Hydroxylammonium derivatives for selective active-site lysine modification in the anti-virulence bacterial target DHQ1 enzyme

Targeted irreversible inhibitors bearing electrophiles that become activated towards covalent bond formation upon binding to a specific protein/enzyme is an emerging area in drug discovery. Targeting lysine residues is challenging due to the intrinsically low reactivity of the amino group at physiological pH. Herein we report the first example of a hydroxylammonium derivative that causes a specific covalent modification of an active-site and a sterically inaccessible lysine residue of an enzyme. The described ligands, compounds 1–3, were rationally designed to be activated towards covalent bond formation upon binding to the type I dehydroquinase (DHQ1) enzyme for the development of new anti-virulence agents to combat the widespread resistance to antibiotics. Evidence in atomic detail for the covalent modifications caused by the ligands to the catalytic Lys170 by the formation of a stable secondary amine is provided by the resolution at 1.08–1.25 Å of the crystal structures of DHQ1 from Salmonella typhi enzyme adducts. In addition, the first crystal structure of the addition intermediate adduct at 1.4 Å of a Schiff base formation reaction by using an analog of the natural substrate, compound 4, is also reported. Molecular dynamics simulation studies on non-covalent enzyme/ligand complexes and a two-dimensional QM/MM umbrella sampling simulation study suggested that a direct displacement by Lys170 with the release of NH2OH would be feasible. These studies might open up new opportunities for the development of novel lysine-targeted irreversible inhibitors bearing a methylhydroxylammonium moiety as a latent electrophile.Financial support from the Spanish Ministry of Economy and Competiveness (SAF2016-75638-R), the Xunta de Galicia [Centro singular de investigación de Galicia accreditation 2016-2019 (ED431G/09) and ED431B 2018/04] and theEuropean Union (European Regional Development Fund –ERDF) is gratefully acknowledged. MM and EL thank the Spanish Ministry of Education, Culture and Sport and the Xunta de Galicia for their respective FPU and postdoctoral fellowshipsS

Red AUTI Red de Aplicaciones y Usabilidad de la Televisión Digital Interactiva (TVDi)

Desde el año 2012 diversas universidades iberoamericanas conforman la Red de Aplicaciones y Usabilidad de la Televisión Digital Interactiva (RedAUTI) de la CYTED coordinada por la UNLP. La línea de investigación y desarrollo presentada consiste en estudiar, desarrollar y evaluar aplicaciones de Televisión Digital Interactiva (TVDi). Uno de los principales objetivos es la formación de recursos humanos y fortalecimiento de la investigación mediante el trabajo intergrupal entre diferentes instituciones nacionales y extranjeras.Eje: Tecnología Informática Aplicada en Educació

Red AUTI Red de Aplicaciones y Usabilidad de la Televisión Digital Interactiva (TVDi)

Desde el año 2012 diversas universidades iberoamericanas conforman la Red de Aplicaciones y Usabilidad de la Televisión Digital Interactiva (RedAUTI) de la CYTED coordinada por la UNLP. La línea de investigación y desarrollo presentada consiste en estudiar, desarrollar y evaluar aplicaciones de Televisión Digital Interactiva (TVDi). Uno de los principales objetivos es la formación de recursos humanos y fortalecimiento de la investigación mediante el trabajo intergrupal entre diferentes instituciones nacionales y extranjeras.Eje: Tecnología Informática Aplicada en Educació

Delivery of Health Care by Spanish Dental Hygienists in Private and Public Dental Services during the COVID-19 De-Escalation Phase (June 2020): A Cross-Sectional Study

Background: The first wave of the COVID-19 pandemic in Spain posed a major challenge for Spanish dental professionals. The objective of this work is to describe the dental hygienists’ work status and employment patterns during the de-escalation phase in order to analyse the standards of knowledge, compliance with official recommendations, and dental activities both in the public health service and in the private sector. Material and Methods: A cross-sectional questionnaire was answered by Spanish dental hygienists via WhatsApp, Facebook, and Instagram. The questionnaire was piloted before it was distributed and carried out during June 2020. Results: Here, 517 dental hygienists were surveyed, of which 86.2% followed the official recommendations to avoid contagion and 63.8% agreed with the gradual return to work by limiting the use of aerosols. Private dental hygienists identified more with returning to work without restrictions (14.5%) versus those working for the public service (1.2%) (p < 0.005). Conclusions: Dental hygienists’ return to work has involved different strategies, aimed at controlling infection and guaranteeing the safety of patients and the rest of the dental team. The availability of personal protective equipment, the adaptation of clinical infrastructure, and patient care management have differed between professionals working in the private and public sectors

