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Single-cell genetics were used to interrogate clonal complexity and the sequence of mutational events in STIL-TAL1+ T-ALL. Single-cell multicolour FISH was used to demonstrate that the earliest detectable leukaemia subclone contained the STIL-TAL1 fusion and copy number loss of 9p21.3 (CDKN2A/CDKN2B locus), with other copy number alterations including loss of PTEN occurring as secondary subclonal events. In three cases, multiplex qPCR and phylogenetic analysis were used to produce branching evolutionary trees recapitulating the snapshot history of T-ALL evolution in this leukaemia subtype, which confirmed that mutations in key T-ALL drivers, including NOTCH1 and PTEN, were subclonal and reiterative in distinct subclones. Xenografting confirmed that self-renewing or propagating cells were genetically diverse. These data suggest that the STIL-TAL1 fusion is a likely founder or truncal event. Therapies targeting the TAL1 auto-regulatory complex are worthy of further investigation in T-ALL.

An open question in empirical economics is whether models should be estimated by using the logarithm of the relevant economic variables or their actual, or "linear", values. This paper applies the principle fo encompassing to suggest specification and mis-specification tests of log versus linear individudal equations fitted to l(1) data, and illustrates tje analysis for US quarterly disposable income. The finite-sample properties of the encompassing tests are examined in a Monte Carlo experiment customized to the parameter values in the empirical analysis.

Dal 1996 ad oggi il territorio toscano fra Firenzuola e Firenze, passando per i comuni di Scarperia, Borgo San Lorenzo, Vaglia, Sesto Fiorentino, è stato interessato dallo scavo del sistema di tunnel TAV (Treno Alta Velocità) per il collegamento ferroviario veloce Firenze-Bologna. Nel Dicembre 2009 la tratta verrà aperta al traffico passeggeri e sarà possibile spostarsi da Firenze a Bologna in 35 minuti. L’opera, di indubbio valore economico per il paese, ha determinato ingenti danni ambientali ad alcuni bacini idrografici dell’Appennino con effetti stagionali o perenni di prosciugamento di sorgenti e torrenti e diminuzione della produttività di pozzi. La presente opera monografica, presentata dalla Provincia di Firenze, si avvale della collaborazione di vari autori, tutti geologi, che, a titolo diverso e con diverso grado di coinvolgimento scientifico e professionale, hanno reso possibile definire un quadro riassuntivo e dettagliato di tutti gli impatti avvenuti ed hanno fornito all’Amministrazione Provinciale uno strumento per predisporre interventi di mitigazione degli impatti medesimi e recupero delle aree coinvolte.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At the IFPA meeting 2013 twelve themed workshops were presented, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of new technologies for placenta research: 1) use of ;omics' in understanding placental development and pathologies; 2) bioinformatics and use of omics technologies; 3) planning and coordination of a placenta research network; 4) clinical imaging and pathological outcomes; 5) placental evolution. (C) 2013 Published by IFPA and Elsevier Ltd.

L'utilizzo dei sistemi informativi geografici, in associazione a strumenti statistici in grado di identificare cluster di malattia nello spazio e nel tempo, offre numerosi vantaggi: consente di individuare le aree a maggior rischio, senza la necessità di specificare, a priori, la loro sospetta localizzazione o estensione; tiene conto delle differenze di densità di popolazione; può essere aggiustato per eventuali covariate. Questo tipo di analisi è stata impiegata per valutare la presenza di cluster di Blue Tongue (BT) nel periodo settembre-dicembre 2006 nel territorio di competenza dell’ASL di Carbonia (16 Comuni, 891 kmq di superficie totale). Sul territorio sono presenti 488 allevamenti ovini e caprini con un patrimonio di circa 80.000 capi. L'epidemia, sostenuta da BTV1, ha interessato 122 allevamenti con oltre 28.000 capi, causando la morte di 1.552 animali. È stato utilizzato il metodo Spatial Scan Statistics (SSS) (SatScan ver.7: Software for spatial and space-time scan statistics, National Cancer Institute, Bethesda, USA), attribuendo ciascun caso di malattia alle coordinate geografie (°Ovest, °Sud) dell'allevamento di provenienza. Il modello utilizzato (Space-time permutation model) prevede che il numero di casi osservati in un cluster venga comparato con quello che ci si potrebbe attendere se la localizzazione nello spazio e nel tempo di tutti i casi fosse indipendente. Pertanto, si ottiene un cluster di malattia quando, in una determinata area geografica, durante uno specifico periodo di tempo, il numero di casi osservati è in eccesso rispetto a quelli che si verificano nelle aree circostanti. L'analisi ha evidenziato un'area a rischio significativamente aumentato (P

Starting from specimens of the intestinal content of the so-called Tyrolean Iceman or Ötzi (5350-5100 years before present), it was possible to PCR amplify fragments of the human mtDNA control region that correspond to the sequence found in 1994 at the Munich and Oxford laboratories and which had been attributed to the original DNA of the mummy. The particularly favorable condition of the specimens, showing very low contamination levels, made it easier to extend the analyses to the coding region which had not been previously considered. The mtDNA of the European population is currently divided into 9 (H, T, U, V, W, X, I, J, K) main groups (haplogroups). The K haplogroup, in particular, is composed by two (K1 and K2) subclusters. The results demonstrate that the Iceman’s mtDNA belongs to the K1 subcluster, yet it does not fit any of the three known branches (a, b, c) into which the K1 subcluster is presently divided. In addition, some other sites, reported to be linked to environmental adaptation or pathologies, were investigated.

Background Sheep (Ovis aries) were domesticated in the Fertile Crescent region about 9,000-8,000 years ago. Currently, few mitochondrial (mt) DNA studies are available on archaeological sheep. In particular, no data on archaeological European sheep are available. Methodology/Principal Findings Here we describe the first portion of mtDNA sequence of a Copper Age European sheep. DNA was extracted from hair shafts which were part of the clothes of the so-called Tyrolean Iceman or Ötzi (5,350 - 5,100 years before present). Mitochondrial DNA (a total of 2,429 base pairs, encompassing a portion of the control region, tRNAPhe, a portion of the 12S rRNA gene, and the whole cytochrome B gene) was sequenced using a mixed sequencing procedure based on PCR amplification and 454 sequencing of pooled amplification products. We have compared the sequence with the corresponding sequence of 334 extant lineages. Conclusions/Significance A phylogenetic network based on a new cladistic notation for the mitochondrial diversity of domestic sheep shows that the Ötzi's sheep falls within haplogroup B, thus demonstrating that sheep belonging to this haplogroup were already present in the Alps more than 5,000 years ago. On the other hand, the lineage of the Ötzi's sheep is defined by two transitions (16147, and 16440) which, assembled together, define a motif that has not yet been identified in modern sheep populations.

The Tyrolean Iceman was a witness to the Neolithic-Copper Age transition in Central Europe 5350-5100 years ago, and his mummified corpse was recovered from an Alpine glacier on the Austro-Italian border in 1991 [1]. Using a mixed sequencing procedure based on PCR amplification and 454 sequencing of pooled amplification products, we have retrieved the first complete mitochondrial-genome sequence of a prehistoric European. We have then compared it with 115 related extant lineages from mitochondrial haplogroup K. We found that the Iceman belonged to a branch of mitochondrial haplogroup K1 that has not yet been identified in modern European populations. This is the oldest complete Homo sapiens mtDNA genome generated to date. The results point to the potential significance of complete-ancient-mtDNA studies in addressing questions concerning the genetic history of human populations that the phylo-geography of modern lineages is unable to tackle.