What is the biological basis of pattern formation of skin lesions?

Pattern recognition is at the heart of clinical dermatology and dermatopathology. Yet, while every practitioner of the art of dermatological diagnosis recognizes the supreme value of diagnostic cues provided by defined patterns of 'efflorescences', few contemplate on the biological basis of pattern formation in and of skin lesions. Vice versa, developmental and theoretical biologists, who would be best prepared to study skin lesion patterns, are lamentably slow to discover this field as a uniquely instructive testing ground for probing theoretical concepts on pattern generation in the human system. As a result, we have at best scraped the surface of understanding the biological basis of pattern formation of skin lesions, and widely open questions dominate over definitive answer. As a symmetry-breaking force, pattern formation represents one of the most fundamental principles that nature enlists for system organization. Thus, the peculiar and often characteristic arrangements that skin lesions display provide a unique opportunity to reflect upon – and to experimentally dissect – the powerful organizing principles at the crossroads of developmental, skin and theoretical biology, genetics, and clinical dermatology that underlie these – increasingly less enigmatic – phenomena. The current 'Controversies' feature offers a range of different perspectives on how pattern formation of skin lesions can be approached. With this, we hope to encourage more systematic interdisciplinary research efforts geared at unraveling the many unsolved, yet utterly fascinating mysteries of dermatological pattern formation. In short: never a dull pattern

Nevus Sebaceus Is a Mosaic RASopathy

The recent discovery that nevus sebaceus is a mosaic RASopathy represents a major breakthrough in research on epidermal nevi. In this issue, both Levinsohn et al. and Sun et al. confirm this advancement with results obtained through whole-exome sequencing. Further molecular studies will almost certainly show that sebaceous and keratinocytic nevi are different disorders, although there is some clinical overlap

Critique [of Institutional Racism]

In the sixties, the scattered attacks against various manifestations of racism briefly coalesced into a broad based movement. Some gains were made, chiefly in the areas of voting rights, consumer discrimination, and education. However, the movement failed to significantly alter the wealth distribution system through the achievement of employment equity, this could only have resulted from affirmative action in all sectors and at all levels of the economy. But in the employment struggle, the confrontation was much closer to the heart of capitalist institutions and was perceived as a greater threat to the stability of those institutions

Interleukin-1β-Induced Inhibition of Hair Growth In Vitro Is Mediated by Cyclic AMP

Interleukin (IL)-1 has been shown to be a potent inhibitor of hair growth in vitro. We hypothesized that this cytokine might be a decisive factor causing hair loss during the lymphocytic attack in alopecia areata. Neither the intracellular pathways involved in hair growth inhibition mediated by IL-1β nor the signal transduction processes within hair follicles in general are known. We therefore investigated the intracellular signals involved in human hair growth in vitro. Hair follicles were isolated from scalp biopsies by microdissection and hair growth was measured daily by image analysis. We assessed intracellular signal transducing elements using specific inhibitors or activators either alone or in combination with IL-1β. The calcium ionophore A 23187 induced a rapid and complete arrest of hair growth and phorbol-12-myristate-13-acetate (PMA), genistein, or IL-1β decreased hair growth by approximately 60%-80%. IL-1β-elicited hair growth arrest was not antagonized by calphostin C, a specific inhibitor of protein kinase C. In contrast, coincubation of IL-1β with pertussis toxin or H 1004 neutralized the effect of IL-1β and dibutyryl-cAMP and cholera toxin, an activator of adenylate cyclase, inhibited hair growth. These data suggest that cAMP acts as a second messenger for IL-1β-induced inhibition of hair growth. Moreover, our data indicate that in vitro hair growth is dependent on intracellular Ca2+ levels and activation of tyrosine kinase as well as protein kinase C. We were unable to detect a signal transducing element responsible for enhanced hair growth in vitro

