Prenatal Diagnosis of β-Thalassemias and Hemoglobinopathies.

Prenatal diagnosis of β-thalassemia was accomplished for the first time in the 1970s by globin chain synthesis analysis on fetal blood obtained by placental aspiration at 18–22 weeks gestation. Since then, the molecular definition of the β-globin gene pathology, the development of procedures of DNA analysis, and the introduction of chorionic villous sampling have dramatically improved prenatal diagnosis of this disease and of related disorders. Much information is now available about the molecular mechanisms of the diseases and the molecular testing is widespread. As prenatal diagnosis has to provide an accurate, safe and early result, an efficient screening of the population and a rapid molecular characterization of the couple at risk, are necessary prerequisites. In the last decades earlier and less invasive approaches for prenatal diagnosis were developed. A overview of the most promising procedure will be done. Moreover, in order to reduce the choice of interrupting the pregnancy in case of affected fetus, Preimplantation or Preconceptional Genetic Diagnosis (PGD) has been setting up for several diseases including thalassemia

A Framework for Digital Emotions

As new media become more ubiquitous, our emotional experiences in digital space are increasing exponentially as well. While there is much talk of “affective” computing and “affective” new media art, a disconnect exists between networked emotions and the popular media that they inhabit. This research presents a theoretical framework for assessing “digital emotions”—a term that describes the feedback process between digital technologies and the body with respect to short, networked inscriptions of emotion and the (re)experience of those inscriptions within the body and through digital space. Digital emotions display five basic characteristics that can be applied to a variety of media environments: (1) They describe a process of feedback that link short, emotive inscriptions in digital environments to users and their (re)experiences of those inscriptions; (2) This feedback process includes, but is not limited to, the inscriber, the medium, and the receiver and the emotive experience fuels the initial connectivity and any further connectivity; (3) The emotional value varies depending on the media, the community of users, and the aesthetic experience of the digital emotion; (4) Digital emotions influence our emotional repertoire by normalizing our paradigm scenarios; and (5) They are highly malleable based on changes in technologies and their ability to both expand and contract emotional experiences in real time. The core characteristics of digital emotions are applied to three broad and overlapping categories: technology, community, and aesthetic experience. Each of these aspects of digital emotions work together, yet they exist along the massive spectrum of our online, emotional experiences—from our casual click of the “like” button to digital community artworks. Applied to digital spaces along this spectrum, digital emotions illuminate the feedback process that occurs between the media, the network, and the environment. The framework ultimately suggests that the process of digital emotions explicates emotions experiences that could only occur in digital space and are therefore unique to digital culture

Characterization of a disease-associated mutation affecting a putative splicing regulatory element in intron 6b of the cystic fibrosis transmembrane conductance regulator (CFTR) gene

Cystic fibrosis (CF) is a common recessive disorder caused by >1600 mutations in the CF transmembrane conductance regulator (CFTR) gene. About 13% of CFTR mutations are classified as “splicing mutations,” but for almost 40% of these, their role in affecting the pre-mRNA splicing of the gene is not yet defined. In this work, we describe a new splicing mutation detected in three unrelated Italian CF patients. By DNA analyses and mRNA studies, we identified the c.1002–1110_1113delTAAG mutation localized in intron 6b of the CFTR gene. At the mRNA level, this mutation creates an aberrant inclusion of a sequence of 101 nucleotides between exons 6b and 7. This sequence corresponds to a portion of intron 6b and resembles a cryptic exon because it is characterized by an upstream ag and a downstream gt sequence, which are most probably recognized as 5′- and 3′-splice sites by the spliceosome. Through functional analysis of this splicing defect, we show that this mutation abolishes the interaction of the splicing regulatory protein heterogeneous nuclear ribonucleoprotein A2/B1 with an intronic splicing regulatory element and creates a new recognition motif for the SRp75 splicing factor, causing activation of the cryptic exon. Our results show that the c.1002–1110_1113delTAAG mutation creates a new intronic splicing regulatory element in intron 6b of the CFTR gene exclusively recognized by SRp75

