Tropical Cyclone ENAWO - Post-Event Report

Tropical Cyclones (TCs) are among the most damaging events. They affect the population with three dangerous effects: strong wind, heavy rain and storm surge. JRC has developed a system used in Global Disaster Alert and Coordination System (GDACS) that includes the analysis of all these effects for every TC occurring worldwide to assess the overall impact. This document is the first POST-EVENT Report, which is a new type of report produced by the JRC after a major event aimed to report the real status of the impact that occurred, based on media reports, onsite analyses, and satellite images. The event analysed in this report is the intense TC ENAWO, that made landfall in north-eastern Madagascar on 7 March 2017, killing more than 80 people and causing extensive damage, especially in Sava and Analanjirofo regions. Authorities issued a "declaration of national emergency" and formally requested international assistance on 14 March. GDACS issued the first RED alert (for high winds) in Madagascar on 3 March. The Emergency Response Coordination Centre (ERCC) of DG ECHO activated ARISTOTLE on 5 March and the Copernicus Emergency Management Service (EMS) on 7 March. The responses of the alert and information systems are analysed and the results are compared with the damage reported by national authorities and satellite images analysis. In order to improve the current early warning system and impact estimations, JRC is implementing a new method to evaluate the areas potentially most affected by a TC, using new datasets and classifications. The results are also included in the report.JRC.E.1-Disaster Risk Managemen

Interoperability of Mobile Devices for Crisis Management: Outcomes of the 1st JRC ECML Crisis Technology Workshop

The 1st JRC ECML Crisis Technology Workshop on Mobile Interoperability for International Field Deployment took place in the European Crisis Management Laboratory (ECML) of the Joint Research Centre in Ispra, Italy, from 12 to 13 March 2012. 37 participants attended the workshop. They were coming from: 11 EU countries and Norway, Brazil and US, 3 UN agencies, and 2 NGOs. The workshop's purpose was to measure the added value of mobile assessment technology for rapid situation assessment in international emergency operations. Seven mobile assessment systems were deployed among the participants and needed to provide, in an interoperable way, real-time data to a single electronic On-Site Operations Coordination Centre (eOSOCC). The performance of the systems was benchmarked against a traditional paper-based assessment that was conducted simultaneously (pOSOCC). In the workshop experiment both paper and electronic On-Site Operations Coordination Centres (OSOCCs) reached a similar situation awareness in the same time, but only the eOSOCC had products available as sharable electronic maps and documents. The final map with all incoming feeds in the eOSOCC was very cluttered and there was considerable information overload. Therefore sophisticated editing, filtering, and visualization functionalities have to be available for eOSOCC staff. Mobile technology is mature and can be deployed in an interoperable way. However, then the information of each system leaves the proprietary applications for processing and analyzing the data. The main impression from the eOSOCC team was that there is a lot of potential. Having access in real-time to field information was felt to be extremely useful. Still missing are tools and procedures for exploiting this benefit. Most important are tools to curate, filter, manipulate, edit, and delete assessment information of all teams. A dedicated eOSOCC software suite is needed that gives full control over the data to the eOSOCC staff.JRC.G.2-Global security and crisis managemen

Measured temporal variations of CO2 concentration and atmospheric emissions in a hydropeaking-impacted river

Rivers are increasingly recognised as active players in the global carbon cycle. They are able to transport, transform, and exchange organic matter, and can emit considerable fluxes of greenhouse gases (e.g., CO2) into the atmosphere, with a magnitude comparable to the global carbon input to the oceans. However, the quantification of these processes is still affected by considerable uncertainties, driven by an incomplete understanding of the interplay between physical, geochemical, and biological parameters, and by a lack of spatially and temporally resolved high-quality data. For instance, and despite a potentially strong impact on kilometres of rivers worldwide, the effects of hydropeaking on riverine CO2 emissions have been almost completely neglected until recently (Calamita et al., Unaccounted CO2 leaks downstream of a large tropical hydroelectric reservoir, PNAS 2020). As a contribution to filling this knowledge gap, we present the results of a field-measurement campaign performed in a single-thread Alpine river (River Noce, Italy) during multiple hydropeaking events. Data of water-dissolved CO2, water temperature, and flow discharge, were collected sub-hourly both downstream and upstream of the outlets of a hydropower plant, revealing a complex pattern of variation in time at both locations. Water released from the hydropower plant during hydropeaking had oversaturated CO2 concentrations relative to the atmosphere, in close agreement with water samples collected in the hypolimnion of the upstream reservoir. Higher flow rates during hydropeaking events were associated with higher rates of gas exchange through the water-air interface. Higher exchange rates and higher CO2 concentrations in water during hydropeaking events enhanced CO2 fluxes, as confirmed by measurements with a floating CO2 flux chamber. Meanwhile, the CO2 concentration upstream of the outlets displayed strong diel fluctuations around the atmospheric equilibrium concentration, which were likely driven by primary production within the residual flow during the day. It is shown that the residual flow can have a previously unacknowledged added value as a CO2 sink during the day, fueled by its biological activity. Hydropower releases bypassed the residual flow and discharged hypolimnetic water oversaturated with CO2 at high flow rates during hydropeaking, offsetting CO2 concentration and fluxes downstream of the outlets and increasing emissions on average. These results highlight the ubiquity of hydropeaking impacts also with respect to greenhouse gas emissions. They illustrate the complexity of the riverine carbon cycle and demonstrate the importance of temporally and spatially-resolved data for the accurate assessment of the riverine carbon balance

Discovery of Substituted (2-Aminooxazol-4-yl)Isoxazole-3-carboxylic Acids as Inhibitors of Bacterial Serine Acetyltransferase in the Quest for Novel Potential Antibacterial Adjuvants

Many bacteria and actinomycetales use L-cysteine biosynthesis to increase their tolerance to antibacterial treatment and establish a long-lasting infection. In turn, this might lead to the onset of antimicrobial resistance that currently represents one of the most menacing threats to public health worldwide. The biosynthetic machinery required to synthesise L-cysteine is absent in mammals; therefore, its exploitation as a drug target is particularly promising. In this article, we report a series of inhibitors of Salmonella thyphimurium serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of L-cysteine biosynthesis. The development of such inhibitors started with the virtual screening of an in-house library of compounds that led to the selection of seven structurally unrelated hit derivatives. A set of molecules structurally related to hit compound 5, coming either from the original library or from medicinal chemistry efforts, were tested to determine a preliminary structure–activity relationship and, especially, to improve the inhibitory potency of the derivatives, that was indeed ameliorated by several folds compared to hit compound 5 Despite these progresses, at this stage, the most promising compound failed to interfere with bacterial growth when tested on a Gram-negative model organism, anticipating the need for further research efforts

Discovery of Substituted (2-Aminooxazol-4-yl)Isoxazole-3-carboxylic Acids as Inhibitors of Bacterial Serine Acetyltransferase in the Quest for Novel Potential Antibacterial Adjuvants

Many bacteria and actinomycetales use L-cysteine biosynthesis to increase their tolerance to antibacterial treatment and establish a long-lasting infection. In turn, this might lead to the onset of antimicrobial resistance that currently represents one of the most menacing threats to public health worldwide. The biosynthetic machinery required to synthesise L-cysteine is absent in mammals; therefore, its exploitation as a drug target is particularly promising. In this article, we report a series of inhibitors of Salmonella thyphimurium serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of L-cysteine biosynthesis. The development of such inhibitors started with the virtual screening of an in-house library of compounds that led to the selection of seven structurally unrelated hit derivatives. A set of molecules structurally related to hit compound 5, coming either from the original library or from medicinal chemistry efforts, were tested to determine a preliminary structure–activity relationship and, especially, to improve the inhibitory potency of the derivatives, that was indeed ameliorated by several folds compared to hit compound 5 Despite these progresses, at this stage, the most promising compound failed to interfere with bacterial growth when tested on a Gram-negative model organism, anticipating the need for further research efforts

Discovery of novel fragments inhibiting O-acetylserine sulphhydrylase by combining scaffold hopping and ligand-based drug design.

Several bacteria rely on the reductive sulphur assimilation pathway, absent in mammals, to synthesise cysteine. Reduction of virulence and decrease in antibiotic resistance have already been associated with mutations on the genes that codify cysteine biosynthetic enzymes. Therefore, inhibition of cysteine biosynthesis has emerged as a promising strategy to find new potential agents for the treatment of bacterial infection. Following our previous efforts to explore OASS inhibition and to expand and diversify our library, a scaffold hopping approach was carried out, with the aim of identifying a novel fragment for further development. This novel chemical tool, endowed with favourable pharmacological characteristics, was successfully developed, and a preliminary Structure-Activity Relationship investigation was carried out

Decreased subunit stability as a novel mechanism for potassium current impairment by a KCNQ2 C terminus mutation causing benign familial neonatal convulsions.

