The Uluzzian in the north of Italy: insights around the new evidence at Riparo Broion

In attempt to enlighten the debate on the Middle to Upper Palaeolithic transition, this work contributes new data from a yet unpublished site, Riparo Broion in the north-east of Italy. Studies confirm the presence of the Uluzzian technocomplex embedded in an archaeological sequence which includes Mousterian, Gravettian and Epigravettian. These layers have yielded finds of bone and lithic technology, shell beads, engraved portable art and the use of red mineral pigments, which make this archive a unique case for evaluating the implications of cultural dynamics in Northern Italy 44.0\u201342.4 ky BP. The diversity of the faunal assemblage recovered in layers 1f and 1g is representative of the different environments surrounding the site, with ungulates being targeted for hunting and consumption. The lithic assemblage records a high fragmentation rate due to the extensive use of the bipolar knapping technique, responsible for a large variety of splintered pieces and associated chips which also affected the backed pieces, lunates and end-scrapers. The features of the bone tools, as well as those of the marine and freshwater beads, echo the technique used in the Uluzzian in the south of Italy, confirming the geographic spread of this technocomplex in the North Adriatic region, as previously envisaged at Grotta Fumane. However, comparisons between these two sites stimulate a discussion around the possible driving forces responsible for the differences observed in technological, typological and structural lithic assemblages. A definitive scenario for the Middle Palaeolithic\u2013Upper Palaeolithic transition in this region of Southern Europe is ongoing and Riparo Broion is adding key contributions

Shifts in flood generation processes exacerbate regional flood anomalies in Europe

Anomalies in the frequency of river floods, i.e., flood-rich or -poor periods, cause biases in flood risk estimates and thus make climate adaptation measures less efficient. While observations have recently confirmed the presence of flood anomalies in Europe, their exact causes are not clear. Here we analyse streamflow and climate observations during 1960-2010 to show that shifts in flood generation processes contribute more to the occurrence of regional flood anomalies than changes in extreme rainfall. A shift from rain on dry soil to rain on wet soil events by 5% increased the frequency of flood-rich periods in the Atlantic region, and an opposite shift in the Mediterranean region increased the frequency of flood-poor periods, but will likely make singular extreme floods occur more often. Flood anomalies driven by changing flood generation processes in Europe may further intensify in a warming climate and should be considered in flood estimation and management.publishedVersio

L'Épigravettien à l'épreuve des faits, une approche systémique

L’Épigravettien a été défini dans les années 1960 pour rendre compte de l’originalité des industries lithiques postérieures au Gravettien en Italie. L’extension progressive de cette entité à une grande partie de l’Europe méditerranéenne et orientale s’est également appuyée essentiellement sur les industries lithiques. Au cours des dernières d´ecennies, le développement de l’approche technologique dans l’étude des industries lithiques, associé à une meilleure prise en compte des contextes archéologiques et des séquences stratigraphiques, a fortement renouvelé la perception de l’Épigravettien, de sa sériation et de son emprise chrono-géographique. Dans plusieurs régions, des travaux portant sur les transferts lithiques documentent des r´eseaux de d´eplacement et de contact s’établissant à différentes échelles. En parallèle, les recherches portant sur d’autres domaines techniques et culturels ont considérablement progress´e au cours des dernières décennies et ont concerné des matériaux variés (parures, faunes, art pari´etal et mobilier, sépultures...). Pourtant, ces recherches ont été généralement menées à l’intérieur du cadre fixé par les industries lithiques et n’ont que rarement conduit à une rediscussion de ce dernier. Dans cette communication, nous proposons une première tentative de synthèse des données acquises et nous tentons de poser les bases d’un dialogue non hiérarchisé entre ces différents domaines de la culture matérielle. Cette position nous conduit à éprouver d’abord la consistance de l’entité épigravettienne en dehors des seules pratiques techniques lithiques et à évaluer les recouvrements et les écarts existant entre les séquences de changements identifiés au sein des différentes composantes des systèmes techniques. Cette discussion est menée en s’appuyant d’abord sur un noyau de connaissances établies autour de deux grands domaines géographiques: le nord-est de l’Italie et l’arc liguro-proven¸cal. Nous élargissons ensuite la réflexion vers le sud et vers l’est. Chronologiquement, notre propos embrasse la durée de l’´Epigravettien (entre ca. 20 ka cal. BP et 11,5 ka cal. BP), mais se concentrera sur certains épisodes critiques ou des changements forts sont perceptibles dans les pratiques culturelles de populations épigravettiennes

NEW EARLY HOLOCENE SETTLEMENT IN CENTRAL ITALY: THE MESOLITHIC SITE OF CONTRADA PACE (MARCHE REGION)

Early Holocene hunter-gatherer settlements are spread throughout Italy and testify to the exploitation of very different landscapes. Nonetheless, their preservation state is not always exceptional. This is not the case for Contrada Pace, an archaeological site recently discovered on a terrace of the Chienti river in central-eastern Italy. This paper reports on the geomorphological, pedo-stratigraphic, and archaeological record of one of the most complete and well-preserved Early Mesolithic open-air sites in Italy and southern Europe. Micro-stratigraphic excavations extended over more than 500 square meters have exposed a buried paleosol with anthropogenic features, which contained thousand lithic artefacts and organic remains framed in the context of a primary forest. These findings appear clustered in different functional areas that yielded multiple structured features. The field evidence integrated by radiocarbon dating and archaeobotanical, archaeomalacological and zooarchaeological data allowed to propose a first interpretation of the general structure of the site and the most significant featuresThe archaeological excavation of the site was carried out by ArcheoLAB (Macerata, Italy) in the framework of construction activities promoted by the Province of Macerata and the Municipality of Tolentino. DV has received funding from the European Union's Horizon 2020 research and innovation programme (Grant Agreement number: 886476 - LiMPH - H2020-MSCA-IF-2019). The archaeobotanical study and 14C dates were funded by the European Research Council (ERC) as part of the Research and Innovation program of the European Community Horizon 2020 (HIDDEN FOODS no.639286 to EC)

