Il sito web dell'Osservatorio Vesuviano

L'Osservatorio Vesuviano ha di recente realizzato una radicale ristrutturazione del proprio sito Web, attivo dalla seconda metà del 1997, al fine di adeguarlo alla sua nuova configurazione giuridica. Infatti, dal 10 gennaio 2001 è entrato a far parte dell'Istituto Nazionale di Geofisica e Vulcanologia (INGV), un ente nazionale di nuova formazione in cui sono confluiti i maggiori enti ed istituzioni di ricerca operanti nel campo della geofisica e della vulcanologia in Italia. Con la nascita dell'INGV si è posta un'esigenza di coordinamento tra i siti web di dette istituzioni, che si configurano attualmente come sezioni del nuovo ente nazionale. Inoltre, è sorta la necessità di creare delle pagine comuni, relative all'ente nella sua totalità, che introducessero i visitatori alle pagine delle singole sezioni ed eventualmente a specifici tematismi riguardanti le attività dell'ente. A tal fine, è stato istituito un gruppo di Coordinamento Nazionale per il Web che comprende personale afferente alle diverse sezioni. Parallelamente sono stati istituiti gruppi di lavoro locali per la ristrutturazione dei siti delle sezioni. Nell'ambito di questa riorganizzazione, presso l'Osservatorio Vesuviano, con Decreto Direttoriale N. 6, del 30 gennaio 2002, è stato istituito un gruppo di lavoro con il compito di curare la progettazione e lo sviluppo del nuovo sito web della sezione. Nello svolgimento di questa attività il gruppo di lavoro si è posto come obbiettivi prioritari l'usabilità e l'accessibilità del sito, in ottemperanza alle indicazioni espresse dalla più recente normativa apparsa in materia. Per perseguire a pieno questi obbiettivi e garantire la massima fruibilità delle informazioni è stata prevista, fin dalla fase progettuale, la realizzazione del sito anche in versione inglese, che attualmente è in allestimento. Il nuovo sito web dell'Osservatorio Vesuviano è stato messo in linea il 22 maggio 2002 ed è visitabile all'indirizzo http://www.ov.ingv.it. Nel seguito del presente rapporto sono introdotte sinteticamente le finalità istituzionali e le principali attività dell'Osservatorio Vesuviano e sono descritte le fasi di progettazione e sviluppo del sito, con particolare dettaglio sulla strutturazione dei contenuti, definita nell'ambito delle linee dettate dal decreto di istituzione del gruppo di lavoro, e sulle scelte tecnologiche adottate

POT1 mutations predispose to familial melanoma

Deleterious germline variants in CDKN2A account for around 40% of familial melanoma cases, and rare variants in CDK4, BRCA2, BAP1 and the promoter of TERT have also been linked to the disease. Here we set out to identify new high-penetrance susceptibility genes by sequencing 184 melanoma cases from 105 pedigrees recruited in the UK, The Netherlands and Australia that were negative for variants in known predisposition genes. We identified families where melanoma cosegregates with loss-of-function variants in the protection of telomeres 1 gene (POT1), with a proportion of family members presenting with an early age of onset and multiple primary tumors. We show that these variants either affect POT1 mRNA splicing or alter key residues in the highly conserved oligonucleotide/oligosaccharide-binding (OB) domains of POT1, disrupting protein-telomere binding and leading to increased telomere length. These findings suggest that POT1 variants predispose to melanoma formation via a direct effect on telomeres.D.J.A., C.D.R.-E., Z.D., J.Z.L., J.C.T., M.P. and T.M.K. were supported by Cancer Research UK and the Wellcome Trust (WT098051). C.D.R.-E. was also supported by the Consejo Nacional de Ciencia y Tecnología of Mexico. K.A.P. and A.M.D. were supported by Cancer Research UK (grants C1287/A9540 and C8197/A10123) and by the Isaac Newton Trust. N.K.H. was supported by a fellowship from the National Health and Medical Research Council of Australia (NHMRC). L.G.A. was supported by an Australia and New Zealand Banking Group Limited Trustees PhD scholarship. A.L.P. is supported by Cure Cancer Australia. The work was funded in part by the NHMRC and Cancer Council Queensland. The work of N.A.G. was in part supported by the Dutch Cancer Society (UL 2012-5489). M.H., J.A.N.-B. and D.T.B. were supported by Cancer Research UK (programme awards C588/A4994 and C588/A10589 and the Genomics Initiative). C.L.-O., A.J.R. and V.Q. are funded by the Spanish Ministry of Economy and Competitiveness through the Instituto de Salud Carlos III (ISCIII), the Red Temática de Investigación del Cáncer (RTICC) del ISCIII and the Consolider-Ingenio RNAREG Consortium. C.L.-O. is an investigator with the Botín Foundation.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.294

word~river literary review (2013)

wordriver is a literary journal dedicated to the poetry, short fiction, and creative nonfiction of adjunct, part-time and fulltime instructors teaching under a semester or yearly contract in our universities, colleges, and community colleges worldwide. Graduate student teachers who have used up their teaching assistant time and are teaching with adjunct contracts for the remainder of their graduate program are also eligible. We’re looking for work that demonstrates the creativity and craft of adjunct/part-time instructors in English and other disciplines. We reserve first publication rights and onetime anthology publication rights for all work published. We do not accept simultaneous submissions.https://digitalscholarship.unlv.edu/word_river/1004/thumbnail.jp

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1. Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells. Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to similar to 370,000 women, we identify 389 independent signals (P <5 x 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain similar to 7.4% of the population variance in age at menarche, corresponding to similar to 25% of the estimated heritability. We implicate similar to 250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$  < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust