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The Virgin Hodegetria, located in the Cathedral of Santa Maria Nuova in Monreale, near Palermo (Italy), probably dating the first half of the 13th century, is one of the earliest examples of medieval panel painting in Sicily. A diagnostic campaign was carried out on the panel aiming to identify the constituting materials and the executive technique, as well as to assess the state of conservation for supporting the methodological choice of the restoration intervention. Both non-invasive (X-ray radiography, digital microscope, multispectral imaging, ED-X-ray fluorescence) and micro-invasive (polarised light microscopy, ESEM-EDX, ATR-FTIR spectroscopy and micro-Raman spectroscopy) analyses were performed. According to the results, the executive technique followed the 13th–14th-century Italian painting tradition. A complex structure was applied on the wooden support, consisting of a double layer of canvas and several ground layers of gypsum and glue-based binder. The underdrawing was made by a brush using carbonaceous black pigment. The original palette includes red ochre, red lead, azurite, carbon black and bone black. During the several restorations, mercury-based red, indigo, smalt blue, orpiment and synthetic mars were used. The original silver leaf of the frame was covered with red tin-based lake and subsequently regilded with gold leaf. Proteinaceous and oil binders were also detected.

The most important painter from Urbino in the last decades of the 15th century (1439 ab.–1494) was Giovanni Santi, the father of Raphael. The lack of scientific literature about Santi’s practice and the possible peculiar role of Urbino in the development of painting techniques in northern Italy suggested in-depth investigations of the entire corpus of his paintings. A well-established sequence of multispectral imaging, spectroscopic and microscopic investigations was performed on 24 wood panel paintings and 2 canvases attributed by most scholars to Giovanni Santi (1439 ab.–1494) to collect a large set of significant data. This systematic research allowed his painting technique to be defined, starting from the type of supports he used and from the features of the underdrawing, which quite frequently included characteristic regular hatching. The pigments used were widely investigated by means of ED-XRF and reflectance spectroscopy (vis-RS); a meaningful multivariate statistical method (PCA and HCA analysis) was also applied to the ED-XRF dataset acquired for representative hues. In particular, the vis-RS technique proved to be a simple and effective diagnostic tool to detect many pigments, including indigo, and to distinguish between two different types of red lakes, avoiding sampling and more complex analyses. Santi used lead white, Fe-Mn-based pigments, vermilion, red lake, natural blue ultramarine, azurite, copper-based green pigments (particularly verdigris), lead-tin yellow, scarcely ever orpiment and, in a few green mixtures, also indigo. Despite the palette being linked to tradition, the master appeared to introduce some peculiarities, such as the addition of glass powder, and mixing pigments both in a traditional way and using them to create chromatic effects unusual for his time. This research confirmed that the systematic use of the integrated non-invasive methods is highly representative, and the results of this wide diagnostic campaign provided a significant dataset which allowed the implementation of a scientific database related to central Italy Renaissance paintings and materials.

Funder: Engineering and Physical Sciences Research Council, Funder: Higher Education Funding Council for England, Funder: NIHR Cambridge Biomedical Research Centre, Funder: British Heart Foundation, In recent years, cardiovascular immuno-imaging by positron emission tomography (PET) has undergone tremendous progress in preclinical settings. Clinically, two approved PET tracers hold great potential for inflammation imaging in cardiovascular patients, namely FDG and DOTATATE. While the former is a widely applied metabolic tracer, DOTATATE is a relatively new PET tracer targeting the somatostatin receptor 2 (SST2). In the current study, we performed a detailed, head-to-head comparison of DOTATATE-based radiotracers and [18F]F-FDG in mouse and rabbit models of cardiovascular inflammation. For mouse experiments, we labeled DOTATATE with the long-lived isotope [64Cu]Cu to enable studying the tracer's mode of action by complementing in vivo PET/CT experiments with thorough ex vivo immunological analyses. For translational PET/MRI rabbit studies, we employed the more widely clinically used [68Ga]Ga-labeled DOTATATE, which was approved by the FDA in 2016. DOTATATE's pharmacokinetics and timed biodistribution were determined in control and atherosclerotic mice and rabbits by ex vivo gamma counting of blood and organs. Additionally, we performed in vivo PET/CT experiments in mice with atherosclerosis, mice subjected to myocardial infarction and control animals, using both [64Cu]Cu-DOTATATE and [18F]F-FDG. To evaluate differences in the tracers' cellular specificity, we performed ensuing ex vivo flow cytometry and gamma counting. In mice subjected to myocardial infarction, in vivo [64Cu]Cu-DOTATATE PET showed higher differential uptake between infarcted (SUVmax 1.3, IQR, 1.2-1.4, N = 4) and remote myocardium (SUVmax 0.7, IQR, 0.5-0.8, N = 4, p = 0.0286), and with respect to controls (SUVmax 0.6, IQR, 0.5-0.7, N = 4, p = 0.0286), than [18F]F-FDG PET. In atherosclerotic mice, [64Cu]Cu-DOTATATE PET aortic signal, but not [18F]F-FDG PET, was higher compared to controls (SUVmax 1.1, IQR, 0.9-1.3 and 0.5, IQR, 0.5-0.6, respectively, N = 4, p = 0.0286). In both models, [64Cu]Cu-DOTATATE demonstrated preferential accumulation in macrophages with respect to other myeloid cells, while [18F]F-FDG was taken up by macrophages and other leukocytes. In a translational PET/MRI study in atherosclerotic rabbits, we then compared [68Ga]Ga-DOTATATE and [18F]F-FDG for the assessment of aortic inflammation, combined with ex vivo radiometric assays and near-infrared imaging of macrophage burden. Rabbit experiments showed significantly higher aortic accumulation of both [68Ga]Ga-DOTATATE and [18F]F-FDG in atherosclerotic (SUVmax 0.415, IQR, 0.338-0.499, N = 32 and 0.446, IQR, 0.387-0.536, N = 27, respectively) compared to control animals (SUVmax 0.253, IQR, 0.197-0.285, p = 0.0002, N = 10 and 0.349, IQR, 0.299-0.423, p = 0.0159, N = 11, respectively). In conclusion, we present a detailed, head-to-head comparison of the novel SST2-specific tracer DOTATATE and the validated metabolic tracer [18F]F-FDG for the evaluation of inflammation in small animal models of cardiovascular disease. Our results support further investigations on the use of DOTATATE to assess cardiovascular inflammation as a complementary readout to the widely used [18F]F-FDG.

