The Belgian Recovery and Resilience Plan: A fresh impetus to prepare the skills of tomorrow’s workforce? Egmont Commentary 17 May 2021.

In the context of a fast recovery, training policy is one of the labour market instruments with the most positive effect on employment, but it is also a very expensive one. On 30 April 2021, the European Commission received the consolidated version of the Belgian Recovery and Resilience Plan (RRP), with €950.64 million dedicated to up- and reskilling. Whilst trends such as digital automation, accentuated by the COVID-19 crisis, will profoundly reshape the future of work, the Belgian RRP could contribute to a successful transition towards new occupations, hence acting as a counter-cycled economic measure by mitigating broader social consequences. The success of this operation will be tributary to its magnitude, its promptness of response, and its capacity to target the most vulnerable persons

From emergency remote learning to a new digital education action plan: an EU attempt to mainstream equality into education. Egmont European Policy Brief No. 66 December 2020.

In the wake of the COVID-19 pandemic, the hastiness of the digital shift in teaching and learning exacerbated pre-existing socioeconomic disparities in national education systems. The gaps in digital accessibility left those already behind even further behind. Taking stock of the unforeseen consequences of the crisis, the Commission updated its Digital Education Action Plan (DEAP). On 17 November, the Egmont Institute and the European Policy Centre invited Commissioner Gabriel, who is in charge of the EU’s education portfolio, to outline her proposal for an education better equipped for the digital age. Although the new strategy acknowledges the need for more inclusiveness and social justice in digital accessibility, it falls short of providing a clear funding plan and a comprehensive understanding of the socioeconomic inequalities at stake. The coming months will be crucial – the first milestone is the third EU Educational Summit on 10 December – in turning this patchwork of disparate initiatives into a concrete framework for action

A revised European Semester under centralised management: the risk of overlooking social policy. Egmont European Policy Brief No. 72 September 2021.

By adopting a €750 billion recovery plan, European leaders intend to avoid a repeat of the controversial management of the Eurozone crisis and the lack of public investment it engendered. The European Commission has set up a new coordination process to steer public investments and reforms foreseen by the national recovery plans, leaving the fully fledged European Semester aside for an indefinite period. In its current form, however, the management of the recovery package does not offer as many social guarantees as the former Semester did. To mitigate its weak social safeguards, the European Commission must strengthen the role of social affairs actors in its monitoring process. The present policy brief assesses past and present social developments in the framework of the European Semester, and the lessons to be learned from them. Although this paper focuses on the dynamics within the European Commission, it should be noted that similar tensions between social and economic affairs actors also arise within the Council

iNOS-Producing Inflammatory Dendritic Cells Constitute the Major Infected Cell Type during the Chronic Leishmania major Infection Phase of C57BL/6 Resistant Mice

Leishmania major parasites reside and multiply in late endosomal compartments of host phagocytic cells. Immune control of Leishmania growth absolutely requires expression of inducible Nitric Oxide Synthase (iNOS/NOS2) and subsequent production of NO. Here, we show that CD11b+ CD11c+ Ly-6C+ MHC-II+ cells are the main iNOS-producing cells in the footpad lesion and in the draining lymph node of Leishmania major-infected C57BL/6 mice. These cells are phenotypically similar to iNOS-producing inflammatory DC (iNOS-DC) observed in the mouse models of Listeria monocytogenes and Brucella melitensis infection. The use of DsRed-expressing parasites demonstrated that these iNOS-producing cells are the major infected population in the lesions and the draining lymph nodes. Analysis of various genetically deficient mouse strains revealed the requirement of CCR2 expression for the recruitment of iNOS-DC in the draining lymph nodes, whereas their activation is strongly dependent on CD40, IL-12, IFN-γ and MyD88 molecules with a partial contribution of TNF-α and TLR9. In contrast, STAT-6 deficiency enhanced iNOS-DC recruitment and activation in susceptible BALB/c mice, demonstrating a key role for IL-4 and IL-13 as negative regulators. Taken together, our results suggest that iNOS-DC represent a major class of Th1-regulated effector cell population and constitute the most frequent infected cell type during chronic Leishmania major infection phase of C57BL/6 resistant mice

A Computational Algebra Approach to the Reverse Engineering of Gene Regulatory Networks

