β7 Integrin Inhibition Can Increase Intestinal Inflammation by Impairing Homing of CD25hiFoxP3+ Regulatory T Cells.

Background & aimsIntegrin α4β7 mediates lymphocyte trafficking to the gut and gut-associated lymphoid tissues, a process critical for recruitment of effector lymphocytes from the circulation to the gut mucosa in inflammatory bowel disease (IBD) and murine models of intestinal inflammation. Antibody blockade of β7 integrins generally is efficacious in IBD; however, some patients fail to respond, and a few patients can experience exacerbations. This study examined the effects of loss of β7 integrin function in murine models of IBD.MethodsIn a mouse IBD model caused by lack of interleukin 10, a cytokine important in CD25hiFoxP3+ regulatory T cell (Treg) function, genetic deletion of β7 integrin or antibody blockade of α4β7-mucosal addressin cell adhesion molecule-1 interaction paradoxically exacerbated colitis.ResultsLoss of β7 impaired the capacity of Tregs homing to the gut and therefore suppress intestinal inflammation in an adoptive T-cell transfer model; however, the intrinsic suppressive function of β7-deficient Tregs remained intact, indicating that the β7 deficiency selectively impacts gut homing. Deletion of β7 integrin did not worsen colitis in an acute dextran sodium sulfate model in which Treg number and function were normal.ConclusionsIn Integrin subunit beta (Itgb)7-/-Il10-/- mice, loss of β7-dependent Treg homing to gut-associated lymphoid tissues combined with loss of intrinsic Treg function exacerbated intestinal inflammation. These results suggest that IBD patients with reduced CD25hiFoxP3+ Treg numbers or function or lack of interleukin 10 could be at risk for failure of α4β7 blocking therapy

Multi-omic approach to evaluate the response of gilt-head sea bream (Sparus aurata) exposed to the UV filter sulisobenzone

Sulisobenzone (BP-4) is one of the benzophenone type UVfiltersmost frequently detected in aquatic ecosystems. As a suspected endocrine disrupting compound, scarce information is available yet about other molecular effects and its mechanismof action. Here, we used an integrated transcriptomic and metabolomic approach to improve the current understanding on the toxicity of BP-4 towards aquatic species. Gilt-head sea bream individualswere exposed at environmentally relevant concentrations (10 μg L-1) for 22 days. Transcriptomic analysis revealed 371 differentially expressed genes in liver while metabolomic analysis identified 123 differentially modulated features in plasma and 118 in liver. Integration of transcriptomic and metabolomic data showed disruption of the energy metabolism(>10 pathways related to the metabolismof amino acids and carbohydrateswere impacted) and lipid metabolism (5 glycerophospholipids and the expression of 3 enzymes were affected), suggesting oxidative stress.We also observed, for the first time in vivo and at environmental relevant concentrations, the disruption of several enzymes involved in the steroid and thyroid hormones biosynthesis. DNA and RNA synthesis was also impacted by changes in the purine and pyrimidine metabolisms. Overall, the multiomic workflow presented here increases the evidence on suspected effects of BP-4 exposure and identifies additional modes of action of the compounds that could have been overlooked by using single omic approaches. ©2021 The Authors. Published by Elsevier B.V.This research was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) (CTM2015-70731-R) and the FPI fellowship (BES-2016-078593). The authors also would like to acknowledge the Laboratory of Aquaculture at the Faculty of Marine and Environmental Sciences (University of Cádiz), Thibaut Dumas and David Rosain (UMR HydroSciences, Université Montpellier, France) for their support

Diseño de una planta de producción de cerveza artesanal.

