36 research outputs found

    The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

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    More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

    Dynamics of soil properties and organic carbon pool in topsoil of zokor-made mounds at an alpine site of the Qinghai–Tibetan Plateau

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    The population of burrowing plateau zokors (Myospalax baileyi) was markedly increased in the Qinghai- Tibetan Plateau. The objective of this study was to investigate the effects of zokor foraging and mound-making disturbance on topsoil properties and organic C pools at an alpine site of the Qinghai-Tibetan Plateau. Surface (0-15 cm) soil samples were collected from mounds with different ages (3 months and 3, 6, and 15 years) and from undisturbed grassland. Above- and below-ground plant biomasses were depleted by zokors in newly created mounds (3 months). Plant cover and root biomass gradually recovered thereafter, but were still lower in the 15-year-old mounds than in the undisturbed soils. Organic C contents of coarse (>2 mm), soil (<2 mm), particulate (2-0.05 mm) fractions, and microbial biomass, organic C mineralization, ÎČ-glucosidase activity, urease activity, alkaline phosphatase activity, acid phosphatase activity, and soil aggregation were significantly lower in the 3, 6, and 15-year-old mound soils than in the undisturbed soils or newly created mound soils. Fifteen years after mound creation, the soil had only 12% of root biomass, 35% of coarse organic C, 83% of particulate organic C, 58% of microbial biomass C, 57% of 30-day respired C, and 45% of water-stable aggregate mean weight diameter, compared to values of the undisturbed soils. Our results suggested that foraging and mound-making by zokors have negative impacts on properties and organic matter content of the topsoil

    Resource dilution effects on specialist insect herbivores in a grassland biodiversity experiment

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    1. The resource concentration hypothesis predicts that specialist insect herbivores attain higher loads (density per unit mass of the host-plant species) when their food plants grow in high-density patches in pure stands. 2. We tested the resource concentration hypothesis for nine specialist insect herbivore species sampled from a field experiment where plant diversity had been manipulated experimentally, generating gradients of host-plant abundance. 3. The specialist insects responded to varying host-plant abundance in two contrasting ways: as expected, specialist herbivore species were more likely to be present when their host-plant species were abundant; however, counter to predictions, in plots where specialists were present we found strong negative linear relationships between herbivore loads and host-plant abundances - a 'resource dilution' rather than concentration effect. 4. Increased plant species-richness had an additional, but weak, negative influence on loads beyond that due to host-plant abundance. 5. We discuss the implications of resource dilution effects for biodiversity manipulation experiments and for the study of plant–herbivore interactions more generally
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