Enantiomeric analysis of pyrethroids and organophosphorus insecticides

The use of pesticides has increased sharply in the last decades, not only in agriculture, but also in industry, public health, and other areas. Pyrethroids and organophosphorus insecticides are among the most employed pesticides. These chemicals usually contain asymmetric chiral atoms; thus, they are characterized by stereoisomerism. Although most of these chiral pesticides are produced, used, and released as racemic mixtures, the different enantiomers of these compounds can present different insecticidal activity, different toxicity against vertebrates and invertebrates, and also different persistence in the environment. In fact, in some cases, only one enantiomer is active, while the other can be less active or even toxic to non-target organisms. Therefore, the development of enantioselective analytical methodologies enabling their determination presents a high interest. Different separation techniques, including high performance liquid chromatography, gas chromatography, supercritical fluid chromatography, and capillary electrophoresis, have been employed to achieve the chiral analysis of pyrethroids and organophosphorus insecticides. This review presents the characteristics of the stereoselective analytical methodologies developed with this aim from 2010 to April 2019 and their applications to the analysis of real samples as well as for toxicity and biodegradation studies

Lectura social y LIJ 2.0 en la universidad. Aplicaciones y redes sociales de lectura

Dentro del desarrollo de nuevos conceptos pedagógicos como las Tecnologías del Aprendizaje y el Conocimiento (TAC) y el Mobile Learning han aparecido algunos aspectos principales como la Lectura Social y la LIJ 2.0 fundamentales para la didáctica de la lengua y la literatura en entornos digitales. Entre las múltiples posibilidades que nos ofrecen los distintos servicios de redes sociales y microblogging, algunos objetivos para su uso didáctico pueden ser el fomento de la lectura y el desarrollo de la competencia lectoliteraria. Las redes sociales pueden ser un espacio de conversación y lectura donde, con dinámicas adecuadas, se trabaje la comprensión lectora desde muy distintas perspectivas. En el siguiente trabajo se hará una revisión de las distintas herramientas, desde los espacios más generalistas como Facebook o los clubes de lectura a través de servicios como Twitter, hasta llegar a aplicaciones y redes sociales específicas centradas en la literatura, como Aldiko, Wattpad, Ibooks, Anobii, Goodreads o Entrelectores, haciendo una descripción de las distintas posibilidades para la formación del alumnado y la promoción de la lectura

The structure of Leptospira interrogans GAPDH sheds light into an immunoevasion factor that can target the anaphylatoxin C5a of innate immunity

Leptospirosis is a neglected worldwide zoonosis involving farm animals and domestic pets caused by the Gram-negative spirochete Leptospira interrogans. This bacterium deploys a variety of immune evasive mechanisms, some of them targeted at the complement system of the host’s innate immunity. In this work, we have solved the X-ray crystallographic structure of L. interrogans glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to 2.37-Å resolution, a glycolytic enzyme that has been shown to exhibit moonlighting functions that potentiate infectivity and immune evasion in various pathogenic organisms. Besides, we have characterized the enzyme’s kinetic parameters toward the cognate substrates and have proven that the two natural products anacardic acid and curcumin are able to inhibit L. interrogans GAPDH at micromolar concentration through a noncompetitive inhibition modality. Furthermore, we have established that L. interrogans GAPDH can interact with the anaphylatoxin C5a of human innate immunity in vitro using bio-layer interferometry and a short-range cross-linking reagent that tethers free thiol groups in protein complexes. To shed light into the interaction between L. interrogans GAPDH and C5a, we have also carried out cross-link guided protein-protein docking. These results suggest that L. interrogans could be placed in the growing list of bacterial pathogens that exploit glycolytic enzymes as extracellular immune evasive factors. Analysis of the docking results indicates a low affinity interaction that is consistent with previous evidence, including known binding modes of other α-helical proteins with GAPDH. These findings allow us to propose L. interrogans GAPDH as a potential immune evasive factor targeting the complement system

Association of HLA-B*41:02 with Henoch-Schönlein Purpura (IgA Vasculitis) in Spanish individuals irrespective of the HLA-DRB1 status

INTRODUCTION: To determine whether the human leukocyte antigen (HLA) B alleles are implicated in the susceptibility to Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies. METHODS: The study population was composed of 349 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria, and 335 sex and ethnically matched controls. HLA-B phenotypes were determined by sequencing-based typing (SBT) and analyzed by chi-square or Fisher exact test. RESULTS: A statistically significant increase of HLA-B*41:02 allele in HSP patients when compared with controls was found (8.3% versus 1.5% respectively; p = 0.0001; OR (odds ratio) =5.76 [2.15-19.3]). These results remained statistically significant after adjusting for Bonferroni correction (p = 0.0028). An internal validation also confirmed the susceptibility effect on HSP associated with HLA-B*41:02 (OR = 5.70 [1.98-16.44]). Since a former study described an association between HLA-DRB1*01:03 and HSP susceptibility, we also evaluated the implication of HLA-B*41:02 independently of HLA-DRB1*01:03. Interestingly, the association remained statistically significant (p = 0.0004, OR = 4.97 [1.8-16.9]). No HLA-B association with specific HSP clinical features was found. CONCLUSIONS: Our study indicates that HLA-B*41:02 is associated with the susceptibility to HSP in Spanish patients irrespective of HLA-DRB1 status

Gene signatures of early response to anti-TNF drugs in pediatric inflammatory bowel disease

T. Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value < 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.This work was funded by Instituto de Salud Carlos III (grants numbers PI16/00559 and PI19/00792), Consejería de Educación y Deporte de la Comunidad de Madrid (grant number PEJ16/MED/AI-1260), and by the Gregorio Marañón Health Research Institute (grant number PRE-2018-2), The study was cofunded by ERDF Funds (FEDER) from the European Commission, “A way of making Europe

Redes sociales de lectura y otras herramientas de la LIJ 2.0 en asignaturas de didáctica de la lengua y la literatura de la Universidad de Alicante

Nuestra red continúa el trabajo de cursos anteriores profundizando en el concepto de LIJ 2.0 (Literatura y Lectura Infantil y Juvenil en la web social) para mostrarnos las últimas novedades que nos ofrece Internet y los nuevos dispositivos para el acceso a la literatura. En este caso nos centramos en dos herramientas que gracias a la generalización de las tabletas y los teléfonos inteligentes han recibido mucha atención y nos permiten acceder a muchos elementos de la lectura social en cualquier lugar y en cualquier momento. Estamos hablando de las aplicaciones y las redes sociales de lectura. En nuestra aportación a las jornadas de redes (Rovira et alii 2015) ya se hizo un recorrido por distintas herramientas y sus principales posibilidades. Ante un panorama tan amplio, la red ha querido centrar esta memoria en las prácticas realizadas a través de la herramienta más conocida, Facebook y mostrando las posibilidades para la didáctica de la lengua y la literatura y para la LIJ 2.0

Successful development and clinical translation of a novel anterior lamellar artificial cornea

We thank the Andalusian Public Foundation Progress and Health, through the Andalusian Initiative for Advanced Therapies, for assuming the roles and responsibilities of sponsoring this clinical trial. We thank Dr. Manuel de la Rosa and Dr. Salvador Arias Santiago for providing insight and expertise that assisted the research.The datasets generated and/or analyzed during the current study are available in the Gene Expression Omnibus (GEO) public repository, ref. GSE86584 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE86584Blindness due to corneal diseases is a common pathology affecting up to 23 million individuals worldwide. The tissue‐engineered anterior human cornea, which is currently being tested in a Phase I/II clinical trial to treat severe corneal trophic ulcers with preliminary good feasibility and safety results. This bioartificial cornea is based on a nanostructured fibrin–agarose biomaterial containing human allogeneic stromal keratocytes and cornea epithelial cells, mimicking the human native anterior cornea in terms of optical, mechanical, and biological behavior. This product is manufactured as a clinical‐grade tissue engineering product, fulfilling European requirements and regulations. The clinical translation process included several phases: an initial in vitro and in vivo preclinical research plan, including preclinical advice from the Spanish Medicines Agency followed by additional preclinical development, the adaptation of the biofabrication protocols to a good manufacturing practice manufacturing process, including all quality controls required, and the design of an advanced therapy clinical trial. The experimental development and successful translation of advanced therapy medicinal products for clinical application has to overcome many obstacles, especially when undertaken by academia or SMEs. We expect that our experience and research strategy may help future researchers to efficiently transfer their preclinical results into the clinical settings.This study was supported by the Spanish National Plan for Scientific and Technical Research and Innovation (I + D + I) from the Spanish Ministry of Economy and Competitiveness (Carlos III Institute of Health), grants FIS PI14/0955 and FIS PI17/0391 (both cofinanced by ERDF‐FEDER, European Union); by the Spanish Ministry of Health, Social Policy and Equity, grant EC10‐285; and by preclinical research funds from the Regional Ministry of Health through the Andalusian Initiative for Advanced Therapies

The polyadenylation factor FIP1 is important for plant development and root responses to abiotic stresses

17 Pág.Root development and its response to environmental changes is crucial for whole plant adaptation. These responses include changes in transcript levels. Here, we show that the alternative polyadenylation (APA) of mRNA is important for root development and responses. Mutations in FIP1, a component of polyadenylation machinery, affects plant development, cell division and elongation, and response to different abiotic stresses. Salt treatment increases the amount of poly(A) site usage within the coding region and 5' untranslated regions (5'-UTRs), and the lack of FIP1 activity reduces the poly(A) site usage within these non-canonical sites. Gene ontology analyses of transcripts displaying APA in response to salt show an enrichment in ABA signaling, and in the response to stresses such as salt or cadmium (Cd), among others. Root growth assays show that fip1-2 is more tolerant to salt but is hypersensitive to ABA or Cd. Our data indicate that FIP1-mediated alternative polyadenylation is important for plant development and stress responses.This research was supported by grants from the Spanish Government (BIO2017-82209-R and BIO2014-52091-R to J.C.P.) and by the "Severo Ochoa Program for Centres of Excellence in R&D” from the Agencia Estatal de Investigación of Spain (grant SEV-2016-0672 (2017-2021)) to the CBGP. B.T. was supported by a predoctoral fellowship (BES-2012-054056) from MINECO (Spain). C.M. was supported by a Marie Skłodowska-Curie fellowship (Root Barriers 655406) from the European Commission. S.M.B is supported by an Howard Hughes Medical Institute (HHMI) Faculty Scholar Fellowship.Peer reviewe

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality). We evaluated both outcomes in patients whose treatment with ACEI/ARB was continued or withdrawn. Between February and June 2020, 11,205 patients were included, mean age 67 years (SD = 16.3) and 43.1% female; 2162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed lower all-cause mortality (p < 0.0001). Hypertensive patients in the ACEI/ARB group had better results in IMV, ICU admission, and the composite outcome of prognosis (p < 0.0001 for all). No differences were found in the incidence of major adverse cardiovascular events. Patients previously treated with ACEI/ARB continuing treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB was associated with better survival than ACEI (HR 0.77, 95%CI 0.62-0.96). ACEI/ARB treatment during COVID-19 hospitalization was associated with protection on mortality. The benefits were greater in hypertensive, those who continue