Actualmente en el país se encuentran registradas 32 plantas que prestan el servicio de realizar cervezas artesanales con un crecimiento anual en el 2016 de un 35 %, este es un mercado que ha ido creciendo paulatinamente y el cual cada vez es más atractivo tanto para los empresarios como para el público en general. Con base en estos crecimientos y las proyecciones estimadas por los expertos en la materia inversionistas españoles ven la oportunidad de negocio y deciden explorar los beneficios que se han suscrito entre estos países hermanos. En primera instancia hacen un estudio de mercado, contratando una firma encuestadora, esto con el fin de corroborar la oportunidad detectada y con base en los resultados obtenidos toman la decisión de conocer cómo y cuántos sería los requisitos, costos y beneficios que conllevaría hacer el diseño y la futura implementación de una planta de producción de cerveza artesanal en Colombia más exactamente en la ciudad capital o sus alrededores

An increase in erythromycin resistance in methicillin-susceptible Staphylococcus aureus from blood correlates with the use of macrolide/lincosamide/streptogramin antibiotics. EARS-Net Spain (2004–2020)

Staphylococcus aureus; Antibiotic resistance; MacrolidesStaphylococcus aureus; Resistència als antibiòtics; MacròlidsStaphylococcus aureus; Resistencia a los antibióticos; MacrólidosObjectives: To describe and analyse erythromycin resistance trends in blood isolates of Staphylococcus aureus (EARS-Net Spain, 2004–2020) and the association of these trends with the consumption of macrolide, lincosamide, and streptogramin B (MLSB) antibiotics. To assess molecular changes that could be involved in erythromycin resistance trends by whole genome analysis of representative isolates. Materials and methods: We collected antibiotic susceptibility data for all first-blood S. aureus isolates in patients from 47 Spanish hospitals according to EARS-Net criteria. MLSB antibiotic consumption was obtained from the Spanish Agency for Medicines and Medical Devices (2008–2020). We sequenced 137 representative isolates for core genome multilocus sequence typing, resistome and virulome analysis. Results: For the 36,612 invasive S. aureus isolates, methicillin resistance decreased from 26.4% in 2004 to 22.4% in 2020. Erythromycin resistance in methicillin-susceptible S. aureus (MSSA) increased from 13.6% in 2004 to 28.9% in 2020 (p < 0.001); however, it decreased from 68.7 to 61.8% (p < 0.0001) in methicillin-resistant S. aureus (MRSA). Total consumption of MLSB antibiotics increased from 2.72 defined daily doses per 1,000 inhabitants per day (DID) in 2014 to 3.24 DID in 2016. By WGS, the macrolide resistance genes detected were erm (59.8%), msrA (46%), and mphC (45.2%). The erm genes were more prevalent in MSSA (44/57, 77.2%) than in MRSA (38/80, 47.5%). Most of the erm genes identified in MSSA after 2013 differed from the predominant ermC gene (17/22, 77.3%), largely because ermT was significantly associated with MSSA after 2013 (11/29, 37.9%). All 13 ermT isolates in this study, except one, belonged to ST398 and came from 10 hospitals and six Spanish provinces. Conclusion: The significant increase in erythromycin resistance in blood MSSA correlated with the consumption of the MLSB antibiotics in Spain. These preliminary data seem support the hypothesis that the human ST398 MSSA clade with ermT-mediated resistance to erythromycin may be involved in this trend.This research was supported by CIBER—Consorcio Centro de Investigación Biomédica en Red (CB21/13/00095, CB21/13/00006, CB21/13/00054, CB21/13/00068, CB21/13/00084, CB21/13/00099 groups of CIBERINFEC; CB06/06/0058 group of CIBERES), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU. This research was also supported by Personalized and precision medicine grant from the Instituto de Salud Carlos III (MePRAM Project, PMP22/00092), and by the Antibiotic Resistance and Staphylococcus aureus Surveillance Programs of the National Center for Microbiology, Instituto de Salud Carlos III

Synthesis and antifungal activity of novel oxazolidin-2-one linked-1,2,3-triazole derivatives

