Campiglia Marittima Skarn (Tuscany): A Challenging Example for the Evolution of Skarn-Forming Models

Campiglia Marittima (hereafter Campiglia) has a long record of attracting interest on its ore deposits that have been intermittently exploited from the Copper Age to the late XX century. Since the XIX century, Campiglia has been a key locality for the debate on skarn-forming processes due to the presence of mining activities ensuring access to ever new rock exposures. The pioneering study of vom Rath and the comparison with attractive chemical model (e.g., Korzhinskii's theory) in the XX century made Campiglia a "classic" example of skarn ore deposit, from the causative intrusion to the marble host rock. In recent years, detailed field investigations integrated by petrographic, geochemical, and isotopic analyses revealed a more complex and stimulating geological history. The Campiglia skarn was later intruded by mafic magma causing textural reworking and chemical redistribution as well as the reverse telescoping process with Fe-Cu sulfides overprinting previously formed Pb-Zn ore. This work aims to trace the evolution of the scientific thinking on the Campiglia ore deposit by comparison with existing skarn-forming models and, ultimately, shows that the current skarn-forming model(s) cannot fully explain the textural and geochemical features of the Campiglia skarn

Believing in Conspiracy Theories : Evidence from an Exploratory Analysis of Italian Survey Data

Beliefs in conspiracy theories have attracted significant international media attention in recent years. This phenomenon has been studied in the US but while anecdotal evidence suggests it is also widespread among the Italian public, little evidence has been collected to assess it empirically. Using data from a 2016 survey, this pioneering study of the Italian case investigates the extent of diffusion of conspiracy theories among Italians and tests several hypotheses concerning individual determinants. The paper finds that conspiracism is indeed widely diffused in Italy. It is negatively associated with education and positively with religiosity, while no correlation is found with political trust. Beliefs in conspiracies are also related to rightwing orientation and support for the populist Five Star Movement

Prevalence of Primary Radiographic Signs of Hip Dysplasia in Dogs

Hip dysplasia is a disabling orthopedic disease in dogs. The aim of this retrospective study was to evaluate the morphological aspects and radiographic changes in the development of hip dysplasia in adult dogs, and to describe the frequency of each radiographic parameter according to each Federation Cynologique Internationale (FCI) grade. Brass descriptive forms for the evaluation of hip dysplasia were obtained from the archive of the Italian Fondazione Salute Animale, and the radiographic evaluation of 642 hips were processed. Sixteen radiographic criteria were assessed, divided into six main parameters: acetabulum, femoral head and its position in the acetabulum, femoral neck, joint space, and Norberg angle. The initial mild alterations were shown in the craniolateral acetabular rim (31.8%), slightly divergent in the joint space in 58.6% of FCI-A. The spherical shape of the femoral head was mildly small/flattened in 56.9% of FCI-B, in addition to a slightly cylindrical-shaped femoral neck (60.5%) and slightly lost contours (55.0%). Changes in acetabular depth (45.0%), and in the cranial acetabular margin (56.7%) were found in FCI-C. The center of the femoral head was lateral to the dorsal acetabular rim in 70.0% of FCI-B; the Norberg angle appeared normal in 70.6% of FCI-B. Elaboration of the radiographic criteria from the Brass descriptive forms allowed for the extrapolation of accurate knowledge regarding morphologic changes in the development of dysplasia by providing detailed information for each individual. In particular, the present survey showed that the morphological alterations of the acetabulum prevailed over those of the femoral head only at the beginning of the development of canine hip dysplasia, and then worsened after the changes occurred in the femoral head and neck

Characterization of FCI (Fédération Cynologique Internationale) Grades for Hip Dysplasia in Five Dog Breeds

