Guanylyl cyclase activation reverses resistive breathing–induced lung injury and inflammation

Inspiratory resistive breathing (RB), encountered in obstructive lung diseases, induces lung injury. The soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway is down-regulated in chronic and acute animal models of RB, such as asthma, chronic obstructive pulmonary disease, and in endotoxin-induced acute lung injury. Our objectives were to: (1) characterize the effects of increased concurrent inspiratory and expiratory resistance in mice via tracheal banding; and (2) investigate the contribution of the sGC/cGMP pathway in RB-induced lung injury. Anesthetized C57BL/6 mice underwent RB achieved by restricting tracheal surface area to 50% (tracheal banding). RB for 24 hours resulted in increased bronchoalveolar lavage fluid cellularity and protein content, marked leukocyte infiltration in the lungs, and perturbed respiratory mechanics (increased tissue resistance and elasticity, shifted static pressure–volume curve right and downwards, decreased static compliance), consistent with the presence of acute lung injury. RB down-regulated sGC expression in the lung. All manifestations of lung injury caused by RB were exacerbated by the administration of the sGC inhibitor, 1H-[1,2,4]oxodiazolo[4,3-]quinoxalin-l-one, or when RB was performed using sGCα1 knockout mice. Conversely, restoration of sGC signaling by prior administration of the sGC activator BAY 58-2667 (Bayer, Leverkusen, Germany) prevented RB-induced lung injury. Strikingly, direct pharmacological activation of sGC with BAY 58-2667 24 hours after RB reversed, within 6 hours, the established lung injury. These findings raise the possibility that pharmacological targeting of the sGC–cGMP axis could be used to ameliorate lung dysfunction in obstructive lung diseases

Deliverable D2.1 - Ecosystem analysis and 6G-SANDBOX facility design

This document provides a comprehensive overview of the core aspects of the 6G-SANDBOX project. It outlines the project's vision, objectives, and the Key Performance Indicators (KPIs) and Key Value Indicators (KVIs) targeted for achievement. The functional and non-functional requirements of the 6G-SANDBOX Facility are extensively presented, based on a proposed reference blueprint. A detailed description of the updated reference architecture of the facility is provided, considering the requirements outlined. The document explores the experimentation framework, including the lifecycle of experiments and the methodology for validating KPIs and KVIs. It presents the key technologies and use case enablers towards 6G that will be offered within the trial networks. Each of the platforms constituting the 6G-SANDBOX Facility is described, along with the necessary enhancements to align them with the project's vision in terms of hardware, software updates, and functional improvements

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

A Grid-enabled CPU scavenging architecture and a case study of its use in Greek School Network

In this paper we present a CPU scavenging architecture suitable for desktop resources, and we study its appropriateness in exploiting the PC Laboratory resources of the Greek School Network and their integration to the existing HellasGrid national infrastructure. School laboratories form an extensive network equipped with computational systems and fast Internet connections. As this infrastructure is utilized at most 8 h per day and 5 days per week, it could be made available during its remaining idle time for computational purposes through the use of Grid technology. The structure and organization of the school laboratories and backbone network enables the CPU scavenging service, as an independent and additional service, which will not violate the operational rules and policies of the school network, while it will add additional resources to the current HellasGrid infrastructure with low adaptation cost

Bringing environmental culture content into the Europeana.eu portal: The natural Europe digital libraries federation infrastructure

Summarization: The aim of the Natural Europe project [1] is to improve the availability and relevance of environmental culture content for education and life-long learning use, in a multilingual and multicultural context. Cultural heritage content related with natural history, natural sciences, and nature/ environment preservation, is collected from six Natural History Museums (NHMs) around Europe into a federation of European Natural History Digital Libraries that is directly connected with Europeana.eu. We present here the Natural History Digital Libraries Federation infrastructure along with the appropriate tools and services that (a) allow the participating NHMs to uniformly describe and semantically annotate their content according to international standards and specifications, (b) interconnect their digital libraries, and (c) expose metadata records for Natural History cultural heritage objects to Europeana.eu.Παρουσιάστηκε στο: 5th International Conference, MTSR 2011, Izmir, Turkey, October 12-14

ChIP-seq analysis revealing the mH2A1.1, mH2A1.2 and mH2A2 binding patterns in MEFs and ESCs. A.

Summary and Tornado plots depicting the binding of mH2A1.1 (left panels), mH2A1.2 (middle panels) and mH2A2 (right panels), in MEFs (upper panels) and ESCs (lower panels). Signal is normalized as log2FC (IP signal/Input signal) and peaks were defined using SICER2. B. Venn diagrams depicting the mH2A individual variant targets of the 73 mH2AMET/EMT genes in MEFs and ESCs. Targets were defined using the broad peaks derived from peak-calling analysis with SICER2 and peaks were annotated to genes with GREAT tool (±10 kb from the TSS). mH2A1.1 and mH2A2 have the most targets in MEFs, whereas in ESCs mH2A1.1 is the primary variant with direct binding at the 73 mH2AMET/EMT gene loci. C. Heatmaps depicting comparative ChIPseq analysis of mH2A1.1, mH2A1.2 and mH2A2 variants bound to the 73 mH2AMET/EMT genes in MEFs and ESCs as indicated. The average mH2A binding was calculated either at the -5kb regulatory region upstream from TSS or at the gene bodies after RPKM normalization. D. Intersection of the data presented in Fig 2B and S3C Fig. Genes with direct binding of a mH2A-bearing nucleosome are depicted in yellow and genes with no significant mH2A binding are depicted in black. (TIF)</p