Artículo IndizadoNovel oxazolidin-2-one-linked 1,2,3-triazole derivatives (4a–k) were synthesized by straightforward and versatile azide–enolate (3 + 2) cycloaddition. The series of compounds was screened for antifungal activity against four filamentous fungi as well as six yeast species of Candida spp. According to their efficiency and breadth of scope, they can be ordered as 4k > 4d > 4h > 4a, especially in relation to the activity displayed against Candida glabrata ATCC-34138, Trichosporon cutaneum ATCC-28592 and Mucor hiemalis ATCC-8690, i.e. compounds 4d, 4h and 4k showed excellent activity against C. glabrata (MIC 0.12, 0.25 and 0.12 μg mL−1, respectively), better than that of itraconazole (MIC 1 μg ml−1). The activity of compound 4d (MIC = 2 μg mL− 1) was higher than that observed for the standard antifungal drug (MIC = 8 μg mL−1) against Trichosporon cutaneum, while compound 4k displayed an excellent antimycotic activity against Mucor hiemalis (MIC = 2 μg mL−1 vs. 4 μg mL−1 for itraconazole). In addition, we describe herein a novel mild and eco-friendly synthetic protocol for obtaining β-ketosulfones (adducts to afford compounds 4a–k) from α-brominated carbonyls in an aqueous nanomicellar medium at room temperature.CONACYT, Secretaría de Investigación de Estudios Avanzados de la UAE

Lattice Study of the Decay B^0-bar -> rho^+ l^- nu_l-bar: Model-Independent Determination of |V_{ub}|

We present results of a lattice computation of the vector and axial-vector current matrix elements relevant for the semileptonic decay B^0-bar -> rho^+ l^- nu_l-bar. The computations are performed in the quenched approximation of lattice QCD on a 24^3 x 48 lattice at beta = 6.2, using an O(a) improved fermionic action. Our principal result is for the differential decay rate, dGamma/dq^2, for the decay B^0-bar -> rho^+ l^- nu_l-bar in a region beyond the charm threshold, allowing a model-independent extraction of |V_{ub}| from experimental measurements. Heavy quark symmetry relations between radiative and semileptonic decays of B-bar mesons into light vector mesons are also discussed.Comment: 22 pages LaTeX-209 (dependent on settings in a4.sty), 23 PostScript figures included with epsf.sty. Complete PostScript file including figures available at http://wwwhep.phys.soton.ac.uk/hepwww/papers/shep9518

Invasión urbana de flebotomineo transmisores de Leishmania en Mérida, Venezuela

Urban development together with uncontrolled construction in endemic areas of leishmaniasis has resulted in a series of environmental transformations that have promoted the spread of cutaneous leishmaniasis, with the adaptation sandflies transmitters to these urban environments. This study aims to determine the presence of sandflies and the epidemiological factors associated with the transmission of leishmaniasis in an urban area of Zea, Venezuela. Five methods of catching sandflies were used indoors in two urbanizations in Zea, Venezuela. Through a survey-type instrument, the epidemiological variables associated with the transmission of leishmaniasis in the housing estates were determined. The presence in the urban dwellings of Lutzomyia youngi, Lutzomyia spinicrassa, Lutzomyia migonei, Lutzomyia ovallesi, Lutzomyia walkeri, Lutzomyia venezuelensis, Lutzomyia atroclavata and Lutzomyia lichyi were demonstrated. 62.5% of the species caught in urbanized areas have antropohematophagy habits. A 67% and 80% of infestation was determined in the dwellings of the studied urbanizations. It was evidenced a low level of knowledge in the inhabitants mainly on the sandflies, which increases the risk of domiciliation and transmission of leishmaniasis, the control entities are warned to implement preventive and educational measures.&nbsp;El desarrollo urbano ha causado una serie de transformaciones ambientales, que ha promovido la propagación de la leishmaniasis con la adaptación de los flebotomíneos transmisores. Este estudio tiene como objetivo determinar la presencia de flebotomíneos y evaluar factores epidemiológicos asociados a la transmisión de leishmaniasis en una zona urbana de Zea, Venezuela. &nbsp;Se emplearon cinco métodos&nbsp; de captura de&nbsp; flebotomíneo en el interior de las viviendas en dos urbanizaciones en Zea, Venezuela. A través de un instrumento tipo encuestas, se determinaron las variables epidemiológicas asociadas a la transmisión de la leishmaniasis. Se demostró la presencia en el interior de la viviendas urbanas de Lutzomyia youngi, Lutzomyia spinicrassa, Lutzomyia migonei, Lutzomyia ovallesi, Lutzomyia walkeri, Lutzomyia venezuelensis,&nbsp; Lutzomyia atroclavata &nbsp;y Lutzomyia lichyi. El 62,5% de las especies capturadas en las áreas urbanizadas poseen hábitos de antropohematofagia. Se determinó un 67 % y 80% de infestación en las viviendas de las&nbsp; urbanizaciones estudiadas. Se evidenció un bajo nivel de conocimiento en los pobladores principalmente sobre los flebotomíneos, lo cual incrementa el riesgo de domiciliación y&nbsp; transmisión de la leishmaniasis. Se alerta a los entes encargados del control de dicha enfermedad a implementar las medidas preventivas y de educación necesaria

