Chemical evidence for the persistence of wine production and trade in Early Medieval Islamic Sicily

As a high-value luxury commodity, wine has been transported across the Mediterranean since the Bronze Age. The wine trade was potentially disrupted during political and religious change brought about by Islamization in the Early Medieval period; wine consumption is prohibited in Islamic scripture. Utilizing a quantitative criterion based on the relative amounts of two fruit acids in transport amphorae, we show that wine was exported from Sicily beyond the arrival of Islam in the ninth century, including to Christian regions of the central Mediterranean. This finding is significant for understanding how regime change affected trade in the Middle Ages. We also outline a robust analytical approach for detecting wine in archaeological ceramics that will be useful elucidating viniculture more broadly.Although wine was unquestionably one of the most important commodities traded in the Mediterranean during the Roman Empire, less is known about wine commerce after its fall and whether the trade continued in regions under Islamic control. To investigate, here we undertook systematic analysis of grapevine products in archaeological ceramics, encompassing the chemical analysis of 109 transport amphorae from the fifth to the eleventh centuries, as well as numerous control samples. By quantifying tartaric acid in relation to malic acid, we were able to distinguish grapevines from other fruit-based products with a high degree of confidence. Using these quantitative criteria, we show beyond doubt that wine continued to be traded through Sicily during the Islamic period. Wine was supplied locally within Sicily but also exported from Palermo to ports under Christian control. Such direct evidence supports the notion that Sicilian merchants continued to capitalize on profitable Mediterranean trade networks during the Islamic period, including the trade in products prohibited by the Islamic hadiths, and that the relationship between wine and the rise of Islam was far from straightforward.All study data are included in the article and/or SI Appendix

The new small tyrosine-kinase inhibitor ARQ531 targets acute myeloid leukemia cells by disrupting multiple tumor-addicted programs

Tyrosine kinases have been implicated in promoting tumorigenesis of several human cancers. Exploiting these vulnerabilities has been shown to be an effective anti-tumor strategy as demonstrated for example by the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, for treatment of various blood cancers. Here, we characterize a new multiple kinase inhibitor, ARQ531, and evaluate its mechanism of action in preclinical models of acute myeloid leukemia. Treatment with ARQ531, by producing global signaling pathway deregulation, resulted in impaired cell cycle progression and survival in a large panel of leukemia cell lines and patient-derived tumor cells, regardless of the specific genetic background and/or the presence of bone marrow stromal cells. RNA-seq analysis revealed that ARQ531 constrained tumor cell proliferation and survival through Bruton's tyrosine kinase and transcriptional program dysregulation, with proteasome-mediated MYB degradation and depletion of short-lived proteins that are crucial for tumor growth and survival, including ERK, MYC and MCL1. Finally, ARQ531 treatment was effective in a patient-derived leukemia mouse model with significant impairment of tumor progression and survival, at tolerated doses. These data justify the clinical development of ARQ531 as a promising targeted agent for the treatment of patients with acute myeloid leukemia

Sicily in Transition : Interim report of investigations at Castronovo di Sicilia 2016

La città di Castronovo di Sicilia (PA) e i suoi dintorni sono attualmente oggetto di ricerche archeologiche condotte dalle università di York, Roma e Lecce in collaborazione con la Soprintendenza per i Beni culturali e ambientali di Palermo e con il sostegno del Comune di Castronovo. Quattro diversi insediamenti sono stati indagati per mezzo di prospezioni e scavi. Sul Monte Kassar, interpretabile, allo stato attuale delle ricerche, come una fortezza bizantina dell’ VIII–IX secolo, nel 2015 sono state individuate strutture con funzione abitativa all’interno e in appoggio alle fortificazioni, mentre nel 2016 sono stati scavati i resti di una “casaforte” (la cosiddetta “casermetta"). Sul Colle San Vitale, i ruderi delle strutture medievali ancora in piedi sono stati oggetto di una prospezione di alta precisione, come anche la città vecchia di Castronovo, dove anche sono stati individuate e cartografate le acque sotterranee e un sistema di irrigazione. Infine, a Casale San Pietro, nella pianura vicino a Castronovo e sulle rive del fiume Platani, un insediamento esteso di epoca tardoromana e bizantina (orientativamente dei secoli V–VII secolo) è stato parzialmente identificato attraverso prospezioni geofisiche, raccolte di superficie e sondaggi. Nel 2015 e 2016 è stato possibile dimostrare in un’area di scavo (Int 5) che l’insediamento di epoca bizantina (la cosiddetta agro-town) è stato rioccupato da uno di epoca islamica e normanna (IX–XII secolo). L’attuale campagna di ricerche sul Medioevo nel Comune di Castronovo di Sicilia (PA) è stata avviata nel 2014 e proseguita nel 2015. Nel corso del 2016, queste indagini hanno assunto un ruolo centrale nel progetto più ampio finanziato dall’European Research Council (SICTRANSIT). L’obiettivo centrale di questo progetto è di comprendere il carattere delle trasformazioni economiche, ambientali e sociali dell’intera Sicilia tra il VI e il XIII secolo . La relazione che segue presenta i risultati ottenuti nel 2016 a Castronovo nei quattro insediamenti principali e una breve descrizione delle ricerche in corso sulla ceramica, la fauna, e i reperti particolari effettuata dai responsabili delle loro analisi. Infine, si conclude con una valutazione del significato della campagna del 2016 e uno sguardo alle prossime tappe del progetto

