"Emerging" parasitic infections in arctic ungulates

Important drivers for emergence of infectious disease in wildlifeinclude changes in the environment, shrinking habitats or concentrationof wildlife, and movement of people, animals, pathogens, orvectors. In this paper we present three case-studies of emergingparasitic infections and diseases in ungulates in the Canadiannorth. First we discuss climate warming as an important driverfor the emergence of disease associated with Umingmakstrongyluspallikuukensis, a nematode lungworm of muskoxen. Then we examinehow Protostrongylus stilesi, the sheep lungworm, emerged (orre-emerged) in muskoxen after re-introduction of this host intoits historical range made it sympatric with Dall's sheep. Finally,we consider Teladorsagia boreoarcticus, a newly described andcommon abomasal nematode of muskoxen that is emerging as a disease-causingparasite and may be an important regulator for muskox populationson Banks Island, Northwest Territories. These and other arctichost-parasite systems are exquisitely tuned and constrainedby a harsh and highly seasonal environment. The dynamics ofthese systems will be impacted by climate change and other ecologicaldisruptions. Baseline knowledge of parasite biodiversity andparasite and host ecology, together with predictive models andlong-term monitoring programs, are essential for anticipatingand detecting altered patterns of host range, geographic distribution,and the emergence of parasitic infections and diseases.     

Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine K-cells in response to nutrient absorption. In this study we have utilized a specific and enzymatically stable GIP receptor antagonist, (Pro3)GIP, to evaluate the contribution of endogenous GIP to insulin secretion and glucose homeostasis in mice. Daily injection of (Pro3)GIP (25 nmol/kg body weight) for 11 days had no effect on food intake or body weight. Non-fasting plasma glucose concentrations were significantly raised (p<0.05) by day 11, while plasma insulin concentrations were not significantly different from saline treated controls. After 11 days, intraperitoneal glucose tolerance was significantly impaired in the (Pro3)GIP treated mice compared to control (p<0.01). Glucose-mediated insulin secretion was not significantly different between the two groups. Insulin sensitivity of 11-day (Pro3)GIP treated mice was slightly impaired 60 min post injection compared with controls. Following a 15 min refeeding period in 18 h fasted mice, food intake was not significantly different in (Pro3)GIP treated mice and controls. However, (Pro3)GIP treated mice displayed significantly elevated plasma glucose levels 30 and 60 min post feeding (p<0.05, in both cases). Postprandial insulin secretion was not significantly different and no changes in pancreatic insulin content or islet morphology were observed in (Pro3)GIP treated mice. The observed biological effects of (Pro3)GIP were reversed following cessation of treatment for 9 days. These data indicate that ablation of GIP signaling causes a readily reversible glucose intolerance without appreciable change of insulin secretion.     

Role of thiocyanate, bromide and hypobromous acid in hydrogen peroxide-induced apoptosis

We have previously reported that H₂O₂-induced apoptosis in HL-60 human leukemia cells takes place in the presence of chloride, requires myeloperoxidase (MPO), and occurs through oxidative reactions involving hypochlorous acid and chloramines. We now report that when chloride is replaced by the pseudohalide thiocyanate, there is little or no H₂O₂-induced apoptosis. Furthermore, thiocyanate inhibits H₂O₂-induced apoptosis when chloride is present at physiological concentrations, and this occurs at thiocyanate concentrations that are present in human serum and saliva. In contrast, bromide can substitute for chloride in H₂O₂-induced apoptosis, but results in a lower percent of the cells induced into apoptosis. Hypobromous acid is likely a short-lived intermediate in this H₂O₂/MPO/bromide apoptosis, and reagent hypobromous acid and bromamines induce apoptosis in HL-60 cells. We conclude that the physiologic concentrations of thiocyanate found in human plasma could modulate the cytototoxicity of H₂O₂ and its resulting highly toxic MPO-generated hypochlorous acid by competing with chloride for MPO. Furthermore, the oxidative products of the reaction of thiocyanate with MPO are relatively innocuous for human leukemic cells in culture. In contrast, bromide can support H₂O₂/MPO/halide apoptosis, but is less potent than chloride and it has no effect in the presence of physiological levels of chloride.     

Overexpression of manganese superoxide dismutase promotes the survival of prostate cancer cells exposed to hyperthermia

It has been hypothesized that exposure of cells to hyperthermia results in an increased flux of reactive oxygen species (ROS), primarily superoxide anion radicals, and that increasing antioxidant enzyme levels will result in protection of cells from the toxicity of these ROS. In this study, the prostate cancer cell line, PC-3, and its manganese superoxide dismutase (MnSOD)-overexpressing clones were subjected to hyperthermia (43°C, 1 h). Increased expression of MnSOD increased the mitochondrial membrane potential (MMP). Hyperthermic exposure of PC-3 cells resulted in increased ROS production, as determined by aconitase inactivation, lipid peroxidation, and H₂O₂ formation with a reduction in cell survival. In contrast, PC-3 cells overexpressing MnSOD had less ROS production, less lipid peroxidation, and greater cell survival compared to PC-3 Wt cells. Since MnSOD removes superoxide, these results suggest that superoxide free radical or its reaction products are responsible for part of the cytotoxicity associated with hyperthermia and that MnSOD can reduce cellular injury and thereby enhance heat tolerance.     