Expression of TCRγδ receptor genes in jejunum mucosa of baby alpacas (Vicugna pacos)

El objetivo de este estudio fue determinar la expresión de genes del receptor TCRγδ (gamma y delta) en el epitelio yeyunal de 16 crías de alpaca aparentemente sanas, de 2 a 47 días de edad, mediante la cuantificación de ARN mensajero (ARNm) utilizando cebadores específicos. Se tomaron porciones de yeyuno (2 cm de longitud). El ARNm total de la mucosa de la porción media del yeyuno actuó como molde para la síntesis de ADN complementario mediante transcripción reversa (RT), seguida de un PCR-tiempo real para la amplificación y cuantificación de los ARNm de los polipéptidos que conforman las cadenas gamma y delta del TCR. Se utilizó el método 2-ΔΔCt para la cuantificación relativa de ARNm, teniendo como calibrador a dos crías neonatas que no habían consumido calostro. Las crías de 1, 2, 3 y ≥4 semanas de edad expresaron el gen gamma en 4.75, 6.78, 16.24 y 103.11 veces lo expresado por los animales calibradores, respectivamente, y el gen delta fue expresado en 9.43, 20.78, 25.08 y 146.46 veces, respectivamente. Los resultados demuestran que los genes gamma y delta se expresan en forma creciente con la edad, y significativamente a partir de la cuarta semana de edad (p&lt;0.05), indicando que los linfocitos Tγδ se incrementan en la mucosa intestinal con la edad.The aim of this study was to determine the expression of TCRγδ receptor genes (gamma and delta) in the jejunal epithelium of 16 apparently healthy baby alpacas (2 to 47 days of age), by quantifying messenger RNA (mRNA) using specific primers. Jejunumsamples (2 cm long) were collected. Total mRNA of the medium portion of the jejunum acted as template for complementary DNA synthesis by reverse transcription (RT), followed by real-time PCR for the amplification and quantification of the mRNAs of the polypeptides that make up the gamma and delta chains of the TCR. The 2-ΔΔCt method was used for the relative mRNA quantification, using as calibrator two neonatal alpacas that had not consumed colostrum. The alpacas of 1, 2, 3 and &gt;4 weeks of age expressed the gamma gene at 4.75, 6.78, 16.24 and 103.11 folds as expressed by the calibrator animals, respectively, and the delta gene was expressed at 9.43, 20.78, 25.08, and 146.46 folds, respectively. The results demonstrate that gamma and delta genes are increasingly expressed with age, and significantly from the fourth week of age (p&lt;0.05), indicating that Tγδ lymphocytes increase in the intestinal mucosa with age

Targeting L-type amino acid transporter 1 in innate and adaptive T cells efficiently controls skin inflammation

