101,274 research outputs found
Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling
No full textABSTRACT
Lysosomal cysteine proteinases of the papain family are involved in lysosomal bulk proteolysis, major histocompatibility complex class II mediated antigen presentation, prohormone processing, and extracellular matrix remodeling. Cathepsin L (CTSL) is a ubiquitously expressed major representative of the papain‐like family of cysteine proteinases. To investigate CTSL in vivo functions, the gene was inactivated by gene targeting in embryonic stem cells. CTSL‐deficient mice develop periodic hair loss and epidermal hyperplasia, acanthosis, and hyperkeratosis. The hair loss is due to alterations of hair follicle morphogenesis and cycling, dilatation of hair follicle canals, and disturbed club hair formation. Hyperproliferation of hair follicle epithelial cells and basal epidermal keratinocytes–both of ectodermal origin–are the primary characteristics underlying the mutant phenotype. Pathological inflammatory responses have been excluded as a putative cause of the skin and hair disorder. The phenotype of CTSL‐deficient mice is reminiscent of the spontaneous mouse mutant furless(fs). Analyses of the ctsl gene of fs mice revealed a G149R mutation inactivating the proteinase activity. CTSL is the first lysosomal proteinase shown to be essential for epidermal homeostasis and regular hair follicle morphogenesis and cycling.—Roth, W., Deussing, J., Botchkarev, V. A., Pauly‐Evers, M., Saftig, P., Hafner, A., Schmidt, P., Schmahl, W., Scherer, J., Anton‐Lamprecht, I., von Figura, K., Paus, R., Peters, C. Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling. FASEB J. 14, 2075–2086 (2000
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
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Noggin is required for induction of the hair follicle growth phase in postnatal skin
No full textDuring postnatal development, the hair follicle (HF) shows cyclic activity with periods of relative resting, active growth (anagen), and regression. We demonstrate that similar to the HF induction in embryonic skin, initiation of a new hair growth phase in postnatal skin requires neutralization of the inhibitory activity of bone morphogenetic protein 4 (BMP4) by the BMP antagonist noggin. In the resting HF, BMP4 mRNA predominates over noggin in the epithelium and mesenchyme, and the BMP receptor IA is prominently expressed in the follicular germ. Anagen development is accompanied by down‐regulation of the BMP4 and increased noggin mRNA in the HF. Furthermore, administration of noggin protein induces new hair growth phase in postnatal telogen skin in vivo. In contrast, BMP4 induces selective arrest of anagen development in the non‐tylotrich (secondary) HF. As a hair growth inducer, noggin increases Shh mRNA in the HF whereas BMP4 down‐regulates Shh. This suggests that modulation of BMP4 signaling by noggin is essential for hair growth phase induction in postnatal skin and that the hair growth‐inducing effect of noggin is mediated, at least in part, by Shh.—Botchkarev, V. A., Botchkareva, N. V., Nakamura, M., Huber, O., Funa, K., Lauster, R., Paus, R., Gilchrest, B. A. Noggin is required for induction of the hair follicle growth phase in postnatal skin. FASEB J. 15, 2205–2214 (2001
Variations on the Author
No full text“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
Neurotrophins in skin biology and pathology
No full textNeurotrophins (NTs) belong to a family of growth factors, which control the development, maintenance, and apoptotic death of neurons and also fulfill multiple regulatory functions outside the nervous system. Biological effects induced by NTs strongly depend on the pattern of NT receptor/ co-receptors expression in target cells, as well as on the set of intracellular adaptor molecules that link NT signalling to distinct biochemical pathways. In this review, we summarize data on the molecular mechanisms underlying the involvement of NTs in the control of non- neuronal functions in normal skin ( e. g. keratinocyte proliferation, melanocyte development and apoptosis, hair growth). We also review the data on the role for NTs and their receptors in a number of pathological skin conditions ( stress- induced hair loss, psoriasis, atopic dermatitis). Although additional efforts are required to fully understand mechanisms underlying the involvement of NTs and their receptors in controlling functions of normal and pathologically altered skin cells, substantial evidence suggests that modulation of NT signalling by NTs receptor agonists/ antagonists may be developed as intervention modalities in distinct skin and hair growth pathologies
Optical and transport properties of GaN/AlGaN quantum wells Phys. Status Solidi A, 178, (2000), 73-78
No full textIntegration of Notch1 and calcineurin/NFAT signaling pathway in keratinocyte growth and differentiation control.
