Notch and NF-kB: Coach and Players of Regulatory T-Cell Resposnse in Cancer

The Notch signaling pathway plays multiple roles in driving T-cell fate decisions, proliferation, and aberrant growth. NF-kB is a cell-context key player interconnected with Notch signaling either in physiological or in pathological conditions. This review focuses on how themultilayered crosstalk between different Notches and NF-kB subunits may converge on Foxp3 gene regulation and orchestrate CD4+ regulatory T (Treg) cell function, particularly in a tumor microenvironment. Notably, Treg cells may play a pivotal role in the inhibition of antitumor immune responses, possibly promoting tumor growth. A future challenge is represented by further dissection of both Notch and NF-kB pathways and consequences of their intersection in tumor-associated Treg biology. This may shed light on themolecularmechanisms regulating Treg cell expansion andmigration to peripheral lymphoid organs thought to facilitate tumor development and still to be explored. In so doing, new opportunities for combined and/or more selective therapeutic Q25 approaches to improve anticancer immunity may be found

A non-conserved amino acid variant regulates differential signalling between human and mouse CD28

CD28 superagonistic antibodies (CD28SAb) can preferentially activate and expand immunosuppressive regulatory T cells (Treg) in mice. However, pre-clinical trials assessing CD28SAbs for the therapy of autoimmune diseases reveal severe systemic inflammatory response syndrome in humans, thereby implying the existence of distinct signalling abilities between human and mouse CD28. Here, we show that a single amino acid variant within the C-terminal proline-rich motif of human and mouse CD28 (P212 in human vs. A210 in mouse) regulates CD28-induced NF-κB activation and pro-inflammatory cytokine gene expression. Moreover, this Y209APP212 sequence in humans is crucial for the association of CD28 with the Nck adaptor protein for actin cytoskeleton reorganisation events necessary for CD28 autonomous signalling. This study thus unveils different outcomes between human and mouse CD28 signalling to underscore the importance of species difference when transferring results from preclinical models to the bedside

Cataloghi: la sfida della concretezza

The Communication presents the activities of the Catalogs Group "Nilde Libraries Committee, the activities are focused on the national catalogs of libraries participating at the NILDE network. The survey launched in 2006 led to the identification of a significant number of libraries that were not included in any national catalog. Subsequently, a procedure was initiated in which these situations have been regularized and a specific policy has been issued. The members of the "Catalogs Group" contacted the individual responsible for the document delivery service providing assistance to overcome encountered problems. The direct involvement of libraries led to good results so that only 32 libraries (in June 2009) were not yet visible on national catalogs. Of crucial importance was the cooperation with ACNP, which become an active partner of NILDE, encouraging the spread of the Network. The monitoring allowed us to understand the variety of Nilde libraries, covering a wide range of disciplines, located throughout the country. The group is also activated as a result of reports received by the CBN or by the List Nilde-forni, also for what concern the visibility of the catalogs. The adoption of advanced tools for linking, such as SFX, provides a solution to connect their electronic resources and to allow better access to users. For the better management of document delivery would be useful to have a single connection point of an entire virtual library of institution or university. Finally, the importance of cataloging of Open Access journals to promote their visibility through inclusion in the ACNP catalogue and the still open issue of cataloging the electronic resources as with paper publications, are mentioned.La comunicazione presenta l\u27attivit? del "Gruppo cataloghi" del Comitato Biblioteche Nilde (CBN), incentrata sul monitoraggio dell\u27adesione ai cataloghi nazionali da parte delle biblioteche partecipanti al network NILDE. Il rilevamento ? stato avviato nel 2006 ed ha portato all\u27individuazione di un significativo numero di biblioteche che non risultavano in alcun catalogo nazionale. Successivamente sono state avviate le procedure per la regolarizzazione della loro situazione, pubblicando anche un apposito regolamento. I componenti del "Gruppo cataloghi" hanno contattato i singoli responsabili dei servizi di document delivery offrendo assistenza per superare i problemi riscontrati. Il coinvolgimento diretto delle biblioteche ha portato a buoni risultati tanto che al giugno 2009 solo 32 biblioteche non erano ancora visibili sui cataloghi nazionali. Fondamentale la collaborazione con ACNP, che ? diventato un partner attivo di NILDE, favorendone la diffusione. L\u27attivit? di monitoraggio ha permesso di comprendere la variet? di biblioteche Nilde che riunisce biblioteche distribuite su tutto il territorio nazionale, che coprono una ampia gamma di discipline. Il gruppo si ? anche attivato a seguito di segnalazioni di malfunzionamento che pervengono al CBN o alla lista Nilde-forni, anche per quanto riguarda la visibilit? dei cataloghi. L\u27adozione di strumenti avanzati di linking come SFX offre alle istituzioni una soluzione per collegare le loro risorse elettroniche e per consentire un migliore accesso agli utenti. Per la migliore gestione del document delivery sarebbe utile poter disporre di un unico indirizzo e-mail come punto di raccordo di una intera biblioteca virtuale elettronica di ente o di ateneo. Infine vengono citate: l\u27importanza di catalogazione dei periodici Open Access per favorirne la visibilit? grazie all\u27inserimento in ACNP e la problematica ancora aperta della catalogazione completa delle risorse elettroniche al pari di quanto ? avvenuto per i documenti su carta