Bagni San Filippo area is characterized by the discharge of thermal waters and deeply produced CO2-rich gases both from vents and soil diffuse degassing. The thermal waters are the results of the mixing between meteoric waters and hot fluids deriving from the condensation, at depth, of vapours uprising from a deep hydrothermal reservoir. This process gives rise to a relatively shallow thermal system at temperature close to 50°C, characterized by SO4-rich and Cl-poor waters and elevated PCO2 (~7 bar). Most of the incondensable gas of deep originated vapour is released as a free gas phase forming cold gas vents and localized spots of anomalous CO2 diffuse degassing. The location and the shape of these degassing zones are strongly controlled by the main tectonic structures of the area. Through detailed soil diffuse degassing surveys and hydrogeochemical modelling, we estimate at 226-326 t d-1 and at 965 t d-1 the deep CO2 emission and the amount of condensates discharged by the thermal springs, respectively. The thermal energy associated to the process results at ~ 29 MW, most of which (~ 25 MW) is associated with condensation occurring at depths greater than groundwater circulation.

Background: Hundreds of candidate genes have been associated with coronary artery disease (CAD) through genome-wide association studies. However, a systematic way to understand the causal mechanism(s) of these genes, and a means to prioritize them for further study, has been lacking. This represents a major roadblock for developing novel disease- and gene-specific therapies for patients with CAD. Recently, powerful integrative genomics analyses pipelines have emerged to identify and prioritize candidate causal genes by integrating tissue/cell-specific gene expression data with genome-wide association study data sets. Methods: We aimed to develop a comprehensive integrative genomics analyses pipeline for CAD and to provide a prioritized list of causal CAD genes. To this end, we leveraged several complimentary informatics approaches to integrate summary statistics from CAD genome-wide association studies (from UK Biobank and CARDIoGRAMplusC4D) with transcriptomic and expression quantitative trait loci data from 9 cardiometabolic tissue/cell types in the STARNET study (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task). Results: We identified 162 unique candidate causal CAD genes, which exerted their effect from between one and up to 7 disease-relevant tissues/cell types, including the arterial wall, blood, liver, skeletal muscle, adipose, foam cells, and macrophages. When their causal effect was ranked, the top candidate causal CAD genes were CDKN2B (associated with the 9p21.3 risk locus) and PHACTR1 ; both exerting their causal effect in the arterial wall. A majority of candidate causal genes were represented in cross-tissue gene regulatory co-expression networks that are involved with CAD, with 22/162 being key drivers in those networks. Conclusions: We identified and prioritized candidate causal CAD genes, also localizing their tissue(s) of causal effect. These results should serve as a resource and facilitate targeted studies to identify the functional impact of top causal CAD genes.

Coronary atherosclerosis results from the delicate interplay of genetic and exogenous risk factors, principally taking place in metabolic organs and the arterial wall. Here we show that 224 gene-regulatory coexpression networks (GRNs) identified by integrating genetic and clinical data from patients with (n = 600) and without (n = 250) coronary artery disease (CAD) with RNA-seq data from seven disease-relevant tissues in the Stockholm–Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study largely capture this delicate interplay, explaining >54% of CAD heritability. Within 89 cross-tissue GRNs associated with clinical severity of CAD, 374 endocrine factors facilitated inter-organ interactions, primarily along an axis from adipose tissue to the liver (n = 152). This axis was independently replicated in genetically diverse mouse strains and by injection of recombinant forms of adipose endocrine factors (EPDR1, FCN2, FSTL3 and LBP) that markedly altered blood lipid and glucose levels in mice. Altogether, the STARNET database and the associated GRN browser (http://starnet.mssm.edu) provide a multiorgan framework for exploration of the molecular interplay between cardiometabolic disorders and CAD.

The microstructure and chemical composition of blue and green pellets, coloured lump pigments and a metal scrap excavated in Persepolis West (Fars, Iran), by the Iranian-Italian Joint Archaeological Mission in Fars in 2008–09, were investigated to clarify their origin and production techniques. The Persepolis West urban area has its eastern limit about five hundred meters away from the Persepolis Terrace and extends for about 1 km in a westward direction. Due to the presence in this area of various kilns and other remains, the existence of a craft zone connected with the construction of imperial and elite buildings in Persepolis was proposed. The colourful residues were submitted to integrated investigations using portable X-ray fluorescence spectrometry, digital and polarized light microscopy, scanning electron microscopy with energy dispersive X-ray spectroscopy, X-ray diffraction, ATR-FTIR and Raman spectroscopy. The integrated analyses allowed to identify azurite, malachite, Egyptian blue, glauconite, yellow and red ochre with hematite, magnetite and goethite. Proteinaceous material was detected only in one red lump. These pigments are in accordance with the palette used to paint the palaces of the Persepolis Terrace, thus supporting the hypothesis that in Persepolis West craft zone, there was a laboratory for production of pigments. The microscopic features of the lumps and their peculiar shape confirmed a local manufacturing process. Moreover, the diopside presence related to the Egyptian blue production, as well as the discovery of a bronze scrap with a crust of Egyptian blue also suggested that this pigment was manufactured locally.

Introduction: Inflammation is a key driver of atherosclerosis. The identification of new treatments and strategies targeting the specific inflammatory signaling that persists in optimally treated atherosclerotic patients remain an unmet clinical need. Hypothesis: The integration of time-of-flight mass cytometry (CyTOF), gene expression analysis, and drug repositioning computational approaches applied to pre-clinical validation in models of the disease using non-invasive imaging will help to identify drugs tailored to residual inflammatory signaling in patients with atherosclerosis. Methods: We developed a new systems biology pipeline to identify new therapeutic/indication pair that combines CyTOF and RNA sequencing (RNA-seq) data analysis of clinical samples from patients with carotid and coronary artery disease (CVD) ( Fig. 1A ). This approach allowed the identification of new uses for existing compounds. The predicted anti-atherosclerotic effect was validated in ApoE-/- mice and in a rabbit model of atherosclerosis using 18 F-Fluorodeoxyglucose (FDG) PET-MRI. Results: We found a specific inflammatory signature in CD14 + monocytes stimulated with CVD plasma that was used to identify 50 small molecules predicted to reverse this signature. CyTOF screening of the top eight candidate compounds showed that Saracatinib—a phase 2a-ready Src/Abl inhibitor—blunted the inflammatory response found in CD14 + monocytes ( Fig. 1B ). The anti-atherosclerotic efficacy of Saracatinib was confirmed in ApoE-/- mice fed a high fat diet ( Fig.1C ). In the atherosclerotic rabbit model, Saracatinib reduced plaque inflammation measured as reduction of 18 F-FDG uptake by PET-MRI ( Fig. 1D ). Conclusions: These data support the use of our integrated systems biology pipeline as a powerful approach to identify new immune signature specific to patients with atherosclerosis that can be leveraged to identify new indications for existing drugs to treat cardiovascular disease.

