An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes

The Endoplasmatic Reticulum Aminopeptidases ERAP1 and ERAP2 are implicated in a variety of immune and non-immune functions. Most studies however have focused on their role in shaping the HLA class I peptidome by trimming peptides to the optimal size. Genome Wide Association Studies highlighted non-synonymous polymorphisms in their coding regions as associated with several immune mediated diseases. The two genes lie contiguous and oppositely oriented on the 5q15 chromosomal region. Very little is known about the transcriptional regulation and the quantitative variations of these enzymes. Here, we correlated the level of transcripts and proteins of the two aminopeptidases in B-lymphoblastoid cell lines from 44 donors harbouring allelic variants in the intergenic region between ERAP1 and ERAP2. We found that the presence of a G instead of an A at SNP rs75862629 in the ERAP2 gene promoter strongly influences the expression of the two ERAPs with a down-modulation of ERAP2 coupled with a significant higher expression of ERAP1. We therefore show here for the first time a coordinated quantitative regulation of the two ERAP genes, which can be relevant for the setting of specific therapeutic approaches

AIF-1 gene does not confer susceptibility to Behçet's disease: Analysis of extended haplotypes in Sardinian population

Background BehcEet's disease (BD) is a polygenic immune-mediated disorder characterized by a close association with the HLA-B∗51 allele. The HLA region has a strong linkage disequilibrium (LD) and carries several genetic variants (e.g. MIC-A, TNF-α genes) identified as associated to BD because of their LD with HLA-B∗51. In fact, the HLA-B∗51 is inherited as part of extended HLA haplotypes which are well preserved in patients with BD. Sardinian population is highly differentiated from other Mediterranean populations because of a distinctive genetic structure with very highly preserved HLA haplotypes. Patients and methods In order to identify other genes of susceptibility to BD within the HLA region we investigated the distribution of human Allograft Inflammatory Factor-1 (AIF-1) gene variants among BD patients and healthy controls from Sardinia. Six (rs2736182; rs2259571; rs2269475; rs2857597; rs13195276; rs4711274) AIF-1 single nucleotide polymorphisms (SNPs) and related extended haplotypes have been investigated as well as their LD within the HLA region and with HLA-B∗51. Overall, 64 BD patients, 43 HLA-B∗51 positive healthy controls (HC) and 70 random HC were enrolled in the study. Results HLA-B∗51 was the only allele with significantly higher frequency (pc = 0.0021) in BD patients (40.6%) than in HC (9.8%). The rs2259571TAIF-1 variant had a significantly reduced phenotypic, but not allelic frequency in BD patients (72.1%; pc = 0.014) compared to healthy population (91.3%). That was likely due to the LD between HLA-B∗51 and rs2259571G(pc= 9E-5), even though the rs2259571Gdistribution did not significantly differ between BD patients and HC. Conclusion No significant difference in distribution of AIF-1 SNPs haplotypes was observed between BD patients and HC and between HLA-B∗51 positive BD patients and HLA-B∗51 positive HC. Taken together, these results suggest that AIF-1 gene is not associated with susceptibility to BD in Sardinia

Free and Enzymatically Hydrolysed Volatile Compounds of Sweet Wines from Malvasia and Muscat Grapes (Vitis vinifera L.) Grown in Sardinia

The aroma of Muscat of Sorso-Sennori and Malvasia di Bosa wines obtained from grapes grown in Sardinia wasevaluated by instrumental analysis. Gas chromatography/mass spectrometry was used to identify and quantifythe content of free and bound volatile compounds. The odour activity value (OAV) was also calculated. Higheralcohols and esters were quantitatively the largest group of free volatile compounds in both wines, while terpeneswere the main class of bound volatiles. A total of 52 free and 26 bound volatiles were detected. Malvasia di Bosasweet wine had a higher content of alcohols, esters and acids in comparison to Muscat of Sorso-Sennori, whichwas richer in some terpenes, like nerol, geraniol and geranic acid, and also in bound volatile compounds. Atotal of 12 compounds were above the OAV. The main aroma-active compounds of Muscat were 3-methylbutylacetate (banana), ethyl octanoate and hexanoate (fruity), and linalool (flowery), Malvasia wine was characterisedparticularly by ethyl octanoate and by 3-methylbutyl acetate

