del gen HFE. El hierro es una molécula necesaria para el organismo pero a su vez, si no se controlan los niveles de almacenamiento, puede causar graves problemas de sobrecarga en órganos pudiendo llegar a causar cirrosis, hepatocarcinoma, miocardiopatía, artritis o diabetes mellitus; se trata de patologías crónicas que a largo plazo podrían causar un desenlace fatal en los enfermos. Sobre las bases moleculares que codifican esta enfermedad engloban a los procesos de absorción y transporte del hierro que no funcionarán correctamente debido a las mutaciones causadas por las distintas variantes de la enfermedad, pero, principalmente, por las ocasionadas al gen HFE. Las distintas mutaciones ocasionarán acumulación de hierro en los órganos con mayor o menor intensidad y con diferente progreso de la enfermedad. Aunque esta sea la enfermedad hereditaria más común en la población la mayoría de los casos de esta enfermedad permanecen sin diagnosticar ya que la mayoría de las mutaciones no presentan síntomas hasta una edad adulta-madura. Por ello, es clave el diagnóstico que se realiza basándose en la técnica de la PCR y la realización de tratamientos como flebotomías o la búsqueda de incorporación de otros nuevos, como inyecciones de hepcidinaUniversidad de Sevilla. Grado en Farmaci

Taxogenomic and Comparative Genomic Analysis of the Genus Saccharomonospora Focused on the Identification of Biosynthetic Clusters PKS and NRPS

Actinobacteria are prokaryotes with a large biotechnological interest due to their ability to produce secondary metabolites, produced by two main biosynthetic gene clusters (BGCs): polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS). Most studies on bioactive products have been carried out on actinobacteria isolated from soil, freshwater or marine habitats, while very few have been focused on halophilic actinobacteria isolated from extreme environments. In this study we have carried out a comparative genomic analysis of the actinobacterial genus Saccharomonospora, which includes species isolated from soils, lake sediments, marine or hypersaline habitats. A total of 19 genome sequences of members of Saccharomonospora were retrieved and analyzed. We compared the 16S rRNA gene-based phylogeny of this genus with evolutionary relationships inferred using a phylogenomic approach obtaining almost identical topologies between both strategies. This method allowed us to unequivocally assign strains into species and to identify some taxonomic relationships that need to be revised. Our study supports a recent speciation event occurring between Saccharomonospora halophila and Saccharomonospora iraqiensis. Concerning the identification of BGCs, a total of 18 different types of BGCs were detected in the analyzed genomes of Saccharomonospora, including PKS, NRPS and hybrid clusters which might be able to synthetize 40 different putative products. In comparison to other genera of the Actinobacteria, members of the genus Saccharomonospora showed a high degree of novelty and diversity of BGCs.FEDER/Spanish Ministry of Science and Innovation-State Research Agency (project CGL2017-83385-P)Autonomous University of the State of Mexico (project 5009/2020CIB)Junta de Andalucía (grants BIO-213 and US-1263771

Medición y análisis de la diversidad de comunidades hidrobiológicas: una perspectiva desde la ingeniería ambiental

Through a set of tools we seek to improve the measurement of biodiversity to understand the hydrobiological communities and their relationship with aquatic ecosystems. We did three field surveys during 2016 and 2017 in three stations in the dam and three in the La Nitrera creek, which provides a greater flow. In the lotic system we find relationship between richness and the Shannon diversity index (r = 0.85). For the lentic system we obtained associations between the evennes index and the diversity index (r = 0.94), therefore, the diversity index may explain changes in the other metrics. The distribution of organisms showed differences between ecosystems. In the creek the availability of habitat was the determining factor. In the dam, the dynamics of water catchment influenced the diversity of the communities.Mediante un conjunto de herramientas se buscó mejorar la medición de la biodiversidad para la compresión de las comunidades hidrobiológicas y su relación con ecosistemas acuáticos. Se estudió la biodiversidad de cuatro comunidades acuáticas. Se realizaron tres campañas de muestreo durante 2016 y 2017 en tres estaciones establecidas en la zona de represa y en la quebrada La Nitrera la cual aporta mayor caudal. El sistema lótico mostró relación entre la riqueza y el índice de diversidad de Shannon (r=0.85). Para el sistema léntico se obtuvieron asociaciones entre el índice de equidad con el de diversidad (r=0.94), por lo tanto, el índice de diversidad puede explicar cambios en las otras métricas. La distribución de los organismos mostró diferencias entre los ecosistemas. En la quebrada la disponibilidad de hábitat fue el factor determinante. En la represa las dinámicas de la captación de agua influyeron en la diversidad de las comunidades.Mediante un conjunto de herramientas se busca optimizar la medición de la diversidad para la compresión de las comunidades biológicas y su relación con el entorno de un embalse. Se planteó diagnosticar la diversidad de cuatro comunidades acuáticas. Se realizaron tres campañas de muestreo durante 2016 y 2017, estableciendo estaciones en el embalse y en la quebrada, que aporta mayor caudal. El sistema lótico obtuvo una relación representativa entre la riqueza numérica y el índice de diversidad (r=0.85 y p<0.05). El sistema léntico obtuvo asociaciones entre el índice de equidad con el de diversidad (r=0.94 y p<0.05). Para ambos sistemas el índice de dominancia presento asociamos inversas con el índice de diversidad (r=0.9 y p<0.05). Indicando que cambios en el índice de diversidad pueden explicar los cambios en las otras métricas. Así mismo se encontró que la distribución de los organismos fue dependiente del tipo de ecosistema.Through a set of tools we seek to improve the measurement of biodiversity to understand the hydrobiological communities and their relationship with aquatic ecosystems. We did three field surveys during 2016 and 2017 in three stations in the dam and three in the La Nitrera creek, which provides a greater flow. In the lotic system we find  relationship between richness and the Shannon diversity index (r = 0.85). For the lentic system we obtained associations between the evennes index and the diversity index (r = 0.94), therefore, the diversity index may explain changes in the other metrics.  The distribution of organisms showed differences between ecosystems. In the creek the availability of habitat was the determining factor. In the dam, the dynamics of water catchment influenced the diversity of the communities