The icon Virgin Hodegetria, now in Santa Maria Nuova Cathedral in Monreale near Palermo (Italy), probably dates from the beginning of thirteen century could be considered one of the earliest examples of medieval icon in Sicily. The icon is distinguished from other southern icons by the strong Byzantine matrix and by its size (169x131x3 cm). Since 2015, the icon is part of the Arab-Norman Palermo UNESCO Heritage. This paper will deal with historical and scientific investigations on the icon to better understand the painting materials, the executive technique and to resolve question about on-going restoration in planning a complex conservation project. Examination of the icon was both non-invasive (IR false colour, IR b/w, UV fluorescence) and micro invasive (optical microscopy, scanning electron microscopy with energy dispersive X-ray spectroscopy, FT-IR spectroscopy and micro-Raman spectroscopy). The executive technique appears to be similar to that used in 13th century according to Italian painting tradition: canvas support is present between the wooden panel and the gypsum/glue-based preparatory layer. The underdrawing includes the occurrence of dark grey accurate lines that seem to have been applied by brush. Silver leaf was used as a background of the paintings and in the haloes of the Virgin and Child without bole layer preparation. Mineral pigments (red and yellow ochre, green earth pigments), carbon and bone black, Cu-based pigments, azurite, indigo, orpiment/realgar, lead white, vermillion were mixed with egg-yolk medium. The presence of several not original paint layers, gilding and varnishes belonging to different previous restorations required a conservation treatment able to return to the original iconography and the stylistic specificities of the masterpiece of Monreale.

Background. Current lipid-lowering drugs often leave significant residual risk for adverse outcomes. Identification of previously approved drugs for new indications, drug repurposing, may provide a cost effective alternative to de novo drug developing.Objectives. We combined clinical, transcriptomic, computational, and experimental strategies to explore lipid-lowering and plaque-stabilizing effects of atypical antidepressant trazodone.Methods. First, a connectivity mapping strategy was used to match rosuvastatin gene expression signature derived from a clinical trial of 85 patients with to the expression patterns of 1,309 different small molecules to discover a similarity between the rosuvastatin and trazodone gene expression signatures. Then, we assessed the lipid-lowering ability of trazodone in vitro using HepG2 cells and in vivo using molecular imaging of rabbit atherosclerotic lesions. In addition, we analyzed electronic medical records of patients from three large medical centers who had a prescription for trazodone and lipid laboratory measurements available.Results. Trazodone significantly reduced cholesterol levels in the HepG2 human hepatocyte model, decreased atherosclerotic plaque burden in a rabbit model and lowered low-density lipoprotein (LDL) cholesterol levels in patients.Conclusion. Our results indicate that trazodone may be a promising candidate for adjunctive lipid lowering therapy. It may provide significant benefits to patients with hyperlipidemia, including lipid level reduction and formation of a more favorable atherosclerotic plaque morphology. Patients diagnosed with major depressive disorder requiring better lipid control would benefit the most from the for adjunctive lipid lowering therapy.

Diagnostic research was carried out to acquire information on Me-taw-ya temple, Pagan archaeological area, Burma (Myanmar). Throughout the centuries the temple was severely damaged by a series of strong earthquakes, the most recent one taking place in 2016. Our principle aim was to acquire information on the building’s constituting materials (i.e. bricks, mortars and stuccoes) to determine how the temple was constructed, an essential tool for the development of conservation/restoration projects in compliance with international guidelines and standards. The archaeometric study used selected samples to undertake an integrated application of preliminary in situ non-invasive ED-XRF investigations and micro invasive analyses. Optical microscopy observations, FT-IR, XRD and TG analyses were performed to identify the mineralogical and chemical composition of materials. Samples were categorized using principal component analysis (PCA). Hierarchical cluster analysis (HCA) were also performed on EDXRF chemical compositional data. Results have delineated a series of considerations linking the geographical origin of the constituting materials to local sources as well as clarifying their formulation and use in the construction of Me-taw-ya temple. Results were used to identify compatible materials for conservation treatments.

During a restoration and diagnostic campaigns carried out on Paestum funerary slabs belonging to the Lucanian funerary art, calcium antimonate (CaSb2O6) was detected for the first time in the pictorial layers. This artificial pigment, widely employed as opacifier both in ancient glass and glaze covering clay objects, was found in the wall paintings, regardless of the colour, supporting the hypothesis of an intentional addition of calcium antimonate to the pigments and the involvement of ceramic painters. A multi-analytical approach was performed on 32 funerary slabs (6th – 3rd century BCE), currently located at the National Archaeological Museum of Paestum (Italy) using both polarized light microscopy and environmental scanning electron microscopy equipped with energy dispersive X-ray spectrometer, micro X-ray fluorescence, micro Raman spectroscopy, Fourier Transform Infrared spectroscopy and powder X-ray diffraction. The results confirmed the use of a limited number of pigments, usually applied with fresco technique, although in many cases the stratigraphy of the painted layer showed morphology of mezzo fresco technique, but no organic binders were found. The hues of vegetal decorations were obtained using green earth, sometimes Egyptian blue mixed with yellow ochre, carbon and bone blacks, and orpiment. The alteration of green earth and other iron-containing pigments are likely responsible for the discolouration of the original hues. In red paints, hematite and red ochre are frequently associated with ilmenite, a typical volcanic mineral. Egyptian blue was used in blue paints while in black paints it was mixed with carbon and bone black pigments.

In this study the Madonna del Soccorsoo della Mazza wooden sculpture has been analysed by an interdisciplinary and integrated approach. The polychrome sculpture, dating back to the 18thcentury, comes from the church of the Madonna del Soccorso or della Mazza (1604) situated in Via Maqueda, in Palermo and it was placed on the main recess of the altar. All steps of the conservation project, from the preliminary study to the choice of materials and the restoration procedures have been accompanied and supported by diagnostic and scientific analysis. In order to evaluate the state of conservation of the sculpture and the technique employed to construct the support, computer tomography study was performed. Optical microscopy allowed to identify the wooden species and to verify the presence of microbial colonization or insect infestation. Scanning electron microscopy, combined with energy dispersive X-ray analysis (SEM/EDS), as well as XRF (X-ray fluorescence spectroscopy), were used to characterize paint stratigraphy and pigments. Sampling by sterile swabs and in vitro microbial culture has been performed to obtain the biological colonization.