No full textNoThe Notch and Calcineurin/NFAT pathways have both been implicated in control of keratinocyte differentiation. Induction of the p21WAF1/Cip1 gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-J¿ protein to the p21 promoter. We show here that Notch 1 activation functions also through a second Calcineurin-dependent mechanism acting on the p21 TATA box-proximal region. Increased Calcineurin/NFAT activity by Notch signaling involves downregulation of Calcipressin, an endogenous Calcineurin inhibitor, through a HES-1-dependent mechanism. Besides control of the p21 gene, Calcineurin contributes significantly to the transcriptional response of keratinocytes to Notch 1 activation, both in vitro and in vivo. In fact, deletion of the Calcineurin B1 gene in the skin results in a cyclic alopecia phenotype, associated with altered expression of Notch-responsive genes involved in hair follicle structure and/or adhesion to the surrounding mesenchyme. Thus, an important interconnection exists between Notch 1 and Calcineurin-NFAT pathways in keratinocyte growth/differentiation control
Mean flow generation by Görtler Vortices in a rotating annulus with librating side walls
No full textLongitudinal libration of the cylinder side walls of a rotating annulus in the supercritical regime induces a centrifugally unstable Stokes boundary layer which generates Görtler vortices only in a portion of a libration cycle. We show for the first time that these vortices propagate into the fluid bulk and generate an azimuthal mean flow which is retrograde (prograde) over the outer (inner) cylinder side wall. Direct numerical simulations (DNS) are carried out and Reynolds-averaged equations and kinetic energy budget of mean and fluctuating flow are used as diagnostic equations to discuss the generation mechanism and scaling behavior of the azimuthal mean flow in the fluid bulk
Multivariate Polarimetric Bistatic Clutter Statistical Analysis
No full textThis paper deals with the analysis of simultaneously collected co- and cross-polarized bistatic sea-clutter returns with special emphasis on their representation as a Spherically Invari-ant Random Process (SIRP). The study is conducted by using appropriate testing procedures involving the complex envelope of the measured data that provide both first- and higher-order compatibility conditions. The results highlight that the SIRP model is a good candidate for the representation of bistatic coherent clutter, and usually the coherence time of the SIRP texture is longer than that in the monostatic case.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Microwave Sensing, Signals & System
A role for p75 neurotrophin receptor in the control of apoptosis‐driven hair follicle regression
No full textABSTRACT
To examine the mechanisms that underlie the neurotrophin‐induced, apoptosis‐driven hair follicle involution (catagen), the expression and function of p75 neurotrophin receptor (p75NTR), which is implicated in apoptosis control, were studied during spontaneous catagen development in murine skin. By RT‐PCR, high steady‐state p75NTR mRNA skin levels were found during the anagen– catagen transition of the hair follicle. By immunohistochemistry, p75NTR alone was strongly expressed in TUNEL+/Bcl2— keratinocytes of the regressing outer root sheath, but both p75NTR and TrkB and/or TrkC were expressed by the nonregressing TUNEL‐/Bcl2+ secondary hair germ keratinocytes. To determine whether p75NTR is functionally involved in catagen control, spontaneous catagen development was compared in vivo between p75NTR knockout (— /—) and wild‐type mice. There was significant catagen retardation in p75NTR knockout mice as compared to wild‐type controls (P<0.05). Instead, transgenic mice‐overexpressing NGF (promoter: K14) showed substantial acceleration of catagen (P<0.001). Although NGF, brain‐derived neurotrophic factor (BDNF), and neurotrophin 3 (NT‐3) accelerated catagen in the organ‐cultured skin of C57BL/6 mice, these neurotrophins failed to promote catagen development in the organ‐cultured p75NTR null skin. These findings suggest that p75NTR signaling is involved in the control of kerotinocyte apoptosis during catagen and that pharmacological manipulation of p75NTR signaling may prove useful for the treatment of hair disorders that display premature entry into catagen.—Botchkarev, V. A., Botchkareva, N. V., Albers, K. M., Chen, L.‐H., Welker, P., Paus, R. A role for p75 neurotrophin receptor in the control of apoptosisdriven hair follicle regression. FASEB J. 14, 1931–1942 (2000
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