cAMP controls cytosolic Ca(2+ )levels in Dictyostelium discoideum

BACKGROUND: Differentiating Dictyostelium discoideum amoebae respond upon cAMP-stimulation with an increase in the cytosolic free Ca(2+ )concentration ([Ca(2+)](i)) that is composed of liberation of stored Ca(2+ )and extracellular Ca(2+)-influx. In this study we investigated whether intracellular cAMP is involved in the control of [Ca(2+)](i). RESULTS: We analyzed Ca(2+)-fluxes in a mutant that is devoid of the main cAMP-phosphodiesterase (PDE) RegA and displays an altered cAMP metabolism. In suspensions of developing cells cAMP-activated influx of extracellular Ca(2+ )was reduced as compared to wild type. Yet, single cell [Ca(2+)](i)-imaging of regA(- )amoebae revealed a cAMP-induced [Ca(2+)](i )increase even in the absence of extracellular Ca(2+). The cytosolic presence of the cAMP PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) induced elevated basal [Ca(2+)](i )in both, mutant and wild type cells. Under this condition wild type cells displayed cAMP-activated [Ca(2+)](i)-transients also in nominally Ca(2+)-free medium. In the mutant strain the amplitude of light scattering oscillations and of accompanying cAMP oscillations were strongly reduced to almost basal levels. In addition, chemotactic performance during challenge with a cAMP-filled glass capillary was altered by EGTA-incubation. Cells were more sensitive to EGTA treatment than wild type: already at 2 mM EGTA only small pseudopods were extended and chemotactic speed was reduced. CONCLUSION: We conclude that there is a link between the second messengers cAMP and Ca(2+). cAMP-dependent protein kinase (PKA) could provide for this link as a membrane-permeable PKA-activator also increased basal [Ca(2+)](i )of regA(- )cells. Intracellular cAMP levels control [Ca(2+)](i )by regulating Ca(2+)-fluxes of stores which in turn affect Ca(2+)-influx, light scattering oscillations and chemotactic performance

Reconceptualising Preservice Teachers’ Subject Knowledge in Climate Change and Sustainability Education: A Framework for Initial Teacher Education from England, UK

Climate Change and Sustainability Education (CCSE) has been gaining prominence with the imminent climate emergency humanity is facing. This paper draws upon a conceptual framework created to support the development of preservice teachers’ subject knowledge of CCSE whilst undertaking Initial Teacher Education (ITE) programs in England. The core aims and learning outcomes within the framework, namely knowledge; attitudes, values and behaviours; and competences and capabilities, are defined to illustrate what subject knowledge looks like, in this area, for preservice teachers in England. This paper highlights data gathered from 71 preservice teachers via an initial presurvey from three ITE institutions across England. The data were gathered from Early Years and Primary and Secondary phase trainees across both postgraduate and undergraduate programmes. The presurvey captured a range of qualitative and quantitative responses from preservice teachers to showcase priority areas, from their perspective, in the teaching of CCSE. The responses were coded and then themed according to the three aims and learning outcomes of the framework (knowledge; attitudes, values and behaviours; and competences and capabilities) to understand preservice teachers’ views on CCSE at the start of their courses. The findings suggest that preservice teachers lack key subject knowledge in CCSE to teach it effectively in schools. Hence, this paper recommends further work needs to be carried out to embed CCSE work in ITE courses across England. It is further suggested that the CCSE framework highlighted in this paper can act as a key national document to support ITE institutions to conceptualise the teaching and learning of CCSE across their ITE programmes

Alopecia Areata: Treatment of Today and Tomorrow

It is the aim of this article to review and appraise available data on treatments for alopecia areata (AA) according to the demands of evidence based medicine. Studies evaluating the efficacy of a treatment for AA should include appropriate controls, use cosmetically acceptable hair regrowth as a parameter for treatment success, include patients with AA totalis, universalis or extensive patchy AA, and exclude patients suffering from AA for less than 3 months. Moreover, the treatment must be safe over a prolonged period of time. Among the various therapeutic approaches presently available for AA, only treatment with contact sensitizers such as diphenylcyclopropenone or squaric acid dibutylester has been shown to be effective in studies that fulfill these criteria.Improved future treatments may be immunosup-pressive or immunomodulatory targeting of the autoimmune pathogenesis of AA, or they may otherwise protect hair follicles from the injurious effects of inflammation. Such possible future therapeutic approaches include the incorporation of immunomodulatory agents into liposomes as an improved vehicle; inhibition of apoptosis mediated by the Fas-FasL system; inhibition of the lymphocyte homing receptor CD44v10; induction of tolerance