This paper proposes a new method to reverse engineer gene regulatory networks from experimental data. The modeling framework used is time-discrete deterministic dynamical systems, with a finite set of states for each of the variables. The simplest examples of such models are Boolean networks, in which variables have only two possible states. The use of a larger number of possible states allows a finer discretization of experimental data and more than one possible mode of action for the variables, depending on threshold values. Furthermore, with a suitable choice of state set, one can employ powerful tools from computational algebra, that underlie the reverse-engineering algorithm, avoiding costly enumeration strategies. To perform well, the algorithm requires wildtype together with perturbation time courses. This makes it suitable for small to meso-scale networks rather than networks on a genome-wide scale. The complexity of the algorithm is quadratic in the number of variables and cubic in the number of time points. The algorithm is validated on a recently published Boolean network model of segment polarity development in Drosophila melanogaster.Comment: 28 pages, 5 EPS figures, uses elsart.cl

G6b-B Inhibits Constitutive and Agonist-induced Signaling by Glycoprotein VI and CLEC-2

Platelets play an essential role in wound healing by forming thrombi that plug holes in the walls of damaged blood vessels. To achieve this, platelets express a diverse array of cell surface receptors and signaling proteins that induce rapid platelet activation. In this study we show that two platelet glycoprotein receptors that signal via an immunoreceptor tyrosine-based activation motif (ITAM) or an ITAM-like domain, namely the collagen receptor complex glycoprotein VI (GPVI)-FcR γ-chain and the C-type lectin-like receptor 2 (CLEC-2), respectively, support constitutive (i.e. agonist-independent) signaling in a cell line model using a nuclear factor of activated T-cells (NFAT) transcriptional reporter assay that can detect low level activation of phospholipase Cγ (PLCγ). Constitutive and agonist signaling by both receptors is dependent on Src and Syk family kinases, and is inhibited by G6b-B, a platelet immunoglobulin receptor that has two immunoreceptor tyrosine-based inhibitory motifs in its cytosolic tail. Mutation of the conserved tyrosines in the two immunoreceptor tyrosine-based inhibitory motifs prevents the inhibitory action of G6b-B. Interestingly, the inhibitory activity of G6b-B is independent of the Src homology 2 (SH2)-domain containing tyrosine phosphatases, SHP1 and SHP2, and the inositol 5′-phosphatase, SHIP. Constitutive signaling via Src and Syk tyrosine kinases is observed in platelets and is associated with tyrosine phosphorylation of GPVI-FcR γ-chain and CLEC-2. We speculate that inhibition of constitutive signaling through Src and Syk tyrosine kinases by G6b-B may help to prevent unwanted platelet activation

Alternative activation of macrophages by filarial nematodes is MyD88-independent

AbstractAlternative macrophage activation is largely defined by IL-4Rα stimulation but the contribution of Toll-like receptor (TLR) signaling to this phenotype is not currently known. We have investigated macrophage activation status under Th2 conditions in the absence of the core TLR adaptor molecule, MyD88. No impairment was observed in the ability of MyD88-deficient bone marrow derived macrophages to produce or express alternative activation markers, including arginase, RELM-α or Ym1, in response to IL-4 treatment in vitro. Further, we observed no difference in the ability of peritoneal exudate cells from nematode implanted wild type (WT) or MyD88-deficient mice to produce arginase or express the alternative activation markers RELM-α or Ym1. Therefore, MyD88 is not a fundamental requirement for Th2-driven macrophage alternative activation, either in vitro or in vivo

Genome-wide analysis of Brucella melitensis genes required throughout intranasal infection in mice

