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 landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

Alpha-protein kinase 3 (ALPK3)-truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy.

AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. METHODS AND RESULTS : In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.01, 95% confidence interval (CI) 7.89-29.74, P < 8.36e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP-), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP- and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP- and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. CONCLUSIONS : Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

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 approach for the characterization of ancient Roman coins in orichalcum

A selected number of Roman orichalcum coins, from private collections, have been studied. Numismatic analysis indicates that (Crawford, 1974; Sutherland, 1984) they are asses, sestertius and dupondium, minted by Julius Caesar, Augustus and Claudius. The aim of this study was to disclose the chemical composition of the orichalcum alloy, the nature of the patina and corrosion products; orichalcum is an ancient copper based alloy with a variable percentage of zinc (Craddock, 1978). With this aim a multi-analytical approach was involved, i.e. X-ray fluorescence (XRF), scanning electron microscope (SEM-EDS), electron micro probe analyser (EMPA). In particular, XRF analysis was performed on different spots of coins’ surfaces to have information about the chemical composition of the external layers. SEM-EDS analysis allowed to investigate alloy’s microtexture (e.g. segregation micro-domains) and to obtain morphological information. In addition, X-ray maps, acquired across section of coins, give information about elemental distribution inside the alloy; whereas EMPA analysis permits a quantitative chemical composition of major, minor and trace elements composing this ancient alloy. All these techniques confirmed that copper and zinc are the main components of the coins. Other metals, i.e. Fe, Pb, Sn, Co, Ni, As, Sn, Sb and Bi, were also found in the alloy. These elements can provide information about sourcing raw materials sites. Si, S, Cl, K and Ca were found on the surfaces, being contaminant from the soil. Quantitative analysis with microprobe permitted to evaluate the different percentage of Cu and Zn in all the samples. The use of invasive technique (EMPA) was necessary to quantify the abundances of each elements composing the original alloy, thus eliminating soil contaminants and alteration product of the layers developed through time on surfaces. These results, could contribute to fill the lack of knowledge about the orichalcum alloy

A shared haplotype for dentatorubropallidoluysian atrophy (DRPLA) in Italian families testifies of the recent introduction of the mutation

To clarify the population history of dentatorubropallidoluysian atrophy (DRPLA) in Italy and to date back the introduction of the mutation, we reconstructed extended haplotypes flanking the CAG repeat in 10 patients of Italian ancestry, analyzing their similarity/dissimilarity as a function of distance from the CAG repeat. Our aim was to compare the hypothesis of a single, recent genealogy connecting all the observed haplotypes with the alternative hypothesis of multiple introductions by more distantly related haplotypes from outer sources. Polymorphic DNA markers were chosen to cover a region of 153 kb flanking the CAG repeat, that is, informative for dating the age of the DNA segment unaffected by recombination. In all patients, an expansion of the ATN1 CAG segment was confirmed residing onto the same narrow haplotype described to be associated with the CAG expansion in the Japanese and Portuguese populations. We also observed the disruption of the DRPLA haplotype at longer distances, on both sides of the CAG. Our results are compatible with a single founder in the last 600 years, most likely before the last 270 years. These estimates for the Sicilian population largely overlap a period in which the Japanese haplotype with the DRPLA mutation could have been introduced by the Portuguese maritime travelers. © 2014 The Japan Society of Human Genetics All rights reserved 1434-5161/14

Solid-state electrochemical characterization of emissions and authorities producing Roman brass coins

The voltammetry of immobilized particles (VIMP) is applied to describe the solid state electrochemistry of brass. This methodology, which involves sampling at the nanogram level, is applied to discriminate mints/authorities producing different Roman monetary emissions covering since the Republic (88 BCE) to Domitianus (55–96 CE) Upon attachment to graphite electrodes in contact with aqueous acetate buffer at pH 4.75, well defined voltammetric responses were obtained centered on Cu- and Zn-localized signals whose intensity can be correlated to EMP data, being sensitive to the contents of Zn (15–30 wt.%) and Sn (0.01–1.1 wt.%). Voltammetric data, combined with ATR-FTIR and FIB-FESEM/EDS, yield information on the structure of the metal patina and permit to characterize different monetary emissions being able, in the case of Augustus’ sestertii, to discriminate between the productions from different monetary authorities

Substance P downregulates expression of the high affinity IgE receptor (Fc\u3b5RI) by human mast cells

The effect of the neuropeptide substance P (SP) on human mast cell (MC) phenotype is poorly understood. In this study, SP effects on human MC expression of the high affinity IgE receptor (Fc\u3b5RI) were characterized. SP downregulated expression of Fc\u3b5RI mRNA and protein by approximately 50% and in a concentration dependent manner, the effect was partially mediated by engagement of the neurokinin-1 receptor (NK1R) and resulted in reduced mast cell activation. Sensitization of MC with IgE prior to SP exposure protected MC from SP-mediated Fc\u3b5RI downregulation. SP release may inhibit MC responses to allergens and these results may have implications in neuroinflammatiion and stress.Peer reviewed: YesNRC publication: Ye