BACKGROUND: Psoriasis is a frequent inflammatory skin disease that is mainly mediated by IL-23, IL-1β, and IL-17 cytokines. Although psoriasis is a hyperproliferative skin disorder, the possible role of amino acid transporters has remained unexplored. OBJECTIVE: We sought to investigate the role of the essential amino acid transporter L-type amino acid transporter (LAT) 1 (SLC7A5) in psoriasis. METHODS: LAT1 floxed mice were crossed to Cre-expressing mouse strains under the control of keratin 5, CD4, and retinoic acid receptor-related orphan receptor γ. We produced models of skin inflammation induced by imiquimod (IMQ) and IL-23 and tested the effect of inhibiting LAT1 (JPH203) and mammalian target of rapamycin (mTOR [rapamycin]). RESULTS: LAT1 expression is increased in keratinocytes and skin-infiltrating lymphocytes of psoriatic lesions in human subjects and mice. LAT1 deletion in keratinocytes does not dampen the inflammatory response or their proliferation, which could be maintained by increased expression of the alternative amino acid transporters LAT2 and LAT3. Specific deletion of LAT1 in γδ and CD4 T cells controls the inflammatory response induced by IMQ. LAT1 deletion or inhibition blocks expansion of IL-17-secreting γ4+δ4+ and CD4 T cells and dampens the release of IL-1β, IL-17, and IL-22 in the IMQ-induced model. Moreover, inhibition of LAT1 blocks expansion of human γδ T cells and IL-17 secretion by human CD4 T cells. IL-23 and IL-1β stimulation upregulates LAT1 expression and induces mTOR activation in IL-17+ γδ and TH17 cells. Deletion or inhibition of LAT1 efficiently controls IL-23- and IL-1β-induced phosphatidylinositol 3-kinase/AKT/mTOR activation independent of T-cell receptor signaling. CONCLUSION: Targeting LAT1-mediated amino acid uptake is a potentially useful immunosuppressive strategy to control skin inflammation mediated by the IL-23/IL-1β/IL-17 axis.Funding This manuscript has been funded by grants SAF 2017-82886-R (FS-M) and SAF 2013-42850-R (MF) from the Spanish Ministry of Economy and Competitiveness; CAM (S2017/BMD-3671-INFLAMUNE-CM) from the Comunidad de Madrid (FS-M); CIBERCV, BIOIMID PIE13/041 from Instituto de Salud Carlos III and Fundación La Marató TV3 (20152330 31). The project leading to these results has also received funding from FUNDACIÓN BBVA A EQUIPOS DE INVESTIGACIÓN CIENTÍFICA 2018 and from “la Caixa” Banking Foundation under the project code HR17-00016 (FS-M), and from Agencia Estatal de Investigación, Fondo Europeo de Desarrollo Regional PI17/01972 (E.D).S

Two multi-fragment recombination events resulted in the beta-lactam-resistant serotype 11A-ST6521 related to Spain9V-ST156 pneumococcal clone spreading in south-western Europe, 2008 to 2016

Background: The successful pneumococcal clone Spain(9V)-ST156 (PMEN3) is usually associated with vaccine serotypes 9V and 14. Aim: Our objective was to analyse the increase of a serotype 11A variant of PMEN3 as cause of invasive pneumococcal disease (IPD) in Spain and its spread in south-western Europe. Methods: We conducted a prospective multicentre study of adult IPD in Spain (2008-16). Furthermore, a subset of 61 penicillin-resistant serotype 11A isolates from France, Italy, Portugal and Spain were subjected to whole genome sequencing (WGS) and compared with 238 genomes from the European Nucleotide Archive (ENA). Results: Although the incidence of serotype 11A in IPD was stable, a clonal shift was detected from CC62 (penicillin-susceptible) to CC156 (penicillin-resistant). By WGS, three major 11A-CC156 lineages were identified, linked to ST156 (n=5 isolates; France, Italy and Portugal), ST166 (n=4 isolates; France and Portugal) and ST838/6521 (n=52 isolates; France, Portugal and Spain). Acquisition of the capsule allowed to escape vaccine effect. AP200 (11A-ST62) was the donor for ST156 and ST838/6521 but not for ST166. In-depth analysis of ST838/6521 lineage showed two multi-fragment recombination events including four and seven fragments from an 11A-ST62 and an NT-ST344 representative, respectively. Conclusion: The increase in penicillin-resistant serotype 11A IPD in Spain was linked to the spread of a vaccine escape PMEN3 recombinant clone. Several recombination events were observed in PMEN3 acquiring an 11A capsule. The most successful 11A-PMEN3 lineage spreading in south-western Europe appeared after two multi-fragment recombination events with representatives of two major pneumococcal clones (11A-ST62 and NT-ST344)