55 research outputs found
Dyscritobaeus comitans Tortorici, Caleca, Noort & Masner, 2016, sp. nov.
No full textcomitans -group This group includes species without a preoccipital lunula. In the Afrotropical region we recorded two species: Dyscritobaeus. comitans and D. ndokii Tortorici et Caleca sp. nov. Based on an analysis of the description and figures of Dyscritobaeus indicus (Mukerjee, 1994), in contrast to Mineo et al. (2010) and O’Connor & Ashe (2011), both of whom included this species in the orientalis -group, we consider it as belonging to the comitans -group, because of the clear absence of a preoccipital lunula. This species appears to be morphologically very similar to D. comitans, but unfortunately the holotype was not located in the collection of the Department of Zoology, Government Post-Graduate College, Rishikesh or in ZSI centre of Dehradun, India (K. Rajmohana, in litteris); the only difference with D. comitans is the absence of a specillum on T2. This feature was only recently observed and described (Mineo & Caleca 1992) and we suspect that, as previously happened for D. orientalis in Dodd’s original description (1915), the specillum was overlooked by the author and T2 was described as striate.Published as part of Tortorici, Francesco, Caleca, Virgilio, Noort, Simon Van & Masner, Lubomir, 2016, Revision of Afrotropical Dyscritobaeus Perkins, 1910 (Hymenoptera: Scelionidae), pp. 1-59 in Zootaxa 4178 (1) on page 10, DOI: 10.11646/zootaxa.4178.1.1, http://zenodo.org/record/26163
Characterization of the activation domain of the Rad53 checkpoint kinase
No full textRad53 protein, the yeast orthologue of the human checkpoint kinase Chk2, presents two highly conserved phosphorylatable threonine residues (T354 and T358) in the activation domain, whose phosphorylation is critical to allow the activation of the kinase. In this study we found that Rad53 protein variants in which alanine and/or aspartate replace the threonine residues 354 and/or 358 do not retain kinase activity and do not undergo auto-phosphorylation, leading to defect in the checkpoint response and iper-sensitivity to DNA damage and DNA replication stress agents. Interestingly, we found that the rad53-T358D mutation severely affects the kinase activity and causes accumulation of the S129-phosphorylated isoform of histone H2A, even during an unperturbed cell cycle, thus indicating the accumulation of spontaneous DNA breaks. We further found that the protein level of Sml1, which is the physiological inhibitor of ribonucleotide reductase, remains high during DNA replication in rad53-T358D cells, suggesting that an inadequate pool of dNTPs in checkpoint defective cells causes the accumulation of spontaneous DNA breaks.
In conclusion, our results indicate that phosphorylation of both T354 and T358 residues strongly influences the catalytic activity of Rad53 also in unperturbed cell cycles, and support the notion that Rad53 is essential to preserve genome integrity, by controlling the level of Sml1 and the functionality of ribonucleotide reductase
Refinement of the assignment to the ACMG/AMP BS3 and PS3 criteria of eight BRCA1 variants of uncertain significance by integrating available functional data with protein interaction assays
No full textThe clinical screening of cancer predisposition genes has led to the identification of a large number of variants of uncertain significance (VUS). Multifactorial likelihood models that predict the odds ratio for VUS in favor or against cancer causality, have been developed, but their use is limited by the amount of necessary data, which are difficult to obtain for rare variants. The guidelines for variant interpretation of the American College of Medical Genetics and Genomics along with the Association for Molecular Pathology (ACMG/AMP) state that “well-established” functional studies provide strong support of a pathogenic or benign impact (criteria PS3 and BS3, respectively) and can be used as evidence type to reach a final classification. Moreover, the Clinical Genome Resource Sequence Variant Interpretation Working Group developed rule specifications to refine the PS3/BS3 criteria. Recently, Lira PC et al. developed the “Hi Set” approach that generated PS3/BS3 codes for over two-thousands BRCA1 VUS. While highly successful, this approach did not discriminate a group of variants with conflicting evidences. Here, we aimed to implement the outcomes of the “Hi-set” approach applying Green Fluorescent Protein (GFP)-reassembly assays, assessing the effect of variants in the RING and BRCT domains of BRCA1 on the binding of these domains with the UbcH5a or ABRAXAS proteins, respectively. The analyses of 26 clinically classified variants, including 13 tested in our previous study, showed 100% sensitivity and specificity in identifying pathogenic and benign variants for both the RING/UbcH5a and the BRCTs/ABRAXAS interactions. We derived the strength of evidences generated by the GFP-reassembly assays corresponding to moderate for both PS3 and BS3 criteria assessment. The GFP-reassembly assays were applied to the functional characterization of 8 discordant variants from the study by Lyra et al. The outcomes of these analyses, combined with those reported in the “Hi Set” study, allowed the assignment of ACMG/AMP criteria in favor or against pathogenicity for all 8 examined variants. The above findings were validated with a semi-quantitative Mammalian Two-Hybrid approach, and totally concordant results were observed. Our data contributes in shedding light on the functional significance of BRCA1 VUS and on their clinical interpretation within the ACMG/AMP framework
As Práticas de Ensino e a sua Relação com os resultados em leitura no 1º e 3º ano de Escolaridade
No full textDissertação de Mestrado realizada sob a orientação da Pro. Doutora Isabel Leal, apresentada no ISPA – Instituto Universitário para obtenção de grau de Mestre na especialidade de Psicologia Educacional.Inexistent
Nuovo modello di analisi per le dipendenze: riflessioni per un miglioramento dell’intervento
No full textLa ricerca nasce dall’esigenza riscontrata dagli operatori afferenti ai servizi ambulatoriali pubblici e privati
- Servizi per le Dipendenze (SerD) e Servizi Multidisciplinari Integrati (SMI) e dalle strutture residenziali e
semiresidenziali accreditate della provincia di Bergamo (Terzo Settore), e dalla stessa Agenzia di Tutela della
Salute (ATS), di avviare una riflessione sul tema delle Dipendenze.
