Fishing the Molecular Bases of Treacher Collins Syndrome

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development

Impact of complex NOTCH1 mutations on survival in paediatric T-cell leukaemia

<p>Abstract</p> <p>Background</p> <p>Molecular alterations occur frequently in T-ALL and the potential impact of those abnormalities on outcome is still controversial. The current study aimed to test whether <it>NOTCH1 </it>mutations and additional molecular abnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases.</p> <p>Methods</p> <p>T-ALL subtypes, status of <it>SIL-TAL1 </it>fusion, ectopic expression of <it>TLX3</it>, and mutations in <it>FBXW7</it>, <it>KRAS</it>, <it>PTEN </it>and <it>NOTCH1 </it>were assessed as overall survival (OS) and event-free survival (EFS) prognostic factors. OS and EFS were determined using the Kaplan-Meier method and compared using the log-rank test.</p> <p>Results</p> <p>The frequencies of mutations were 43.5% for <it>NOTCH1</it>, while <it>FBXW7</it>, <it>KRAS </it>and <it>PTEN </it>exhibited frequencies of 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of <it>NOTCH1 </it>mutations and other molecular alterations was observed. In multivariate analysis no statistical association was revealed between <it>NOTCH1 </it>mutations and any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. <it>SIL-TAL1 </it>was identified as an adverse prognostic factor. <it>NOTCH1 </it>mutation status was not associated with outcome, while the presence of <it>NOTCH1 </it>complex mutations (indels) were associated with a longer overall survival (<it>p </it>= 0.031) than point mutations.</p> <p>Conclusion</p> <p><it>NOTCH1 </it>mutations alone or in combination with <it>FBXW7 </it>did not impact T-ALL prognosis. Nevertheless, complex <it>NOTCH1 </it>mutations appear to have a positive impact on OS and the <it>SIL-TAL1 </it>fusion was validated as a negative prognostic marker in our series of T-ALL.</p

The history of leishmaniasis

In this review article the history of leishmaniasis is discussed regarding the origin of the genus Leishmania in the Mesozoic era and its subsequent geographical distribution, initial evidence of the disease in ancient times, first accounts of the infection in the Middle Ages, and the discovery of Leishmania parasites as causative agents of leishmaniasis in modern times. With respect to the origin and dispersal of Leishmania parasites, the three currently debated hypotheses (Palaearctic, Neotropical and supercontinental origin, respectively) are presented. Ancient documents and paleoparasitological data indicate that leishmaniasis was already widespread in antiquity. Identification of Leishmania parasites as etiological agents and sand flies as the transmission vectors of leishmaniasis started at the beginning of the 20th century and the discovery of new Leishmania and sand fly species continued well into the 21st century. Lately, the Syrian civil war and refugee crises have shown that leishmaniasis epidemics can happen any time in conflict areas and neighbouring regions where the disease was previously endemic

Participation in the hybrid political newsmaking and its consequences on journalism epistemology

The contemporary hybrid media system has certainly enriched as well as entangled the forms of political participation. Among the wide array of participatory practices, this essay considers specifically those aimed at creating, gathering, spreading and verifying information. It discusses new participatory practices in the process of newsmaking. In the more inclusive contemporary cycles of political information, multiple new media actors, emerging elites and non-elites, can produce news and news outlets which can become \u201cspreadable\u201d in the older and newer media, creating hype around an issue and often influencing journalists\u2019 agendas. Moreover, newer media actors can participate in the circulation of news by endorsing and contesting news items produced by professional and amateur, top-down and bottom-up, mainstream and alternative news media. This article discusses, summarizes and lists those participatory practices; it then analyses them closely in terms of journalism epistemology. Although issues related to epistemology are overwhelmingly important in journalism, particularly in the contemporary hybrid media system, they have been largely neglected in journalism studies. Epistemology in journalism is to be understood as the criterion of validity that enables journalists to distinguish the false from the true, the probable from the actual. The legitimacy of journalism is intimately bound up with claims of knowledge and truth. Hanitzsch (2007) identifies two dimensions of journalism epistemology: the objectivism/subjectivism and the empiricism/analytical approaches. This essay explores theoretically whether and how new forms of creating, gathering, spreading and verifying information by non-elite media actors and newer media elites can modify journalists\u2019 epistemology. The journalists\u2019 attitude to reality is producing contradictory results: it includes new elites in the newsmaking process as well as favoring the diffusion of misinformation

