Multicultural literature through the magic of storytelling

Creative dynamics and literature

Genetic Analysis of Fin Development in Zebrafish Identifies Furin and Hemicentin1 as Potential Novel Fraser Syndrome Disease Genes

Using forward genetics, we have identified the genes mutated in two classes of zebrafish fin mutants. The mutants of the first class are characterized by defects in embryonic fin morphogenesis, which are due to mutations in a Laminin subunit or an Integrin alpha receptor, respectively. The mutants of the second class display characteristic blistering underneath the basement membrane of the fin epidermis. Three of them are due to mutations in zebrafish orthologues of FRAS1, FREM1, or FREM2, large basement membrane protein encoding genes that are mutated in mouse bleb mutants and in human patients suffering from Fraser Syndrome, a rare congenital condition characterized by syndactyly and cryptophthalmos. Fin blistering in a fourth group of zebrafish mutants is caused by mutations in Hemicentin1 (Hmcn1), another large extracellular matrix protein the function of which in vertebrates was hitherto unknown. Our mutant and dose-dependent interaction data suggest a potential involvement of Hmcn1 in Fraser complex-dependent basement membrane anchorage. Furthermore, we present biochemical and genetic data suggesting a role for the proprotein convertase FurinA in zebrafish fin development and cell surface shedding of Fras1 and Frem2, thereby allowing proper localization of the proteins within the basement membrane of forming fins. Finally, we identify the extracellular matrix protein Fibrillin2 as an indispensable interaction partner of Hmcn1. Thus we have defined a series of zebrafish mutants modelling Fraser Syndrome and have identified several implicated novel genes that might help to further elucidate the mechanisms of basement membrane anchorage and of the disease's aetiology. In addition, the novel genes might prove helpful to unravel the molecular nature of thus far unresolved cases of the human disease

Adenovirus Gene Transfer to Amelogenesis Imperfecta Ameloblast-Like Cells

To explore gene therapy strategies for amelogenesis imperfecta (AI), a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5) vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR) on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including “pK7” and/or “RGD” motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3) fiber “knob” domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold) of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both αvβ3/αvβ5 integrins and heparan sulfate proteoglycans (HSPGs) highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Letramentos em rede: textos, máquinas, sujeitos e saberes em translação Networked literacies: texts, machines, subjects and knowledges in translation

Este trabalho apresenta uma proposta de (re)descrição do fenômeno do(s) (novos) letramento(s) fundamentada teórico-metodologicamente na Teoria Ator-Rede e ilustra o percurso que levou a tal proposta com uma vinheta descritiva de parte dos resultados de um estudo de cunho etnográfico que envolveu dois estudantes universitários do sudeste do Brasil por um período de dois anos. Os dados incluídos no estudo foram gerados por várias estratégias, tais como o monitoramento dos computadores pessoais dos informantes por meio de um software especializado, notas de campo, diários pessoais, observação simples e participante, além de entrevistas semiestruturadas. Objetiva convidar a comunidade de pesquisa em novos letramentos no Brasil a avaliar a utilidade de conceberem-se letramentos e subjetividades como atores-redes, assim como os limites de tal manobra teórico-metodológica. Revisa brevemente estudos sobre (novos) letramento(s) que utilizaram conceitos da Teoria Ator-Rede e conclui que a mesma ainda não foi explorada em todo o seu potencial nesse campo de pesquisa.<br>The study proposes a (re)description of the phenomenon of (new) literacy(ies) on the theoretical-methodological basis of Actor-Network Theory and illustrates the process that led to such a proposal with a descriptive vignette based on some results of a two-year ethnography-oriented study that involved two university students from southeastern Brazil. The data included in the study were generated through various strategies such as monitoring the informants' personal computers, field notes, personal journals, participant and non-participant observation as well as semi-structured interviews. It is intended that the article works as an invitation for the literacy research community in Brazil to assess the usefulness of conceiving literacies and subjectivities as actor-networks, as well as the limits of such a theoretical-methodological move. Previous studies on (new) literacy(ies) that used concepts from Actor-Network Theory are reviewed, and it is concluded that the theory has yet to be fully explored in this research field

Amor e gênero em quadrinhas Love and gender in popular verses

O texto analisa a obra Quadrinhas populares, de Áurea Queiroz, a partir da categoria gênero. Identifica nas quadrinhas uma fonte de significação do feminino, do masculino e de suas relações. Do mesmo modo, evidencia que no conjunto de quadrinhas analisado predominam aquelas que dizem respeito aos significados do amor, do namoro e do casamento em suas interfaces com o feminino e o masculino. Os sentidos atribuídos aos verbos namorar, amar e casar ora confirmam concepções que se tornam normativas durante a primeira metade do século XX, ora as rebatem, apontando para o universo plural das relações de gênero no período.<br>The text analyses the work Quadrinhas populares [Popular verses], by Áurea Queiroz, from the perspective of gender. It identifies in the scenes a source of meaning of the feminine, the masculine and the relations between them. In the same way, it provides evidence that in the set of scenes analyzed those that deal with the meanings of love, courtship and marriage in their interfaces with the feminine and the masculine predominate. The meanings attributed to the verbs to court, to love and to marry, now confirm conceptions that became the norm during the first half of the 20th century, now rebut them, pointing to the multifarious nature of gender relationships in the period