Characterizing innate immune cell activation by fungal pathogens

Candida albicans (C. albicans) and Candida glabrata (C. glabrata) are the two most prevalent Candida species causing bloodstream infections. Isolated NK cells get stronger activated by C. albicans than C. glabrata. In contrast, activation of blood NK cells was more pronounced during C. glabrata infection. NK cell activation in blood is mediated by humoral mediators released by other immune cells and does not depend on direct activation by fungal cells. Cross-talk between Candida-confronted monocyte-derived dendritic cells (moDC) and NK cells resulted in the same NK activation phenotype like NK cells in human blood. Blocking experiments and cytokine substitution identified interleukin 12 as a critical mediator in regulation of primary NK cells by moDC-derived cytokines. On the other hand, we focused on the identification of changes in polymorphonuclear cells (PMN) behavior induced by C. albicans and C. glabrata since these immune cells are of outstanding importance in the response against invasive Candida infections. Sorting and extraction of PMN were performed after a one-hour confrontation in human whole blood in presence of fungal cells. Then, infected isolated PMN were used for separate analysis in live cell imaging experiments to visualize their dynamic features in comparison to mock-infected PMN. PMN in the acquired microscopic images were analyzed using a migration and interaction tracking algorithm and further classified using different morphokinetics features. Compared to mock-treated PMN, PMN isolated from whole-blood infected with either C. albicans or C. glabrata presented a higher percentage of PMN with a spreading morphology. Furthermore, C. glabrata presented a significantly higher number of cells with a spreading morphology compared to C. albicans. Combination of live cell imaging with automated analysis allowed a classification and distinction of PMN isolated from mock-infected blood and Candida-infected blood based on their morphology

Ports as Drivers of Urban and Regional Growth

AbstractTraded volumes – from raw materials to final consumer goods through intermediary products – are projected to continue growing in the foreseeable future: sheer domestic EU and global competition will impose challenging requirements to providing innovative supply-chain and logistics solutions, including not only smart business models but also smart and foresighted infrastructural planning and management capacities.Public planning and funding face critical limitations, such as: (i) not duly accounting for the induced pressures on inland transportation infrastructure allowing access from/to the port to/from interesting trade links/destinations; (ii) not duly accounting for indirect costs and benefits resulting from either new infrastructural developments or re-deployment of existing infrastructures, and (iii) not duly accounting for the impacts of ports on the cities in which they are localised.Fragmented projections and impact assessments lead to sub-optimal economic performance of multi-modal terminals, the transportation network and the area they impact on increasing the risk of depleting initial investments or requiring on-going/permanent – public support, including to overcome local negative impacts.This article has two main purposes. On the one hand, it strives to identify shortcomings that hinder the achievement of expected benefits on urban and regional growth linked to port activity expansion. It is not based on a comprehensive analysis of case studies but on literature review and for that reason limiting factors mentioned in the article are not necessarily suited to specific situations. On the other hand, the article proposes a reflection on the relevant analytical and policy intervention tools having the potential to tackle and – ideally – resolve shortcomings. It advocates that a wider use of such tools would enhance the efficiency of handling freight volumes through ports and onto surface transport corridors maximizing positive spillover effects while minimizing nuisances and drawbacks for the urban and regional areas concerned.Congestion reduction in and around port areas and enhanced competitiveness are the expected results from balanced multimodal transport solutions. Many benefits are associated with efficient ports yet there tends to be a mismatch with gains spilling over to other regions and negative impacts borne locally.This area of research is expected to become all the more relevant in view of growing size of ships and therefore reduced number of ports/operators capable of handling those as well as higher induced pressure on – often already congested – inland transportation corridors.Conversely, development of the Motorways of the Sea and implementation of Short Sea Shipping foresee the increased use of medium and small ports to relieve the heavy burden on land transport, but this implies revised shipping patterns as well as overcoming fragmentation in transport infrastructure planning

Review Essay—Official History, Not “Instant Analysis”