Management of acute diverticulitis with pericolic free gas (ADIFAS). an international multicenter observational study

Background: There are no specific recommendations regarding the optimal management of this group of patients. The World Society of Emergency Surgery suggested a nonoperative strategy with antibiotic therapy, but this was a weak recommendation. This study aims to identify the optimal management of patients with acute diverticulitis (AD) presenting with pericolic free air with or without pericolic fluid. Methods: A multicenter, prospective, international study of patients diagnosed with AD and pericolic-free air with or without pericolic free fluid at a computed tomography (CT) scan between May 2020 and June 2021 was included. Patients were excluded if they had intra-abdominal distant free air, an abscess, generalized peritonitis, or less than a 1-year follow-up. The primary outcome was the rate of failure of nonoperative management within the index admission. Secondary outcomes included the rate of failure of nonoperative management within the first year and risk factors for failure. Results: A total of 810 patients were recruited across 69 European and South American centers; 744 patients (92%) were treated nonoperatively, and 66 (8%) underwent immediate surgery. Baseline characteristics were similar between groups. Hinchey II-IV on diagnostic imaging was the only independent risk factor for surgical intervention during index admission (odds ratios: 12.5, 95% CI: 2.4-64, P =0.003). Among patients treated nonoperatively, at index admission, 697 (94%) patients were discharged without any complications, 35 (4.7%) required emergency surgery, and 12 (1.6%) percutaneous drainage. Free pericolic fluid on CT scan was associated with a higher risk of failure of nonoperative management (odds ratios: 4.9, 95% CI: 1.2-19.9, P =0.023), with 88% of success compared to 96% without free fluid ( P <0.001). The rate of treatment failure with nonoperative management during the first year of follow-up was 16.5%. Conclusion: Patients with AD presenting with pericolic free gas can be successfully managed nonoperatively in the vast majority of cases. Patients with both free pericolic gas and free pericolic fluid on a CT scan are at a higher risk of failing nonoperative management and require closer observation

Observation of the Rare Decay of the η Meson to Four Muons

A search for the rare η→μ+μ−μ+μ− double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101  fb−1. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ+μ− decay as normalization, the branching fraction B(η→μ+μ−μ+μ−)=[5.0±0.8(stat)±0.7(syst)±0.7(B2μ)]×10−9 is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions

Search for new physics in multijet events with at least one photon and large missing transverse momentum in proton-proton collisions at 13 TeV

A search for new physics in final states consisting of at least one photon, multiple jets, and large missing transverse momentum is presented, using proton-proton collision events at a center-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 137 fb−1, recorded by the CMS experiment at the CERN LHC from 2016 to 2018. The events are divided into mutually exclusive bins characterized by the missing transverse momentum, the number of jets, the number of b-tagged jets, and jets consistent with the presence of hadronically decaying W, Z, or Higgs bosons. The observed data are found to be consistent with the prediction from standard model processes. The results are interpreted in the context of simplified models of pair production of supersymmetric particles via strong and electroweak interactions. Depending on the details of the signal models, gluinos and squarks of masses up to 2.35 and 1.43 TeV, respectively, and electroweakinos of masses up to 1.23 TeV are excluded at 95% confidence level

Measurements of inclusive and differential cross sections for the Higgs boson production and decay to four-leptons in proton-proton collisions at s \sqrt{s} = 13 TeV

Measurements of the inclusive and differential fiducial cross sections for the Higgs boson production in the H → ZZ → 4ℓ (ℓ = e, μ) decay channel are presented. The results are obtained from the analysis of proton-proton collision data recorded by the CMS experiment at the CERN LHC at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb−1. The measured inclusive fiducial cross section is 2.73 ± 0.26 fb, in agreement with the standard model expectation of 2.86 ± 0.1 fb. Differential cross sections are measured as a function of several kinematic observables sensitive to the Higgs boson production and decay to four leptons. A set of double-differential measurements is also performed, yielding a comprehensive characterization of the four leptons final state. Constraints on the Higgs boson trilinear coupling and on the bottom and charm quark coupling modifiers are derived from its transverse momentum distribution. All results are consistent with theoretical predictions from the standard model

Search for Scalar Leptoquarks Produced via τ-Lepton-Quark Scattering in pppp Collisions at s=13TeV\sqrt{s}=13 TeV

The first search for scalar leptoquarks produced in τ-lepton–quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138  fb$^{−1}$. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength