Crystallization Of The CHAP Domain Of The Endolysin From Staphylococcus Aureus Bacteriophage K

CHAPK is the N-terminal cysteine, histidine-dependent amidohydrolase/peptidase domain (CHAP domain) of the Staphylococcus aureus bacteriophage K endolysin LysK. It is formed from the first 165 residues of LysK and functions by cleaving specific peptidoglycan peptide bonds, causing bacterial lysis. CHAPK can lyse S. aureus when applied exogenously, making it a good candidate for the treatment of multidrug-resistant Staphylococcus aureus infections. Here, the crystallization of CHAPK and the collection of native and derivative data to high resolution, which allowed structure solution, are reported. The structure may help to elucidate the mechanism of action and in the design of chimeric proteins or mutants with improved antibacterial activity

Acompanyar l'escriptura. Anàlisi del biaix entre la consigna i la creativitat de les respostes de l'alumnat en el marc d'un taller de rondalles de 1r d'ESO

Aquest treball de recerca - acció parteix de l'anàlisi d'una seqüència didàctica basada en l'escriptura d'un conte tradicional per tal de reflexionar sobre el dispositiu dissenyat i l'acompanyament que es va fer, atès que els objectius d'aprenentatge marcats no s'assoliren. En primer lloc, s'ofereix una anàlisi comparativa dels diversos suports i pautes per avaluar-ne la coherència i les possibles mancances. Després, s'estudien els esborranys dels alumnes per observar quines han estat les estratègies creatives que han adoptat per respondre a la consigna

Room Temperature In-plane <100> Magnetic Easy Axis for Fe3O4/SrTiO3(001):Nb Grown by Infrared PLD

We examine the magnetic easy-axis directions of stoichiometric magnetite films grown on SrTiO3:Nb by infrared pulsed-laser deposition. Spin-polarized low-energy electron microscopy reveals that the individual magnetic domains are magnetized along the in-plane film directions. Magneto-optical Kerr effect measurements show that the maxima of the remanence and coercivity are also along in-plane film directions. This easy-axis orientation differs from bulk magnetite and films prepared by other techniques, establishing that the magnetic anisotropy can be tuned by film growth.Comment: 3 pages, 3 figure

Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression

Obesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis

Influence of air pollutants on circulating inflammatory cells and microRNA expression in acute myocardial infarction.

Air pollutants increase the risk and mortality of myocardial infarction (MI). The aim of this study was to assess the inflammatory changes in circulating immune cells and microRNAs in MIs related to short-term exposure to air pollutants. We studied 192 patients with acute coronary syndromes and 57 controls with stable angina. For each patient, air pollution exposure in the 24-h before admission, was collected. All patients underwent systematic circulating inflammatory cell analyses. According to PM2.5 exposure, 31 patients were selected for microRNA analyses. STEMI patients exposed to PM2.5 showed a reduction of CD4+ regulatory T cells. Furthermore, in STEMI patients the exposure to PM2.5 was associated with an increase of miR-146a-5p and miR-423-3p. In STEMI and NSTEMI patients PM2.5 exposure was associated with an increase of miR-let-7f-5p. STEMI related to PM2.5 short-term exposure is associated with changes involving regulatory T cells, miR-146a-5p and miR-423-3p.This work was supported by Ministerio de Ciencia e Innovación [SAF2017-82886-R, to F.S.M] Proyecto de Investigación en Salud [PI21/01583 to H.F.]. Grant from the Sociedad Española de Cardiologia to F.A. Ministerio de Ciencia, Innovación y Universidades, Carlos III Institute of Health-Fondo de Investigación Sanitaria [PI19/00545 to P.M.] From the Comunidad de Madrid [S2017/BMD-3671-INFLAMUNE-CM] to FSM and PM. Tis research has been co-fnanced by Fondo Europeo de Desarrollo Regional (FEDER).S

Tumor burden monitoring using cell-free tumor DNA could be limited by tumor heterogeneity in advanced breast cancer and should be evaluated together with radiographic imaging

Clinical and pathological variables. (XLSX 16 kb

Investigating Local Patterns of Mumps Virus Circulation, Using a Combination of Molecular Tools

Mumps is a vaccine-preventable disease caused by the mumps virus (MuV). However, MuV has re-emerged in many countries with high vaccine coverage. The World Health Organization (WHO) recommends molecular surveillance based on sequencing of the small hydrophobic (SH) gene. Additionally, the combined use of SH and non-coding regions (NCR) has been described in different studies, proving to be a useful complement marker to discriminate general patterns of circulation at national and international levels. The aim of this work is to test local-level usefulness of the combination of SH and MF-NCR sequencing in tracing hidden transmission clusters and chains during the last epidemic wave (2015-2020) in Spain. A database with 903 cases from the Autonomous Community of Madrid was generated by the integration of microbiological and epidemiological data. Of these, 453 representative cases were genotyped. Eight different SH variants and thirty-four SH haplotypes were detected. Local MuV circulation showed the same temporal pattern previously described at a national level. Only two of the thirteen previously identified outbreaks were caused by more than one variant/haplotype. Geographical representation of SH variants allowed the identification of several previously undetected clusters, which were analysed phylogenetically by the combination of SH and MF-NCR, in a total of 90 cases. MF-NCR was not able to improve the discrimination of geographical clusters based on SH sequencing, showing limited resolution for outbreak investigations.A.M.G. was funded by CIBER de Epidemiología y Salud Pública (CIBERESP), ISCIII. This work was supported by the “Instituto de Salud Carlos III” (PI15CIII/00023 and PI19ICIII/0041).S

A Single-Run Next-Generation Sequencing (NGS) Assay for the Simultaneous Detection of Both Gene Mutations and Large Chromosomal Abnormalities in Patients with Myelodysplastic Syndromes (MDS) and Related Myeloid Neoplasms

Chromosomal abnormalities and somatic mutations are found in patients with myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in around 50-80% of cases. The identification of these alterations is important for the accurate diagnosis and prognostic classification of these patients. Often, an apparently normal or failed karyotype might lead to an inadequate estimation of the prognostic risk, and several strategies should be combined to solve these cases. The aim of this study was to introduce a novel next-generation sequencing (NGS)-based strategy for the simultaneous detection of all the clinically relevant genetic alterations associated with these disorders. We validated this approach on a large cohort of patients by comparing our findings with those obtained with standard-of-care methods (i.e., karyotype and SNP-arrays). We show that our platform represents a significant improvement on current strategies in defining diagnosis and risk stratification of patients with MDS and myeloid-related disorders. Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms are clonal disorders that share most of their cytogenetic and molecular alterations. Despite the increased knowledge of the prognostic importance of genetics in these malignancies, next-generation sequencing (NGS) has not been incorporated into clinical practice in a validated manner, and the conventional karyotype remains mandatory in the evaluation of suspected cases. However, non-informative cytogenetics might lead to an inadequate estimation of the prognostic risk. Here, we present a novel targeted NGS-based assay for the simultaneous detection of all the clinically relevant genetic alterations associated with these disorders. We validated this platform in a large cohort of patients by performing a one-to-one comparison with the lesions from karyotype and single-nucleotide polymorphism (SNP) arrays. Our strategy demonstrated an approximately 97% concordance with standard clinical assays, showing sensitivity at least equivalent to that of SNP arrays and higher than that of conventional cytogenetics. In addition, this NGS assay was able to identify both copy-neutral loss of heterozygosity events distributed genome-wide and copy number alterations, as well as somatic mutations within significant driver genes. In summary, we show a novel NGS platform that represents a significant improvement to current strategies in defining diagnosis and risk stratification of patients with MDS and myeloid-related disorder