3,834 research outputs found
SF3B1 Mutations in Hematological Malignancies
No full textRecently, mutations in the genes involved in the spliceosome have attracted considerable interest in different neoplasms. Among these, SF3B1 mutations have acquired great interest, especially in myelodysplastic syndromes, as they identify a subgroup of patients who can benefit from personalized therapy. The SF3B1 gene encodes the largest subunit of the splicing factor 3b protein complex and is critical for spliceosome assembly and mRNA splicing. The mutated SF3B1 gene encodes for a protein with a different mRNA processing mechanism that results in the aberrant splicing of many mRNAs, which can be downregulated. Although there are many mRNAs affected by a splicing alteration, only a few of these have been directly related to the pathogenesis of several diseases. In this review, we took a snapshot of the current knowledge on the implications of SF3B1 mutations in different hematological malignancies
Variations on the Author
No full text“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
Method for the detection of type 1 and 2 mutations of calreticulin (CALR) gene and relative
No full textImparare le lingue per abbracciare il mondo
No full textL’autrice che si colloca, come Daniela Zorzi, tra i fautori di una linguistica “impegnata”, propone in ricordo della studiosa amica, una riflessione sul ruolo cruciale del multilinguismo e delle lingue- culture, per il successo professionale e il benessere sociale, nella società contemporanea. Il multilinguismo appare come un’urgenza educativa che interpella studiosi e formatori a tutti i livelli al fine di promuovere nei giovani un apprendimento consapevole efficace ed autonomo.Multilingualism constitutes an urgent objective for education, which needs to involve teachers and researchers at all levels if we are to promote effective and autonomous learning in the young. Like Daniela Zorzi, the author considers herself a socially engaged linguist, and in memory of her friend’s work, offers a reflection on the key roles of languages and cultures and of multilingualism for professional success and social welfare today
Strategies for minimal residual disease detection: current perspectives
No full textGiacomo Andreani, Daniela Cilloni Department of Clinical and Biological Sciences, University of Turin, Turin, Italy Abstract: Currently, the post-remission treatment in acute leukemia is based on the genetic profile of leukemic cells at diagnosis (ie, FLT3 ITD positivity) and on the level of measurable residual disease (MRD) after induction and consolidation chemotherapy. Two methods are currently preferred for MRD evaluation in many centers: multiparameter flow cytometry and real-time quantitative PCR. Additional methods such as next-generation sequencing and digital PCR are under investigation, in an attempt to increase the sensitivity and thus allowing the detection of small clones. Many studies suggest that MRD positivity after chemotherapy is associated with negative prognosis, and the reappearance of MRD during follow-up allows impending relapse to be identified and consequently enables early intervention. Finally, MRD positivity before hematopoietic stem cell transplantation is predictive of the outcome. Although the significance of MRD in acute leukemia has been widely explored, the assessment of molecular MRD is not yet a routine practice. In this review, we describe the significance of MRD in different settings and the main markers and methods used for MRD detection. Keywords: minimal residual disease, acute leukemia, multiparameter flow cytometry, real-time quantitative polymerase chain reaction, next-generation sequencing, digital PC
Digital PCR in Myeloid Malignancies: Ready to Replace Quantitative PCR?
No full textNew techniques are on the horizon for the detection of small leukemic clones in both, acute leukemias and myeloproliferative disorders. A promising approach is based on digital polymerase chain reaction (PCR). Digital PCR (dPCR) is a breakthrough technology designed to provide absolute nucleic acid quantification. It is particularly useful to detect a low amount of target and therefore it represents an alternative method for detecting measurable residual disease (MRD). The main advantages are the high precision, the very reliable quantification, the absolute quantification without the need for a standard curve, and the excellent reproducibility. Nowadays the main disadvantages of this strategy are the costs that are still higher than standard qPCR, the lack of standardized methods, and the limited number of laboratories that are equipped with instruments for dPCR. Several studies describing the possibility and advantages of using digital PCR for the detection of specific leukemic transcripts or mutations have already been published. In this review we summarize the available data on the use of dPCR in acute myeloid leukemia and myeloproliferative disorders
New mechanisms of resistance in Philadelphia chromosome acute lymphoblastic leukemia
No full textThe outcome for adults and children with Philadelphia chromosome acute lymphoblastic leukemia (ALL) has been improved dramatically with the use of tyrosine kinase inhibitors but relapse is an expected event in the majority of patients. We reviewed recent findings obtained from both gene-expression profiling analysis and single nucleotide polymorphism arrays and characterized by the identification of multiple novel genetic alterations targeting key cellular pathways, including lymphoid differentiation, cell cycle, tumor suppression, apoptosis and drug responsiveness. By gene-expression profiling analysis a new subtype known as 'BCR-ABL1-like' was identified, which includes 15-20% of all precursor B-ALL cases and is associated with an unfavorable outcome. By single nucleotide polymorphism array analysis, deletions of genes such as IKAROS, PAX5 and CDKN2A-CDKN2B were frequently identified. New therapeutic approaches are now available, such as dasatinib, nilotinib and bosutinib, and we highlight those that may be applicable to the treatment of adult BCR-ABL1-positive ALL
Reclamações ambientais em Aveiro, Portugal: atores, preocupações, padrão territorial e resoluções
No full textThis paper presents an environmental diagnosis based on public complaints on environmental
issues submitted to the Environmental Department of the Aveiro City Council, Portugal, between
2000 and 2005. It discusses the potential influences of these in local environmental planning
and governance. The paper has been organised into five sections. The first of these introduces
the study. The second section focuses on the conceptual approaches relating to environmental
grassroots movements, the main actors involved in these movements and the role played by
local government. It also contains a brief review of the most recent urban environmental
quality challenges in the European context together with a description of the main features of
the associated political and legal framework in Portugal. The third section describes the case
study and the methodology used. The results of the empirical study are detailed in the fourth
section. The final section critically analyses these results with emphases on the temporal
evolution of the submission of complaints, the actors involved, the local environmental problems
and their associated spatial pattern as well as the responses given by the City Council. This
information may then be used to provide a useful indicator for the perception of environmental
quality as well as a credible instrument for the visualisation and evaluation of local performance
in terms of environmental planning and management.AlBan Programme - n. E05M053040B
Jak rozumieć „historyczność” biblijnego Daniela? Różne kierunki wyjaśniania orędzia Księgi Daniela
No full textThe subject of this article is the issue of the historicity of the figure of Daniel, who is the main character of the biblical book bearing his name. The question of whether Daniel is a historical or just a literary figure is important because it influences the exegesis of the text of the Book of Daniel. First, the author will indicate the reasons for questioning the historicity of Daniel, and then he will present different approaches to interpreting the content of the Book of Daniel.Przedmiotem artykułu jest kwestia historyczności postaci Daniela, który jest głównym bohaterem księgi biblijnej noszącej jego imię. Pytanie o to, czy Daniel jest postacią historyczną, czy tylko literacką, jest ważne z tego powodu, że ma wpływ na egzegezę tekstu Księgi Daniela. Najpierw autor wskaże powody, na podstawie których podważa się historyczność Daniela, a następnie przedstawi różne podejścia w interpretacji treści Księgi Daniela
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