Recommendations by the Spanish Society of Epidemiology and Oral Public Health (SESPO) for the healthcare adaptation of public health dental clinics in Spain during the COVID-19 pandemic

In March 2020, the World Health Organization (WHO) declared the COVID-19 pandemic and, a few days later, the Spanish Government declared a State of Emergency and the population lockdown. This crisis situation crisis forced deep changes in health care. A

Red AUTI : Red de Aplicaciones y Usabilidad de la Televisión digital Interactiva

Desde el año 2012 diversas universidades iberoamericanas conforman la Red de Aplicaciones y Usabilidad de la Televisión Digital Interactiva (RedAUTI) de la CYTED coordinada por la UNLP. La línea de investigación y desarrollo presentada consiste en estudiar, desarrollar y evaluar aplicaciones de Televisión Digital Interactiva (TVDi). Uno de los principales objetivos es la formación de recursos humanos y fortalecimiento de la investigación mediante el trabajo intergrupal entre diferentes instituciones nacionales y extranjeras.Eje: Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI

Red AUTI : Red de Aplicaciones y Usabilidad de la Televisión digital Interactiva

Desde el año 2012 diversas universidades iberoamericanas conforman la Red de Aplicaciones y Usabilidad de la Televisión Digital Interactiva (RedAUTI) de la CYTED coordinada por la UNLP. La línea de investigación y desarrollo presentada consiste en estudiar, desarrollar y evaluar aplicaciones de Televisión Digital Interactiva (TVDi). Uno de los principales objetivos es la formación de recursos humanos y fortalecimiento de la investigación mediante el trabajo intergrupal entre diferentes instituciones nacionales y extranjeras.Eje: Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI

Red AUTI : Red de Aplicaciones y Usabilidad de la Televisión digital Interactiva

Desde el año 2012 diversas universidades iberoamericanas conforman la Red de Aplicaciones y Usabilidad de la Televisión Digital Interactiva (RedAUTI) de la CYTED coordinada por la UNLP. La línea de investigación y desarrollo presentada consiste en estudiar, desarrollar y evaluar aplicaciones de Televisión Digital Interactiva (TVDi). Uno de los principales objetivos es la formación de recursos humanos y fortalecimiento de la investigación mediante el trabajo intergrupal entre diferentes instituciones nacionales y extranjeras.Eje: Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI

Understanding the active sites of boron nitride for CWPO: An experimental and computational approach

[EN] Hexagonal boron nitride (h-BN) has been explored as a catalyst for degrading persistent organic pollutants in wastewater by Catalytic Wet Peroxide Oxidation (CWPO). Herein, the superior activity of the h-BN on the phenol degradation (model pollutant) compared to other metal-free catalysts, such as carbon-based ones, and the lower selectivity to CO encourage the potential application of h-BN catalysts in CWPO processes. Through a combined density functional theory calculations, experimental reactions and catalyst characterization approach, a comprehensive study on the reaction mechanism has been conducted. According to this, only defected B atoms in the h-BN layer, protonated as B-(OH), decompose the hydrogen peroxide into highly reactive hydroxyl radicals. The radical species diffuse towards inner h-BN regions and react with the phenol adsorbed by π-π interaction on the h-BN surface. Oxidation by-products cause carbonaceous deposits and progressive deactivation of the h-BN catalyst that can be directly regenerated by burning off in air.The authors thank the financial support by the Community of Madrid and the Government of Spain through the projects: S2018/EMT- 4341 and RTI2018-095052-B-I00 (MCIU/AEI/FEDER, UE), respectively. The work done at the University of Sevilla was funded by Spanish Ministerio de Ciencia e Innovación and EU-FEDER, grant PID2019-106871 GB-I00, and the Junta de Andalucía-FEDER, grant: US-1381410. Also, G. Vega acknowledges the Community of Madrid for the Predoctoral contract PEJD-2018-PRE/AMB-9019, co-financed by the European Social Fund through the Youth Employment Operational Program and the Youth Employment Initiative (YEI) 2018. J. Carbajo thanks the financial support by the Government of Spain for a grant under the Juan de la Cierva_Incorporación programme (IJCI-2017- 32682). The authors would like to thank A. Pérez for performing the BET and TGA measurements

Resistencia a antibióticos de Streptococcus suis aislados en España

Este estudio fue financiado por el proyecto TRANSIT (Ref. LMP58_21) de I+D+i de la Dirección General de Aragó