1,721,048 research outputs found
Causative and common PHOX2B variants define a broad phenotypic spectrum
No full textPaired Like homeobox 2B (PHOX2B) is a gene crucial for the differentiation of the neural lineages of the autonomic nervous system (ANS), whose coding mutations cause congenital central hypoventilation syndrome (CCHS). The vast majority of PHOX2B mutations in CCHS is represented by expansions of a polyalanine region in exon 3, collectively defined PARMs (PolyAlanine Repeat Mutations), the minority being frameshift, missense and nonsense mutations, defined as NPARMs (Non‐PARMs). While PARMs are nearly exclusively associated with isolated CCHS, most of NPARMs is detected in syndromic CCHS, presenting with neuroblastoma and/or Hirschsprung disease. More recently, evidence of a complex role of PHOX2B in the pathogenesis of a wider spectrum of ANS disorders has emerged. Indeed, common and hypomorphic PHOX2B variants, including synonymous, polyalanine‐contractions, gene deletions may influence the occurrence of either apparent life‐threatening event (ALTE), Sudden Infant Death Syndrome (SIDS), neuroblastoma, or isolated HSCR, likely through small effects on PHOX2B expression levels. After an introduction to the role of PHOX2B in the ANS development, causative mutations, common variants, and gene expression deregulation of the PHOX2B gene are discussed, though the involvement of synonymous variants and contractions requires further confirmations with respect to ANS disorders and molecular mechanisms underlying the PHOX2B phenotypic heterogeneity
L'Egitto sul Tevere
No full textLa moda egiziana a Roma dopo la venuta di Cleopatra, dal 46 a. C. è testimoniata dalla presenza in città di numerosi obelischi, statue e monumenti del paese nordafricano. Vicino al Pantheon venne costruito addirittura un enorme tempio di Iside, chiamato Iseo Campense, che ha lasciato alla zona del Collegio Romano numerose testimonianze
MiR-204 mediates post-transcriptional down-regulation of PHOX2B gene expression in neuroblastoma cells
No full textNeuroblastoma (NB) is a rare childhood cancer of the peripheral sympathetic nervous system and accounts for approximately 10% of all pediatric tumors. Heterozygous PHOX2B mutations have been found in association with NB development in familial, sporadic and syndromic cases. In addition, the PHOX2B gene is widely over-expressed both in tumor samples and NB cell lines. Post-transcriptional gene regulation is known to be involved in mRNA stability and, in NB, microRNAs (miRNAs) seem to be responsible for altered expression of genes driving differentiation, apoptosis, and migration. To assess the possible impact of post-transcriptional regulation in NB cell lines, we have focused on the PHOX2B mRNA stability by both in silico analysis and functional studies on its 3′untranslated region (3′UTR). PHOX2B gene expression has resulted under post-transcriptional control, as suggested by: i) instability of PHOX2B mRNA, demonstrated by short mRNA half-life levels in both IMR32 and LAN-1 cell lines, ii) role of the PHOX2B-3′UTR, confirmed by the activity of proper reporter constructs, and iii) miRNA-204, shown to enhance the PHOX2B 3′UTR mediated down-regulation of the reporter construct activity. Finally, miRNA-204 has resulted to decrease the stability of the PHOX2B mRNA at different extents in the presence of different SNP rs1063611 alleles. Therefore, post-transcriptional down-regulation of the PHOX2B gene takes place in NB cell lines and miRNA-204 participates in such a 3′UTR mediated control
PAPA and FMF in two siblings: possible amplification of clinical presentation? A case report
Full text linkBackground: Familial Mediterranean Fever is a monogenic autoinflammatory disease, typically characterized by recurrent attacks of fever, serositis, aphthous of oral mucosa, erythema.
“Pyogenic arthritis, pyoderma gangrenosum and acne syndrome” is a rare autoinflammatory disease with variable expression and typically involving joints and skin. Both the diseases are linked by the overproduction of IL-1.
Case presentation: We report on the case of two siblings affected by recurrent attacks of fever, oral aphthous stomatitis, abdominal pain, arthritis, undefined dermatitis at the hands, associated with increased AST, ALT, C-reactive protein, erythrocyte sedimentation rate, serum amyloid A, leucocytosis with neutrophilia. Infectious diseases were excluded. The genetic study for Familial Mediterranean Fever, tumor necrosis factor receptor-associated periodic syndrome, Mevalonate kinase deficiency, showed the homozygous mutation p.M680I of exon 10 in MEFV. Their parents were heterozygous for the same mutation p.M680I, however, the mother showed severe symptoms of FMF (recurrent attacks of fever, arthralgia and arthritis, abdominal pain, thoracic pain), the father showed recurrent pustulosis prevalent on the hands and limbs, with arthralgia and abdominal pain. Both the patients started colchicine, with an improvement in clinical manifestations and a reduction of serum amyloid A. For the atypical dermatologic signs present in the two siblings and in the father, the study of other autoinflammatory
syndromes was performed with next generation sequencing and showed the heterozygous rare missense mutation of unknown significance: p.(Val408Ile) of PSTPIP1 gene in the two siblings and in the mother, the father was negative. Canakinumab treatment was started in the younger patient, with the resolution of the clinical symptoms and the normalization of serum amyloid A.
Conclusions: Further studies are needed to better describe the correlation between genotype and phenotype in patients with PAPA syndrome and with PAPA syndrome associated with FMF, considering that the presence of mutations in both genes may amplify clinical presentation and evolution of both diseases
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
Variations 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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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