The paper deals with the results of a multi-method archaeometric study focused on the different stones used in the facade of Santa Maria della Piazza church (Ancona, Central Italy). The church is an excellent example of the Italian Romanesque style. It was built at the end of the 12th century close to the old harbour of Ancona (Ankon in ancient Greek) upon the ruins of an early Christian church, founded at the end of the 4-5th century (barsanti, 1995; Marano, 2019). The architect Magister Philippus projected the construction of the Romanesque church. The current facade was built in 1210 and consists of three parts showing a rich iconography. The splayed Byzantine style portal created by Magister Leonardus is decorated with an impressive and symbolic bas-reliefs.Partially damaged by numerous earthquakes, Santa Maria della Piazza was restored many times. First renovation was carried out in Romanesque epoch and the second in the Gothic period, until in the recent past. From 2003 to 2008, Architectural and Environmental Heritage Superintendence of the Marche Region (Ancona) supported a conservation project concerning the whole facade. At that time, a diagnostic campaign was also carried out to investigate the different weathering processes affecting the stones.In 2018, the Superintendence planned a facade monitoring to evaluate the efficacy of the last restoration intervention. Besides, an archaeometric project was carried out both to classify all the stone materials and to determine their provenance. Mineralogical- petrographic investigations and isotopic analyses provided useful results to update the database of stones used in the architectural heritage of the Marche Region. A schematic colour map indicating all the lithotypes employed in Santa Maria della Piazza facade was drawn.The stones used in the facade are carbonatic lithotypes represented by Maiolica, Scaglia Rossa and Corniola Formations, belonging to the Umbria-Marche Succession, local travertine and extra-regional stones such as Istria stone, Aurisina stone, Breccia Corallina and Occhio di Pavone. Among different types of marbles Carrara, Thasian, Proconnesian, Iassense and Pavonazzetto were identified. Several elements, such as figural reliefs, slabs, and columns, representing fascinating examples of reused materials (spolia), come from both local geological formations and various Mediterranean areas.

Pagán is an ancient city located in Myanmar that is renowned for the remains of about 4000 pagodas, stupas, temples and monasteries dating from the 11th to 13th centuries. Due to a magnitude 6.8 earthquake in 2016, more than 300 ancient buildings were seriously damaged. As a part of the post-earthquake emergency program, a diagnostic pilot project was carried out on Me-taw-ya temple wall paintings to acquire further information on the materials and on their state of conservation. This article presents our attempts at characterising the painting materials at Me-taw-ya temple using non-invasive portable energy dispersive X-ray fluorescence (ED-XRF), portable Raman spectroscopy and micro-invasive attenuated total reflectance—Fourier transform infrared spectroscopy (ATR-FTIR), micro-Raman spectroscopy (µ-Raman), gas chromatography-mass spectrometry (GC-MS), polarized light microscopy (PLM) and environmental scanning electron microscope—X-ray energy dispersive system (ESEM-EDS) investigations with the aim of identifying the composition of organic binders and pigments. The presence of a proteinaceous glue mixed with the lime-based plaster was ascertained and identified by GC-MS. In addition, this technique confirmed the occurrence of plant-derived gums as binders pointing to the a secco technique. Fe-based compounds, vermillion, carbon black and As-compounds were identified to have been incorporated in the palette of the murals.

Background Genetic loss-of-function variants (LoFs) associated with disease traits are increasingly recognized as critical evidence for the selection of therapeutic targets. We integrated the analysis of genetic and clinical data from 10,511 individuals in the Mount Sinai BioMe Biobank to identify genes with loss-of-function variants (LoFs) significantly associated with cardiovascular disease (CVD) traits, and used RNA-sequence data of seven metabolic and vascular tissues isolated from 600 CVD patients in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study for validation. We also carried out in vitro functional studies of several candidate genes, and in vivo studies of one gene. Results We identified LoFs in 433 genes significantly associated with at least one of 10 major CVD traits. Next, we used RNA-sequence data from the STARNET study to validate 115 of the 433 LoF harboring-genes in that their expression levels were concordantly associated with corresponding CVD traits. Together with the documented hepatic lipid-lowering gene, APOC3, the expression levels of six additional liver LoF-genes were positively associated with levels of plasma lipids in STARNET. Candidate LoF-genes were subjected to gene silencing in HepG2 cells with marked overall effects on cellular LDLR, levels of triglycerides and on secreted APOB100 and PCSK9. In addition, we identified novel LoFs in DGAT2 associated with lower plasma cholesterol and glucose levels in BioMe that were also confirmed in STARNET, and showed a selective DGAT2-inhibitor in C57BL/6 mice not only significantly lowered fasting glucose levels but also affected body weight. Conclusion In sum, by integrating genetic and electronic medical record data, and leveraging one of the world’s largest human RNA-sequence datasets (STARNET), we identified known and novel CVD-trait related genes that may serve as targets for CVD therapeutics and as such merit further investigation. Electronic supplementary material The online version of this article (10.1186/s12920-019-0542-3) contains supplementary material, which is available to authorized users.

SUMMARYAtherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. Yet the specific immune dysregulations within the atherosclerotic lesions that lead to clinical cerebro- and cardiovascular complications (i.e. ischemic stroke and myocardial infarction) are poorly understood. Here, using single-cell mass cytometry with Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) we found that atherosclerotic plaques were enriched in activated, differentiated, and exhausted subsets of T cells vs. blood. Next, using single-cell proteomic, transcriptomic, and cell-to-cell interaction analyses we found unique functional dysregulations of both T cells and macrophages in plaques of patients with clinically symptomatic (SYM; recent stroke of TIA) or asymptomatic (ASYM, no recent stroke) carotid artery disease. SYM plaques were enriched with a distinct CD4+T cell subset, and T cells were activated, differentiated and presented subset specific exhaustion. SYM macrophages presented alternatively activated phenotypes including subsets associated with plaque vulnerability. In ASYM plaques, T cells and macrophages were activated and displayed a strong IL-1β signaling across cell types, that was absent in SYM plaques. The identification of plaque-specific innate and adaptive immune dysregulations associated with cerebrovascular events provides the basis for the design of precisely tailored cardiovascular immunotherapies.

