Variation of the 3’RR1 HS1.2 Enhancer and Its Genomic Context

In humans, the HS1.2 enhancer in the Ig heavy-chain locus is modular, with length polymorphism. Previous studies have shown the following features for this variation: (i) strong population structuring; (ii) association with autoimmune diseases; and (iii) association with developmental changes in Ig expression. The HS1.2 region could then be considered as a contributor to inter-individual diversity in humoral response in adaptive immunity. We experimentally determined the HS1.2-length class genotype in 72 of the 1000 Genomes CEU cell lines and assigned the HS1.2 alleles to haplotypes defined by 18 landmark SNPs. We also sequenced the variable portion and ~200 bp of the flanking DNA of 34 HS1.2 alleles. Furthermore, we computationally explored the ability of different allelic arrangements to bind transcription factors. Non-random association between HS1.2 and Gm allotypes in the European population clearly emerged. We show a wealth of variation in the modular composition of HS1.2, with five SNPs further contributing to diversity. Longer alleles offer more potential sites for binding but, for same-length alleles, SNP variation creates/destroys potential binding sites. Altogether, the arrangements of modules and SNP alleles both inside and outside HS1.2 denote an organization of diversity far from randomness. In the context of the strong divergence of human populations for this genomic region and the reported disease associations, our results suggest that selective forces shaped the pattern of its diversity

the rem observing software

The Rapid Eye Mount (REM) is a 60 cm robotic telescope located at La Silla, Chile. Its Observing Software (REMOS) is constituted by a set of distributed intercommunicating processes organized around a central manager. Together they grant the system safety, automatically schedule and perform observations with two simultaneous cameras of user-defined targets, and drive fast reaction to satellite alerts. Subsequent data reduction is left to pipelines managed by each camera

REM: Automatic for the People

We present the result of a year-long effort to think, design, build, realize, and manage the robotic, autonomous REM observatory, placed since June 2003 on the cerro La Silla, ESO Chile. The various aspects of the management and control are here surveyed, with the nice ideas and the wrong dead ends we encountered under way. Now REM is offered to the international astronomical community, a real, schedulable telescope, automatic for the People

Biparametric versus multiparametric mri with non-endorectal coil at 3t in the detection and localization of prostate cancer

Aim: To assess the sensitivity of biparametric magnetic resonance imaging (bpMRI) with non-endorectal coil in the detection and localization of index (dominant) and nonindex lesions in patients suspected of having prostate cancer. Patients and Methods: We carried-out a retrospective analysis of multiparametric MRI (mpMRI) of 41 patients who underwent radical prostatectomy. Results of MRI for detection and localization of index and non-index lesions were correlated with those of histology. Results: No statistically significant difference in size was seen between tumor lesion at histology and index lesion at MRI. In 41 patients, a total of 131 tumors were identified at histology, while bpMRI (T2-weighted and diffusionweighted MRI) approach detected 181 lesions. bpMRI gave 27.6% false-positives and 3.3% false-negatives. Sensitivity in lesion detection by bpMRI increased with lesion size assuming high values for lesions 10 mm. For bpMRI and mpMRI, the sensitivity for detecting index lesions was the same and equal: 100% in the peripheral zone 97.6% and 94.7% in the entire prostate and transitional zone, respectively. Conclusion: bpMRI can be used alternatively to mpMRI to detect and localize index prostate cancer

Cinque anni di Media Inaf: report 2015-2019

In questo report, inizialmente realizzato in occasione della presentazione dei prodotti di Terza missione per la VQR 2015-2019, sono illustrate la linea editoriale della testata Media Inaf, le principali attività redazionali e i risultati conseguiti nel quinquennio di riferimento. Per i risultati quantitativi, in particolare, sono esplicitati e descritti gli indicatori utilizzati

A Path to the Stars: The Evolution of the Species

During the last years, a number of telescopes have been dedicated to the followup of the GRBs. But after the Swift launch, the average observed intensity of the GRBs showed to be lower than thought before. Our experience with the robotic 60 cm REM telescope confirmed this evidence, with a large number oflostGRBs. Then, we proposed to study the feasibility of a 4 m fast pointing class telescope, equipped with a multichannel imagers, from Visible to Near Infrared. In this paper, we present the main result of the feasibility study we performed so far

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies