Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease

BACKGROUND: The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. SUMMARY: The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of proximal tubular cell function, and cysteine-S-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.info:eu-repo/semantics/publishedVersio

Observation of Single-Top-Quark Production in Association with a Photon Using the ATLAS Detector

This Letter reports the observation of single top quarks produced together with a photon, which directly probes the electroweak coupling of the top quark. The analysis uses 139  fb−1 of 13 TeV proton-proton collision data collected with the ATLAS detector at the Large Hadron Collider. Requiring a photon with transverse momentum larger than 20 GeV and within the detector acceptance, the fiducial cross section is measured to be 688±23(stat) +75−71(syst)  fb, to be compared with the standard model prediction of 515+36−42  fb at next-to-leading order in QCD

Blockchain for global vaccinations efforts: State of the art, challenges, and future directions

The emergence of the coronavirus disease 2019 (COVID-19) global crisis negatively affected all aspects of human life. One of the most important methods used worldwide to survive this global crisis is the vaccination process to circumvent the proliferation of this pandemic. Many restrictions were alleviated in many countries such as access to public facilities and events. There is a huge amount of data about vaccination campaigns that are collected and maintained worldwide. Although the vaccination data can be analyzed to find out how the alleviation of restrictions can be applied if the data management process requires preserving key aspects like trust, transparency, and availability for easy and reliable access to such data. In this regard, blockchain technology is an excellent choice for meeting the requirements and providing a secure trusted framework for global verification. In this article, the related literature on blockchain technology is surveyed and summarized for all systems that embody solutions. The pros and cons of each solution are presented and provide a comparative summary. Furthermore, a detailed analysis is given to present the current problems and provide a promising mechanism to verify the vaccinated persons anywhere in the world, in a secure manner while retaining individual privacy

Diversity in Acinetobacter baumannii isolates from paediatric cancer patients in Egypt

Acinetobacter baumannii is an important nosocomial pathogen, commonly causing infections in immunocompromised patients. It is increasingly reported as a multidrug-resistant organism, which is alarming because of its capability to resist all available classes of antibiotics including carbapenems. The aim of this study was to examine the genetic and epidemiological diversity of A. baumannii isolates from paediatric cancer patients in Egypt, by sequencing the intrinsic blaOXA -51-like gene, genotyping by pulsed-field gel electrophoresis and multi-locus sequence typing in addition to identifying the carbapenem-resistance mechanism. Results showed a large diversity within the isolates, with eight different blaOXA -51-like genes, seven novel sequence types and only 28% similarity by pulsed-field gel electrophoresis. All three acquired class-D carbapenemases (OXA-23, OXA-40 and OXA-58) were also identified among these strains correlating with resistance to carbapenems. In addition, we report the first identification of ISAba2 upstream of blaOXA -51-like contributing to high-level carbapenem resistance. This indicates the presence of several clones of A. baumannii in the hospitals and illustrates the large genetic and epidemiological diversity found in Egyptian strains

Hybrid metaheuristic for combinatorial optimization based on immune network for optimization and VNS

Metaheuristics for optimization based on the immune network theory are often highlighted by being able to maintain the diversity of candidate solutions present in the population, allowing a greater coverage of the search space. This work, however, shows that algorithms derived from the aiNET family for the solution of combinatorial problems may not present an adequate strategy for search space exploration, leading to premature convergence in local minimums. In order to solve this issue, a hybrid metaheuristic called VNS-aiNET is proposed, integrating aspects of the COPT-aiNET algorithm with characteristics of the trajectory metaheuristic Variable Neighborhood Search (VNS), as well as a new fitness function, which makes it possible to escape from local minima and enables it to a greater exploration of the search space. The proposed metaheuristic is evaluated using a scheduling problem widely studied in the literature. The performed experiments show that the proposed hybrid metaheuristic presents a convergence superior to two approaches of the aiNET family and to the reference algorithms of the literature. In contrast, the solutions present in the resulting immunological memory have less diversity when compared to the aiNET family approaches

Ferroelectricity driven-resistive switching and Schottky barrier modulation at CoPt/MgZnO interface for non-volatile memories