Scopo del presente lavoro è indagare i bisogni e le risorse del territorio per ottenere un riscontro operativo
ai temi di presa in carico da parte di tutti i servizi e, contemporaneamente, ipotizzare linee strategiche
di sviluppo, promuovendo iniziative che tendono verso una maggiore integrazione della rete sociosanitaria e degli interventi di rilievo sociale; prevedendo una maggiore governance delle realtà presenti sul territorio
provinciale. Elemento rilevante per la presente ricerca è l’utilizzo di due metodologie di analisi. Un’indagine quantitativa condotta dal Servizio Epidemiologico di ATS Bergamo ed un’indagine qualitativa condotta dall’Università di Bergamo - Dipartimento Scienze Umane e Sociali, arricchita dal lavoro di rete e di governance svolto dall’Ufficio Dipendenze di ATS. Avvicinandosi alla lettura dei dati si vuole porre una lente d’ingrandimento al fine di fornire chiavi di lettura rispetto all’offerta esistente sul territorio, includendo il monitoraggio relativo alle domande di accesso a percorsi residenziali extraregionali e residenziali regionali per il disturbo da gioco d’azzardo. Nasce qui la necessità di promuovere un processo di dialogo all’interno della rete dei servizi, attraverso azioni di sistema a cui orientare le scelte istituzionali-politiche.
Sulla base di questi elementi, per raggiungere un livello superiore di comprensione del fenomeno delle dipendenze, ormai sempre più complesso e che investe diverse dimensioni, è apparso necessario adottare più paradigmi: ancorando il ragionamento all’analisi epidemiologica dei comportamenti di consumo e abuso,
ampliando la ricerca con uno studio qualitativo, attraverso una ricognizione delle esperienze dei responsabili
dei servizi e degli operatori che lavorano sul campo. Data la complessità del fenomeno, affrontato da più angolazioni e l’evoluzione della stesso negli anni, è prevista inoltre la somministrazione di un questionario
rivolto agli utenti in carico ai servizi stessi; leggere in filigrana questi argomenti àncora maggiormente
l’analisi in atto, al fine d’integrare modelli teorici di riferimento, approcci metodologici e concetti psicosociali con le caratteristiche dell’utenza, proponendo alcune direttrici, orientando lo sguardo per offrire criteri di interpretazione dell’attualità al fine di promuovere un linguaggio comune. La narrazione nuova che può emergere e si sta costruendo, proseguirà con altri elementi di sistema, attraverso una lettura condivisa da parte degli operatori che compongono la rete dei servizi delle Dipendenze, con un ruolo di coordinamento svolto da ATS che lega in modo sistemico tutti gli attori che a vario titolo (pubblico, terzo settore e formativo-accademico) si occupano del fenomeno. Tutto ciò al fine di poter operare su dati ed elementi di diversa natura e giungere ad una comprensione dei nuovi bisogni e delle nuove frontiere a cui il sistema delle Dipendenze è chiamato ad organizzarsi ed evolvere per sapervi rispondere
L’edizione dell’Abecedario Pittorico di Pellegrino Antonio Orlandi, aggiornata da Pietro Maria Guarienti (1753), una fonte per la storia dell’arte portoghese
No full textLe présent travail se consacre à l’étude et à l’édition annotée des informations historico-artistiques sur le Portugal exposées dans l’Abecedario Pittorico de Pellegrino Antonio Orlandi, réédité par Pietro Guarienti à Venise en 1753.
Guarienti réside à Lisbonne entre 1733 et 1741 où il exerce une activité d'expert, de marchand et de restaurateur d’œuvres d’art.
