1,720,974 research outputs found
INVESTIGATING THE MOLECULAR MECHANISMS UNDERLYING SKIN FRAGILITY IN TP63-LINKED ECTODERMAL DYSPLASIAS
No full textAnkyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome and ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome are two rare autosomal dominant disorders caused by heterozygous mutations occurring in the TP63 gene. Individuals with AEC and EEC experience abnormal development of ectodermally-derived tissues such as hair, nails, teeth and most notably skin. Further, AEC patients as well as a subgroup of EEC patients experience severe skin erosions, which puts them at high risk of developing life-threatening infections. Currently, symptomatic care is the only available therapy to individuals with AEC or EEC. To develop novel therapeutic strategies, the underlying molecular mechanisms responsible for AEC and EEC must be understood. We hypothesize that the skin fragility experienced by individuals with AEC and EEC is linked to abnormal expression of genes involved in hemidesmosomal and desmosomal cell adhesion as well as in keratinocyte differentiation. The rationale for this hypothesis is based on preliminary data generated by the Koch and Koster laboratories suggesting defects in these keratinocyte properties. Further, previous work from others demonstrates that defects in keratinocyte adhesion and proper keratinocyte differentiation can lead to skin blistering disorders with symptoms similar to those observed in AEC and EEC. To test this hypothesis, we analyzed gene and protein expression of hemidesmosomal, desmosomal, and differentiation-associated components in keratinocytes derived from AEC and EEC patient induced pluripotent stem cells (iPSCs). Using qRT-PCR and Western blot analyses, we found that gene and protein expression of hemidesmosomal, desmosomal, and differentiation markers were abnormally expressed in iPSC-derived keratinocytes of AEC and EEC patients. Based on our findings, we conclude that skin fragility in AEC patients is caused, at least in part, by reduced expression of hemidesmosomal components. In EEC, the skin fragility is likely caused by another mechanism. Our data suggest defects in keratinocyte terminal differentiation in EEC keratinocytes. These data provide novel insights into the cause of skin fragility in AEC and EEC and may lead to the identification of new therapeutic targets
p63 in Skin Development and Ectodermal Dysplasias
No full textThe transcription factor p63 is critically important for skin development and maintenance. Processes that require p63 include epidermal lineage commitment, epidermal differentiation, cell adhesion, and basement membrane formation. Not surprisingly, alterations in the p63 pathway underlie a subset of ectodermal dysplasias, developmental syndromes in which the skin and skin appendages do not develop normally. This review summarizes the current understanding of the role of p63 in normal development and ectodermal dysplasias
Building Models for Keratin Disorders
No full textPalmoplantar keratoderma is a hallmark of pachyonychia congenita (PC) and focal non-epidermolytic palmoplantar keratoderma (FNEPPK). By generating keratin 16 (Krt16)–deficient mice, Lessard and Coulombe, as described in this issue, have generated a mouse model to replicate these palmoplantar lesions. Studies using this model may provide novel insights into the molecular mechanisms responsible for the formation of palmoplantar lesions in PC and FNEPPK patients
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Asymmetric Cell Division in Skin Development: A New Look at an Old Observation
No full textDuring skin development, the single-layered surface ectoderm covering the mouse embryo must initiate stratification and terminal differentiation to develop a functional epidermis. A recent article by Lechler and Fuchs in Nature (Lechler and Fuchs, 2005) suggests that these events are triggered by asymmetric cell division
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe 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
Sorting Out the p63 Signaling Network
No full textp63 is a transcription factor required for normal epidermal development and differentiation. Because of the complexity of these processes, p63 is expected to regulate a myriad of target genes, providing impetus to many laboratories to identify these genes. p63 target genes have been shown to encode a diverse group of proteins, including structural proteins, proteins that control cell cycle withdrawal, and proteins that regulate the epidermal differentiation program. In this issue, Antonini et al., describe a novel p63 target gene whose evolutionary conservation suggests a critical role for this gene in the epidermis
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