Integrated three-dimensional models for noninvasive monitoring and valorization of the Morgantina silver treasure (Sicily)

The Morgantina silver treasure belonging to the Archaeological Museum of Aidone (Sicily) was involved in a three-dimensional (3-D) survey and diagnostics campaign for monitoring the collection over time in anticipation of their temporary transfer to the Metropolitan Museum of Art in New York for a period of 4 years. Using a multidisciplinary approach, a scientific and methodological protocol based on noninvasive techniques to achieve a complete and integrated knowledge of the precious items and their conservation state, as well as to increase their valorization, has been developed. All acquired data, i.e., 3-D models, ultraviolet fluorescence, x-ray images, and chemical information, will be made available, in an integrated way, within a web-oriented platform, which will present an in-progress tool to deepen existing archaeological knowledge and production technologies and to obtain referenced information of the conservation state before and after moving of the collection from its exposure site

Archaeometric Study of Two Tanagra Type Statuettes of Unknown Provenance to Support Forensic Study

This paper is concerned with a morphological-stylistic and archaeometric study of two small pottery statues, confiscated by the Cosenza Carabinieri Unit for the Protection of Cultural Heritage and Anti-Counterfeiting (Calabria, Italy). The research aimed to establish the authenticity of the artworks and to verify a possible origin from the same workshop manufacturing, by providing indications about the textural features and raw materials used for their production. For these purposes, the analytical approach involved the use of minero-petrographic and physical analysis, as follows: petrographic analysis (OM), X-ray diffraction (XRD) and thermoluminescence tests (TL). The preliminary observation, which highlights differences in the stylistic features of the two statuettes as well as in the color, morphology and distribution of the white-greyish patina, is further confirmed by the TL investigations. The TL test revealed an ancient production only for one of the analyzed finds and the investigations on the raw materials allowed to relate this to a possible local historical-artistic context. The second statuette, on the other hand, is attributable to a modern production as confirmed by TL measurement

TECNICHE NON INVASIVE DI SUPERFICIE E DI VOLUME PER IL MONITORAGGIO STRUTTURALE DELLE SCULTURE MARMOREE

L’analisi delle proprietà strutturali di una scultura in marmo, attraverso l’impiego di tecniche di indagine non invasive da realizzare direttamente in situ, è di fondamentale importanza per la valutazione dello stato di conservazione e, conseguentemente, per il monitoraggio di eventuali fenomeni di degrado che possono compromettere l’integrità dell’opera d’arte. Lo studio condotto sul bassorilievo raffigurante la Madonna con Bambino conservato presso la Cappella del Monastero delle Clarisse Totus Tuus di Gorizia ha permesso di verificare la complementarietà delle informazioni restituite da tecniche di analisi della superficie (acquisizioni in fluorescenza ultravioletta) e tecniche di analisi del volume (tomografia ultrasonica). Le indagini in fluorescenza ultravioletta consentono di individuare e differenziare i materiali (originali, di restauro o di degrado) presenti sulla superficie lapidea. La tomografia ultrasonica, attraverso la stima delle velocità ultrasoniche caratteristiche del materiale, permette di ottenere una caratterizzazione strutturale dell’intero volume dell’opera. Generalmente, tale indagine è associata a un rilievo pacometrico necessario per rilevare la presenza di perni metallici all'interno dell'opera o nel supporto di ancoraggio, anche per interpretare eventuali anomalia riscontrate. Nel caso studio presentato, il modello tomografico ad ultrasuoni ha evidenziato la presenza di piccole zone ad alta velocità correlabili alla presenza di perni metallici e da una zona a maggiore degrado che si concentra nella parte inferiore dell’opera. Le indagini in fluorescenza ultravioletta hanno mostrato la reale estensione della frattura che coinvolge la porzione inferiore del bassorilievo, verificando il perimetro dell’area caratterizzata da un maggior degrado ed evidenziata dall’indagine ad ultrasuoni

Transcriptomics and metabolomics integration reveals redox-dependent metabolic rewiring in breast cancer cells

Rewiring glucose metabolism toward aerobic glycolysis provides cancer cells with a rapid generation of pyruvate, ATP, and NADH, while pyruvate oxidation to lactate guarantees refueling of oxidized NAD+ to sustain glycolysis. CtPB2, an NADH-dependent transcriptional co-regulator, has been proposed to work as an NADH sensor, linking metabolism to epigenetic transcriptional reprogramming. By integrating metabolomics and transcriptomics in a triple-negative human breast cancer cell line, we show that genetic and pharmacological down-regulation of CtBP2 strongly reduces cell proliferation by modulating the redox balance, nucleotide synthesis, ROS generation, and scavenging. Our data highlight the critical role of NADH in controlling the oncogene-dependent crosstalk between metabolism and the epigenetically mediated transcriptional program that sustains energetic and anabolic demands in cancer cells

Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response

Cancer cells, which use more glucose than normal cells and accumulate extracellular lactate even under normoxic conditions (Warburg effect), have been reported to undergo cell death under glucose deprivation, whereas normal cells remain viable. As it may be relevant to exploit the molecular mechanisms underlying this biological response to achieve new cancer therapies, in this paper we sought to identify them by using transcriptome and proteome analysis applied to an established glucoseaddicted cellular model of transformation, namely, murine NIH-3T3 fibroblasts harboring an oncogenic K-RAS gene, compared with parental cells. Noteworthy is that the analyses performed in high-and low-glucose cultures indicate that reduction of glucose availability induces, especially in transformed cells, a significant increase in the expression of several unfolded protein response (UPR) hallmark genes. We show that this response is strictly associated with transformed cell death, given that its attenuation, by reducing protein translation or by increasing cell protein folding capacity, preserves the survival of transformed cells. Such an effect is also observed by inhibiting c-Jun NH2-terminal kinase, a pro-apoptotic signaling mediator set downstream of UPR. Strikingly, addition of N-acetyl-D-glucosamine, a specific substrate for the hexosamine biosynthesis pathway (HBP), to glucose-depleted cells completely prevents transformed cell death, stressing the important role of glucose in HBP fuelling to ensure UPR attenuation and increased cell survival. Interestingly, these results have been fully recognized in a human model of breast cancer, MDA-MB-231 cells. In conclusion, we show that glucose deprivation, leading to harmful accumulation of unfolded proteins in consequence of a reduction of protein glycosylation, induces a UPR-dependent cell death mechanism. These findings may open the way for new therapeutic strategies to specifically kill glycolytic cancer cells

Cancer cell growth and survival as a system-level property sustained by enhanced glycolysis and mitochondrial metabolic remodeling

Systems Biology holds that complex cellular functions are generated as system level properties endowed with robustness, each involving large networks of molecular determinants, generally identified by "omics" analyses. In this paper we describe four basic cancer cell properties that can easily be investigated in vitro: enhanced proliferation, evasion from apoptosis, genomic instability, and inability to undergo oncogene-induced senescence. Focusing our analysis on a K-ras dependent transformation system, we show that enhanced proliferation and evasion from apoptosis are closely linked, and present findings that indicate how a large metabolic remodeling sustains the enhanced growth ability. Network analysis of transcriptional profiling gives the first indication on this remodeling, further supported by biochemical investigations and metabolic flux analysis (MFA). Enhanced glycolysis, down-regulation of TCA cycle, decoupling of glucose and glutamine utilization, with increased reductive carboxylation of glutamine, so to yield a sustained production of growth building blocks and glutathione, are the hallmarks of enhanced proliferation. Low glucose availability specifically induces cell death in K-ras transformed cells, while PKA activation reverts this effect, possibly through at least two mitochondrial targets. The central role of mitochondria in determining the two investigated cancer cell properties is finally discussed. Taken together the findings reported herein indicate that a system level property is sustained by a cascade of interconnected biochemical pathways that behave differently in normal and in transformed cells

Clobetasol promotes neuromuscular plasticity in mice after motoneuronal loss via sonic hedgehog signaling, immunomodulation and metabolic rebalancing

Motoneuronal loss is the main feature of amyotrophic lateral sclerosis, although pathogenesis is extremely complex involving both neural and muscle cells. In order to translationally engage the sonic hedgehog pathway, which is a promising target for neural regeneration, recent studies have reported on the neuroprotective effects of clobetasol, an FDA-approved glucocorticoid, able to activate this pathway via smoothened. Herein we sought to examine functional, cellular, and metabolic effects of clobetasol in a neurotoxic mouse model of spinal motoneuronal loss. We found that clobetasol reduces muscle denervation and motor impairments in part by restoring sonic hedgehog signaling and supporting spinal plasticity. These effects were coupled with reduced pro-inflammatory microglia and reactive astrogliosis, reduced muscle atrophy, and support of mitochondrial integrity and metabolism. Our results suggest that clobetasol stimulates a series of compensatory processes and therefore represents a translational approach for intractable denervating and neurodegenerative disorders