Popolarizzazione della politica o politicizzazione del popolare : etnografia di Striscia la Notizia

La frammentazione della comunicazione politica spinge i pubblici a costruire percorsi \uabibridi\ubb tra generi informativi tipici e quelli popolarizzati nelle forme di infotainment. Se la ricerca sociale sta studiando le modalit\ue0 attraverso cui questi formati forniscono risorse cognitive ai pubblici, non ha indagato adeguatamente come questi contenuti siano prodotti, con quali meccanismi, attraverso quali logiche. Questo articolo presenta i risultati di una etnografia della produzione della durata di cinque mesi effettuata all\u2019interno di Striscia la Notizia (in particolare nel suo Ufficio stampa), corroborata da 12 interviste in profondit\ue0 effettuate con chi copre ruoli strategici per la produzione del programma: autori, regista, addetto alle luci, Ufficio stampa. L\u2019analisi evidenzia i meccanismi della produzione e li analizza alla luce della linea editoriale del programma. Fa emergere poi come alcune scelte espressive siano legate anche a routine produttive che semplificano l\u2019efficacia del lavoro sul campo

Entertainment is serious stuff : the politicisation of everyday laughs

The Italian media system is characterised by a high level of political parallelism, which is usually investigated in relation to journalism but rarely in relation to TV entertainment. This article offers an analysis of one of the most influential Italian infotainment shows, which usually deals with sensitive social and political events. The conceptual framework of the article is the one offered by the mediatization of politics. We present the findings of a media production analysis: we have spent four months observing the production process, and have carried out 12 in-depth interviews with persons who cover key roles as authors, directors and producers. Additionally, one month of news articles from dailies and periodicals archived by the TV programme\u2019s press office have been analysed. Even though the programme is broadcast by Berlusconi\u2019s network, its independence is rarely called into question. Its significance also lies in the failure of journalism itself to pursue its traditional objectives. The greatest legitimisation of the role of Striscia la Notizia in pursuing an alternative and independent agenda against politics derives precisely from newspapers themselves. Therefore, we conclude that the mediatization of politics \u2013 the fact that politicians and politics adapt themselves to the TV programme\u2019s logic and language \u2013 arises from the routines involved in its production; the role of a media system which not infrequently bases its agenda on the programme itself, and the needs of the politicians called upon to reply or defend themselves before sizeable audiences

Backstage : studi sulla produzione dei media in Italia

Macchinisti, fonici, producer, assistenti di varia natura, amministratori, videomaker, uomini di marketing, impiegati, scrittori freelance: sono figure che lavorano nell\u2019industria dei media ma che di solito restano completamente invisibili ai lettori, agli spettatori, agli utenti. Professionisti che costituiscono la spina dorsale della produzione mediale, ma vivono e rimangono nel backstage, il settore non esposto al pubblico in cui si prepara per andare \u201cin scena\u201d o \u201cin onda\u201d. Questo libro vuole aprire la \u201cscatola nera\u201d dei media e rivelarne appunto il backstage, la \u201ccucina\u201d dove si preparano i prodotti mediali parte del nostro quotidiano. I contenuti e gli immaginari proposti dai mezzi di comunicazione italiani \u2013 dalla televisione alla radio, dall\u2019intrattenimento al giornalismo, dall\u2019editoria al videogioco e ai social \u2013 sono infatti sempre il risultato di scelte, decisioni, pratiche produttive, organizzazioni e attivit\ue0 molteplici, da indagare per meglio comprenderne l\u2019impatto e il valore. Attraverso una serie di saggi dedicati a una variet\ue0 di media, di metodi e di oggetti di studio, il libro si occupa per la prima volta in modo compiuto della produzione mediale italiana e delle modalit\ue0 con cui si pu\uf2 studiare, articolando le radici del campo di studi, le sue prospettive contemporanee e le direzioni di ricerca ancora aperte