Son succès en tant que connaisseur l’amène à entrer en contact avec un vaste public de collectionneurs lui permettant de connaître de nombreuses collections et de se familiariser avec l'art portugais.
Quand Guarienti, à la fin de sa carrière, prépare la nouvelle édition élargie de l'Abecedario, un universel dictionnaire encyclopédique d’artistes, il y introduit toutes les informations sur l'art et sur les collections portugaises recueillies durant son séjour.
Au Portugal de la première moitié du XVIIIe siècle la littérature spécialisée est pratiquement inexistante et l'Abecedario représente la première publication sur la vie des artistes de ce pays.
Cet ouvrage contient vingt-cinq biographies de maîtres, principalement des peintres exerçant au Portugal à partir du XVe siècle jusqu'aux années trente - quarante du dix-huitième siècle.
Guarienti recueille des documents manuscrits ainsi que des informations orales auprès des peintres, des collectionneurs et des érudits en y ajoutant ses notes personnelles issues de l'observation directe des œuvres d'art.
Par conséquent, les entrées sur les artistes contiennent non seulement les données biographiques mais également des informations sur les œuvres présentes à Lisbonne à cette période, ainsi que d’intéressantes remarques sur la fortune des maîtres en question.
En plus des biographies, l'Abecedario contient également de nombreuses indications sur les collectionneurs. L'auteur, en effet, cite ponctuellement les peintures de toutes les écoles qu’il a pu voir dans les endroits qu’il a visités : le palais royal, les églises et les monastères situés entre Lisbonne, Mafra et Evora ainsi que dans les demeures d’une trentaine de collectionneurs privés.
Il s’agit d’un corpus qui n’a pas son égal dans la littérature spécialisé portugaise étant donné que les sources publiées offrant quelques informations sur le collectionnisme d’art au XVIIIe siècle dans le pays sont rares et fragmentaires.
Parmi les amateurs d'art mentionnés par l'auteur peu ont été étudiées, d’autres restaient complètement inconnus. Il est à noter de surcroit qu’outre les personnalités appartenant traditionnellement à l’aristocratie, émerge désormais un public plus large de hauts fonctionnaires, commerçants et artistes. Mais surtout, il est apparu un patrimoine extraordinaire formé de peintures de meilleurs maîtres italiens, flamands, néerlandais et ibériques qui jusqu'à présent n'a jamais été étudié.This dissertation, presents a study and commented edition of artistic-historical information regarding Portugal included in the Abecedario Pittorico by Pellegrino Antonio Orlandi, republished by Pietro Guarienti in Venice in 1753.
Guarienti lived in Lisbon from 1733 until 1741 and among his main activities he was an art critic and merchant, in addition to a restorer.
His success as connoisseur allowed him to get in touch with a wide range of collectors, therefore giving him the chance to see innumerable collections and familiarise himself with Portuguese art.
At the end of his career, while working on the new expanded edition of the Abecedario, an encyclopediac universal dictionary of artists, he inserted, all the information on Portuguese art and collections he had gathered during his stay into this masterpiece.
During the first half of the eighteenth century in Portugal, art literature basically did not exist, so the Abecedario represents the first printed work which sheds light on the life of various artists in that country.
It includes biographies of twentyfive masters, mostly painters working in Portugal, going from those living in the fifteenth century to those still alive in the thirties and forties of the eighteenth century.
Guarienti collected manuscripts and oral information from painters, collectors and erudite people, adding his personal notes derived from the direct observation of works of art.
As a consequence, the lives of the artists do not simply carry biographical data, but also include news on the masterpieces present in Lisbon at that time.
On top of the lives, the Abecedario also contains much information as far as collections are concerned.
The author after all, accurately recalls the paintings from all the various schools he was able to see in the places he visited: the Royal Palace, churches and monasteries around Lisbon, Mafra and Evora and many homes of over thirty private collectors.
This is a corpus without comparison in Portuguese art literature, since the published sources which give information on eighteenth century art collecting in Portugal, are rare and rather incomplete.
Few of the art amateurs mentioned by the author have been studied; as a matter of fact, some were even unknown.
It is also clear that, on top of people traditionally belonging to the aristocracy, a wider public of high officials, merchants and artists existed.
But above all this corpus reveals the existence of an extraordinary collection of paintings from the most famous Italian, Flemish, Dutch and Spanish masters, a patrimony that, up until now, has not been studied.Nel presente lavoro si sono realizzati lo studio e l’edizione commentata delle notizie storico-artistiche sul Portogallo presenti nell’Abecedario Pittorico di Pellegrino Antonio Orlandi, riedito da Pietro Guarienti a Venezia nel 1753.
Guarienti risiede a Lisbona dal 1733 al 1741 e la sua attività è quella di esperto di pittura, mercante d’arte e restauratore.
