589 research outputs found

    Modelling ecosystem adaptation and dangerous rates of global warming

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    This is the author accepted manuscript. The final version is available from Portland Press via the DOI in this recordWe are in a period of relatively rapid climate change. This poses challenges for individual species and threatens the ecosystem services that humanity relies upon. Temperature is a key stressor. In a warming climate, individual organisms may be able to shift their thermal optima through phenotypic plasticity. However, such plasticity is unlikely to be sufficient over the coming centuries. Resilience to warming will also depend on how fast the distribution of traits that define a species can adapt through other methods, in particular through redistribution of the abundance of variants within the population and through genetic evolution. In this paper, we use a simple theoretical ‘trait diffusion’ model to explore how the resilience of a given species to climate change depends on the initial trait diversity (biodiversity), the trait diffusion rate (mutation rate), and the lifetime of the organism. We estimate theoretical dangerous rates of continuous global warming that would exceed the ability of a species to adapt through trait diffusion, and therefore lead to a collapse in the overall productivity of the species. As the rate of adaptation through intraspecies competition and genetic evolution decreases with species lifetime, we find critical rates of change that also depend fundamentally on lifetime. Dangerous rates of warming vary from 1°C per lifetime (at low trait diffusion rate) to 8°C per lifetime (at high trait diffusion rate). We conclude that rapid climate change is liable to favour short-lived organisms (e.g. microbes) rather than longer-lived organisms (e.g. trees).University of ExeterCSSP-Brazi

    Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer's disease-like mice

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    Pathological aggregation of amyloid-β (Aβ) is a main hallmark of Alzheimer's disease (AD). Recent genetic association studies have linked innate immune system actions to AD development, and current evidence suggests profound gender differences in AD pathogenesis. Here, we characterise gender-specific pathologies in the APP23 AD-like mouse model and find that female mice show stronger amyloidosis and astrogliosis compared with male mice. We tested the gender-specific effect of lack of IL12p40, the shared subunit of interleukin (IL)-12 and IL-23, that we previously reported to ameliorate pathology in APPPS1 mice. IL12p40 deficiency gender specifically reduces A plaque burden in male APP23 mice, while in female mice, a significant reduction in soluble Aβ without changes in Aβ plaque burden is seen. Similarly, plasma and brain cytokine levels are altered differently in female versus male APP23 mice lacking IL12p40, while glial properties are unchanged. These data corroborate the therapeutic potential of targeting IL-12/IL-23 signalling in AD, but also highlight the importance of gender considerations when studying the role of the immune system and AD

    Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer's disease-like mice

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    Pathological aggregation of amyloid-β (Aβ) is a main hallmark of Alzheimer's disease (AD). Recent genetic association studies have linked innate immune system actions to AD development, and current evidence suggests profound gender differences in AD pathogenesis. Here, we characterise gender-specific pathologies in the APP23 AD-like mouse model and find that female mice show stronger amyloidosis and astrogliosis compared with male mice. We tested the gender-specific effect of lack of IL12p40, the shared subunit of interleukin (IL)-12 and IL-23, that we previously reported to ameliorate pathology in APPPS1 mice. IL12p40 deficiency gender specifically reduces A plaque burden in male APP23 mice, while in female mice, a significant reduction in soluble Aβ without changes in Aβ plaque burden is seen. Similarly, plasma and brain cytokine levels are altered differently in female versus male APP23 mice lacking IL12p40, while glial properties are unchanged. These data corroborate the therapeutic potential of targeting IL-12/IL-23 signalling in AD, but also highlight the importance of gender considerations when studying the role of the immune system and AD

    Encodings of Range Maximum-Sum Segment Queries and Applications

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    Given an array A containing arbitrary (positive and negative) numbers, we consider the problem of supporting range maximum-sum segment queries on A: i.e., given an arbitrary range [i,j], return the subrange [i' ,j' ] \subseteq [i,j] such that the sum of the numbers in A[i'..j'] is maximized. Chen and Chao [Disc. App. Math. 2007] presented a data structure for this problem that occupies {\Theta}(n) words, can be constructed in {\Theta}(n) time, and supports queries in {\Theta}(1) time. Our first result is that if only the indices [i',j'] are desired (rather than the maximum sum achieved in that subrange), then it is possible to reduce the space to {\Theta}(n) bits, regardless the numbers stored in A, while retaining the same construction and query time. We also improve the best known space lower bound for any data structure that supports range maximum-sum segment queries from n bits to 1.89113n - {\Theta}(lg n) bits, for sufficiently large values of n. Finally, we provide a new application of this data structure which simplifies a previously known linear time algorithm for finding k-covers: i.e., given an array A of n numbers and a number k, find k disjoint subranges [i_1 ,j_1 ],...,[i_k ,j_k ], such that the total sum of all the numbers in the subranges is maximized.Comment: 19 pages + 2 page appendix, 4 figures. A shortened version of this paper will appear in CPM 201

    On Smooth Orthogonal and Octilinear Drawings: Relations, Complexity and Kandinsky Drawings

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    We study two variants of the well-known orthogonal drawing model: (i) the smooth orthogonal, and (ii) the octilinear. Both models form an extension of the orthogonal, by supporting one additional type of edge segments (circular arcs and diagonal segments, respectively). For planar graphs of max-degree 4, we analyze relationships between the graph classes that can be drawn bendless in the two models and we also prove NP-hardness for a restricted version of the bendless drawing problem for both models. For planar graphs of higher degree, we present an algorithm that produces bi-monotone smooth orthogonal drawings with at most two segments per edge, which also guarantees a linear number of edges with exactly one segment.Comment: Appears in the Proceedings of the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

    BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer

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    The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case–control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region of BRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation in BRCA1 was estimated to be 3.8% (95% Cl 0.3–12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence. © 1999 Cancer Research Campaig
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