The Drosophila melanogaster Genetic Reference Panel (DGRP) is a community resource of 205 sequenced inbred lines, derived to improve our understanding of the effects of naturally occurring genetic variation on molecular and organismal phenotypes. We used an integrated genotyping strategy to identify 4,853,802 single nucleotide polymorphisms (SNPs) and 1,296,080 non-SNP variants. Our molecular population genomic analyses show higher deletion than insertion mutation rates and stronger purifying selection on deletions. Weaker selection on insertions than deletions is consistent with our observed distribution of genome size determined by flow cytometry, which is skewed toward larger genomes. Insertion/ deletion and single nucleotide polymorphisms are positively correlated with each other and with local recombination, suggesting that their nonrandom distributions are due to hitchhiking and background selection. Our cytogenetic analysis identified 16 polymorphic inversions in the DGRP. Common inverted and standard karyotypes are genetically divergent and account for most of the variation in relatedness among the DGRP lines. Intriguingly, variation in genome size and many quantitative traits are significantly associated with inversions. Approximately 50% of the DGRP lines are infected with Wolbachia, and four lines have germline insertions of Wolbachia sequences, but effects of Wolbachia infection on quantitative traits are rarely significant. The DGRP complements ongoing efforts to functionally annotate the Drosophila genome. Indeed, 15% of all D. melanogaster genes segregate for potentially damaged proteins in the DGRP, and genome-wide analyses of quantitative traits identify novel candidate genes. The DGRP lines, sequence data, genotypes, quality scores, phenotypes, and analysis and visualization tools are publicly available.[Supplemental material is available for this article.]Studies in Drosophila melanogaster have revealed basic principles and mechanisms underlying fundamental genetic concepts of linkage and recombination and were instrumental in identifying canonical and evolutionarily conserved cell signaling pathways.Most D. melanogaster genes are evolutionarily conserved, leading to fly models for understanding common human diseases and behavioral disorders, dipteran disease vectors, and insects impacting agriculture, medicine, and forensics. Despite nearly a century of research on D. melanogaster, however, a large fraction of its coding and noncoding sequence has no known function (McQuilton et al. 2012). Recent efforts to induce mutations in every protein coding gene utilize transposable elements (Bellen et al. 2004(Bellen et al. , 2011, which have a different spectrum of allelic effects than SNPs and small insertions and deletions (indels). Comprehensive efforts to identify regulatory DNA elements in Drosophila (The Ó 2014 Huang et al.

No abstract

Inhibitory effects of macrophytes on the growth of blue-green algae (i.e. Microcystis aeruginosa, Anabaena flos-aquae, or Phormidium tenue) were evaluated in a coexistence culture system in which concentrations of different macrophyte species were varied (i.e. Egeria densa, Cabomba caroliniana, Myriophyllum spicatum, Ceratophyllum demersum, Eleocharis acicularis, Potamogeton oxyphyllus, Potamogeton crispus, Limnophila sessiliflora, or Vallisneria denseserrulata). Coexistence assay results showed that only the macrophytes C. caroliniana or M. spicatum inhibited the growth of all blue-green algae, with the inhibitory effects of M. spicatum being stronger than those of C. caroliniana and being produced by the release of allelopathic compounds. In subsequent initial addition assays using M. spicatum with the alga M. aeruginosa, no significant growth inhibition was observed; whereas, in contrast, quasi-continuous addition assays showed strong growth inhibition by M. spicatum. These results provide the first evidence that unstable, growth-inhibiting allelopathic compounds are continuously secreted by M. spicatum.

We investigated the properties and interaction domains of Ca2ϩ efflux (i.e., the forward mode) in NCX1-transfected fibroblasts. SN-6 was 3-to 5-fold more inhibitory to 45 Ca 2ϩ uptake in NCX1 (IC 50 ϭ 2.9 M) than to that in NCX2 or NCX3 but not to that in NCKX2. We searched for regions that may form the SN-6 receptor by NCX1/ NCX3-chimeric analyses and determined that amino acid regions 73 to 108 and 193 to 230 in NCX1 are mostly responsible for the differential drug response between NCX1 and NCX3. Further sitedirected mutagenesis revealed that double substitutions of Val227 and Tyr228 in NCX1, which exist within the exchanger inhibitory peptide (XIP) region, mimicked the different drug response. In addition, F213R, G833C, and N839A mutations in NCX1 resulted in loss of drug sensitivity. Exchangers with mutated XIP regions, which display either undetectable or accelerated Na ϩ -dependent inactivation, had markedly reduced sensitivity or hypersensitivity to SN-6, respectively. Cell ATP depletion enhanced the inhibitory potency of SN-6. Therefore, SN-6 at lower doses (IC 50 ϭ 0.63 M) potently protected against hypoxia/reoxygenation-induced cell damage in renal tubular cells overexpressing NCX1, suggesting that this drug predominantly works under hypoxic/ischemic conditions. These properties of SN-6, which may be derived from its interaction with the XIP region, are advantageous to developing it as a new anti-ischemic drug.

No abstract