Ferroelectric memristors have attracted much attention as a type of nonvolatile resistance switching memories in neuromorphic computing, image recognition, and information storage. Their resistance switching mechanisms have been studied several times in perovskite and complicated materials systems. It was interpreted as the modulation of carrier transport by polarization control over Schottky barriers. Here, we experimentally report the isothermal resistive switching across a CoPt/MgZnO Schottky barrier using a simple binary semiconductor. The crystal and texture properties showed high-quality and single-crystal Co$_{0.30}$Pt$_{0.70}$/Mg$_{0.20}$Zn$_{0.80}$O hetero-junctions. The resistive switching was examined by an electric-field cooling method that exhibited a ferroelectric T$_C$ of MgZnO close to the bulk value. The resistive switching across CoPt/MgZnO Schottky barrier was accompanied by a change in the Schottky barrier height of 26.5 meV due to an interfacial charge increase and/or orbital hybridization induced reversal of MgZnO polarization. The magnitude of the reversed polarization was estimated to be a reasonable value of 3.0 (8.25) $\mu$ C/cm$^2$ at 300 K (2 K). These findings demonstrated the utilities of CoPt/MgZnO interface as a potential candidate for ferroelectric memristors and can be extended to probe the resistive switching of other hexagonal ferroelectric materials

Parceria família-creche na transição do bebé para a creche

Este estudo apresenta atitudes e probabilidade de comportamentos de parceria família-creche, relatadas por mães e educadoras, durante o período de entrada de bebés na creche. Mães e educadoras de 90 bebés responderam à Escala de Parceria Educadores-Pais. Os resultados indicam uma grande valorização, por parte das mães e educadoras, da parceria creche-família para dar resposta às necessidades das crianças, bem como uma elevada probabilidade de se envolverem em comporta - mentos de parceria. Os relatos das mães são relativamente mais positivos do que os das educadoras quer no que se refere às atitudes, quer no que se refere à probabilidade de comportamentos de parceria. Verificaram-se associações positivas entre os relatos das mães e das educadoras, assim como entre as atitudes das mães e a qualidade do ambiente familiar. Encontraram-se associações negativas entre a idade e experiência das educadoras em contexto de creche e as suas respostas relativas a atitudes e à probabilidade de comportamentos de parceria. Na discussão, destaca-se a necessidade de investir na formação e na melhoria da qualidade das creches, de modo a promover parcerias família-creche mais efetivas.info:eu-repo/semantics/publishedVersio

Telomerase mediates lymphocyte proliferation but not the atherosclerosis-suppressive potential of regulatory T-cells

Objective: Atherosclerosis is an age-related disease characterised by systemic oxidative stress and low-grade inflammation. The role of telomerase and telomere length in atherogenesis remains contentious. Short telomeres of peripheral leukocytes are predictive for coronary artery disease. Conversely, attenuated telomerase has been demonstrated to be protective for atherosclerosis. Hence a potential causative role of telomerase in atherogenesis is critically debated. Approach and Results: In this study we used multiple mouse models to investigate the regulation of telomerase under oxidative stress as well as its impact on atherogenesis in vitro and in vivo. Using primary lymphocytes and myeloid cell cultures we demonstrate that cultivation under hyperoxic conditions induced oxidative stress resulting in chronic activation of CD4+ cells and significantly reduced CD4+ T-cell proliferation. The latter was telomerase dependent, as oxidative stress had no effect on the proliferation of primary lymphocytes isolated from telomerase-knock-out mice. In contrast, myeloid cell proliferation was unaffected by oxidative stress nor reliant on telomerase. Telomerase reverse transcriptase (TERT) deficiency had no effect on Treg numbers in vivo or suppressive function ex vivo. Adoptive transfer of TERT-/- Tregs into Rag2-/- ApoE-/- double knock out mice demonstrated that telomerase function was not required for the ability of Tregs to protect against atherosclerosis. However, telomere length was critical for Treg function. Conclusions: Telomerase contributes to lymphocyte proliferation but plays no major role in Treg function, provided that telomere length is not critically short. We suggest that oxidative stress may contribute to atherosclerosis via suppression of telomerase and acceleration of telomere attrition in Tregs.This study was supported, in part, by British Heart Foundation Project Grants PG/15/85/31744 and PG/12/47/29681 (www.BHF.org.uk) as well as the Newcastle Healthcare Charity (www.newcastle-hospitals. org.uk/patient-guides/charity-matters-at-newcastle-hospitals_charitable- funds.aspx). N.M. Al Zhrany was funded by a stipend from the Government of Saudi Arabia