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1.
J Vet Intern Med ; 27(5): 1278-82, 2013.
Article in English | MEDLINE | ID: mdl-24033424

ABSTRACT

BACKGROUND: Oral melanoma (OM) in dogs is an aggressive malignancy, with clinical behavior resembling cutaneous melanomas in humans. Melanoma in humans is promoted by an inflammatory environment that is contributed to by leptin and inducible nitric oxide synthase (iNOS). OBJECTIVE: To determine if the patterns of leptin and iNOS expression are similar in OM in dogs and cutaneous melanomas in humans. ANIMALS: Twenty client-owned dogs. METHODS: Retrospective case study. Immunostaining of the OM tumors from each dog was scored for percentage and intensity of leptin and iNOS expression. Mitotic index was used as an indicator of tumor aggression. RESULTS: Leptin was detected in ≥75% of the tumor cells in specimens from 11 dogs. One tumor expressed leptin in ≤25% of the cells. The intensity of leptin expression was variable with 6, 9, and 5 cases exhibiting low-, moderate-, and high-intensity staining, respectively. OM with the lowest percentage of iNOS positive cells displayed the highest mitotic indices (P = .006, ANOVA). CONCLUSIONS AND CLINICAL IMPORTANCE: The expression of leptin is a common finding in melanomas in dogs. These data suggest that the possibility of future clinical applications, such as measuring the concentrations of plasma leptin as a screening tool or leptin as a target for therapy. The relevance of iNOS is not as clear in dogs with OM, for which other directed therapeutics might be more appropriate.


Subject(s)
Dog Diseases/metabolism , Leptin/metabolism , Melanoma/veterinary , Mouth Neoplasms/veterinary , Nitric Oxide Synthase Type II/metabolism , Animals , Dogs , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Leptin/genetics , Melanoma/metabolism , Mouth Neoplasms/metabolism , Nitric Oxide Synthase Type II/genetics
2.
Nature ; 407(6805): 739-42, 2000 Oct 12.
Article in English | MEDLINE | ID: mdl-11048719

ABSTRACT

In On the Origin of Species, Darwin proposed that natural selection had a fundamental role in speciation. But this view receded during the Modern Synthesis when allopatric (geographic) models of speciation were integrated with genetic studies of hybrid sterility and inviability. The sympatric hypothesis posits that ecological specialization after a host shift can result in speciation in the absence of complete geographic isolation. The apple maggot, Rhagoletis pomonella, is a model for sympatric speciation in progress. Hawthorn (Crataegus spp.) is the native host for R. pomonella in N. Americas. But in the mid-1800s, a new population formed on introduced, domesticated apple (Malus pumila). Recent studies have conferred 'host race' status on apple flies as a potentially incipient species, partially isolated from haw flies owing to host-related adaptation. However, the source of selection that differentiates apple and haw flies is unresolved. Here we document a gene-environment interaction (fitness trade-off) that is related to host phenology and that genetically differentiates the races.


Subject(s)
Biological Evolution , Diptera/physiology , Selection, Genetic , Animals , Climate , Diptera/genetics , Models, Biological , Rosales
3.
Gene ; 246(1-2): 49-57, 2000 Apr 04.
Article in English | MEDLINE | ID: mdl-10767526

ABSTRACT

Insects express a battery of potent antimicrobial proteins in response to injury and infection. Recent work from several laboratories has demonstrated that this response is neither stereotypic nor completely nonspecific, and that different pathways are responsible for inducing the expression of antifungal and antibacterial peptides. Here we report the cloning of two closely linked attacin genes from Drosophila melanogaster. We compare their protein coding sequences and find the amino acid sequences to be more highly conserved than the nucleotide sequences, suggesting that both genes are expressed. Like other antimicrobial peptides, attacin expression is strongly induced in infected and injured flies. Unlike others, attacin transcription is uniquely sensitive to mutations in the 18-Wheeler receptor protein, and thus may be regulated by a distinct signaling pathway. The number and organization of binding sites for kappaB and other transcription factors in the promoter regions of both attacin genes are consistent with strong and rapid immune induction. We demonstrate that these promoter regions are sufficient to direct beta-galactosidase expression in transformed Drosophila third-instar larval fat body in a bacterially inducible manner. We present a comparison of the promoter regions of the two attacin genes to those cloned from other antimicrobial peptide genes to assist a better understanding of how antimicrobial genes are differentially regulated.


Subject(s)
Drosophila Proteins , Drosophila melanogaster/genetics , Insect Proteins/genetics , Amino Acid Sequence , Animals , Anti-Infective Agents , Base Sequence , DNA/chemistry , DNA/genetics , Gene Expression , Gene Expression Regulation , Genes, Insect/genetics , Molecular Sequence Data , Promoter Regions, Genetic , Protein Isoforms/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Regulatory Sequences, Nucleic Acid , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , beta-Galactosidase/genetics , beta-Galactosidase/metabolism
4.
Proc Natl Acad Sci U S A ; 94(21): 11417-21, 1997 Oct 14.
Article in English | MEDLINE | ID: mdl-11038585

ABSTRACT

Whether phytophagous insects can speciate in sympatry when they shift and adapt to new host plants is a controversial question. One essential requirement for sympatric speciation is that disruptive selection outweighs gene flow between insect populations using different host plants. Empirical support for host-related selection (i.e., fitness trade-offs) is scant, however. Here, we test for host-dependent selection acting on apple (Malus pumila)- and hawthorn (Crataegus spp.)-infesting races of Rhagoletis pomonella (Diptera: Tephritidae). In particular, we examine whether the earlier fruiting phenology of apple trees favors pupae in deeper states of diapause (or with slower metabolisms/development rates) in the apple fly race. By experimentally lengthening the time period preceding winter, we exposed hawthorn race pupae to environmental conditions typically faced by apple flies. This exposure induced a significant genetic response at six allozyme loci in surviving hawthorn fly adults toward allele frequencies found in the apple race. The sensitivity of hawthorn fly pupae to extended periods of warm weather therefore selects against hawthorn flies that infest apples and helps to maintain the genetic integrity of the apple race by counteracting gene flow from sympatric hawthorn populations. Our findings confirm that postzygotic reproductive isolation can evolve as a pleiotropic consequence of host-associated adaptation, a central tenet of nonallopatric speciation. They also suggest that one reason for the paucity of reported fitness trade-offs is a failure to consider adequately costs associated with coordinating an insect's life cycle with the phenology of its host plant.

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