1,721,037 research outputs found
Characterisation of a second gain of function EDAR variant, encoding EDAR380R, in East Asia
No full textBash scripts, R scripts, rehh output data.Schoenebeck, Jeffrey; Riddell, Jon; Headon, Denis. (2020). Characterisation of a second gain of function EDAR variant, encoding EDAR380R, in East Asia, [dataset]. University of Edinburgh. Roslin Institute and Royal (Dick) School of Veterinary Studies. https://doi.org/10.7488/ds/279
Systems for intricate patterning of the vertebrate anatomy
Full text linkPeriodic patterns form intricate arrays in the vertebrate anatomy, notably the hair and feather follicles of the skin, but also internally the villi of the gut and the many branches of the lung, kidney, mammary and salivary glands. These tissues are composite structures, being composed of adjoined epithelium and mesenchyme, and the patterns that arise within them require interaction between these two tissue layers. In embryonic development, cells change both their distribution and state in a periodic manner, defining the size and relative positions of these specialized structures. Their placement is determined by simple spacing mechanisms, with substantial evidence pointing to a variety of local enhancement/lateral inhibition systems underlying the breaking of symmetry. The nature of the cellular processes involved, however, has been less clear. While much attention has focused on intercellular soluble signals, such as protein growth factors, experimental evidence has grown for contributions of cell movement or mechanical forces to symmetry breaking. In the mesenchyme, unlike the epithelium, cells may move freely and can self-organize into aggregates by chemotaxis, or through generation and response to mechanical strain on their surrounding matrix. Different modes of self-organization may coexist, either coordinated into a single system or with hierarchical relationships. Consideration of a broad range of distinct biological processes is required to advance understanding of biological pattern formation. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.</p
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
The morphological and molecular basis of human ectodermal appendage formation
Full text linkThe presence of hair is a key trait of mammals. Hair follicles develop in the skin, with early follicles composed of an epidermal placode and a dermal condensate. Most experimental studies of hair follicle development have used the mouse as a model. This thesis aimed to define the development of human hair follicles at a molecular and morphological level, and to assess the suitability of mouse primary hair follicles as a model for human development. Variations in the developmental mechanisms exist between distinct types of mouse pelage hair follicles, and as clear physiological differences can be seen between adult human terminal and vellus hair follicles, I aimed to elucidate any differences in their initial development. Using morphological measurements, localisation of protein and gene expression, and RNA sequencing to make these comparisons, no significant differences were found between presumptive terminal and vellus hair follicles. The differences in hair follicle development that I detected were instead related to anatomical region of the body. I report that human follicle development shares many similarities with mouse, with their morphology, spatial scale, and cell signalling being largely conserved. Some key differences were identified, including in the expression of the DKK4 and EDA genes in the placode, and the timing of the initiation of SOX2 expression in the dermal condensate. Analysis of sweat gland and primary fingerprint ridge development, showed that many signalling factors and the early morphology are conserved, with different appendage fates being specified after the initiation.
Embryonic chicken skin has been used extensively as a model for epithelial appendage development, and requires sufficient dermal cell density to permit appendage formation. I aimed to determine if, in mammals, dermal cell density and proliferation contribute to the formation of hair follicles, analogous to their requirement in avian skin. I found little distinction between dense and loose dermis in mouse and human at different anatomical sites, in contrast to the structure of embryonic avian skin, and that the dermal density does not play as important a role in hair placode induction as in chicken feather formation. Density of the epidermal layer however, strongly correlated with the onset of primary fingerprint ridge formation, and my findings support cell proliferation as a driver of downgrowth in hair follicles and fingerprints.
Novel human induced pluripotent stem cell-derived 3D skin organoids present a new model for studying human skin and hair follicle development, permitting experimental interventions not possible in intact tissues. I aimed to replicate a published protocol and evaluate the suitability of this system as a model for human hair follicle and skin
development through comparisons to foetal skin. The organoids show similar responses in proliferation and LEF1 expression to cultured ex vivo skin when WNT and BMP pathways were manipulated, while donated organoids showed differences in hair follicle morphological measurements.
In conclusion, I find that human hair follicle types, though exhibiting profound differences after birth, cannot be distinguished at their initial development. My findings show that mouse primary hair follicles present an appropriate model for most aspects of human hair follicle development, but with some key characteristics that must be taken into account when extrapolating from experimental results between these species. Mammalian hair follicle development is not correlated in the same way as feather formation with a dense dermis, and fingerprint ridge development is likely to be more reliant on epidermal cell density changes than hair follicles, with proliferation a key driver of downgrowth in both
Comparative analysis between developing hair follicles and fingerprint ridges by use of single nucleus RNA-sequencing
Full text linkDuring human embryonic development the palm and ventral side of the digits develop a series of transverse epithelial ridges that form complex patterns at the digit tips called fingerprints. The molecular mechanisms that underpin the development of the fingerprint ridges are unknown. However, recent work by the Headon lab has shown that early hair follicles and fingerprint ridges share morphological similarities. The development of fingerprint ridges then diverges from hair follicles, as hair follicles recruit an aggregation of fibroblasts known as dermal condensates, while fingerprint ridges do not, forming epithelial ridges that are densely populated with mechanosensory Merkel cells. Previous research has established that epidermal SHH and WNT signalling are essential for the formation of dermal condensates in haired skin.
To investigate the underlying differences in gene expression and resulting intercellular signalling between hair-bearing and ventral digit skin, I conducted a comparative single nucleus mRNA-sequencing study. Here I found diminished epithelial SHH and WNT signalling in the ventral digit skin which may explain the failure to recruit a dermal condensate. Additionally, I also identified differences in the cellular composition between skin regions, with the presence of fibroblast sub-populations specific to the ventral digit skin. These were found to potentially mediate the neuronal Neuregulin and Semaphorin 3 signalling pathways, which are absent in the hair bearing skin.
In summary I have identified signalling and transcriptional differences between hair-bearing and fingerprint ridge containing skin, providing insight into the molecular mechanisms that regulate fingerprint ridge development
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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