RESUMO
Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic mutations that must drive clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world.
Assuntos
Doenças do Cão/genética , Cães/genética , Estudos de Associação Genética , Tumores Venéreos Veterinários/genética , Animais , Apoptose , Autoantígenos/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Linhagem da Célula/genética , Colágeno Tipo XI/genética , Proteínas de Ligação a DNA/genética , Doenças do Cão/diagnóstico , Variação Genética , Genoma , Fatores de Troca do Nucleotídeo Guanina/genética , Proteoglicanas de Heparan Sulfato/genética , Proteínas dos Microfilamentos/genética , Mutação , Miotonina Proteína Quinase/genética , Filogenia , Análise de Componente Principal , Análise de Sequência de DNA , Tumores Venéreos Veterinários/diagnósticoRESUMO
Offshore renewables are expanding, yet more information is required to understand their possible impacts on the environment. Little is known about the effects of Electromagnetic Fields (EMF) from subsea power cables on marine life. This study simulated an EMF of 500 µT, as modelled for an export cable over a rocky shore, where the industry standard cable burial would not be possible. Righting reflex, refractive index of haemolymph/coelomic fluid, and total haemocyte/coelomocyte counts were measured for four coastal invertebrates (Asterias rubens, Echinus esculentus, Necora puber, and Littorina littorea). No significant differences were found in either behavioural or physiological responses. This was the first study to investigate EMF exposure on righting reflex, and the first ever EMF study on edible sea urchins and periwinkles, and only one of a couple for common starfish and velvet crabs. It therefore, provides valuable data for environmental impact assessments, marine spatial planning, and commercial fisheries.
Assuntos
Braquiúros , Gastrópodes , Animais , Campos Eletromagnéticos , Reflexo de Endireitamento , Energia Renovável , Meio AmbienteRESUMO
European oyster (Ostrea edulis) restoration often requires the timely deployment of shell habitat for larval settlement. To inform this increasingly popular process, the present study investigated temporal and spatial abundance patterns of O. edulis larvae in a rare commercial fishery (Loch Ryan, Scotland, UK). Patterns in larval abundance were analysed against variability in temperature, salinity, chlorophyll, oxygen, tidal/moon phase, light, date, and location. 'Temperature sum' (sum total of degrees per day above 7 °C) was the most significant seasonal predictor of larval abundance; with a peak at 617 degree-days. Oyster larval abundance did not significantly vary between oyster bed and non-bed habitats but was significantly higher in the mid and near-surface part of the water column. The findings are discussed in the context of emerging international restoration initiatives and have implications for: where habitat restoration would be successful; the prediction of larval connectivity between sites; and a transferable indicator to optimise shell-habitat deployment timing.
Assuntos
Ostrea , Animais , Ecossistema , Larva , Escócia , Alimentos MarinhosRESUMO
Radioimmunotherapy (RIT) is effective treatment for indolent non-Hodgkin lymphomas (NHLs), but response durations are usually limited, especially in aggressive NHL. We hypothesized that administration of bortezomib as a radiosensitizer with RIT would be tolerable and improve efficacy in NHL. This phase 1 dose-escalation study evaluated escalating doses of bortezomib combined with 131I-tositumomab in patients with relapsed/refractory NHL. Twenty-five patients were treated. Treatment was well tolerated, with primarily hematologic toxicity. The maximum tolerated dose (MTD) was determined to be 0.9 mg/m2 bortezomib, in combination with a standard dose of 75 cGy 131I-tositumomab. Sixteen patients responded (64%), including 44% complete responses (CRs), with 82% CR in patients with follicular lymphoma (FL). At a median follow-up of 7 months, median progression-free survival was 7 months, and seven of 11 patients with FL remained in remission at a median of 22 months. In conclusion, bortezomib can be safely administered in combination with 131I-tositumomab with promising response rates.