The chemerin/CMKLR1 axis regulates intestinal graft-versus-host disease

: Gastrointestinal graft-versus-host disease (GvHD) is a major cause of mortality and morbidity following allogeneic bone marrow transplantation (allo-BMT). Chemerin is a chemotactic protein that recruits leukocytes to inflamed tissues by interacting with ChemR23/CMKLR1, a chemotactic receptor expressed by leukocytes, including macrophages. During acute GvHD, chemerin plasma levels were strongly increased in allo-BM-transplanted mice. The role of the chemerin/CMKLR1 axis in GvHD was investigated using Cmklr1-KO mice. WT mice transplanted with an allogeneic graft from Cmklr1-KO donors (t-KO) had worse survival and more severe GvHD. Histological analysis demonstrated that the gastrointestinal tract was the organ mostly affected by GvHD in t-KO mice. The severe colitis of t-KO mice was characterized by massive neutrophil infiltration and tissue damage associated with bacterial translocation and exacerbated inflammation. Similarly, Cmklr1-KO recipient mice showed increased intestinal pathology in both allogeneic transplant and dextran sulfate sodium-induced colitis. Notably, the adoptive transfer of WT monocytes into t-KO mice mitigated GvHD manifestations by decreasing gut inflammation and T cell activation. In patients, higher chemerin serum levels were predictive of GvHD development. Overall, these results suggest that CMKLR1/chemerin may be a protective pathway for the control of intestinal inflammation and tissue damage in GvHD

Lack of CC chemokine ligand 2 differentially affects inflammation and fibrosis according to the genetic background in a murine model of steatohepatitis

Expression of CCL2 (CC chemokine ligand 2) (or monocyte chemoattractant protein-1) regulates inflammatory cell infiltration in the liver and adipose tissue, favouring steatosis. However, its role in the pathogenesis of steatohepatitis is still uncertain. In the present study, we investigated the development of non-alcoholic steatohepatitis induced by an MCD diet (methionine/choline-deficient diet) in mice lacking the CCL2 gene on two different genetic backgrounds, namely Balb/C and C57/Bl6J. WT (wild-type) and CCL2-KO (knockout) mice were fed on a lipid-enriched MCD diet or a control diet for 8 weeks. In Balb/C mice fed on the MCD diet, a lack of CCL2 was associated with lower ALT (alanine transaminase) levels and reduced infiltration of inflammatory cells, together with a lower generation of oxidative-stress-related products. Sirius Red staining demonstrated pericellular fibrosis in zone 3, and image analysis showed a significantly lower matrix accumulation in CCL2-KO mice. This was associated with reduced hepatic expression of TGF-β (transforming growth factor-β), type I procollagen, TIMP-1 (tissue inhibitor of metalloproteinases-1) and α-smooth muscle actin. In contrast, in mice on a C57Bl/6 background, neither ALT levels nor inflammation or fibrosis were significantly different comparing WT and CCL2-KO animals fed on an MCD diet. In agreement, genes related to fibrogenesis were expressed to comparable levels in the two groups of animals. Comparison of the expression of several genes involved in inflammation and repair demonstrated that IL (interleukin)-4 and the M2 marker MGL-1 (macrophage galactose-type C-type lectin 1) were differentially expressed in Balb/C and C57Bl/6 mice. No significant differences in the degree of steatosis were observed in all groups of mice fed on the MCD diet. We conclude that, in experimental murine steatohepatitis, the effects of CCL2 deficiency are markedly dependent on the genetic background

Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted

Lithic raw material circulation and settlement dynamics in the Upper Palaeolithic of the Venetian Prealps (NE Italy). A key-role for palaeoclimatic and landscape changes across the LGM?

The Venetian Prealps preserve one of the richest archives relating to prehistoric human settlement in the Southern Alps. Our study focused on the lithic assemblages from some main Upper Palaeolithic sites of this area in order to investigate the raw materials procurement behavior of Modern Humans throughout time. Climate changes between MIS 3 and MIS 2 played an important role by affecting human settlement and life-styles. Modern Humans arrived in north-eastern Italy around 42 kyrs cal BP attesting an almost exclusive exploitation of regional lithic resources with few evidence (1%) of mid-distance procurement. In the Gravettian record, that is only preserved in the Lessini mountains and Berici hills, exploited cherts are exclusively local, with procurement distances never exceeding 40 km. A lack of data marks the period between ca. 28 and 24 kyrs cal BP while a sharp climatic and environmental change characterizes the LGM. During this period, Late Gravettian and Early Epigravettian assemblages are documented only in the eastern Berici hills and are represented by occasional hunting stands. Most of the exploited lithic raw materials come from the Umbria-Marches Apennines, attesting displacements of more than 250 km. Similar environmental conditions persisted until the early Lateglacial even if a climate improvement is attested since around 18.5 kyrs cal BP. At Riparo Tagliente a few Umbria-Marches Apennines cherts are still attested between ca. 17 and 15 kyrs cal BP, represented by retouched tools, a few cores and some maintenance and production blanks, within a lithic assemblage mostly realized on local (Lessini) cherts. Climate amelioration, followed by a rap- id diffusion of forest environments across the Po plain is documented after 14.5 yrs cal BP. In connection with this widespread afforestation the importation of long distance Apennines cherts ceases and the sites of the Venetian area undergo a “regionalization” process marked by the exclusive exploitation of local resources