Background: Antiretroviral therapy (ART) for HIV infection increases risk for coronary artery disease (CAD), presumably by causing dyslipidemia and increased atherosclerosis. We applied systems pharmacology to identify and validate specific regulatory gene networks through which ART drugs may promote CAD. Methods: Transcriptional responses of human cell lines to 15 ART drugs retrieved from the Library of Integrated Cellular Signatures (overall 1127 experiments) were used to establish consensus ART gene/transcriptional signatures. Next, enrichments of differentially expressed genes and gene-gene connectivity within these ART-consensus signatures were sought in 30 regulatory gene networks associated with CAD and CAD-related phenotypes in the Stockholm Atherosclerosis Gene Expression study. Results: Ten of 15 ART signatures were significantly enriched both for differential expression and connectivity in a specific atherosclerotic arterial wall regulatory gene network (AR-RGN) causal for CAD involving RNA processing genes. An atherosclerosis in vitro model of cholestryl ester-loaded foam cells was then used for experimental validation. Treatments of these foam cells with ritonavir, nelfinavir, and saquinavir at least doubled cholestryl ester accumulation ( P =0.02, 0.0009, and 0.02, respectively), whereas RNA silencing of the AR-RGN top key driver, PQBP1 (polyglutamine binding protein 1), significantly curbed cholestryl ester accumulation following treatment with any of these ART drugs by >37% ( P Conclusions: By applying a novel systems pharmacology data analysis framework, 3 commonly used ARTs (ritonavir, nelfinavir, and saquinavir) were found altering the activity of AR-RGN, a regulatory gene network promoting foam cell formation and risk of CAD. Targeting AR-RGN or its top key driver PQBP1 may help reduce CAD side effects of these ART drugs.

Background Genetic loss-of-function variants (LoFs) associated with disease traits are increasingly recognized as critical evidence for the selection of therapeutic targets. We integrated the analysis of genetic and clinical data from 10,511 individuals in the Mount Sinai BioMe Biobank to identify genes with loss-of-function variants (LoFs) significantly associated with cardiovascular disease (CVD) traits, and used RNA-sequence data of seven metabolic and vascular tissues isolated from 600 CVD patients in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study for validation. We also carried out in vitro functional studies of several candidate genes, and in vivo studies of one gene. Results We identified LoFs in 433 genes significantly associated with at least one of 10 major CVD traits. Next, we used RNA-sequence data from the STARNET study to validate 115 of the 433 LoF harboring-genes in that their expression levels were concordantly associated with corresponding CVD traits. Together with the documented hepatic lipid-lowering gene, APOC3, the expression levels of six additional liver LoF-genes were positively associated with levels of plasma lipids in STARNET. Candidate LoF-genes were subjected to gene silencing in HepG2 cells with marked overall effects on cellular LDLR, levels of triglycerides and on secreted APOB100 and PCSK9. In addition, we identified novel LoFs in DGAT2 associated with lower plasma cholesterol and glucose levels in BioMe that were also confirmed in STARNET, and showed a selective DGAT2-inhibitor in C57BL/6 mice not only significantly lowered fasting glucose levels but also affected body weight. Conclusion In sum, by integrating genetic and electronic medical record data, and leveraging one of the world's largest human RNA-sequence datasets (STARNET), we identified known and novel CVD-trait related genes that may serve as targets for CVD therapeutics and as such merit further investigation. Correction in: BMC MEDICAL GENOMICS, Volume: 12, Issue: 1, Article Number: 154, DOI: 10.1186/s12920-019-0573-9

An interdisciplinary archaeometric study concerning the Amtoudi Agadir, declared World Cultural Heritage (northern border of the Sahara Desert, southern Morocco), was performed consisting in lithostratigraphic reconstruction of the bedrock, diagnosis of constitutive materials (stones, mortars, and wooden elements), and analyses of constructive techniques and architectonic elements (load-bearing and supported structural elements). The medieval agadir (fortified granary) was built directly on a rocky piton with rocks of the substratum with traditional materials and ancestral techniques. The stones have been identified and classified into four petrofacies. Degradation such as biological attacks, chromatic alteration, erosion, exfoliation, and fissuration on the stones have been characterized. Recommendations for conservation and maintenance of the rocks have been proposed in compatibility with the environment. Load-bearing (masonry walls) and supported structural elements (ceiling structures) have also been studied in order to define their stability. Worst cases of 1- and 2-height walls, together with worst cases of the wooden or stone ceiling structures have been analyzed. Materials, techniques, and dimensions have been characterized for possible failures to shearing, bending, and flexural buckling as guide for maintenance of the agadir. The main problems of the walls derive from excessively thin construction with a lack of interlocking of the rocks and a diminished proportion or quality of mortar joining the rocks due to washing. It has been recommended to avoid thicknesses lower than 0.4 m for 2-height walls and lower than 0.3 m for 1-height walls. A nominal load has been estimated in the worst case (with wooden elements) for the ceiling structures of about 7.0 KN/m2. The calculations have indicated that a 25% increase over the nominal load would imply a risk of failure, the use of stone elements being preferable over wooden ones. With these propositions for the Amtoudi Agadir, new management and prospects for cultural tourism are feasible. This research was supported by Urbino University found (Resp. F. Guerrera); by CGL2011-30153-CO2-02 and CGL2012-32169 research project (Spanish Ministry of Education and Science) and by Research Groups and projects of the “Generalitat Valenciana” from Alicante University (CTMA-IGA).

Atherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. However, specific characteristics of dysregulated immune cells within atherosclerotic lesions that lead to clinical events such as ischemic stroke or myocardial infarction are poorly understood. Here, using single-cell proteomic and transcriptomic analyses, we uncovered distinct features of both T cells and macrophages in carotid artery plaques of patients with clinically symptomatic disease (recent stroke or transient ischemic attack) compared to asymptomatic disease (no recent stroke). Plaques from symptomatic patients were characterized by a distinct subset of CD4+ T cells and by T cells that were activated and differentiated. Moreover, some T cell subsets in these plaques presented markers of T cell exhaustion. Additionally, macrophages from these plaques contained alternatively activated phenotypes, including subsets associated with plaque vulnerability. In plaques from asymptomatic patients, T cells and macrophages were activated and displayed evidence of interleukin-1β signaling. The identification of specific features of innate and adaptive immune cells in plaques that are associated with cerebrovascular events may enable the design of more precisely tailored cardiovascular immunotherapies.

The Villa of the Papyri is one of the most imposing architectural examples of Herculaneum dated before the eruption occurred on 79 A.D. During the earliest years of the excavation of the site (18th century), the Villa has been explored through a thick network of tunnels dug into the hard bank of tuff rock. Recent excavations went on discontinuously between 1990s and 2008, until the discovery of a room located in the lower floor of the building, showing serious phenomena of colour change of some areas of the painted walls. Some dark green parts of mural paintings after volcanic mud removal became white and powdered, detaching from the plaster. During the last restoration works a scientific approach became necessary in order to acquire detailed information about the wall painting technique and the degradation phenomena occurring in some decorative elements in the vault of the Basis Villa (a room in the lower floor of the building); it was established to perform a scientific recognition. Integrated investigations – carried out by optical microscopy, scanning electron microscopy with X-ray microanalysis (EDS), X-ray diffractometry (XRD), ion chromatography (IC), FT-IR spectroscopy, gas chromatography mass spectrometry (GC-MS) – had primarily the goal to characterize the materials used for the realization of the these impressive wall paintings, as well as to assess their state of conservation. A second aim of the research was to test the reliability of non-invasive analyses that are sometimes performed in situ to study mural paintings, like reflectance spectrometry in the visible range (vis-RS), X-ray fluorescence (ED-XRF) and micro-Raman spectroscopy, as well as imaging analyses like false colour IR (IRC) and visible induced IR luminescence (VIL). The whole set of analyses allowed to identify a typical Vitruvian plaster with the following pigments: Egyptian blue, red and yellow ochre, goethite and hematite particles, green earth and carbon black particles. The high content of soluble salts, which is related to the sulphur-rich water in the site located few metres above water level in the walls and floors, caused a worsening in the state of conservation of mural paintings.

Atherosclerosis is a disease characterized by chronic inflammation. However, identifying new molecularly targeted interventions in human atherosclerosis has proven difficult. In this study, we used phosphoCyTOF to comprehensively characterize functional responses of peripheral immune populations in human atherosclerosis at the single-cell level. Healthy PBMCs were exposed to plasma of patients with atherosclerosis (n=20) or healthy donors (n=10) and the activation of major signaling pathways across all major immune subsets using 18 surface markers and 10 intracellular phospho-proteins. Using viSNE we visualized and defined 10 major immune cell populations: B cells, Basophils, CD1c DCs, CD4 T cells, CD8 T cells, CD14 and CD16 monocytes, NK cells, NKT cells, and pDCs. Next, we evaluated the relative expression of 10 phospho-proteins (IkBa, pCREB, pERK1/2, pMAPKAP2, pp38, pPLCg2, pS6, pSTAT1, pSTAT3, and pSTAT5) across this immunological map and visualized functional pathways that were differentially induced in response to plasma of atherosclerotic patients vs. healthy donors. Monocytes exhibited the greatest immune activation, showing increased phosphorylation of p38, MAPKAP2, ERK1/2, CREB and S6 in response to atherosclerotic plasma. To identify plasma cytokines responsible for this effect, we measured a panel of 41 cytokines and identified CCL5, CXCL10 (IP-10), CXCL1 (GRO), PDGF-AA and PDGF-BB as the most differentially expressed in atherosclerotic vs. healthy plasma. PhosphoCyTOF analysis showed that only CCL5 reproduced the phosphorylation pattern induced by atherosclerotic plasma in monocytes, an effect that was completely inhibited by a CCL5 blocking antibody (Fig. 1). These results suggest that CCL5 in plasma of patients with atherosclerotic disease drives specific innate immune cell signaling functions that mark the inflammatory response in atherosclerotic disease.

This paper deals with the archaeometric characterization of the bricks belonging to Tol-a Ajori Gate, one of the most important excavated sites on the Iranian plateau (Fars, Iran), close to the World Cultural Heritage of Persepolis. The archaeological excavations were carried out between 2011 and 2016 and brought to light a monumental building. The wall of the structure is built with mud and fired bricks sometimes glazed that are very similar to the elements of Babylon's Ishtar Gate. Several investigations were carried out on the bricks in order to investigate the technology process and to compare their composition with local clays, as potential raw materials collected nearby the archaeological site. The brick samples were investigated using different analytical techniques (Optical Microscopy, XRD, XRF, SEM-EDX, FT-IR/ATR, TGA, STA and Micro-Raman) to point out differences in chemical and mineralogical composition. Raw clay samples were submitted to XRD, XRF, SEM-EDX and FT-IR/ATR analyses. A wide homogeneity is present for all the considered bricks: Ca-rich clays with quartz-rich temper were used, this possibly suggesting a common raw material origin. Firing temperatures interval was estimated around 850–900 °C. A multivariate data treatment (PCA and HCA analysis) was applied to the XRF data set acquired for both clays and bricks. PCA suggests that Polvar alluvial clays could be the source raw material for mostly of Tol-e Ajori's bricks and more than one clay deposit was probably used.

This paper presents the results of a comprehensive diagnostic investigation carried out on five paintings (three wood panels and two paintings on canvas) by Lorenzo Lotto, one of the most significant artists of the Italian Renaissance in the first half of 16th century. The paintings considered belong to 1508-1522 period, corresponding to the most significant years of Lotto's evolution. A wide array of non-invasive (reflectance spectrometry and X-ray fluorescence) and micro-invasive analytical techniques (optical microscopy, scanning electron microscopy with energy dispersive spectroscopy, micro-FTIR spectroscopy, micro-Raman spectroscopy, gas chromatography coupled with mass spectrometry and high performance liquid chromatography coupled with photodiode array detection and mass spectrometry) were applied in order to provide a large set of significant data, limiting as much as possible the sampling. This study has proved that Lotto's painting palette was typical of Venetian practice of that period, but some significant peculiarities emerged: the use of two kinds of red lakes, the addition of calcium carbonate and colourless powdered glass, the latter frequently found in pictorial and ground layers. Moreover, the integrated investigation showed that Lotto's technique was sometimes characterized by the use of coloured priming and multi-layer sequences with complex mixtures. Chromatographic analyses allowed to identify in all specimens: azelaic, palmitic and stearic acids, generally referring to the presence of drying oils. The extension of additional non-invasive examination to about 50 paintings by the same author, spanning from 1505 to around 1556, helped to verify the evolution in the use of some pigments, such as the yellow ones, where Pb-Sb yellow was used alongside Pb-Sn yellow.