Evidence for a new metal in a known active site: purification and characterization of an iron-containing quercetin 2,3-dioxygenase from Bacillus subtilis

The protein YxaG from Bacillus subtilis, of previously unknown function, was found to have quercetin 2,3-dioxygenase activity when overexpressed in Escherichia coli. The enzyme converts the flavonol quercetin to 2-protocatechuoylphloroglucinol carboxylic acid and carbon monoxide, indicating that it performs the same reaction and yields the same products as the well-characterized copper-containing quercetin 2,3-dioxygenase from Aspergillus. In contrast to the Aspergillus protein, YxaG contains iron, and the enzyme is sensitive to strong Fe(II) chelators, similar to the extensively studied catechol dioxygenases. The active site metal was probed by EPR spectroscopy using the label nitric oxide to confirm the presence of an Fe(II) atom. The kinetic parameters and pH activity profiles are also markedly different from those of the copper-containing quercetin 2,3-dioxygenases from Aspergillus. YxaG represents the first example of a prokaryotic quercetin 2,3-dioxygenase.     

Nitric oxide and attenuated reflex cutaneous vasodilation in aged skin

Thermoregulatory cutaneous vasodilation is diminished in the elderly. The goal of this study was to test the hypothesis that a reduction in nitric oxide (NO)-dependent mechanisms contributes to the attenuated reflex cutaneous vasodilation in older subjects. Seven young (23 +/- 2 yr) and seven older (71 +/- 6 yr) men were instrumented with two microdialysis fibers in the forearm skin. One site served as control (Ringer infusion), and the second site was perfused with 10 mM N(G)-nitro-l-arginine methyl ester to inhibit NO synthase (NOS) throughout the protocol. Water-perfused suits were used to raise core temperature 1.0 degrees C. Red blood cell (RBC) flux was measured with laser-Doppler flowmetry over each microdialysis fiber. Cutaneous vascular conductance (CVC) was calculated as RBC flux per mean arterial pressure, with values expressed as a percentage of maximal vasodilation (infusion of 28 mM sodium nitroprusside). NOS inhibition reduced CVC from 75 +/- 6% maximal CVC (CVC(max)) to 53 +/- 3% CVC(max) in the young subjects and from 64 +/- 5% CVC(max) to 29 +/- 2% CVC(max) in the older subjects with a 1.0 degrees C rise in core temperature. Thus the relative NO-dependent portion of cutaneous active vasodilation (AVD) accounted for approximately 23% of vasodilation in the young subjects and 60% of the vasodilation in the older subjects at this level of hyperthermia (P < 0.001). In summary, NO-mediated pathways contributed more to the total vasodilatory response of the older subjects at high core temperatures. This suggests that attenuated cutaneous vasodilation with age may be due to a reduction in, or decreased vascular responsiveness to, the unknown neurotransmitter(s) mediating AVD.     

Free mutual mate preferences in house mice affect reproductive success and offspring performance

When social constraints on the expression of mate preferences are absent, variation in offspring viability is predicted to favour females and males that display mate preferences. Earlier studies showed that female and male house mice, Mus domesticus, tested individually and mated with preferred (P) partners had higher reproductive success and better progeny performance than individuals mated with nonpreferred (NP) partners. Here we tested the effects of mutual mate preferences on reproductive success, offspring viability and performance. We conducted mate preference tests and created four types of reproductive pairings. One involved females and males that preferred each other (P-P); the second type had females that preferred the male but the male did not prefer the female (P-NP); the third had females that did not prefer the male but the male did prefer the female (NP-P). The last set consisted of females and males that did not prefer each other (NP-NP). We measured components of fitness for breeders (reproductive success) and offspring viability (birth-to-weaning viability and weight variation) as well as measures of offspring performance. There were no statistical differences in reproductive success of breeders or offspring viability and quality (weight variation) among the four types of pairings. There were, however, consistent differences between P-P versus NP-NP matings. The number of pups weaned, time to first litter, birth-to-weaning viability, pup body weight at birth and weaning, and the growth rates for pups of both sexes were consistently greater for progeny from P-P matings than NP-NP matings. Significant differences occurred among the four mating types in dominance of sons during aggression trials, nest construction and predator avoidance. Progeny from P-P matings displayed behaviour associated with higher fitness more often than progeny from NP-NP matings. These data show that breeders produce more highly competent progeny, most likely to survive, when social constraints on the expression of mate preferences in both sexes are relaxed.Copyright 2003 The Association for the Study of Animal Behaviour. Published by Elsevier Science Ltd. All rights reserved.