Spectrometer for X-ray emission experiments at FERMI free-electron-laser

A portable and compact photon spectrometer to be used for photon in-photon out experiments, in particular x-ray emission spectroscopy, is presented. The instrument operates in the 25\u2013800 eV energy range to cover the full emissions of the FEL1 and FEL2 stages of FERMI. The optical design consists of two interchangeable spherical varied-lined-spaced gratings and a CCD detector. Different input sections can be accommodated, with/without an entrance slit and with/without an additional relay mirror, that allow to mount the spectrometer in different end-stations and at variable distances from the target area both at synchrotron and at free-electron-laser beamlines. The characterization on the Gas Phase beamline at ELETTRA Synchrotron (Italy) is presented

Intrathymic Notch3 and CXCR4 combinatorial interplay facilitates T-cell leukemia propagation.

Notch hyperactivation dominates T-cell acute lymphoblastic leukemia development, but the mechanisms underlying "pre-leukemic-cells" dissemination are still unclear. Here we describe how deregulated Notch3 signaling enhances CXCR4 cell-surface expression and migratory ability of CD4+CD8+ thymocytes, possibly contributing to “pre-leukemic” cell propagation, early in disease progression. In transgenic mice overexpressing the constitutively active Notch3 intracellular domain, we detect the progressive increase in circulating blood and bone marrow of CD4+CD8+-cells, characterized by high and combined surface expression of Notch3 and CXCR4. We report for the first time that transplantation of such CD4+CD8+-cells, reveals their competence in infiltrating spleen and bone marrow of immunocompromised recipient mice. We also show that CXCR4 surface expression is central to the migratory ability of CD4+CD8+-cells and that such an expression is regulated by Notch3 through -arrestin in human leukemia cells. De novo, we propose that hyperactive Notch3 signaling by boosting CXCR4-dependent migration promotes anomalous egression of CD4+CD8+-cells from the thymus in early leukemia stages. In fact, in vivo CXCR4 antagonism prevents bone marrow colonization by such CD4+CD8+ cells in young Notch3 transgenic mice. Therefore, our data suggest that combined therapies precociously counteracting intrathymic Notch3/CXCR4 crosstalk, may prevent dissemination of “pre-leukemic” CD4+CD8+-cells, by a “thymus-autonomous” mechanism

Three-Dimensional Shapes of Spinning Helium Nanodroplets

A significant fraction of superfluid helium nanodroplets produced in a free-jet expansion have been observed to gain high angular momentum resulting in large centrifugal deformation. We measured single-shot diffraction patterns of individual rotating helium nanodroplets up to large scattering angles using intense extreme ultraviolet light pulses from the FERMI free-electron laser. Distinct asymmetric features in the wide-angle diffraction patterns enable the unique and systematic identification of the three-dimensional droplet shapes. The analysis of a large dataset allows us to follow the evolution from axisymmetric oblate to triaxial prolate and two-lobed droplets. We find that the shapes of spinning superfluid helium droplets exhibit the same stages as classical rotating droplets while the previously reported metastable, oblate shapes of quantum droplets are not observed. Our three-dimensional analysis represents a valuable landmark for clarifying the interrelation between morphology and superfluidity on the nanometer scale

Strategies and Alliances into Action to Improve National Collaboration

The Italian NILDE network of libraries continues to grow through the use of the NILDE system and currently comprises more than 600 Italian librarians and about 10.000 registered end-users.The system allows to daily manage and to record all the Inter-Library-Loan (ILL) operations, with a high national coverage. This paper presents the NILDE network governance and evolution and the strategies that have been put into action to improve collaboration in resource sharing among the participants. These strategies include: − release of best practices and worst practices; − activities to promote the knowledge about the network; − cooperation with the Italian national catalogs and consortia; − data analysis about ILL and its performance, related to: turn around time, reciprocity factor, requested/supplied documents imbalance analysis, analysis of ILL requested serial titles and their relationship with consortial e-only acquisitions. The availability of such a high volume of ILL data has allowed for the first time to analyze the trends and gaps of ILL and to help future cooperative acquisitions planning

The Rethinking Resource Sharing Initiative: the NILDE case study in the frame of Italian experiences

NILDE (Network for Inter-Library Document Exchange) is born at the CNR Bologna Research Area Library to provide an effective answer to the needs of libraries in order to guarantee information accessibility, sharing resources through Inter Library Loan (ILL) of returnable and non-returnable items (books and journal articles)

The Low Density Matter (LDM) beamline at FERMI: Optical layout and first commissioning

The Low Density Matter (LDM) beamline has been built as part of the FERMI free-electron laser (FEL) facility to serve the atomic, molecular and cluster physics community. After the commissioning phase, it received the first external users at the end of 2012. The design and characterization of the LDM photon transport system is described, detailing the optical components of the beamline