PTCH1+/− Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts

Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3) and NBCCS fibroblasts bearing either nonsense (n = 3) or missense (n = 3) PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1+/− genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients

A Functional Role of RB-Dependent Pathway in the Control of Quiescence in Adult Epidermal Stem Cells Revealed by Genomic Profiling

Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. We observed that a large number of transcripts are underexpressed in hair follicle stem cells when compared to non-stem cells. Importantly, the majority of these downregulated genes are involved in cell cycle. Using bioinformatics tools, we identified the E2F transcription factor family as a potential element involved in the regulation of these transcripts. To determine their functional role, we used engineered mice lacking Rb gene in epidermis, which showed increased expression of most E2F family members and increased E2F transcriptional activity. Experiments designed to analyze epidermal stem cell functionality (i.e.: hair regrowth and wound healing) imply a role of the Rb-E2F axis in the control of stem cell quiescence in epidermis

Vegan diets : practical advice for athletes and exercisers.

With the growth of social media as a platform to share information, veganism is becoming more visible, and could be becoming more accepted in sports and in the health and fitness industry. However, to date, there appears to be a lack of literature that discusses how to manage vegan diets for athletic purposes. This article attempted to review literature in order to provide recommendations for how to construct a vegan diet for athletes and exercisers. While little data could be found in the sports nutrition literature specifically, it was revealed elsewhere that veganism creates challenges that need to be accounted for when designing a nutritious diet. This included the sufficiency of energy and protein; the adequacy of vitamin B12, iron, zinc, calcium, iodine and vitamin D; and the lack of the long-chain n-3 fatty acids EPA and DHA in most plant-based sources. However, via the strategic management of food and appropriate supplementation, it is the contention of this article that a nutritive vegan diet can be designed to achieve the dietary needs of most athletes satisfactorily. Further, it was suggested here that creatine and β-alanine supplementation might be of particular use to vegan athletes, owing to vegetarian diets promoting lower muscle creatine and lower muscle carnosine levels in consumers. Empirical research is needed to examine the effects of vegan diets in athletic populations however, especially if this movement grows in popularity, to ensure that the health and performance of athletic vegans is optimised in accordance with developments in sports nutrition knowledge

Non-Timber Forest Product Livelihood-Focused Interventions in Support of Mangrove Restoration: A Call to Action

Mangroves of tropical and subtropical shores and deltas contribute to ecosystem functioning and human wellbeing in numerous ways but continue to be lost or degraded worldwide at a rapid pace. Overexploitation driven by poverty is often the root cause of mangrove destruction and degradation. The negative feedback cycle between destruction and poverty can only be broken by justly valuing current or introducing new sustainable livelihood options to foster long-lasting local support for mangroves. The large array of non-timber forest products (NTFPs) that mangroves offer have rarely been developed beyond the subsistence level and remain undervalued as “products of the poor”. In light of the global trends towards sustainability and bio-economy, today they represent a major business opportunity for forest communities to produce high value-added end-user products. Even though mangrove NTFPs have been recognized to have high potential toward inclusive development and poverty alleviation and to be highly gender-equal, the development of mangrove NTFPs has continued to attract very little funding or research interest. Several ecological characteristics make commercialization of mangrove NTFPs particularly challenging. Production at economies of scale, including quality standards, as well as marketing and value chain management are all essential in order to develop these products beyond their subsistence role. To be most effective, a systems perspective on NTFP development is needed, whereby product-market development occurs in unison and based on a participative, inclusive and fair development approach. The species/product of choice for value-added product-market development in any specific community or area will depend on several factors. To address many of the typical constraints and maximize the chances of success, we suggest that the use of village or district-level cooperatives may be particularly useful. A better use of the untapped potential of mangroves for local livelihoods may form a most convincing advocate for local protection and restoration of mangrove forests. Therefore, funding agencies, governments and researchers alike are called to invest in mangrove NTFP development as a way to locally incentivize sustainable mangrove protection and restoration. View Full-Tex

Heterozygous mutations in the tumor suppressor gene PATCHED provoke basal cell carcinoma-like features in human organotypic skin cultures

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Changing pathology with changing drugs: skin cancer

Today skin cancer is mainly treated by surgical interventions. New findings concerning molecular biology and the signaling pathways in epithelial skin cancers such as basal cell carcinoma, squamous cell carcinoma or melanoma, and mesenchymal skin cancers such as angiosarcoma and dermatofibrosarcoma protuberans (DFSP) have identified new molecular targets for a systemic or local treatment approach. For DFSP there is an opportunity already today to reduce the intensity of surgical procedures by pretreatment with targeted therapy. This article highlights important aspects in several skin cancer types