Effect of Bottle Storage on Colour, Phenolics and Volatile Composition of Malvasia and Moscato White Wines

The effect of bottle storage on the colour, phenolics and volatile composition of Malvasia and Muscat winesobtained from grapes grown in Sardinia was evaluated. Colour was evaluated by UV-VIS spectrophotometryand by tristimulus colorimetry. Polyphenols were analysed by UV-VIS spectrophotometry and HPLCDAD.GC/MS was used to identify and quantify the content of free and bound volatile compounds. Asexpected, the absorbance values at 420 nm increased significantly for both wines during storage, due tooxidative browning, while difference in colour (DE*) from the beginning of storage and after 18 monthswas more intense in the Muscat wine than in the Malvasia wine. A significant decrease was observed indifferent phenolic compounds over time, especially in the Malvasia wine. In-bottle storage for 18 monthsat 20°C in the dark resulted in a significant decrease in all the classes of free and bound volatiles. Thesefinding enhance knowledge regarding the effects of bottle storage on Muscat and Malvasia wines. Thisis of interest because, rather surprisingly, this topic has been poorly investigated in relation to these twovarieties

Integrated geophysical and aerial sensing methods for archaeology: A case history in the Punic site of Villamar (Sardinia, Italy)

In this paper, the authors present a recent integrated survey carried out on an archaeological urban site, generally free of buildings, except some temporary structures related to excavated areas where multi-chamber tombs were found. The two methods used to investigate this site were thermal infrared and ground penetrating radar (GPR). The thermography was carried out with the sensor mounted under a helium balloon simultaneously with a photographic camera. In order to have a synthetic view of the surface thermal behavior, a simplified version of the existing night thermal gradient algorithm was applied. By this approach, we have a wide extension of thermal maps due to the balloon oscillation, because we are able to compute the maps despite collecting few acquisition samples. By the integration of GPR and the thermal imaging, we can evaluate the depth of the thermal influence of possible archaeological targets, such as buried Punic tombs or walls belonging to the succeeding medieval buildings, which have been subsequently destroyed. The thermal anomalies present correspondences to the radar time slices obtained from 30 to 50 cm. Furthermore, by superimposing historical aerial pictures on the GPR and thermal imaging data, we can identify these anomalies as the foundations of the destroyed building

Methotrexate and vasculoprotection: Mechanistic insights and potential therapeutic applications in old age

Increasing age is a strong, independent risk factor for atherosclerosis and cardiovascular disease. Key abnormalities driving cardiovascular risk in old age include endothelial dysfunction, increased arterial stiffness, blood pressure, and the pro-atherosclerotic effects of chronic, low-grade, inflammation. The identification of novel therapies that comprehensively target these alterations might lead to a major breakthrough in cardiovascular risk management in the older population. Systematic reviews and meta-analyses of observational studies have shown that methotrexate, a first-line synthetic disease-modifying anti-rheumatic drug, significantly reduces cardiovascular morbidity and mortality in patients with rheumatoid arthritis, a human model of systemic inflammation, premature atherosclerosis, and vascular aging. We reviewed in vitro and in vivo studies investigating the effects of methotrexate on endothelial function, arterial stiffness, and blood pressure, and the potential mechanisms of action involved. The available evidence suggests that methotrexate might have beneficial effects on vascular homeostasis and blood pressure control by targeting specific inflammatory pathways, adenosine metabolism, and 5' adenosine monophosphate-activated protein kinase. Such effects might be biologically and clinically relevant not only in patients with rheumatoid arthritis but also in older adults with high cardiovascular risk. Therefore, methotrexate has the potential to be repurposed for cardiovascular risk management in old age because of its putative pharmacological effects on inflammation, vascular homeostasis, and blood pressure. However, further study and confirmation of these effects are essential in order to adequately design intervention studies of methotrexate in the older population

Baseline staging tests after a new diagnosis of breast cancer: further evidence of their limited indications

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