Um ambiente inteligente para aprendizado colaborativo no ensino a distância utilizando o método de casos /

Tese (Doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico.O ensino a distância baseado em estudos de casos envolve habilitar a colaboração entre dois ou mais estudantes a distância numa atividade de estudo de caso. A presente tese apresenta um sistema baseado na World Wide Web para suportar a atividade de grupo no ensino através de estudos de casos a distância. Tal sistema permite a colaboração entre os estudantes assim como colabora com estes no processo de solução de um estudo de caso realizado através da World Wide Web, com o apoio de tecnologia inteligente. Ele guia, promove e monitora a discussão do caso. De forma a desempenhar essas funções o design do sistema é baseado tanto numa metodologia para resolver um estudo de caso assim como no papel do professor que trabalha com casos na sala de aula tradicional. Essas premissas do design modelam as interações entre os estudantes e o sistema. Além disso o design do sistema também leva em consideração os problemas de aprendizado com o método

AIRE acetylation and deacetylation: effect on protein stability and transactivation activity

The AIRE protein plays a remarkable role as a regulator of central tolerance by controlling the promiscuous expression of tissue-specific antigens in thymic medullary epithelial cells. Defects in AIRE gene cause the autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy, a rare disease frequent in Iranian Jews, Finns, and Sardinian population. AIRE protein is primarily known as a transcriptional regulator and is capable of interacting with numerous proteins. The first characterized partner of AIRE is the ubiquitous transcription factor CREB-binding protein (CBP), which regulates DNA transcription through the acetylation and deacetylation of histones. More recently, the role of p300 in AIRE acetylation, which could influence the selection of AIRE activated genes, has been described. Results: In this study, we have precisely mapped, by mass spectrometry experiments, the sites of protein acetylation and, by mutagenesis assays, we have described a set of acetylated lysines as being crucial in influencing the subcellular localization of AIRE. Furthermore, we have also determined that the de-acetyltransferase enzymes HDAC1-2 are involved in the lysine de-acetylation of AIRE. Conclusions: On the basis of our results and those reported in literature, we propose a model in which lysines acetylation increases the stability of AIRE in the nucleus. In addition, we observed that the interaction of AIRE with deacetylases complexes inhibits its transcriptional activity and is probably responsible for the instability of AIRE, which becomes more susceptible to degradation in the proteasome

An Architectural Model for Component Groupware

This paper proposes an architectural model to facilitate the design of component-based groupware systems. This architectural model has been defined based on (1) three pre-defined component types, (2) a refinement strategy that relies on these component types, (3) the identification of layers of collaboration concerns, and (4) rules for the coupling and distribution of the components that implement these concerns. Our architectural model is beneficial for controlling the complexity of the development process, since it gives concrete guidance on the concerns to be considered and decomposition disciplines to be applied in each development step. The paper illustrates the application of this architectural model with an example of an electronic voting system

seismic response of a deep continental basin including velocity inversion the sulmona intramontane basin central apennines italy

n/

Performance of Optically Readout GEM-based TPC with a 55Fe source

Optical readout of large Time Projection Chambers (TPCs) with multiple Gas Electron Multipliers (GEMs) amplification stages has shown to provide very interesting performances for high energy particle tracking. Proposed applications for low-energy and rare event studies, such as Dark Matter search, ask for demanding performance in the keV energy range. The performance of such a readout was studied in details as a function of the electric field configuration and GEM gain by using a $^{55}$Fe source within a 7 litre sensitive volume detector developed as a part of the R\&D for the CYGNUS project. Results reported in this paper show that the low noise level of the sensor allows to operate with a 2~keV threshold while keeping a rate of fake-events lesser than 10 per year. In this configuration, a detection efficiency well above 95\% along with an energy resolution ($\sigma$) of 18\% is obtained for the 5.9 keV photons, demonstrating the very promising capabilities of this technique