Karst geomorphology of the “Canale di Pirro” polje, Apulia (Southern Italy).

In karst environment, a geomorphological map is a powerful instrument, which play a crucial role in understanding earth surface processes and landscape evolution. Furthermore, it could be very useful for speleological perspectives, natural resources exploitation and geo-hazards management (flood, sinkhole, subsidence, etc.), providing useful information that enhance the knowledge of the territory. In this work, we present a geomorphological map of the polje of “Canale di Pirro”, sited in the central part of Apulia Region, in Southern Italy, among the most interesting karst lands in the Mediterranean area. The map covers150km2withanelevationrangeof100-450ma.s.l.Thisareaisoneofthemostremarkablekarstlandforms in the region, characterized underground by a very interesting system of caves, that reaches the water table at a depth of -264 meters. The karst system, known as “Inghiottitoio di Masseria Rotolo”, following scuba-diving exploration below the watertable, has become with a depth of 324m, the deepest known cave in Apulia. The polje is bounded on both sides by tectonically-controlled ridges, showing an overall length of some 12 km. In ancient maps, dating back to the 16th century, the area is represented as crossed by a long river, called Cana. The map obtained derives from the integration of interpretation of aerial photographs, analysis of a digital elevation model and field surveys in order to obtain a correct distribution of landforms and fluvial processes, such as different varieties of karst depressions, conical hills, erosional gullies, alluvial fans and tectonic structures. It provides relevant information about the surface drainage processes, and for understanding, among other things, the groundwater circulation and the related recharge processes. This geomorphological map is part of a wider project, that combined geological, hydrogeological research and chemical analyses of the groundwater. It provides support to the ongoing studies of this part of Apulia region aimedto betterunderstand thegeological processes that originatedthe polje and its later evolution, and the related underground cave system. Further, it might also suggest possible improvements in land management and in the future choice of useful tools for the control of the quality and quantity of karst groundwater

Wnt3a neutralization enhances T-cell responses through indirect mechanisms and restrains tumor growth

The Wnt/beta-catenin pathway regulates T-cell functions, including the repression of effector functions to the advantage of memory development via Tcf1. In a companion study, we demonstrate that, in human cancers, Wnt3a/beta-catenin signaling maintains tumor-infiltrating T cells in a partially exhausted status. Here, we have investigated the effects of Wnt3a neutralization in vivo in a mouse tumor model. Abundant Wnt3a was released, mostly by stromal cells, in the tumor microenvironment. We tested whether Wnt3a neutralization in vivo could rescue the effector capacity of tumor-infiltrating T cells, by administering an antibody to Wnt3a to tumor-bearing mice. This therapy restrained tumor growth and favored the expansion of tumor antigen-specific CD8(+) effector memory T cells with increased expression of Tbet and IFN gamma and reduced expression of Tcf1. However, the effect was not attributable to the interruption of T-cell-intrinsic beta-catenin signaling, because Wnt3a/beta-catenin activation correlated with enhanced, not reduced, T-cell effector functions both ex vivo and in vitro. Adoptively transferred CD8(+) T cells, not directly exposed to the anti-Wnt3a antibody but infiltrating previously Wnt3a-neutralized tumors, also showed improved functions. The rescue of T-cell response was thus secondary to T-cell-extrinsic changes that likely involved dendritic cells. Indeed, tumor-derived Wnt3a strongly suppressed dendritic cell maturation in vitro, and anti-Wnt3a treatment rescued dendritic cell activities in vivo. Our results clarify the function of the Wnt3a/beta-catenin pathway in antitumor effector T cells and suggest that Wnt3a neutralization might be a promising immunotherapy for rescuing dendritic cell activities. (C) 2018 AACR

A Compact Solid State Detector for Small Angle Particle Tracking

MIDAS (MIcrostrip Detector Array System) is a compact silicon tracking telescope for charged particles emitted at small angles in intermediate energy photonuclear reactions. It was realized to increase the angular acceptance of the DAPHNE detector and used in an experimental program to check the Gerasimov-Drell-Hearn sum rule at the Mainz electron microtron, MAMI. MIDAS provides a trigger for charged hadrons, p/pi identification and particle tracking in the region 7 deg < theta < 16 deg. In this paper we present the main characteristics of MIDAS and its measured performances.Comment: 13 pages (9 figures). Submitted to NIM

Towards specific T–H relationships: FRIBAS database for better characterization of RC and URM buildings

FRIBAS database is an open access database composed of the characteristics of 312 buildings (71 masonry, 237 reinforced concrete and 4 mixed types). It collects and harmonizes data from different surveys performed on buildings in the Basilicata and Friuli Venezia Giulia regions (Southern and Northeastern Italy, respectively). Each building is defined by 37 parameters related to the building and foundation soil characteristics. The building and soil fundamental periods were experimentally estimated based on ambient noise measurements. FRIBAS gave us the opportunity to study the influence of the main characteristics of buildings and the soil-building interaction effect to their structural response. In this study, we have used the FRIBAS dataset to investigate how the building period varies as a function of construction materials and soil types. Our results motivate the need of going beyond a 'one-fits-all' numerical period-height (T-H) relationship for generic building typologies provided by seismic codes, towards specific T-H relationships that account for both soil and building typologies

The scavenger receptors SRA-1 and SREC-I cooperate with TLR2 in the recognition of the hepatitis C virus non-structural protein 3 by dendritic cells

Backgrounds &amp; AimsThe hepatitis C virus NS3 protein is taken up by myeloid cells in a TLR2-independent manner and activates myeloid cells via TLR2. This study aimed to identify the endocytic receptor(s) involved in the uptake of NS3 by myeloid cells and its relation with TLR2. Methods Inhibitors and transfected cells were used to identify the nature of the NS3-binding receptors expressed by myeloid cells. The cooperation between scavenger receptors (SRs) and TLR2 in the NS3-mediated activation of myeloid cells was evaluated using inhibitors, cells from TLR2−/− mice, and confocal microscopy. The involvement of SRs in NS3 cross-presentation was evaluated in vitro using an NS3-specific human T-cell clone. Results We observed that SRs are the main binding structures for NS3 on myeloid cells and identified the SRs SRA-1 and SREC-I as endocytic receptors for NS3. Moreover, both SRs and TLR2 cooperate in NS3-induced myeloid cell activation. Conclusion This study highlights a central role for SRs in NS3 uptake and cross-presentation, and demonstrates a tightly orchestrated cooperation between signalling and endocytic innate receptors in NS3 recognition

Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections

BACKGROUND & AIMS: Chronic microial infections aare frequently associated with B-cell activation and polyclonal proliferation, potentially leading to autoimmunity and lymphoproliferative disorders. We assessed B-cell phenotype and function in chronic hepatitis B (HBV) and chronic hepatitis C (HCV) virus infection. METHODS: We studied 70 patients with chronic HCV infection, 34 with chronic HBV infection and 54 healthy controls, B-cell phenotype was assessed by flow cytometry using monoclonal antibodies specific for CD27, the CD69, CD71, and CD86 activation markers and the chemokine receptor CXCR3. Differentiation into immunoglobulin-producing cells (IPC) was analysed by ELISpot upon stimulation and with CD40 ligand+IL-10 as surrogate bystander T-cell help or CpG oligodeoxynucleotide+IL-2, as innate immunity signal. Proliferation was examined by cytometry using carboxyfluorescein diacetate succinimidyl ester (CFSE) after stimulation with CpG. RESULTS: A significantly higher proportion of B cells from both HCV-and HBV-infected patients expressed activation markers compared with controls and a positive correlation was found between CXCR3(+) B cells and HCV RNA values. Memory B cells from patients with chronic HCV and HBV infections showed enhanced differentiation into IPC compared with controls, although this was restricted to IgG and at a lower level in HCV-compared with HBV-infected patients. Moreover, patients' activated B cells displayed significantly lower proliferative ability compared to healthy donors despite low expression of the FcRL4 exhaustin marker. CONCLUSIONS: B-cell activation, but not exhaustion, is common in chronic viral hepatitis. However, enhanced B-cell differentiation and deficient proliferative capacity were not associated with commitment to terminal differentiation

Regulatory T cells with multiple suppressive and potentially pro-tumor activities accumulate in human colorectal cancer

Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor. Ex vivo, those Tregs suppressed the proliferation of tumor-infiltrating CD8(+) and CD4(+) T cells. A differential compartmentalization was detected between Helioshigh and Helios(low) Treg subsets (thymus-derived versus peripherally induced): while Helios(low) Tregs were enriched in both sites, only Helios(high) Tregs accumulated significantly and specifically in tumors, displayed a highly demethylated TSDR region and contained high proportions of cells expressing CD39 and OX40, markers of activation and suppression. Besides the suppression of T cells, Tregs may contribute to CRC progression also through releasing IL-17, or differentiating into Tfr cells that potentially antagonize a protective Tfh response, events that were both detected in tumor-associated Tregs. Overall, our data indicate that Treg accumulation may contribute through multiple mechanisms to CRC establishment and progression

IL-18 receptor marks functional CD8+ T cells in non-small cell lung cancer

IL-18 is an inflammasome-related cytokine, member of the IL-1 family, produced by a wide range of cells in response to signals by several pathogen-or damage-associated molecular patterns. It can be highly represented in tumor patients, but its relevance in human cancer development is not clear. In this study, we provide evidence that IL-18 is principally expressed in tumor cells and, in concert with other conventional Th1 cell-driven cytokines, has a pivotal role in establishing a pro-inflammatory milieu in the tumor microenvironment of human non-small cell lung cancer (NSCLC). Interestingly, the analysis of tumor-infiltrating CD8(+) T cell populations showed that (i) the relative IL-18 receptor (IL-18R) is significantly more expressed by the minority of cells with a functional phenotype (T-bet(+)Eomes(+)), than by the majority of those with the dysfunctional phenotype T-bet(+)Eomes(+) generally resident within tumors; (ii) as a consequence, the former are significantly more responsive than the latter to IL-18 stimulus in terms of IFN gamma production ex vivo; (iii) PD-1 expression does not discriminate these two populations. These data indicate that IL-18R may represent a biomarker of the minority of functional tumor-infiltrating CD8(+) T cells in adenocarcinoma NSCLC patients. In addition, our results lead to envisage the possible therapeutic usage of IL-18 in NSCLC, even in combination with other checkpoint inhibitor approaches