Microstructure and chemical composition of Roman orichalcum coins emitted after the monetary reform of Augustus (23 B.C.)

A collection of ancient Roman orichalcum coins, i.e., a copper-zinc alloy, minted under the reigns from Caesar to Domitianus, have been characterised using scanning electron microscopy (SEM-EDS) and electron microprobe analysis (EMPA). We studied, for the first time, coins emitted by Romans after the reforms of Augustus (23 B.C.) and Nero (63-64 A.D). These coins, consisting of asses, sestertii, dupondii and semisses, were analysed using non- and invasive analyses, aiming to explore microstructure, corrosive process and to acquire quantitative chemical analysis. The results revealed that the coins are characterized by porous external layers, which are affected by dezincification and decuprification processes. As pictured by the X-ray maps, the elemental distribution of Cu and Zn shows patterns of depletion that in some cases penetrate in deep up to 1 mm. The composition of the un-corroded nucleus is a Cu-Zn alloy containing up to 30% of Zn, typical of coins produced via cementation process

Genetic Immunization with CDR3-Based Fusion Vaccine Confers Protection and Long-Term Tumor-Free Survival in a Mouse Model of Lymphoma

Therapeutic vaccination against idiotype is a promising strategy for immunotherapy of B-cell malignancies. We have previously shown that CDR3-based DNA immunization can induce immune response against lymphoma and explored this strategy to provide protection in a murine B-cell lymphoma model. Here we performed vaccination employing as immunogen a naked DNA fusion product. The DNA vaccine was generated following fusion of a sequence derived from tetanus toxin fragment C to the VHCDR3109−116 epitope. Induction of tumor-specific immunity as well as ability to inhibit growth of the aggressive 38C13 lymphoma and to prolong survival of vaccinated mice has been tested. We determined that DNA fusion vaccine induced immune response, elicited a strong protective antitumor immunity, and ensured almost complete long-term tumor-free survival of vaccinated mice. Our results show that CDR3-based DNA fusion vaccines hold promise for vaccination against lymphoma

Lack of association between genetic variants in the mannose-binding lectin 2 (MBL2) gene and HPV infection

Genetic variants in the immunomodulatory gene mannose-binding lectin 2 (MBL2), were associated with risk, severity, and frequency of viral infections. In a case-control setting, we investigated the association of MBL2 functional polymorphisms with Human Papillomas Virus (HPV) infection. No differences between cases (HPV+) and controls (HPV-) were found in the distribution of each single genotypes or allele. Haplotype analysis did not show any difference between HPV+ and HPV- groups

High Specificity of Quantitative Methylation-Specific PCR Analysis for MGMT Promoter Hypermethylation Detection in Gliomas

Normal brain tissue from 28 individuals and 50 glioma samples were analyzed by real-time Quantitative Methylation-Specific PCR (QMSP). Data from this analysis were compared with results obtained on the same samples by MSP. QMSP analysis demonstrated a statistically significant difference in both methylation level (P = .000009 Mann Whitney Test) and frequencies (P = .0000007, Z-test) in tumour samples as compared with normal brain tissues. Although QMSP and MSP showed similar sensitivity, the specificity of QMSP analysis was significantly higher (93%; CI95%: 84%–100%) as compared with MSP (64%; 95%CI: 46%–82%). Our results suggest that QMSP analysis may represent a powerful tool to identify glioma patients that will benefit from alkylating agents chemotherapy

Characterizing the tumor microenvironment in rare renal cancer histological types

The tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high-grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann-Whitney and Kruskal-Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53-4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22-5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42-3.9]). Spatial analysis revealed CD3+ T-cell and CD20+ B-cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance-dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies

Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development

Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). Based on bulk and single-cell RNA sequencing, we observed 13 TPs during transition of normal PCs throughout SLOs, PB, and BM. We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation–related TPs are upregulated in AL. Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies

The genomic and epigenomic evolutionary history of papillary renal cell carcinomas

From Springer Nature via Jisc Publications RouterHistory: received 2019-09-11, accepted 2020-05-10, registration 2020-05-12, pub-electronic 2020-06-18, online 2020-06-18, collection 2020-12Publication status: PublishedFunder: This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHSAbstract: Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of spatial features of clonal expansion, which shows congruent patterns of genomic and epigenomic evolution. In contrast to previous studies of ccRCC, in pRCC, driver gene mutations and most arm-level somatic copy number alterations (SCNAs) are clonal. These findings suggest that a single biopsy would be sufficient to identify the important genetic drivers and that targeting large-scale SCNAs may improve pRCC treatment, which is currently poor. While type 1 pRCC displays near absence of structural variants (SVs), the more aggressive type 2 pRCC and the rarer subtypes have numerous SVs, which should be pursued for prognostic significance

Study of dezincification in orichalcum Roman coins

A group of orichalcum Roman coins, from private collections, have been studied for this research. Numismatic examination indicated that they are asses, sestertium and dupondius, minted from Julius Caesar to Nero. Orichalcum is an ancient copper based alloy with a variable percentage of zinc. The aim of this study was to investigate the process of dezincification from the external layers to the core of the samples. Furthermore, the research was aimed to disclose the real chemical composition of the orichalcum alloy. In scientific literature is reported that the percentage of zinc in the alloy is related to the age in which the coin was minted. The samples were firstly analysed by means of X-ray fluorescence spectroscopy to obtain information about the elemental composition (qualitative method) of the external layers. This non-invasive analysis allowed to discriminate coins made with zinc alloy from the bronze ones. Because of the degradation of the external layers of orichalcum and the dezincification; process, other analysis were also carried out on cross section of some zinc based samples, such as scanning electron microscope (SEM-EDS) and electron micro probe analyser (EMPA). The first technique was useful to investigate the depth of corrosion and dezincification processes and to examine alloy’s microtexture (e.g. segregation micro-domains); the second one permitted a quantitative chemical analysis of major, minor and trace elements composing this ancient alloy, understanding the difference of chemical compositions between the unaltered core and the altered layers. All the techniques performed both on the cross sections and on the external layers of the coins revealed that other metals, i.e. Fe, Sn, Pb, As, were also present in the alloy. Finally, results were chronologically ordered and compared with literature’s data

A multi-analytical study of architectural fragments from the Marzamemi II “Church Wreck”

A minero-petrographic and physico-chemical investigation was carried out on several archaeological samples of green architectural stone material from the Marzamemi II site (Sicily). The samples belonged to a Byzantine wreck sunk off the cost of Marzamemi, also known as “Church Wreck”. In addition, geological samples from Larisa quarries in Thessaly, Greece, were analysed, with the aim of identifying the area of origin of the geo-materials selected for the realization of the architectural decorations. Optical Microscopy (OM), Scanning Electron Microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDS), X-Ray Powder Diffraction (XRPD), and Raman spectroscopy permitted to define the material as Green Thessalian stone, named also as verde antico or lapis atracius in the recent times. From a mineralogical point of view, the samples can be defined as ophicarbonate breccia composed of inhomogeneous material that consists of mixtures of serpentine minerals and calcite. Accessory minerals such as magnetite and chromite were also present both in archaeological and quarry samples. The archaeological samples were also studied to define their state of conservation and their degree of degradation caused by their stay underwater for several centuries. Physical characterization of porosity was obtained by Nuclear Magnetic Resonance (NMR) to set the ground for the future conservation procedures. Indeed, only a wide characterization which consider the material degradation, the material composition and the microclimate is fundamental to address the conservation of such important remains