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The DNA pooling technique applied to the mutational screening of human congenital afibrinogenemia : identification of 3 novel mutations
No full textThe DNA-pooling technique allowed for the identification of three novel mutations responsible for afibrinogenemia
No full textBACKGROUND AND OBJECTIVES: Afibrinogenemia and hypofibrinogenemia are rare inherited coagulation disorders characterized by hemorrhagic manifestations of variable entity and by plasma fibrinogen deficiency. So far, 57 mutations have been associated with these disorders, and 18 of these are missense mutations. The aim of this study was to characterize the molecular mechanism underlying severe hypofibrinogenemia in a proband from India. DESIGN AND METHODS: The mutational screening was accomplished by DNA sequencing of the three fibrinogen genes. The mutant protein was expressed in COS-1 cells, and intracellular and secreted mutant fibrinogen was analyzed by means of pulse-chase experiments. RESULTS: A novel homozygous G-->A transition in exon 8 (nucleotide position 8017) was found in the proband's fibrinogen Bbeta-chain gene. The resulting G434D missense mutation (fibrinogen Mumbai) involves a highly conserved amino acid residue, located in the C-terminal globular D domain. In vitro expression experiments demonstrated intracellular retention of the mutant fibrinogen and marked reduction of its secretion. INTERPRETATION AND CONCLUSIONS: The G434D substitution causes severe hypofibrinogenemia by impairing fibrinogen secretion. Expression data confirm the importance of Bbeta-chain D domain folding in the intracellular processing of fibrinogen
Fibrinogen Mumbai: impaired secretion due to a novel missense mutation in the Bbeta-chain gene
No full textCongenital afibrinogenemia (CAF, OMIM #202400) is a rare autosomal recessive coagulation disorder characterized by hemorrhagic manifestations of variable entity and by severe plasma fibrinogen deficiency. Missense mutations responsible for CAF are rare (10%) and are interestingly clustered in a small subdomain of the protein (the C-terminal globular region of the Bbeta-chain). We here report a novel homozygous missense mutation in the same domain (Bbeta-G434D or “Fibrinogen Mumbai”) identified in an Indian CAF patient, and provide insights into the altered secretory pathway of the mutant protein. Fibrinogen Bbeta-G434D was in vitro expressed and pulse-chase experiments were performed to analyze intracellular and secreted mutant fibrinogen. Endoglycosidase-H sensitivity was used to evaluate translocation from the endoplasmic reticulum to the Golgi. Experimental data showed that Bbeta-G434D impairs fibrinogen secretion probably by altering its translocation to trans-Golgi stacks. Clustering of CAF missense mutations highlights the crucial role of the C-terminal globular region of the Bbeta-chain for the fibrinogen secretion
Uniparental disomy of chromosome 4 including a novel deletion in the FGA gene that causes congenital afibrinogenemia
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Two novel homozygous mutations in the fibrinogen genes identified in two Iranian afibrinogenemic patients
No full textFibrinogen Mumbai : intracellular retention due to a novel G434D mutation in the Bbeta-chain gene
No full textBACKGROUND AND OBJECTIVES: Afibrinogenemia and hypofibrinogenemia are rare inherited coagulation disorders characterized by hemorrhagic manifestations of variable entity and by plasma fibrinogen deficiency. So far, 57 mutations have been associated with these disorders, and 18 of these are missense mutations. The aim of this study was to characterize the molecular mechanism underlying severe hypofibrinogenemia in a proband from India. DESIGN AND METHODS: The mutational screening was accomplished by DNA sequencing of the three fibrinogen genes. The mutant protein was expressed in COS-1 cells, and intracellular and secreted mutant fibrinogen was analyzed by means of pulse-chase experiments. RESULTS:. A novel homozygous G--&rt;A transition in exon 8 (nucleotide position 8017) was found in the probandOs fibrinogen Bbeta-chain gene. The resulting G434D missense mutation (fibrinogen Mumbai) involves a highly conserved amino acid residue, located in the C-terminal globular D domain. In vitro expression experiments demonstrated intracellular retention of the mutant fibrinogen and marked reduction of its secretion. INTERPRETATION AND CONCLUSIONS: The G434D substitution causes severe hypofibrinogenemia by impairing fibrinogen secretion. Expression data confirm the importance of Bbeta- chain D domain folding in the intracellular processing of fibrinogen
Congenital afibrinogenemia : two novel fibrinogen gene mutations identified in two patients from Iran
No full textVariations on the Author
Full text link“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
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