KCNQ2 and KCNQ3 K+ channel subunits underlie the muscarinic-regulated K+ current (I(KM)), a widespread regulator of neuronal excitability. Mutations in KCNQ2- or KCNQ3-encoding genes cause benign familiar neonatal convulsions (BFNCs), a rare autosomal-dominant idiopathic epilepsy of the newborn. In the present study, we have investigated, by means of electrophysiological, biochemical, and immunocytochemical techniques in transiently transfected cells, the consequences prompted by a BFNC-causing 1-bp deletion (2043deltaT) in the KCNQ2 gene; this frameshift mutation caused the substitution of the last 163 amino acids of the KCNQ2 C terminus and the extension of the subunit by additional 56 residues. The 2043deltaT mutation abolished voltage-gated K+ currents produced upon homomeric expression of KCNQ2 subunits, dramatically reduced the steady-state cellular levels of KCNQ2 subunits, and prevented their delivery to the plasma membrane. Metabolic labeling experiments revealed that mutant KCNQ2 subunits underwent faster degradation; 10-h treatment with the proteasomal inhibitor MG132 (20 microm) at least partially reversed such enhanced degradation. Co-expression with KCNQ3 subunits reduced the degradation rate of mutant KCNQ2 subunits and led to their expression on the plasma membrane. Finally, co-expression of KCNQ2 2043deltaT together with KCNQ3 subunits generated functional voltage-gated K+ currents having pharmacological and biophysical properties of heteromeric channels. Collectively, the present results suggest that mutation-induced reduced stability of KCNQ2 subunits may cause epilepsy in neonates

Measuring the Impact of COVID-19 Confinement Measures on Human Mobility using Mobile Positioning Data: A European regional analysis

This paper presents a mobility indicator derived from anonimised aggregated mobile positioning data. Even though the indicator does not provide information about the behaviour of individuals, it captures valuable insights into the mobility patterns of the population in the EU and it is expected to inform responses against the COVID-19 pandemic. Spatio-temporal harmonisation is carried out so that the indicator can provide mobility estimates comparable across European countries. The indicators are provided at a high spatial granularity (up to NUTS3). As an application, the indicator is used to study the impact of COVID-19 confinement measure on mobility in Europe. It is found that a large proportion of the mobility patterns can be explained by these measures. The paper also presents a comparative analysis between mobility and the infection reproduction number Rt over time.JRC.E.6-Demography, Migration and Governanc

The Interference of Notch1 target Hes1 affects cell growth, differentiation and invasiveness of glioblastoma stem cells through modulation of multiple oncogenic targets

The invasive and lethal nature of Glioblastoma multiforme (GBM) necessitates the continuous identification of molecular targets and search of efficacious therapies to inhibit GBM growth. The GBM resistance to chemotherapy and radiation it is attributed to the existence of a rare fraction of cancer stem cells (CSC) that we have identified within the tumor core and in peritumor tissue of GBM. Since Notch1 pathway is a potential therapeutic target in brain cancer, earlier we highlighted that pharmacological inhibition of Notch1 signalling by γ-secretase inhibitor-X (GSI-X), reduced cell growth of some c-CSC than to their respective p-CSC, but produced negligible effects on cell cycle distribution, apoptosis and cell invasion. In the current study, we assessed the effects of Hes1-targeted shRNA, a Notch1 gene target, specifically on GBM CSC refractory to GSI-X. Depletion of Hes1 protein induces major changes in cell morphology, cell growth rate and in the invasive ability of shHes1-CSC in response to growth factor EGF. shHes1-CSC show a decrease of the stemness marker Nestin concurrently to a marked increase of neuronal marker MAP2 compared to pLKO.1-CSC. Those effects correlated with repression of EGFR protein and modulation of Stat3 phosphorylation at Y705 and S727 residues. In the last decade Stat3 has gained attention as therapeutic target in cancer but there is not yet any approved Stat3-based glioma therapy. Herein, we report that exposure to a Stat3/5 inhibitor, induced apoptosis either in shHes1-CSC or control cells. Taken together, Hes1 seems to be a favorable target but not sufficient itself to target GBM efficaciously, therefore a possible pharmacological intervention should provide for the use of anti-Stat3/5 drugs either alone or in combination regimen

Interferon-α-Conditioned Human Monocytes Combine a Th1-Orienting Attitude with the Induction of Autologous Th17 Responses: Role of IL-23 and IL-12

IFN-α exerts multiple effects leading to immune protection against pathogens and cancer as well to autoimmune reactions by acting on monocytes and dendritic cells. We analyzed the versatility of human monocytes conditioned by IFN-α towards dendritic cell differentiation (IFN-DC) in shaping the autologous T-helper response. Priming of naïve CD4 T cells with autologous IFN-DC in the presence of either SEA or anti-CD3, resulted, in addition to a prominent expansion of CXCR3+ IFN-γ-producing CD4 Th1 cells, in the emergence of two distinct subsets of IL-17-producing CD4 T cells: i) a predominant Th17 population selectively producing IL-17 and expressing CCR6; ii) a minor Th1/Th17 population, producing both IL-17 and IFN-γ. After phagocytosis of apoptotic cells, IFN-DC induced Th17 cell expansion and IL-17 release. Notably, the use of neutralizing antibodies revealed that IL-23 was an essential cytokine in mediating Th17 cell development by IFN-DC. The demonstration of the IFN-DC-induced expansion of both Th1 and Th17 cell populations reveals the intrinsic plasticity of these DC in orienting the immune response and provides a mechanistic link between IFN-α and the onset of autoimmune phenomena, which have been correlated with both IL-17 production and exposure to IFN-α