Treatment with an Anti-CD44v10-Specific Antibody Inhibits the Onset of Alopecia Areata in C3H/HeJ Mice

A murine CD44v10-neutralizing antibody has been reported to impair delayed-type hypersensitivity reactions. Because alopecia areata is characterized by a delayed-type hypersensitivity-like T cell mediated immune response, we addressed the question whether an anti-CD44v10-antibody influences the onset of alopecia areata. Therefore, we used the C3H/HeJ mouse model with the induction of alopecia areata in unaffected mice by the grafting of lesional alopecia areata mouse skin. Six grafted mice were injected (intraperitoneally) with anti-CD44v10, six grafted mice with anti-CD44standard, and six with phosphate-buffered saline only. After 11 wk phosphate-buffered saline injected animals on average had developed alopecia areata on 36.8% of their body. The onset of hair loss was slightly delayed and its extent reduced to 17.2% of their body in anti-CD44standard-treated mice. By contrast, five of six anti-CD44v10-treated mice did not show any hair loss and one mouse developed alopecia areata on only 1% of the body. Immunohistochemical examination revealed a marked reduction of perifollicular CD8+ lymphocytes and, to a lesser degree, CD4+ cells as well as a decreased expression of major histocompatibility complex class I on hair follicle epithelium in anti-CD44v10-treated mice as compared with phosphate-buffered saline or anti-CD44 standard-treated mice. Our data show that anti-CD44v10 is able to inhibit the onset of alopecia areata in C3H/HeJ mice. This might be accomplished by an anti-CD44v10-triggered impairment of immune cell homing (e.g., CD8+ T cells), resulting in a decrease of their number in target tissues

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

Denosumab treatment for fibrous dysplasia

Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)‐regulating protein, α‐subunit of the Gs stimulatory protein (G s α). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF‐κB ligand (RANKL) is a cell‐surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD‐like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal‐related events from bone metastases. We present the case of a 9‐year‐old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross‐linked C‐telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD‐related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases. © 2012 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92121/1/1603_ftp.pd

Benign follicular tumors

Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients.info:eu-repo/semantics/publishedVersio

Climate change and sustainability education framework: an opportunity for pre-service teaching

The National Climate Education Action Plan (NCEAP) included 9-actions. Action 2: develop an initial teacher (pre-service) education framework for embedding climate change and sustainability education responding to needing a climate action pedagogy to address the requirements of UK National Policy and Department for Education policy paper ‘Sustainability and climate change: a strategy for the education and children’s services systems’ (Department for Education, 2022). This paper presents a research project for implementing a framework across three age phases: early years, primary and secondary (2022–23). It explores the development and alignment of teaching to incorporate understanding of climate and su-stainability education enabling climate action. A qualitative approach was employed, drawing on surveys, reflective statements and interviews. Using thematic analysis the reflective statements from 10-teacher educators and a student focus group were analysed along with a student end point survey responses from 79 pre-service teachers. Exploring the extent to which the framework had facilitated the development of pre-service teachers’ understanding about how to teach climate change and sustainability education. The findings suggest that, whilst the sample size was small, there was the potential to embed climate change and sustainability education using a flexible framework, underpinned by thinking related to competencies across different initial teacher education programmes. Further research is needed to explore how this framework is applied and contextualised, and the impact it has in developing self-efficacy and competencies. An exploration of early adopters as part of a Delphi study or survey might help to contribute to this important area of research

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