New insights into early medieval Islamic cuisine : Organic residue analysis of pottery from rural and urban Sicily

Sicily, during the 9th-12th century AD, thrived politically, economically, and culturally under Islamic political rule and the capital of Palermo stood as a cultural and political centre in the Mediterranean Islamic world. However, to what extent the lifeways of the people that experienced these regimes were impacted during this time is not well understood, particularly those from lesser studied rural contexts. This paper presents the first organic residue analysis of 134 cooking pots and other domestic containers dating to the 9th -12th century in order to gain new insights into the culinary practices during this significant period. Ceramics from three sites in the urban capital of Palermo and from the rural town of Casale San Pietro were analysed and compared. The multi-faceted organic residue analysis identified a range of commodities including animal products, vegetables, beeswax, pine and fruit products in the ceramics, with a complex mixing of resources observed in many cases, across all four sites and ceramic forms. Alongside the identification of commodities and how they were combined, new light has been shed on the patterning of resource use between these sites. The identification of dairy products in calcite wares from the rural site of Casale San Pietro and the absence of dairy in ceramics from the urban centre of Palermo presents interesting questions regarding the role of rural sites in food consumption and production in Islamic Sicily. This is the first time organic residue analysis of ceramics has been used to explore foodways in a medieval multi-faith society and offers new pathways to the understanding of pottery use and resources that were prepared, consumed and combined, reflecting cuisine in different socio-economic environments within the pluralistic population of medieval Sicily

Sicily in transition : new research on early medieval Sicily, 2017-2018

Il testo che segue riguarda la nostra ricerca archeologica sulla Sicilia bizantina, islamica e normanno-sveva e in particolare riporta le ultime scoperte a Castronovo di Sicilia, che includono il riconoscimento di una chiesa del XII-XIII secolo sul Monte Kassar, la continuazione dello scavo a Casale San Pietro e una sintesi delle nuove ricognizioni nelle sue vicinanze. Quest’ultimo sito rimane il focus principale del Progetto ERC sictransit, ma in questa sede diamo anche conto dei primi risultati di un’indagine più ampia, che include una grossa quantità di reperti che provengono da tutta la Sicilia da siti scavati in precedenza (Fig 1). Questi reperti consistino in ceramiche, metalli e vetri assieme a resti umani, animali e vegetali, che vengono analizzati nei laboratori delle università partner del progetto: York, Roma e Lecce. I principali metodi scientifici applicati sono: analisi tipologiche, petrografiche e del contenuto organico delle ceramiche da cucina e da trasporto; degli isotopi stabili e del DNA antico sui resti umani e animali per determinare la dieta e l’ascendenza genetica; infine la identificazione tassonomica e la caratterizzazione isotopica degli insiemi di resti botanici per comprendere le loro relazioni con il clima e con le diverse fasi storiche. Sictransit combina quindi ricerche archeologiche, bioarcheologiche e biomolecolari in un unico progetto integrato. Gli obiettivi attesi sono stati suddivisi, per comodità e chiarezza, in tre principali aree di studio, vale a dire: agricoltura (e cibo), scambi e demografia. Infine concludiamo con una valutazione della ricerca svolta sul campo e delle prospettive di indagine dei tre laboratori

Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge

We have previously shown in triple-negative breast cancer (TNBC) models that a triple therapy (TT) including intermittent cyclophosphamide (C), vinorelbine (V), and anti-PD-1 activates antigen-presenting cells (APC) and generates stem like-T cells able to control local and metastatic tumor progression. In the present manuscript, we report the generation of a highly aggressive, anti-PD-1 resistant model of a high-grade, Myc-driven B-cell non-Hodgkin’s lymphoma (NHL) that can be controlled in vivo by TT but not by other chemotherapeutic agents, including cytarabine (AraC), platinum (P), and doxorubicin (D). The immunological memory elicited in tumor-bearing mice by TT (but not by other treatments) can effectively control NHL re-challenge even at very high inoculum doses. TT re-shaped the landscape of circulating innate NK cells and adaptive immune cells, including B and T cells, and significantly reduced exhausted CD4+ and CD8+ TIM3+PD-1+ T cells in the spleens of treated mice

Identifying wine in archaeological pottery? A case study from the Late Antique and Early Medieval Sicily

International audienceWine, an emblematic fermented commodity of the Mediterranean, remains difficult to identify in archaeology, despite being the focus of many investigations (amphora morphology and provenance, aDNA, carpological studies, etc.). While the search for wine biomarkers (particularly tartaric acid) began with the very first attempts of organic residue analysis of archaeological pottery, a wide range of methods have been used with little consensus.In order to study the wine trade in Sicily between Late Antiquity and the Early Middle Ages, and the possible impact of the successive Byzantine and Arab conquests, it was necessary to set up a rigorous methodology, which optimises extraction yields and avoids false positives. The comparative analysis of authentic references and archaeological samples through different approaches revealed the high efficiency of butylation under acidic conditions to extract tartaric acid. The difficulty in understanding the natural origin of other small acids makes their presence in archaeological ceramics misleading. The specificity of tartaric acid in terms of its natural origin was investigated using a context where the grape is not attested (Russian prehistoric potsherds). Analyses showed that in the absence of other archaeological or historical evidence, tartaric acid could only be interpreted as a fruit biomarker. Finally, the analysis of control samples (cooking pots, handles, tiles, sediments) and a large corpus of amphorae produced and imported in Sicily from the 5th to 11th century AD demonstrated the need for tartaric acid quantification and the use of a limit of interpretationto avoid false positives. Based on these methodological developments and the selection of morphologically and petrographicallywell-characterised vessels, it has been possible to demonstrate an unexpected continuity of the exploitation and trade of grapevineproducts from the Late Roman period to the Early Middle Ages in Sicily, in spite of the succession of regimes that have dominatedthe island

Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol.

Journal Article;Lipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications.This work was partly supported by the Fondazione Banco di Sardegna (grant N° 2013.1308, 2014.6035 to L.G.D.), the University of Sassari (Italy), the Sardinia Region (grant N° CRP-59720 to L.G.D.), the Gianfranco del Prete Association “The future: medicine, biology and nanotechnology Award” to L.G.D, the Instituto de Salud Carlos III (FEDER funds, grant N° PI10/02295 to J.A.M), the Consejería de Economía, Innovación y Ciencia (Junta de Andalucía, excellence grant N° (CTS-6568 to J.A.M) and by the grant N° (MAT2013-43922-R).Ye

Cuisine in transition? Organic residue analysis of domestic containers from 9th-14th century Sicily

From the 9th to 14th centuries AD, Sicily experienced a series of rapid and quite radical changes in political regime, but the impact of these regime changes on the lives of the people that experienced them remains largely elusive within the historical narrative. We use a multi-faceted lipid residue approach to give direct chemical evidence of the use of 248 everyday domestic ceramic containers from Islamic and postIslamic contexts in western Sicily to aid our understanding of daily habits throughout this period of political change. A range of commodities was successfully identified, including animal fats, vegetable products, fruit products (potentially including wine) and plant resins. The study highlights the complexity of residues in early medieval Mediterranean society as, in many cases, mixtures of commodities were observed reflecting sequential cooking events and/or the complex mixtures reflective of medieval recipes. However, overall, there were no clear changes in the composition of the residues following the imposition of Norman control over the island and through subsequent periods, despite some differences between urban centers and rural sites. Thus, lending to the idea that post-Islamic populations largely flourished and benefited from the agricultural systems, resources and recipes left by their predecessors