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1.
Nat Commun ; 9(1): 3474, 2018 08 27.
Article in English | MEDLINE | ID: mdl-30150763

ABSTRACT

Malaria is a fatal human parasitic disease transmitted by a mosquito vector. Although the evolution of within-host malaria virulence has been the focus of many theoretical and empirical studies, the vector's contribution to this process is not well understood. Here, we explore how within-vector resource exploitation would impact the evolution of within-host Plasmodium virulence. By combining within-vector dynamics and malaria epidemiology, we develop a mathematical model, which predicts that non-competitive parasitic resource exploitation within-vector restricts within-host parasite virulence. To validate our model, we experimentally manipulate mosquito lipid trafficking and gauge within-vector parasite development and within-host infectivity and virulence. We find that mosquito-derived lipids determine within-host parasite virulence by shaping development (quantity) and metabolic activity (quality) of transmissible sporozoites. Our findings uncover the potential impact of within-vector environment and vector control strategies on the evolution of malaria virulence.


Subject(s)
Malaria/parasitology , Plasmodium/pathogenicity , Animals , Humans , Malaria/transmission , Mosquito Vectors/parasitology , Virulence
2.
Am J Surg ; 174(5): 507-12, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9374226

ABSTRACT

BACKGROUND: Interleukin 8 (IL-8) is an important cytokine involved in tumor growth and angiogenesis in a variety of malignancies. We hypothesize that IL-8 plays an important role in the cellular proliferation and angiogenesis seen in head and neck squamous cell carcinoma (HNSCC) and set out to identify its receptors, IL-8RA and IL-8RB. METHODS: Immunohistochemical analysis was performed on specimens from 38 HNSCC patients with stage I to IV disease and control tissues. RESULTS: All of cancer specimens demonstrated positive staining for IL-8RA. The IL-8RA staining of microvessel endothelial cells was seen in 51%. The IL-8RB pattern was similar to the IL-8RA pattern in that 97% of cancer sections demonstrated positive cancer cell staining, and 74% of the specimens demonstrated positive staining for microvessel endothelial cells. CONCLUSION: Our studies demonstrate that IL-8 receptors are expressed by cancer cells and microvessel endothelial cells in HNSCC, suggesting that IL-8 may act in an autocrine/paracrine fashion to stimulate cellular proliferation and angiogenesis.


Subject(s)
Antigens, CD/biosynthesis , Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/metabolism , Interleukin-8/biosynthesis , Receptors, Interleukin/biosynthesis , Animals , Carcinoma, Squamous Cell/pathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Mice , Mice, Nude , Neoplasm Transplantation , Receptors, Chemokine/biosynthesis , Receptors, Interleukin-8A , Receptors, Interleukin-8B , Transplantation, Heterologous
3.
J Parasitol ; 81(3): 385-94, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7776123

ABSTRACT

Isoenzyme and random amplified polymorphic DNA (RAPD) markers were used to characterize the genetics of geographic variation among population samples of Ascaris suum from midwestern localities. Independent estimates of fixation indices (FST) based on isoenzyme and RAPD markers showed the same general patterns of differentiation and substantial statistical correlation (r = 0.70). Of the total estimated gene diversity, 9.4% (isoenzyme) and 9.2% (RAPD) was distributed among infrapopulations. Geographic localities accounted for 7.8% (isoenzyme) and 6.2% (RAPD) of the total gene diversity. Only infrapopulations from a single farm were characterized by low fixation indices (isoenzyme and RAPD FST < 0.05). Isoenzyme and RAPD markers revealed moderate genetic differentiation among infrapopulations and localities, which indicates significant population subdivision among A. suum from farms within geographic regions. Departures from random mating were revealed by deficiencies of heterozygotes within infrapopulations and by high positive values of FIS among and between infrapopulations. The average inbreeding (FIS) coefficient among all infrapopulations was 0.22. Thus, the genetic composition of these A. suum infrapopulations, whether from a general geographic region of a single farm, was not consistent with a model of random recruitment from a larger panmictic pool of parasite life cycle stages.


Subject(s)
Ascaris suum/genetics , Genetic Variation , Isoenzymes/genetics , Alleles , Aminopeptidases/genetics , Animals , Ascaris suum/enzymology , Base Sequence , DNA Fingerprinting , DNA Primers/chemistry , DNA, Helminth/analysis , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases , Female , Gene Frequency , Genetic Markers , Male , Mannose-6-Phosphate Isomerase/genetics , Midwestern United States , Molecular Sequence Data , Phosphogluconate Dehydrogenase/genetics , Polymorphism, Genetic
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