Brucellae are facultative intracellular Gram-negative coccobacilli that chronically infect various mammals and cause brucellosis. Human brucellosis is among the most common bacterial zoonoses and the vast majority of cases are attributed to B .melitensis .Using transposon sequencing (Tn-seq) analysis, we showed that among 3369 predicted genes of the B .melitensis genome, 861 are required for optimal growth in rich medium and 186 additional genes appeared necessary for survival of B .melitensis in RAW 264.7 macrophages in vitro .As the mucosal immune system represents the first defense against Brucella infection, we investigated the early phase of pulmonary infection in mice. In situ analysis at the single cell level indicates a succession of killing and growth phases, followed by heterogenous proliferation of B .melitensis in alveolar macrophages during the first 48 hours of infection. Tn-seq analysis identified 94 additional genes that are required for survival in the lung at 48 hours post infection. Among them, 42 genes are common to RAW 264.7 macrophages and the lung conditions, including the T4SS and purine synthesis genes. But 52 genes are not identified in RAW 264.7 macrophages, including genes implicated in lipopolysaccharide (LPS) biosynthesis, methionine transport, tryptophan synthesis as well as fatty acid and carbohydrate metabolism. Interestingly, genes implicated in LPS synthesis and β oxidation of fatty acids are no longer required in Interleukin (IL)-17RA -/- mice and asthmatic mice, respectively. This demonstrates that the immune status determines which genes are required for optimal survival and growth of B .melitensis in vivo .info:eu-repo/semantics/publishe

Aconitate decarboxylase 1 participates in the control of pulmonary Brucella infection in mice

Brucellosis is one of the most widespread bacterial zoonoses worldwide. Here, our aim was to identify the effector mechanisms controlling the early stages of intranasal infection with Brucella in C57BL/6 mice. During the first 48 hours of infection, alveolar macrophages (AMs) are the main cells infected in the lungs. Using RNA sequencing, we identified the aconitate decarboxylase 1 gene ( Acod1 ;also known as Immune responsive gene 1), as one of the genes most upregulated in murine AMs in response to B .melitensis infection at 24 hours post-infection. Upregulation of Acod1 was confirmed by RT-qPCR in lungs infected with B .melitensis and B .abortus .We observed that Acod1 -/- C57BL/6 mice display a higher bacterial load in their lungs than wild-type (wt) mice following B .melitensis or B .abortus infection, demonstrating that Acod1 participates in the control of pulmonary Brucella infection. The ACOD1 enzyme is mostly produced in mitochondria of macrophages, and converts cis-aconitate, a metabolite in the Krebs cycle, into itaconate. Dimethyl itaconate (DMI), a chemically-modified membrane permeable form of itaconate, has a dose-dependent inhibitory effect on Brucella growth in vitro .Interestingly, structural analysis suggests the binding of itaconate into the binding site of B .abortus isocitrate lyase. DMI does not inhibit multiplication of the isocitrate lyase deletion mutant Δ aceA B .abortus in vitro .Finally, we observed that, unlike the wt strain, the Δ aceA B .abortus strain multiplies similarly in wt and Acod1 -/- C57BL/6 mice. These data suggest that bacterial isocitrate lyase might be a target of itaconate in AMs.info:eu-repo/semantics/publishe

Route of Infection Strongly Impacts the Host-Pathogen Relationship

Live attenuated vaccines play a key role in the control of many human and animal pathogens. Their rational development is usually helped by identification of the reservoir of infection, the lymphoid subpopulations associated with protective immunity as well as the virulence genes involved in pathogen persistence. Here, we compared the course of Brucella melitensis infection in C57BL/6 mice infected via intraperitoneal (i.p.), intranasal (i.n.) and intradermal (i.d.) route and demonstrated that the route of infection strongly impacts all of these parameters. Following i.p. and i.n. infection, most infected cells observed in the spleen or lung were F4/80+ myeloid cells. In striking contrast, infected Ly6G+ neutrophils and CD140a+ fibroblasts were also observed in the skin after i.d. infection. The virB operon encoding for the type IV secretion system is considered essential to deflecting vacuolar trafficking in phagocytic cells and allows Brucella to multiply and persist. Unexpectedly, the ΔvirB Brucella strain, which does not persist in the lung after i.n. infection, persists longer in skin tissues than the wild strain after i.d. infection. While the CD4+ T cell-mediated Th1 response is indispensable to controlling the Brucella challenge in the i.p. model, it is dispensable for the control of Brucella in the i.d. and i.n. models. Similarly, B cells are indispensable in the i.p. and i.d. models but dispensable in the i.n. model. γδ+ T cells appear able to compensate for the absence of αβ+ T cells in the i.d. model but not in the other models. Taken together, our results demonstrate the crucial importance of the route of infection for the host pathogen relationship.SCOPUS: ar.jinfo:eu-repo/semantics/publishe