The BCL6 proto-oncogene encodes a transcriptional repressor that is required for the germinal center (GC) reaction and is implicated in lymphomagenesis. BCL6 protein stability is regulated by F-box protein 11 (FBXO11)–mediated ubiquitination and degradation, which is impaired in ∼6% of diffuse large B-cell lymphomas that carry inactivating genetic alterations targeting the FBXO11 gene. In order to investigate the role of FBXO11 in vivo, we analyzed GC-specific FBXO11 knockout mice. FBXO11 reduction or loss led to an increased number of GC B cells, to an altered ratio of GC dark zone to light zone cells, and to higher levels of BCL6 protein in GC B cells. B-cell receptor–mediated degradation of BCL6 was reduced in the absence of FBXO11, suggesting that FBXO11 contributes to the physiologic downregulation of BCL6 at the end of the GC reaction. Finally, FBXO11 inactivation was associated with the development of lymphoproliferative disorders in mice.

The restoration of the wooden statue of Madonna of Montserrat at the Diocesan Museum of Palermo was preceded by a series of chemical-physical and biological investigations which have allowed a better knowledge of the work. In particular the following analyses have been performed on fragment of original material, sampled near the gaps of the wooden statue,: • observations of cross sections to the reflected light Optical Microscope (OM) to identify the stratigraphy and the pictorial materials; • SEM (Scanning Electron Microscopy) observations on cross sections and analysis in microprobe with Energy Dispersive Spectroscopy (EDS) for structural and chemical analysis of the single pictorial layers; • X-Rray Diffractometry (XRD) on dust samples to identify the principal mineralogical composition of plasters and pictorial layers; • Fourier Transform - Infrared Spectroscopy (FT-IR) for the characterization of plasters and pictorial layers; • Time of Flight - Secondary Ions Mass Spectometry (ToF-SIMS) for the elementary analysis of the pictorial material; • microscopic (SEM), microbiological (in vitro crops) and molecular (PCR, Polymerase Chain Reaction) investigations for the evaluation of the biological decay. The obtained results have given information both on the executive techniques of the support and the pictorial film and on the conservation state of the work.

Dissemination of Della Robbia glazed terracotta in the Marche (Italy) region started from the third decade of the 16th century. Numerous altarpieces, some of which no longer exist, document this artistic production. The protagonists of this diffusion phase were two of Andrea Della Robbia’s sons, Marco (Fra Mattia) and Francesco (Fra Ambrogio). This paper shows the results of the scientific investigations carried out on constitutive materials of different altarpieces located in South Marche belonging to the Fra Mattia’s production: the Coronation of Virgin between Saints Rocco, Sebastian, Peter martyr and Antonio abbot, dated back to 1527–1530, located in the collegiate church of S. Maria Assunta in Montecassiano; the Annunciation, dated back to 1520, placed in the church of S. Maria del Soccorso in Arcevia; the fragmentary Crowned Madonna and saints altarpiece, probably realized after 1531, today preserved in Civic Museum of Ripatransone. The first altarpiece was made in Montecassiano using two different assembling or production techniques: the external part of the lunette and the pillar strips are made of glazed polychrome terracotta, while the altar step and the internal part are an interesting and uncommon example of polychrome painted terracotta. The provenance of the glazed Arcevia altarpiece is not clear yet: some historians hypothesize a local manufacture of Fra Mattia and some others a Roman or Florentine production. The remaining parts of Ripatransone altarpiece are partially glazed and partially not coated perhaps because they were unfinished and not yet painted. Clay body samples collected from the above mentioned altarpieces were investigated using different analytical techniques (OM, XRD, XRF, PIXE) to point out differences in chemical and mineralogical composition and to determine if the altarpieces were made by using local raw clay materials or other clays from Tuscany or Campania as in the Della Robbia previous production. A comparison has also been made with literature data on the Della Robbia terracotta masterpieces. From the chemical point of view, the clay bodies show a good compositional homogeneity and result calcium and iron-rich according with the raw local materials. The presence of gehlenite, pyroxenes, and hematite and the incomplete decomposition of clay minerals indicate that firing for all different terracotta parts occurred in a thermal range between 800 and 950 °C, mostly in oxidizing conditions.

During the last restoration (2008-2011) of the polychrome terracotta altarpiece called Coronation of Virgin between Saints Rocco, Sebastian, Peter martyr and Antonio abbot, located in the collegiate church of S. Maria Assunta in Montecassiano (Macerata, Italy), scientific investigations were carried out to acquire detailed information about the painting technique. The identification of materials allowed a correct restoration. The altarpiece is almost entirely realized by Marco della Robbia (Fra Mattia), dates back to the first half of the XVI century and represents an interesting example of painted terracotta produced by using two different techniques: glazed polychrome terracotta and the "cold painting" technique. The characterization of the samples' material constituents was obtained by analysing the cross-sections and the fragments by different techniques (optical, SEM-EDS and ATR-FTIR microscopy as well as GC-MS), as the real nature of a component is often difficult to assess with one single technique. The optical microscope examination of paint cross-sections shows the presence of many layers, indicating the complexity of the paint stratigraphic morphologies. The original polychromy of della Robbia's masterpiece is constituted of cinnabar, red lake, red lead, orpiment, red ochre, lead white, lead tin yellow, green earth and raw umber. Two different types of gilding technique have been distinguished. The first one presents a glue mordant, and the second one shows an oil mordant composed by a mixture of red lead, red ochre, cinnabar and orpiment. The GC-MS analysis allowed the characterisation of linseed oil and a mixture of animal glue and egg as binding media stratigraphically located by the use of ATR-FTIR mapping microscopy. The analytical results of the painted terracotta integrated investigations show that original technique adopted is characterised by the application of pigments in an oil-binding medium directly applied on the substrates, probably treated with oil and animal glue. A large number of overpaintings above the original scheme of polychromy was found, which could be ascribed to almost three different interventions; the absence of modern pigments suggests that they could be realized long ago.

