Assembly of cell regulatory systems through protein interaction domains

The sequencing of complete genomes provides a list that includes the proteins responsible for cellular regulation. However, this does not immediately reveal what these proteins do, nor how they are assembled into the molecular machines and functional networks that control cellular behavior. The regulation of many different cellular processes requires the use of protein interaction domains to direct the association of polypeptides with one another and with phospholipids, small molecules, or nucleic acids. The modular nature of these domains, and the flexibility of their binding properties, have likely facilitated the evolution of cellular pathways. Conversely, aberrant interactions can induce abnormal cellular behavior and disease. The fundamental properties of protein interaction domains are discussed in this review and in detailed reviews on individual domains at Science's STKE at http://www.sciencemag.org/cgi/content/full/300/5618/445/DC1.     

Finite Mixture of Regression Modeling for High-Dimensional Count and Biomass Data in Ecology

Understanding how species distributions respond as a function of environmental gradients is a key question in ecology, and will benefit from a multi-species approach. Multi-species data are often high dimensional, in that the number of species sampled is often large relative to the number of sites, and are commonly quantified as either presence–absence, counts of individuals, or biomass of each species. In this paper, we propose a novel approach to the analysis of multi-species data when the goal is to understand how each species responds to their environment. We use a finite mixture of regression models, grouping species into “Archetypes” according to their environmental response, thereby significantly reducing the dimension of the regression model. Previous research introduced such Species Archetype Models (SAMs), but only for binary assemblage data. Here, we extend this basic framework with three key innovations: (1) the method is expanded to handle count and biomass data, (2) we propose grouping on the slope coefficients only, whilst the intercept terms and nuisance parameters remain species-specific, and (3) we develop model diagnostic tools for SAMs. By grouping on environmental responses only, the model allows for inter-species variation in terms of overall prevalence and abundance. The application of our expanded SAM framework data is illustrated on marine survey data and through simulation. Supplementary materials accompanying this paper appear on-line.     

A diverse range of Phytophthora species are associated with dying urban trees

Surveys of dying vegetation within remnant bushland, parks and gardens, and streetscapes throughout the urban forest of Perth and the South-west of Western Australia revealed symptoms typical of those produced by Phytophthora species. A total of nine Phytophthora species, including P. alticola, P. multivora, P. litoralis, P. inundata, P. nicotianae and P. palmivora were isolated. In addition, three previously undescribed species, Phytophthora aff. arenaria, Phytophthora aff. humicola and Phytophthora sp. ohioensis were isolated. Isolates were recovered from a wide range of native and non-native host genera, including Agonis, Allocasuarina, Brachychiton, Calothamnus, Casuarina, Corymbia, Dracaena, Eucalyptus, Ficus, Pyrus and Xanthorrhoea. Phytophthora multivora was the most commonly isolated species. Out of 230 samples collected 69 were found to be infected with Phytophthora. Of those 69, 54% were located within parks and gardens, 36% within remnant bushland, and 10% within streetscapes. These pathogens may play a key role in the premature decline in health of the urban forest throughout Perth, and should be managed according to the precautionary principle and given high priority when considering future sustainable management strategies.     

Morphologic, immunohistochemical, and molecular characterization of hepatosplenic T-cell lymphoma in a dog

A 13-year-old neutered male Jack Russell Terrier (Parson Russell Terrier) was presented to the Texas Veterinary Medical Center with a history of lethargy, depression, vomiting, and fever. The dog had mildly regenerative anemia, severe thrombocytopenia and low antithrombin activity. Marked splenomegaly was found on physical examination and imaging studies, and malignant round cell neoplasia and marked extramedullary hematopoiesis were diagnosed on aspirates of the spleen. The dog underwent exploratory laporatomy and splenectomy. Because of a rapid decline in clinical condition postsurgery, the dog was euthanized. Splenic and hepatic biopsies were submitted for histopathologic evaluation. A neoplastic population of round cells was found throughout the splenic parenchyma and within hepatic sinusoids. The neoplastic cells stained strongly positive for CD3 (T-cell marker) and were negative for CD79a (B-cell marker) and lysozyme (histiocytic marker). A diagnosis of T-cell lymphoma was confirmed by assessment of T-cell clonality using canine-specific polymerase chain reaction-based techniques. Although expression of the gammadelta T-cell receptor was not evaluated, this case shares many similarities with a rare syndrome in humans known as hepatosplenic gammadelta T-cell lymphoma.     

Natural killer cell activity in untreated and treated dogs with lymphoma

Natural killer (NK) cell activity and function were determined for 11 untreated and treated dogs with lymphoma. Concurrent chromium release and single cell binding assays, methods used to measure overall cytotoxic activity and that from individual cells, respectively, were performed at effector-to-target cell ratios of 50:1 and 100:1, with incubation periods of 12 and 16 hours. Significant reduction was achieved in overall activity for untreated dogs, using a 16-hour incubation period and an effector-to-target ratio of 100:1 (P less than 0.05). Decreased activity (P less than 0.025) was also achieved for those dogs that were administered combination chemotherapy, consisting of such drugs as cyclophosphamide, vincristine, prednisone, and doxorubicin. There was no significant difference in binding or cytotoxic activity by individual cells in the untreated or treated dogs, compared with the healthy controls. Short- or long-term treatment with glucocorticoids did not influence overall NK cll activity or individual cell cytotoxicity. The overall cytotoxic activity in untreated dogs was reduced, but these dogs had relatively normal numbers of NK cells compared with paracontrols. This suggests that a defect in recycling or the ability to kill targets repetitively, may be involved. A similar defect was found in NK cells of dogs treated aggressively with combination chemotherapy.