1,721,026 research outputs found
Ciliary signalling and mechanotransduction in the pathophysiology of craniosynostosis
Full text linkCraniosynostosis (CS) is the second most prevalent inborn craniofacial malformation; it results from the premature fusion of cranial sutures and leads to dimorphisms of variable severity. CS is clinically heterogeneous, as it can be either a sporadic isolated defect, more frequently, or part of a syndromic phenotype with mendelian inheritance. The genetic basis of CS is also extremely heterogeneous, with nearly a hundred genes associated so far, mostly mutated in syndromic forms. Several genes can be categorised within partially overlapping pathways, including those causing defects of the primary cilium. The primary cilium is a cellular antenna serving as a signalling hub implicated in mechanotransduction, housing key molecular signals expressed on the ciliary membrane and in the cilioplasm. This mechanical property mediated by the primary cilium may also represent a cue to understand the pathophysiology of non‐syndromic CS. In this review, we aimed to highlight the implication of the primary cilium components and active signalling in CS pathophysiology, dissecting their biological functions in craniofacial development and in suture biomechanics. Through an in‐depth revision of the literature and computational annotation of disease‐associated genes we categorised 18 ciliary genes involved in CS aetiology. Interestingly, a prevalent implication of midline sutures is observed in CS ciliopathies, possibly explained by the specific neural crest origin of the frontal bone
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
Gene therapy for in vivo bone formation: recent advances
No full textGene therapy has developed during the last two decades as a promising strategy for orthopaedics applications, since several different gene transfer techniques proved to be effective, both in vitro and in vivo, for the induction of bone formation. Successful results have been achieved with gene-based bone healing strategies in several preclinical studies, using different animal models. New genes and new viral and non-viral vector constructs have been developed to reduce the risks and safety issues, widening the field of possible applications and improving the potential therapeutical effects. We review the latest gene transfer technologies employed for in vivo bone formation, focusing on the recently identified network of growth factors and genes involved in the modulation of the osteogenetic process and on the variety of vectors utilized for gene delivery
Nuova metodica di terapia genica per indurre l osteogenesi: risultati della sperimentazione in Fase I in tre differenti modelli animali
No full textNumerose tecniche di terapia genica sono state sperimentate negli
ultimi anni in campo ortopedico al fine di migliorare la rigenerazione
ossea in diverse condizioni patologiche. In questo lavoro presentiamo
una nuova metodica di terapia genica ex vivo per indurre
l osteogenesi. A tale scopo sono stati utilizzati culture di fibroblasti
cutanei autologhi, la cui realizzazione in vitro è estremamente
semplice e che hanno il notevole vantaggio di essere ottenibili rapidamente
con una semplice biopsia cutanea. Le cellule così ottenute
sono state poi modificate ex vivo con Ad-LMP-3 (Adenovirus
per l espressione della Lim Mineralization Protein-3) e ritrapiantate,
tramite uno scaffold osteoconduttivo in idrossiapatite e collagene
(HA/Col), in tre differenti modelli animali sperimentali: formazione
di osso ectopico nel muscolo tricipite, fusione vertebrale in
topi immunocompetenti e guarigione di un modello di difetto osseo
critico di mandibola in ratti immunocompetenti. La metodica qui
descritta è risultata efficace in tutti i modelli utilizzati per l induzione
di osso, confermando le proprietà osteoinduttive di hLMP-3
(human Lim Mineralization Protein-3) in vivo, l efficacia del
modello di scaffold in HA/Col, ma soprattutto aprendo interessanti
prospettive per una possibile sperimentazione clinica sull uomo
In Vivo Results of a Clinically Relevant Gene Therapy Approach for Orthopaedic Applicaions
No full textNuova metodica di terapia genica per indurre l'osteogenesi: risultati della sperimentazione in Fase I in 3 differenti modelli animali
No full textNumerose tecniche di terapia genica sono state sperimentate negli ultimi anni in campo ortopedico al fine di migliorare la rigenerazione ossea in diverse condizioni patologiche. In questo lavoro presentiamo una nuova metodica di terapia genica ex vivo per indurre l osteogenesi. A tale scopo sono stati utilizzati culture di fibroblasti cutanei autologhi, la cui realizzazione in vitro è estremamente semplice e che hanno il notevole vantaggio di essere ottenibili rapidamente con una semplice biopsia cutanea. Le cellule così ottenute sono state poi modificate ex vivo con Ad-LMP-3 (Adenovirus per l espressione della Lim Mineralization Protein-3) e ritrapiantate, tramite uno scaffold osteoconduttivo in idrossiapatite e collagene (HA/Col), in tre differenti modelli animali sperimentali: formazione di osso ectopico nel muscolo tricipite, fusione vertebrale in topi immunocompetenti e guarigione di un modello di difetto osseo critico di mandibola in ratti immunocompetenti. La metodica qui descritta è risultata efficace in tutti i modelli utilizzati per l induzione di osso, confermando le proprietà osteoinduttive di hLMP-3 (human Lim Mineralization Protein-3) in vivo, l efficacia del modello di scaffold in HA/Col, ma soprattutto aprendo interessanti prospettive per una possibile sperimentazione clinica sull uomo
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
Targeted Sequencing of Candidate Regions Associated with Sagittal and Metopic Nonsyndromic Craniosynostosis
Full text linkCraniosynostosis (CS) is a major birth defect in which one or more skull sutures fuse prematurely. We previously performed a genome-wide association study (GWAS) for sagittal nonsyndromic CS (sNCS), identifying associations downstream from BMP2 on 20p12.3 and intronic to BBS9 on 7p14.3; analyses of imputed variants in DLG1 on 3q29 were also genome-wide significant. We followed this work with a GWAS for metopic non-syndromic NCS (mNCS), discovering a significant association intronic to BMP7 on 20q13.31. In the current study, we sequenced the associated regions on 3q29, 7p14.3, and 20p12.3, including two candidate genes (BMP2 and BMPER) near some of these regions in 83 sNCS child-parent trios, and sequenced regions on 7p14.3 and 20q13.2-q13.32 in 80 mNCS child-parent trios. These child-parent trios were selected from the original GWAS co-horts if the probands carried at least one copy of the top associated GWAS variant (rs1884302 C allele for sNCS; rs6127972 T allele for mNCS). Many of the variants sequenced in these targeted regions are strongly predicted to be within binding sites for transcription factors involved in crani-ofacial development or bone morphogenesis. Variants enriched in more than one trio and predicted to be damaging to gene function are prioritized for functional studies
- …