Shield and Sword: The United States Navy and the Persian Gulf Wa

Crosstalk between CXCR4/ACKR3 and EGFR signaling in breast cancer cells

A better understanding of the complex crosstalk among key receptors and signaling pathways involved in cancer progression is needed to improve current therapies. We have investigated in cell models representative of the major subtypes of breast cancer (BC) the interplay between the chemokine CXCL12/CXCR4/ACKR3 and EGF receptor (EGFR) family signaling cascades. These cell lines display a high heterogeneity in expression profiles of CXCR4/ACKR3 chemokine receptors, with a predominant intracellular localization and different proportions of cell surface CXCR4+, ACKR3+ or double-positive cell subpopulations, and display an overall modest activation of oncogenic pathways in response to exogenous CXCL12 alone. Interestingly, we find that in MDA-MB-361 (luminal B subtype, Her2-overexpressing), but not in MCF7 (luminal A) or MDA-MB-231 (triple negative) cells, CXCR4/ACKR3 and EGFR receptor families share signaling components and crosstalk mechanisms to concurrently promote ERK1/2 activation, with a key involvement of the G protein-coupled receptor kinase 2 (GRK2) signaling hub and the cytosolic tyrosine kinase Src. Our findings suggest that in certain BC subtypes, a relevant cooperation between CXCR4/ACKR3 and growth factor receptors takes place to integrate concurrent signals emanating from the tumor microenvironment and foster cancer progressio

The organization of the Presidency of Republic: a study between lines of continuity and evolutionary outlines

L’attività servente delineata dalla prassi del Segretariato Generale della Presidenza della Repubblica rappresenta un importante snodo per cogliere alcuni degli aspetti più problematici ed oscuri che ineriscono al tema della posizione costituzionale del Presidente della Repubblica; in particolare, si fa riferimento alla “meccanica” del complesso e costante enlargement of powers, che è uno dei tratti maggiormente caratterizzanti il parlamentarismo italiano. Per cogliere questi punti, è essenziale far riferimento alle modalità di azione degli Uffici del Quirinale in quelle prerogative, dove il Presidente è coinvolto profondamente nei processi decisionali di indirizzo politico allo scopo di conferire prestazioni di unificazione politica ed istituzionale nelle situazioni patologiche; esse sono state individuate nelle attività serventi al potere di rinvio delle leggi ed al potere di grazia. In aggiunta si è proceduto ad esaminare nello specifico quale sia la natura giuridica da ascrivere a questo organo servente e la sua posizione di “autonomia costituzionale”, riconducibile all’alveo dell’organo costituzionale monocratico del Capo dello Stato. Dall’indagine effettuata si è tratto che sotto l’indirizzo presidenziale l’azione del Segretariato si è calibrata in modo tale da attivare meccanismi convenzionali con gli organi di indirizzo, processi di leale collaborazione e di prevenzione di situazioni di grave conflitto istituzionale. L’obiettivo finale del Segretariato si può ascrivere alla volontà di rendere maggiormente fluidi gli ingranaggi della forma di governo, risultando per queste ragioni, altresì, scevre da prese di posizione personalistiche o di stampo “presidenzialistico”.The practice of the General Secretariat of the Presidency of the Republic is a backing activity and represents a crucial turning point to find out the most problematic and unclear features of the constitutional role of the Italian Head of State. The thesis aims to draw attention to the “mechanics” of the complicated “enlargement of powers” of the Italian President of Republic, which is one of the most important features of the Italian parliamentary system. To highlight these issues, it is necessary to examine the practice of the “Uffici del Quirinale”, especially when the President of the Republic is mainly involved in the national political guidance and has to solve pathological situations and preserve the national unity: namely, when the President decides to return an Act and decides to grant pardons. Additionally, the thesis focuses on the problem of the legal status and the “constitutional autonomy” of the Secretariat, in order to consider where this institution is located in the constitutional legal framework. The current research shows how the practice of the Secretariat, which is still under the guidance of the President, has been triggering conventions of Constitution, implementing the fair cooperation and solving huge conflicts between institutions. Therefore, the final aim of the Secretariat is to smooth the mechanisms of the form of government: in the light of the above, the practice of the Secretariat could be not considered a symptom of a presidential system