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  • 2010-2014  (6)
  • 1
    Publication Date: 2013-08-08
    Description: The severity of the toxic side effects of chemotherapy varies among patients, and much of this variation is likely genetically based. Here, we use the model system Drosophila melanogaster to genetically dissect the toxicity of methotrexate (MTX), a drug used primarily to treat childhood acute lymphoblastic leukemia and rheumatoid arthritis. We use the Drosophila Synthetic Population Resource, a panel of recombinant inbred lines derived from a multiparent advanced intercross, and quantify MTX toxicity as a reduction in female fecundity. We identify three quantitative trait loci (QTL) affecting MTX toxicity; two colocalize with the fly orthologs of human genes believed to mediate MTX toxicity and one is a novel MTX toxicity gene with a human ortholog. A fourth suggestive QTL spans a centromere. Local single-marker association scans of candidate gene exons fail to implicate amino acid variants as the causative single-nucleotide polymorphisms, and we therefore hypothesize the causative variation is regulatory. In addition, the effects at our mapped QTL do not conform to a simple biallelic pattern, suggesting multiple causative factors underlie the QTL mapping results. Consistent with this observation, no single single-nucleotide polymorphism located in or near a candidate gene can explain the QTL mapping signal. Overall, our results validate D. melanogaster as a model for uncovering the genetic basis of chemotoxicity and suggest the genetic basis of MTX toxicity is due to a handful of genes each harboring multiple segregating regulatory factors.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 2
    Publication Date: 2014-01-05
    Description: Human genome-wide association studies (GWAS) of longevity attempt to identify alleles at different frequencies in the extremely old, relative to a younger control sample. Here, we apply a GWAS approach to "synthetic" populations of Drosophila melanogaster derived from a small number of inbred founders. We used next-generation DNA sequencing to estimate allele and haplotype frequencies in the oldest surviving individuals of an age cohort and compared these frequencies with those of randomly sampled individuals from the same cohort. We used this case–control strategy in four independent cohorts and identified eight significantly differentiated regions of the genome potentially harboring genes with relevance for longevity. By modeling the effects of local haplotypes, we have more power to detect regions enriched for longevity genes than marker-based GWAS. Most significant regions occur near chromosome ends or centromeres where recombination is infrequent, consistent with these regions harboring unconditionally deleterious alleles impacting longevity. Genes in regions of normal recombination are enriched for those relevant to immune function and a gene family involved in oxidative stress response. Genetic differentiation between our experimental cohorts is comparable to that between human populations, suggesting in turn that our results may help explain heterogeneous signals in human association studies of extreme longevity when panels have diverse ancestry.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 3
    Publication Date: 2012-11-06
    Description: The impact of human activity on the biophysical world raises myriad challenges for sustaining Earth system processes, ecosystem services, and human societies. To engage in meaningful problem-solving in the hydrosphere, this necessitates an approach that recognizes the coupled nature of human and biophysical systems. We argue that, in order to produce the next generation of problem-solvers, hydrology education should ensure that students develop an appreciation and working familiarity in the context of coupled human-environmental systems. We illustrate how undergraduate-level hydrology assignments can extend beyond rote computations or basic throughput scenarios to include consideration of the dynamic interactions with social and other biophysical dimensions of complex adaptive systems. Such an educational approach not only builds appropriate breadth of dynamic understanding, but can also empower students toward assuming influential and effective roles in solving sustainability challenges.
    Print ISSN: 1027-5606
    Electronic ISSN: 1607-7938
    Topics: Geography , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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  • 4
    Publication Date: 2012-08-09
    Description: Drylands cover about 40% of the terrestrial land surface and account for approximately 40% of global net primary productivity. Water is fundamental to the biophysical processes that sustain ecosystem function and food production, particularly in drylands where a tight coupling exists between ecosystem productivity, surface energy balance, biogeochemical cycles, and water resource availability. Currently, drylands support at least 2 billion people and comprise both natural and managed ecosystems. In this synthesis, we identify some current critical issues in the understanding of dryland systems and discuss how arid and semiarid environments are responding to the changes in climate and land use. The issues range from societal aspects such as rapid population growth, the resulting food and water security, and development issues, to natural aspects such as ecohydrological consequences of bush encroachment and the causes of desertification. To improve current understanding and inform upon the needed research efforts to address these critical issues, we identify some recent technical advances in terms of monitoring dryland water dynamics, water budget and vegetation water use, with a focus on the use of stable isotopes and remote sensing. These technological advances provide new tools that assist in addressing critical issues in dryland ecohydrology under climate change.
    Print ISSN: 1027-5606
    Electronic ISSN: 1607-7938
    Topics: Geography , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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  • 5
    Publication Date: 2012-06-19
    Description: The impact of human activity on the biophysical world raises myriad challenges for sustaining earth system processes, ecosystem services, and human societies. To engage in meaningful problem-solving in the hydrosphere, this necessitates an approach that recognizes the coupled nature of human and biophysical systems. We argue that in order to produce the next generation of problem-solvers, hydrology education should ensure that students develop an appreciation and working familiarity in the context of coupled human-environmental systems. We illustrate how undergraduate-level hydrology assignments can extend beyond rote computations or basic throughput scenarios to include consideration of the dynamic interactions with social and other biophysical dimensions of complex adaptive systems. Such an educational approach not only builds appropriate breadth of dynamic understanding, but can also empower students toward assuming influential and effective roles in solving sustainability challenges.
    Print ISSN: 1812-2108
    Electronic ISSN: 1812-2116
    Topics: Geography , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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  • 6
    Publication Date: 2012-04-16
    Description: Drylands cover about 40% of the terrestrial land surface and account for approximately 40% of global net primary productivity. Water is fundamental to the biophysical processes that sustain ecosystem function and food production, particularly in drylands, where a tight coupling exists between water resource availability and ecosystem productivity, surface energy balance, and biogeochemical cycles. Currently, drylands support at least 2 billion people and comprise both natural and managed ecosystems. In this synthesis, we identify some current critical issues in the understanding of dryland systems and discuss how arid and semiarid environments are responding to the changes in climate and land use. Specifically, we focus on dryland agriculture and food security, dryland population growth, desertification, shrub encroachment and dryland development issues as factors of change requiring increased understanding and management. We also review recent technical advances in the quantitative assessment of human versus climate change related drivers of desertification, evapotranspiration partitioning using field deployable stable water isotope systems and the remote sensing of key ecohydrological processes. These technological advances provide new tools that assist in addressing major critical issues in dryland ecohydrology under climate change
    Print ISSN: 1812-2108
    Electronic ISSN: 1812-2116
    Topics: Geography , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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