Il suo successo come connoisseur lo porta a entrare in contatto con un ampio pubblico di collezionisti, permettendogli di conoscere numerosissime raccolte e di familiarizzare con l’arte portoghese.
Quando egli, alla fine della sua carriera, cura la nuova ampliata edizione dell’Abecedario, un dizionario enciclopedico universale di artisti, immette in quest’opera tutte le informazioni sull’arte e sulle collezioni portoghesi che ha raccolto durante il suo soggiorno.
Nella prima metà del Settecento, in Portogallo la letteratura artistica è ancora pressoché inesistente e l’Abecedario rappresenta la prima pubblicazione di vite di artisti di questo paese.
Esso contiene venticinque biografie di maestri, essenzialmente pittori, attivi in Portogallo, da quelli vissuti nel Quattrocento fino a personalità ancora viventi negli anni Trenta – Quaranta del Settecento.
Guarienti raccoglie materiale manoscritto e informazioni orali presso pittori, collezionisti ed eruditi e vi aggiunge la sue personali note, ricavate dall’osservazione diretta delle opere d’arte.
Conseguentemente, le voci sugli artisti contengono non solo dati biografici ma notizie sulle opere presenti a Lisbona in questo periodo, così come interessanti considerazioni sulla fortuna dei maestri in questione.
Parallelamente alle vite, l’Abecedario contiene, inoltre, numerosissime indicazioni di natura collezionistica.
L’autore, infatti, cita puntualmente pitture di tutte le scuole, che ha potuto vedere nei luoghi che ha visitato: il palazzo reale, chiese e monasteri situati tra Lisbona, Mafra e Evora e, infine, le case di ben trenta collezionisti privati.
È un corpus, questo, che non ha pari nella letteratura artistica portoghese, dato che le fonti edite che offrono qualche ragguaglio sul collezionismo d’arte nel Settecento in Portogallo sono rare e molto frammentarie.
Degli amateurs d’arte menzionati dall’autore, pochi erano stati studiati e, addirittura, parecchi erano del tutto sconosciuti. Si è constatato che, oltre alle personalità tradizionalmente appartenenti all’aristocrazia, emerge ora un pubblico più ampio di alti funzionari, mercanti e artisti. Ma sopratutto, è emerso uno straordinario patrimonio formato da pitture dei migliori maestri italiani, fiamminghi, olandesi e iberici, patrimonio che fino ad ora non era mai stato studiato
The rs12975333 variant in the miR-125a and breast cancer risk in Germany, Italy, Australia and Spain
No full textNot availabl
Atypical cancer risk profile in carriers of Italian founder BRCA1 variant p.His1673del: Implications for classification and clinical management
No full textBackground: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence. Methods: Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1-ABRAXAS1 interaction was assessed using a GFP-fragment reassembly-based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2. Results: Variant-carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0-155.0; cumulative risk at age 70 = 27.6%, 95% CI = 12.6-40.0%) but not for breast cancer (HR = 0.7, 95% CI = 0.2-2.2). An increased risk of uterine cancer (HR = 8.0, 95% CI = 1.03-61.6) emerged, warranting further evaluation. Likelihood-ratio in favor of pathogenicity was 98898642.82 under assumption of standard BRCA1 breast and ovarian penetrance, and 104240832.84 after excluding breast cancer diagnoses (based on penetrance results). Functional analysis demonstrated that the variant abrogates the BRCA1-ABRAXAS1 binding, supporting the PS3 code assignment within the ACMG/AMP rule-based model. Collectively, these findings allowed to classify the variant as pathogenic. Conclusion: Pathogenicity of BRCA1:c.5017_5019del(p.His1673del) has been confirmed; however, breast cancer risk in Italian families is not increased, unlike in families from other countries and in carriers of most BRCA1 pathogenic variants. The knowledge of atypical risk profiles for this and other variants will pave the way for personalized management based on specific genotype
The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
No full textCàncer de mama; Genètica del càncerCáncer de mama; Genética del cáncerBreast cancer; Cancer geneticsBreast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.Peterlongo laboratory is supported by Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo and by a fellowship from Fondazione Umberto Veronesi to G. Figlioli. Surrallés laboratory is supported by the ICREA-Academia program, the Spanish Ministry of Health (projects FANCOSTEM and FANCOLEN), the Spanish Ministry of Economy and Competiveness (projects CB06/07/0023 and RTI2018-098419-B-I00), the European Commission (EUROFANCOLEN project HEALTH-F5-2012-305421 and P-SPHERE COFUND project), the Fanconi Anemia Research Fund Inc, and the “Fondo Europeo de Desarrollo Regional, una manera de hacer Europa” (FEDER). CIBERER is an initiative of the Instituto de Salud Carlos III, Spain
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