A study has been performed on the Cretaceous to Early Miocene succession of the Vrancea Nappe (Outer Carpathians, Romania), based on field reconstruction of the stratigraphic record, mineralogical-petrographic and geochemical analyses. Extra-basinal clastic supply and intra-basinal autochthonous deposits have been differentiated, appearing laterally inter-fingered and/or interbedded. The main clastic petrofacies consist of calcarenites, sub-litharenites, quartzarenites, sub-arkoses, and polygenic conglomerates derived from extra-basinal margins. An alternate internal and external provenance of the different supplies is the result of the paleogeographic re-organization of the basin/margins system due to tectonic activation and exhumation of rising areas. The intra-basinal deposits consist of black shales and siliceous sediments (silexites and cherty beds), evidencing major environmental changes in the Moldavidian Basin. Organic-matter-rich black shales were deposited during anoxic episodes related to sediment starvation and high nutrient influx due to paleogeographic isolation of the basin caused by plate drifting. The black shales display relatively high contents in sub-mature to mature, Type II lipidic organic matter (good oil and gas-prone source rocks) constituting a potentially active petroleum system. The intra-basinal siliceous sediments are related to oxic pelagic or hemipelagic environments under tectonic quiescence conditions although its increase in the Oligocene part of the succession can be correlated with volcanic supplies. The integration of all the data in the “progressive reorientation of convergence direction” Carpathian model, and their consideration in the framework of a foreland basin, led to propose some constrains on the paleogeographic-geodynamic evolutionary model of the Moldavidian Basin from the Late Cretaceous to the Burdigalian. This research was supported by Urbino University grant (responsible F. Guerrera), Italy; CGL2009-09249 and CGL2011-30153-CO2-02 research projects (Spanish Ministry of Education and Science), Research Groups and projects of the Generalitat Valenciana and from Alicante University (CTMA-IGA Spain); Research Contr. IDEI 436/01.10.2007 (CNCSIS-Romania).

In the frame of an extensive research project concerning the study of archaeological finds from the sea of Pantelleria Island (Sicily, Italy), about two hundred Punic, Greek-Italic, and Roman amphorae have been examined. In particular, thirty five Punic amphorae belonging to six different typologies of the second century BC have been studied. They were probably produced in that Punic-Tunisian area comprising Carthage and other Punic sites nearby the Sahel area. These ceramic artifacts were recovered from shipwrecks dating back to the II century BC, belonging to a shipload, i.e. associated with Greek-Italian amphorae (first half of the second century BC) and with Roman- Tyrrhenian amphorae (second half of the second century BC). Selected amphorae underwent archaeometric studies which are aimed at identifying their origin, at validating the archaeological hypothesis, at identifying the production technology, and at studying their conservation status. Results obtained allowed to recognize three ceramic-body groups characterized by different relative distributions of grain size fractions. Furthermore chemical composition results show some analogies with sherds from Carthage. Diatoms, algae and bryozoa encrustations have been identified as well, together with surface chromatic alterations (i.e. black areas), probably ascribable to chemical reduction processes, due to the activity of sulphur- bacteria., Dans le contexte d'un vaste projet de recherche concernant le matériel archéologique de Pantelleria, on a étudié près de deux cents amphores puniques, gréco-italiques et romaines. En particulier on a sélectionné trente-cinq amphores puniques qu'on associe à six typologies du IIème siècle av. J.-C. (Torres, 1996) produites sans doute dans la région punique-tunisienne comprenant Carthage et les centres puniques de la côte aux environs de la région du Sahel. Il s'agit de produits céramiques récupérés dans des épaves du IIème siècle av. J.-C, qui appartiennent à une charge de genre mixte, c'est-à-dire associés à d'autres amphores gréco-italiques (première moitié du IIème siècle av. J.-C.) et à des amphores romaines tyrrhénéennes (seconde moitié du IIème siècle av. J.-C). Le groupe d'amphores sélectionnées a été soumis à des études archéométriques afin d'identifier leur origine et de confirmer, éventuellement, les hypothèses archéologiques, pour identifier la technologie de production et pour connaître leur état de conservation. Les résultats de ces recherches ont permis de créer trois groupes de pâte caractérisés par différentes distributions des fractions granulomètrique. Les résultats de l'analyse chimique montrent des similitudes avec les obtenues sur les matériaux céramiques de Carthage. De plus, on a mis en évidence des incrustations de diatomées, algues et bryozoaires, ainsi que des altérations superficielles de la pâte de genre chromatique (noircissements) qu'on peut ramener à une activité de réduction de la part de sulphobactéries., Amadori Maria Letizia, Baldassari Roberta, Lanza Stefania, Maione Michela, Penna Antonella, Acquaro Enrico. Archaeometric study of punic amphorae from the underwater recoveries of Pantelleria Island (Sicily).. In: Revue d'Archéométrie, n°26, 2002. pp. 79-91.

The walls of the Oratorio of San Giovanni Battista in Urbino are decorated with outstanding mural paintings dating back to the 15th century. Due to degradation processes that have occurred in the past years, such paintings require a conservative restoration project. In order to evaluate reasons of the decay, some scientific studies have been performed. They consist of macroscopic observations and chemical (EDS), morphological (SEM) and mineralogical (XRD) analyses of samples both from the original preparatory layers under the painted layers and from the restored plasters at the surbase of the wall. In addition, environmental studies have been performed to verify microclimatic conditions of the church in which the mural paintings are located. Finally, a conservative restoration project was proposed.

The aim of this study is to setup a first chemical database that could represent the starting point for a reliable classification method to discriminate between Archaic Phoenician and Punic pottery on the base of their chemical data. This database up to now can discriminate between several different areas of production and provenance and can be applied also to unknown ceramic samples of comparable age and production areas. More than 100 ceramic fragments were involved in this research, coming from various archaeological sites having a crucial importance in the context of the Phoenician and Punic settlement in central and western Mediterranean: Carthage (Tunisia), Toscanos (South Andalusia, Spain), Sulci, Monte Sirai, Othoca, Tharros (Sardinia, Italy) and Pithecusa (Campania, Italy). Since long-time archaeologists hypothesised that Mediterranean Archaic Phoenician and Punic pottery had mainly a local or just a regional diffusion, with the exception of some particular class like transport amphorae. To verify the pottery provenance, statistical analyses were carried out to define the existence of different ceramic compositional groups characterised by a local origin or imported from other sites. The existing literature data are now supplemented by new archaeometric investigations both on Archaic Phoenician ceramics and clayey raw materials from Sardinia. Therefore, diffractometric analyses, optical microscopy observations and X-ray fluorescence analyses were performed to identify the mineralogical and chemical composition of Othoca ceramics and clayey raw material. The obtained results were then compared with own literature data concerning Phoenician and Punic pottery in order to find features related to the different ceramic productions and their provenance. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were also performed on the chemical compositional data in order to discriminate ceramic groups. A very complex situation was found: imported ceramics coming from Carthage, with a large-scale distribution, were found together with a predominant local production pottery. The archaeometric results demonstrate that historical and typological approach has to be supported by scientific analyses to better understand local or Mediterranean exchanges.