1,721,419 research outputs found
G. Negri, Il diritto minerario nelle giurisprudenza
No full textG. Negri, Il diritto minerario nelle giurisprudenza. In: Revue internationale de droit comparé. Vol. 29 N°1, Janvier-mars 1977. p. 255
G. Negri, Il diritto minerario nelle giurisprudenza
No full textG. Negri, Il diritto minerario nelle giurisprudenza. In: Revue internationale de droit comparé. Vol. 29 N°1, Janvier-mars 1977. p. 255
Poichiloderma con Neutropenia (PN) : una rara sindrome di predisposizione alle mielodisplasie (MDS ): definizione dello spettro clinico e di quello mutazionale del gene C16orf57 e scanning preliminare di pazienti MDS
No full textQuesto lavoro è finalizzato ad espandere le conoscenze cliniche e molecolari della sindrome rara Poichilodema con Neutropenia (PN) causata da mutazioni del gene C16orf57, identificato nel 2010 nel nostro laboratorio grazie a tecniche di sequenziamento di nuova generazione. Orfano fino a tale data, il gene C16orf57, molto conservato ed espresso ubiquitariamente con consistenti livelli nelle cellule mieloidi, è risultato mutato in 37 pazienti PN comprensivi di dieci da noi caratterizzati sotto il profilo clinico e molecolare, sei dei quali sono oggetto di questa tesi. In base al coinvolgimento del compartimento ematopoietico in individui con mutazioni germinali di C16orf57, documentato dalla predisposizione allo sviluppo in giovane età di sindromi mielodisplastiche (MDS) e leucemia mieloide acuta (AML), C16orf57 è un potenziale candidato all'eziologia delle MDS acquisite attraverso difetti della sua funzione nelle cellule mieloidi. Questo razionale ha motivato l' analisi di C16orf57 in una casistica di oltre cento casi di MDS/AML che ha portato all'identificazione di 3 varianti non riportate con possibile significato di fattori di rischio. Seppur preliminare questo studio rappresenta la prima esplorazione circa il coinvolgimento di C16orf57 nell'eziologia delle MDS.Poikiloderma with Neutropenia (PN; OMIM#604173) is a rare autosomal recessive genodermatosis characterized by early onset poi-kiloderma and severe non cyclic neutropenia which leads to recurrent infections and bone marrow alterations predisposing to myelodisplastic syndrome (MDS) and, eventually, to acute myeloid leukaemia (AML).
C16orf57 has recently been identified as causative gene for PN in our laboratory by means of next generation sequencing (NGS) techniques. 37 PN patients are reported in literature with loss of function muta-tions in C16orf57, including 10 cases clinically and molecularly char-acterized in our laboratory, six of whom are described in this work.
All our patients carry biallelic mutations in C16orf57 including six splicing mutations, four non in frame deletions and one early truncat-ing mutation, most of them in homozygous state.
The geographical distribution of the six most frequent recurrent muta-tions points out mutational clusters restricted to defined geographical areas suggesting a founder effect the likely hypothesis to explain mu-tation clusters restricted to specific ethnic groups.
Transcripts analysis highlights that mutant transcripts are detectable even in the presence of early truncating mutations, suggesting they are relatively stable and potentially translatable in aberrant proteins.
C16orf57 protein structure and function are unknown but the presence of two similarly spaced histidine containing tetrapeptides H-X-T/S-X, which identified the active site, and the bioinformatic prediction, which recognized an internally 2-fold symmetric structure organized around histidines H120 and H208, suggest that C16orf57 protein belongs to the phosphoesterase superfamily which encompasses enzymes in-teracting with RNA substrates and involved in rRNA processing.
Depending on this model, the effects of the 19 described C16orf57 mutations are the loss of the correct protein folding, and/or the de-struction of the symmetric structure leading to the catalytic activity depletion. The possible involvement of C16orf57 in ribosomes synthesis and as-sembly interconnects PN to other rare inherited syndromes such as Shwachman-Diamond syndrome, Diamond-Blackfan Anemia, Disk-eratosis Congenita and Cartilage-Hair Hypolasia, grouped in the cate-gory of “Ribosomopathies” because of the role of their causative genes in ribogenesis. Indeed, all these diseases are rare MDS predisposing syndromes, as PN. Given that 6 C16orf57-positive PN patients has developed bone mar-row alterations, 10 a myelodysplastic syndrome since the second dec-ade of life and 2 AML, and that defects in ribogenesis have been re-ported for all acquired MDS subtypes and in the context or rare inher-ited syndromes, C16orf57 is a candidate gene in acquired MDS aeti-ology: actually, alterations of C16orf57 activity in controlling myeloid cells homeostasis may contribute to neoplastic transformation. To investigate whether disruption of the gene may also concur to the more common acquired myelodisplastic syndrome, a collection of 111 bone marrow DNA samples from a clinical and cytogenetically well characterized consecutive cohort including MDS, myelodysplas-tic/myeloproliferative neoplasms (MPN/MDS), AML, acquired neu-tropenia and MDS evolving from neutropenia cases has been investi-gated by direct sequencing of C16orf57. Three not reported sequence variations, all in heterozygous state, have been identified: i) c.-56G>A in the 5’UTR region, in a patient with RCMD and 8+, ii) c.450-67dupT in IVS3, in two different patients with RAEB2 and del5q and iii) c.587+21A>G in IVS4 in two patients with normal karyotype and one with MDS/MPN and the other with RAEB1. No malignant tissue analysis confirms the germline status of all variations. To assess if c.-56G>A and c.587+21A>G are mutations or susceptibility variants, a panel of 111 matched controls has been analysed. All controls are WT for c.-56G>A variant but a sample results heterozygous for c.587+21A>G suggesting it is a rare polymorphism.
Even if it is a preparatory study, this work represents the first explora-tion of the possible involvement of C16orf57 in MDS aetiology. The cohort will be extend: actually, even if we have not identified causa-tive C16orf57 mutations, we can’t exclude the role of this gene in a very small subset of cases or in a particular subtype of MDS. A paedi-atric cohort of acquired MDS/AML, more similar to PN patients as age of onset, will be analysed too
EP300 (E1A binding protein p300)
No full textp300 was first discovered on the basis of its interaction with the adenoviral protein E1A and EP300 locus was subsequently mapped to the long arm of chromosome 22, spanning about 88 k
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Rubinstein Taybi Syndrome in an Indian Child due to EP300 Gene Mutation : correspondence
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