Simple Summary Hip dysplasia is one of the most frequently occurring orthopedic diseases in medium to large purebred dogs. For this reason, much attention is paid to screening programs for breeding animals. The Federation Cynologique Internationale uses the same evaluation criteria regardless of breed. The aim of this study was to evaluate whether or not the evolution of a hip pathology in dogs with or without dysplasia was consistent with prior scientific knowledge in five breeds. In addition, whether there were significant radiographic differences between breeds which might require a breed-specific method for assessing the grade of hip dysplasia was investigated. Evaluations of 16 radiographic parameters analyzed using the Brass method were collected from 5 breeds: Labrador Retrievers, Golden Retrievers, German Shepherd dogs, Bernese Mountain dogs, and Rottweilers. No significant changes were found among the five breeds regarding the grade of hip dysplasia; however, some significant variations were found in the individual radiographic parameters suggesting that, although the criteria regarded all breeds, there were specific alterations which could be caused by the different morphologies, aptitudes and abilities of each breed. The aim of this retrospective study was to verify whether the radiographic morphologic differences detected within the first three grades of hip dysplasia (A, B, C) of each of the five selected breeds and within the same breeds were statistically significant enough to require a breed-specific evaluation. A total of 422 technical evaluation forms of hip dysplasia (HD) in Labrador Retrievers, Golden Retrievers, Rottweilers, Bernese Mountain dogs, and German Shepherd dogs were obtained from the Federation Cynologique Internationale (FCI) archive. The data were evaluated using a descriptive statistical analysis. In Labrador Retrievers, the craniolateral acetabular rim and femoral head position were already altered in unaffected dogs; however, within the various FCI grades, the most severe changes involved the conformation of the femoral neck. All the radiographic parameters of the Golden Retriever hips changed progressively and evenly. Significant radiographic changes between FCI grades were found in the German Shepherd dogs, and the alterations involving the acetabulum were more severe and appeared earlier than in the femoral head and neck. In the Bernese Mountain dogs, the most severe alterations were in the position of the femoral head and joint space while the femoral head and neck showed no significant progression between grades. All the radiographic parameters of non-dysplastic Rottweilers were normal; however, the progression of the primary signs was similar to the other breeds, although with lower severity. In conclusion, no significant prevalence of the radiographic features was observed for any specific breed. However, significant individual breed variations in the primary radiographic parameters were found between dogs with and without dysplasia which could be useful for better understanding the consequences of biomechanical differences between breeds

Hypomorphic mutation in the RAG2 gene affects dendritic cell distribution and migration.

In Omenn syndrome, altered dendritic cell distribution and impaired migration represent an additional level of immune dysregulation, contributing to the pathogenesis of autoimmunity. OS is a severe combined immunodeficiency characterized by erythrodermia and protracted diarrhea as a result of infiltration of oligoclonal-activated T cells, caused by hypomorphic mutations in RAGs. The RAG2(R229Q) mouse model fully recapitulates the clinical OS phenotype. We evaluated whether T and B cell defects, together with the abnormal lymphoid structure, could affect DC homeostasis and function. High density of LCs was observed in skin biopsies of Omenn patients and in the derma of RAG2(R229Q) mice, correlating with the presence of erythrodermia. In vivo models of cutaneous skin painting and CHS demonstrated a decreased migration of RAG2(R229Q) DCsin particular, LCsinto draining LNs. Interestingly, at steady state, RAG2(R229Q) mice showed a reduction in DC number in all hematopoietic organs except LNs. Analysis of the MHCII marker revealed a diminished expression also upon the LPS-driven inflammatory condition. Despite the decreased number of peripheral DCs, BM pre-cDCs were present in normal number compared with RAG2(+/+) controls, whereas pDCs and monocytes were reduced significantly. Overall, these results point to a secondary defect in the DC compartment, which contributes to clinical manifestations and autoimmunity in OS

Dendritic Cells Cause Bone Lesions in a New Mouse Model of Histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare disease caused by the clonal accumulation of dendritic Langerhans cells, which is often accompanied by osteolytic lesions. It has been reported that osteoclast-like cells play a major role in the pathogenic bone destruction seen in patients with LCH and these cells are postulated to originate from the fusion of DCs. However, due to the lack of reliable animal models the pathogenesis of LCH is still poorly understood. In this study, we have established a mouse model of histiocytosis- recapitulating human disease for osteolytic lesions seen in LCH patients. At 12 weeks after birth, severe bone lesions were observed in our multisystem histiocytosis (Mushi) model, when CD8α conventional dendritic cells (DCs) are transformed (MuTuDC) and accumulate. Most importantly, our study demonstrates that bone loss in LCH can be accounted for the transdifferentiation of MuTuDCs into functional osteoclasts both in vivo and in vitro. Moreover, we have shown that injected MuTuDCs reverse the osteopetrotic phenotype of oc/oc mice in vivo. In conclusion, our results support a crucial role of DCs in bone lesions in histiocytosis patients. Furthermore, our new model of LCH based on adoptive transfer of MuTuDC lines, leading to bone lesions within 1-2 weeks, will be an important tool for investigating the pathophysiology of this disease and ultimately for evaluating the potential of anti-resorptive drugs for the treatment of bone lesions

Valorizzazione del geosito «Sezione Coquand», miniera del Temperino (Parco Archeominerario di San Silvestro , Campiglia Marittima)

il patrimonio geologico della Toscana è uno dei più vari, più studiati e ricchi di storia (industriale e scientifica) di tutto il territorio nazionale, rappresentando un’area di ricerca e formazione didattica non solo per gli atenei toscani ma anche per altre strutture accademiche italiane e straniere. a partire dagli anni ’90 del secolo scorso, la riconversione da regione a vocazione mineraria a regione a indirizzo prevalentemente turi- stico ha portato ad una più attenta gestione del bene ambientale- paesaggistico precludendo però l’accesso a importanti affiora- menti geologici di interesse scientifico e didattico (per chiusura delle miniere o per ripristini ambientali). La creazione di Parchi per la tutela del ricco patrimonio naturalistico, storico e arche- ologico toscano costituisce un’occasione per sviluppare delle sinergie tra queste strutture e la comunità degli scienziati della Terra tese all’individuazione, conservazione e valorizzazione di geositi di particolare pregio scientifico-didattico. La colla- borazione tra il personale della Parchi Val di Cornia S.p.a., e dell’Università e CNR di Pisa ha permesso di recuperare e valorizzare un geosito toscano di notevole interesse, la «Sezio- ne Coquand»: un anfiteatro di circa 10 metri di raggio che espone la sezione tipo degli skarn a solfuri di Cu-Fe-Pb-zn coltivati un tempo dalla miniera del Temperino, attualmente nel Parco archeominerario di San Silvestro, Campiglia Marittima. il rilevamento topografico e geologico di dettaglio ha permesso di ricostruire la complessa storia di questo sistema magmatico- idrotermale e di confrontarla con i numerosi lavori scientifici pubblicati a partire dalla prima metà del XiX secolo.The geological heritage of Tuscany is one of the most varied, studied and history-rich (from the industrial and scientific stand point) of italy, represent- ing an area of active research and educational training not only for Tuscan Universities but also for other italian and foreign academic institutions. Since the 90’s of last century, Tuscany changed its economic strategy from mining-directed to mainly touristic, starting a more careful management of the environment and landscape. Backfilling of former quarries, stabilization of road cuts and closure of underground works in mining areas represent a correct environmental practice but in turn it precludes the access at important geological outcrops of high scientific and educational interest. The creation of parks for the protection of the rich Tuscan natural, historical and archaeological heritage is an opportunity to develop syn- ergies between conservation institutions and the community of Earth scientists aimed to the identification, preservation and improvement of geosites of special scientific and edu- cational value. The collaboration between the Parchi Val di Cornia S.p.a, University of Pisa and CNR allowed recovering and development of a Tuscan geosite of great interest, the «Coquand Section»: a 20 meter large amphitheater where the type-section of a Cu-Fe-Pb-zn sulfide bearing skarn body is exposed (exploited in the past by the Temperino mine; now in the archaeological and Mining Park of San Silvestro). The detailed topographic and geological survey provided new data for the reconstruction of the complex genetic history of this magmatic-hydrothermal system. Comparison with the numer- ous scientific papers published since the early nineteenth cen- tury on this geological outcrop allows to follow the evolution of scientific thought about relationships between magmatism, release of hydrothermal fluids and metasomatic processes

B lymphocytes limit senescence-driven fibrosis resolution and favor hepatocarcinogenesis in mouse liver injury

Hepatocellular carcinoma (HCC) is a frequent neoplasia and a leading cause of inflammation-related cancer mortality. Despite that most HCCs arise from persistent inflammatory conditions, pathways linking chronic inflammation to cancer development are still incompletely elucidated. We dissected the role of adaptive immunity in the Mdr2 knockout (Mdr2\u2013/\u2013) mouse, a model of inflammation-associated cancer, in which ablation of adaptive immunity has been induced genetically (Rag2\u2013/\u2013Mdr2\u2013/\u2013 and \u3bcMt-Mdr2\u2013/\u2013 mice) or with in vivo treatments using lymphocyte-specific depleting antibodies (anti-CD20 or anti-CD4/CD8). We found that activated B and T lymphocytes, secreting fibrogenic tumor necrosis factor alpha (TNF\u3b1) and other proinflammatory cytokines, infiltrated liver of the Mdr2\u2013/\u2013 mice during chronic fibrosing cholangitis. Lymphocyte ablation, in the Rag2\u2013/\u2013Mdr2\u2013/\u2013 and \u3bcMt-Mdr2\u2013/\u2013 mice, strongly suppressed hepatic stellate cell (HSC) activation and extracellular matrix deposition, enhancing HSC transition to cellular senescence. Moreover, lack of lymphocytes changed the intrahepatic metabolic/oxidative state, resulting in skewed macrophage polarization toward an anti-inflammatory M2 phenotype. Remarkably, hepatocarcinogenesis was significantly suppressed in the Rag2\u2013/\u2013Mdr2\u2013/\u2013 mice, correlating with reduced TNF\u3b1/NF-\u3baB (nuclear factor kappa B) pathway activation. Ablation of CD20+ B cells, but not of CD4+/CD8+ T cells, in Mdr2\u2013/\u2013 mice, promoted senescence-mediated fibrosis resolution and inhibited the protumorigenic TNF\u3b1/NF-\u3baB pathway. Interestingly, presence of infiltrating B cells correlated with increased tumor aggressiveness and reduced disease-free survival in human HCC. Conclusion: Adaptive immunity sustains liver fibrosis (LF) and favors HCC growth in chronic injury, by modulating innate components of inflammation and limiting the extent of HSC senescence. Therapies designed for B-cell targeting may be an effective strategy in LF. (Hepatology 2018;67:1970-1985)

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe