Dalston Roof Park

How can new types of shared urban spaces support well-being wholeheartedly and attempt to "seed" ideas for innovative and adaptive use through collective appropriation? How to cultivate a new "breed" of community spaces in the city through bottom-up processes: a case-study in co-design

Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours

The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world's largest carnivorous marsupial.Beata Ujvari, Anne-Maree Pearse, Kate Swift, Pamela Hodson, Bobby Hua, Stephen Pyecroft, Robyn Taylor, Rodrigo Hamede, Menna Jones, Katherine Belov and Thomas Madse

Gomesin peptides prevent proliferation and lead to the cell death of devil facial tumour disease cells.

The Tasmanian devil faces extinction due to devil facial tumour disease (DFTD), a highly transmittable clonal form of cancer without available treatment. In this study, we report the cell-autonomous antiproliferative and cytotoxic activities exhibited by the spider peptide gomesin (AgGom) and gomesin-like homologue (HiGom) in DFTD cells. Mechanistically, both peptides caused a significant reduction at G0/G1 phase, in correlation with an augmented expression of the cell cycle inhibitory proteins p53, p27, p21, necrosis, exacerbated generation of reactive oxygen species and diminished mitochondrial membrane potential, all hallmarks of cellular stress. The screening of a novel panel of AgGom-analogues revealed that, unlike changes in the hydrophobicity and electrostatic surface, the cytotoxic potential of the gomesin analogues in DFTD cells lies on specific arginine substitutions in the eight and nine positions and alanine replacement in three, five and 12 positions. In conclusion, the evidence supports gomesin as a potential antiproliferative compound against DFTD disease

New Insights into the Role of MHC Diversity in Devil Facial Tumour Disease

Devil facial tumour disease (DFTD) is a fatal contagious cancer that has decimated Tasmanian devil populations. The tumour has spread without invoking immune responses, possibly due to low levels of Major Histocompatibility Complex (MHC) diversity in Tasmanian devils. Animals from a region in north-western Tasmania have lower infection rates than those in the east of the state. This area is a genetic transition zone between sub-populations, with individuals from north-western Tasmania displaying greater diversity than eastern devils at MHC genes, primarily through MHC class I gene copy number variation. Here we test the hypothesis that animals that remain healthy and tumour free show predictable differences at MHC loci compared to animals that develop the disease

Genomic Restructuring in the Tasmanian Devil Facial Tumour: Chromosome Painting and Gene Mapping Provide Clues to Evolution of a Transmissible Tumour

Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that threatens the world's largest marsupial carnivore, the Tasmanian devil, with extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild devil numbers, and intense research efforts to understand and contain the disease have since demonstrated that the tumour is a clonal cell line transmitted by allograft. We used chromosome painting and gene mapping to deconstruct the DFTD karyotype and determine the chromosome and gene rearrangements involved in carcinogenesis. Chromosome painting on three different DFTD tumour strains determined the origins of marker chromosomes and provided a general overview of the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence in situ hybridisation provided a finer level of resolution of genome rearrangements in DFTD strains. Our findings demonstrate that only limited regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD. Regions rearranged in DFTD are also highly rearranged between different marsupials. Differences between strains are limited, reflecting the unusually stable nature of DFTD. Finally, our detailed maps of both the devil and tumour karyotypes provide a physical framework for future genomic investigations into DFTD

The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer

The Tasmanian devil, a marsupial carnivore, is endangered because of the emergence of a transmissible cancer known as devil facial tumor disease (DFTD). This fatal cancer is clonally derived and is an allograft transmitted between devils by biting. We performed a large-scale genetic analysis of DFTD with microsatellite genotyping, a mitochondrial genome analysis, and deep sequencing of the DFTD transcriptome and microRNAs. These studies confirm that DFTD is a monophyletic clonally transmissible tumor and suggest that the disease is of Schwann cell origin. On the basis of these results, we have generated a diagnostic marker for DFTD and identify a suite of genes relevant to DFTD pathology and transmission. We provide a genomic data set for the Tasmanian devil that is applicable to cancer diagnosis, disease evolution, and conservation biology

Dental pulp stem cells - exploration in a novel animal model: the Tasmanian Devil (Sarcophilus harrisii)

Dental pulp stem cells (DPSC) are a heterogeneous population of highly proliferative stem cells located in the soft inner pulp tissue of the tooth. Demonstrated to have an affinity for neural differentiation, DPSC have been reported to generate functional Schwann cells (SC) through in vitro differentiation. Both DPSC and SC have neural crest origins, recently a significant population of DPSC have been reported to derive from peripheral nerve-associated glia. The predisposition DPSC have towards the SC lineage is not only a very useful tool for neural regenerative therapies in the medical field, it also holds great promise in the veterinary field. Devil Facial Tumour (DFT) is a clonally transmissible cancer of SC origin responsible for devastating wild populations of the Tasmanian devil. Very few studies have investigated the healthy Tasmanian devil SC (tdSC) for comparative studies between tdSC and DFT cells, and the development and isolation of a tdSC population is yet to be undertaken. A Tasmanian devil DPSC model offers a promising new outlook for DFT research, and the link between SC and DPSC may provide a potential explanation as to how a cancerous SC initially arose in a single Tasmanian devil to then go on to infect others as a parasitic clonal cell line. In this review we explore the current role of DPSC in human regenerative medicine, provide an overview of the Tasmanian devil and the devastating effect of DFT, and highlight the promising potential DPSC techniques pose for DFT research and our current understanding of DFT.Chelsea M. Graham, Karlea L. Kremer, Simon A. Koblar, Monica A. Hamilton-Bruce, Stephen B. Pyecrof

The Immunohistochemical Characterization of Devil Facial Tumor Disease (DFTD) in the Tasmanian Devil (Sarcophilus harrisii)

Immunohistochemical techniques were used to characterize the disfiguring and debilitating fatal neoplastic disease, devil facial tumor disease (DFTD), which has recently affected a significant proportion of the wild population of Tasmanian Devils (Sarcophilus harrisii). The diagnostic values of a number of immunohistochemical stains were employed to further characterize 50 representative cases. The neoplasms were negative for cytokeratin (0/48), epithelial membrane antigen (0/42), von Willebrand factor (vWF) (0/11), smooth muscle actin (SMA) (0/26), desmin (0/47), glial fibrillary acid protein (0/13), CD16 (0/13), CD57 (0/43), CD3 (0/18), and LSP1 (0/16). DFTD cells were positive for vimentin (50/50), S-100 (41/48), melan A (11/39), neuron specific enolase (35/35), chromogranin A (12/12) and synaptophysin (29/30). The cells were negative for amyloid (0/30) and stained negatively with Singh's silver (0/34) but were weakly argyrophilic (3/40) using Grimelius histochemical stain. These staining characteristics are consistent with cells of neuroectodermal origin

Doxorubicin and carboplatin trials in Tasmanian devils (Sarcophilus harrisii) with Tasmanian devil facial tumor disease

Abstract not availableDavid N. Phalen, Angela E. Frimberger, Sarah Peck, Stephen Pyecroft, Colette Harmsen, Suzanneth Lola, Antony S. Moor