Prevalence of risk factors for cardiovascular disease in Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992

BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification.     

Expression and function of formyl peptide receptors on human fibroblast cells

The migration of polymorphonuclear leukocytes from the blood to sites of infection in tissues is a hallmark of the innate immune response. Formylated peptides produced as a byproduct of bacterial protein synthesis are powerful chemoattractants for leukocytes. Formyl peptides bind to two different G protein-coupled receptors (formyl peptide receptor (FPR) and the low affinity formyl peptide receptor-like-1 (FPRL1)) to initiate a signal transduction cascade leading to cell activation and migration. Our analysis of expressed sequences from many cDNA libraries draws attention to the fact that FPRs are widely expressed in nonlymphoid tissues. Here we demonstrate that FPRs are expressed by normal human lung and skin fibroblasts and the human fibrosarcoma cell line HT-1080. The expression on fibroblasts of receptors for bacteria-derived peptides raises questions about the possible function of these receptors in nonleukocyte cells. We studied the function of FPRs on fibroblasts and find that stimulation with fMLP triggers dose-dependent migration of these cells. Furthermore, fMLP induces signal transduction including intracellular calcium flux and a transient increase in F-actin. The fMLP-induced adhesion and motility of fibroblasts on fibronectin require functional protein kinase C and phosphatidylinositol 3-kinase. This first report of a functional formyl peptide receptor in cells of fibroblast origin opens new possibilities for the role of fibroblasts in innate immune responses.     

Two carbohydrate binding sites in the H(CC)-domain of tetanus neurotoxin are required for toxicity

Tetanus neurotoxin binds via its carboxyl-terminal H(C)-fragment selectively to neurons mediated by complex gangliosides. We investigated the lactose and sialic acid binding pockets of four recently discovered potential binding sites employing site-directed mutagenesis. Substitution of residues in the lactose binding pocket drastically decreased the binding of the H(C)-fragment to immobilized gangliosides and to rat brain synaptosomes as well as the inhibitory action of recombinant full length tetanus neurotoxin on exocytosis at peripheral nerves. The conserved motif of S(1287)XWY(1290) em leader G(1300) assisted by N1219, D1222, and H1271 within the lactose binding site comprises a typical sugar binding pocket, as also present, for example, in cholera toxin. Replacement of the main residue of the sialic acid binding site, R1226, again caused a dramatic decline in binding affinity and neurotoxicity. Since the structural integrity of the H(C)-fragment mutants was verified by circular dichroism and fluorescence spectroscopy, these data provide the first biochemical evidence that two carbohydrate interaction sites participate in the binding and uptake process of tetanus neurotoxin. The simultaneous binding of one ganglioside molecule to each of the two binding sites was demonstrated by mass spectroscopy studies, whereas ganglioside-mediated linkage of native tetanus neurotoxin molecules was ruled out by size exclusion chromatography. Hence, a subsequent displacement of one ganglioside by a glycoprotein receptor is discussed.     

A THEORY OF FAUNAL BUILDUP FOR COMPETITION COMMUNITIES

Invasion-structured communities have more species than do coevolution-structured communities assembled using the same resource distribution. Species in invasion-structured communities are tightly packed, occupying the upper portion of the resource axis; species in coevolution-structured communities are more widely spaced, and most are located in the lower portion of the resource axis. As a consequence, coevolution-structured communities tend to be more stable than comparable invasion-structured communities, but more open to invasion. Both invasion-structured and coevolution-structured communities have niche separations that are significantly different than would be expected if species were assorted at random. Two-species communities formed by the invasion-only algorithm under asymmetric competition had the majority of their niche separations in the range 0–0.5. All other communities had niche separations that were greater than expected. The most common separations were in the range 1.0–3.5. Thus, while not a common feature of many communities, nicheseparation patterns similar to those described by Hutchinson (1959) appear as an “ensemble” property of many communities. The faunal-buildup graphs formed by the coevolutionary algorithm differ from those formed by the invasion-only algorithm, showing community cycling whenever asymmetric competition is present. Through this cycling behavior the coevolutionary faunal-buildup algorithm provides both a theoretical basis for Wilson's (1959) taxon cycle and a hypothesis explaining the distribution of Anolis lizards in the Lesser Antilles.     

Long-term seasonal abundance patterns of Helicoverpa zea and Heliothis virescens (Lepidoptera: Noctuidae) in the Texas High Plains

Bollworm, Helicoverpa zea (Boddie), and tobacco budworm, Heliothis virescens (F.), male adult (moth) activities were monitored between 1982 and 1995 by using sex pheromone traps in the Texas High Plains. Moths were monitored weekly from early March to mid-November near Lubbock and Halfway, two prominent cotton production areas in the Texas High Plains region. Based on trap captures, the bollworm-budworm complex consisted of approximately 98% bollworms and approximately 2% tobacco budworms. Seasonal activity patterns varied between location for bollworm but not for tobacco budworm. The 14-yr average (+/- SE) bollworm moth abundance (moths per trap per week) at Lubbock was significantly higher (226.5 +/- 10.4) compared with that at Halfway (153.7 +/- 8.1). Correlation analyses showed a significant positive relationship between moth abundance and average weekly temperatures, whereas a significant negative relationship was observed between moth abundance and average weekly wind velocity for both species. Analyses also showed a positive correlation between moth abundance and cumulative degree-days (> 0.0 degrees C) from 1 January. A strong positive relationship was observed between moth abundance and weekly average precipitation for both species. Average weekly abundances were positively correlated between adjacent months during most of the active cotton fruiting season (June-September). However, the relationship between populations that contributed to the overwintering generation and the following spring populations varied between species and study sites. Nevertheless, data from this study indicated that late-season moth catches could be indicative of the dynamics of the early-season moth catches the following year in the High Plains. The mean population abundance curve based on 14-yr averages showed two bollworm population peaks at Lubbock, but only one peak at Halfway. Separate degree-day-based models were developed to describe long-term seasonal abundance patterns of bollworm moths for the Lubbock and Halfway sites.     

Molecular evolution modeled as a fractal Poisson process in agreement with mammalian sequence comparisons

The fractal doubly stochastic Poisson process (FDSPP) model of molecular evolution, like other doubly stochastic Poisson models, agrees with the high estimates for the index of dispersion found from sequence comparisons. Unlike certain previous models, the FDSPP also predicts a positive geometric correlation between the index of dispersion and the mean number of substitutions. Such a relationship is statistically proven herein using comparisons between 49 mammalian genes. There is no characteristic rate associated with molecular evolution according to this model, but there is a scaling relationship in rates according to a fractal dimension of evolution. The FDSPP is a suitable replacement for the homogeneous Poisson process in tests of the lineage dependence of rates and in estimating confidence intervals for divergence times. As opposed to other fractal models, this model can be interpreted in terms of Darwinian selection and drift.      

Two groups control light-induced schiff base deprotonation and the proton affinity of asp(85) in the Arg(82)His mutant of bacteriorhodopsin

Arg(82) is one of the four buried charged residues in the retinal binding pocket of bacteriorhodopsin (bR). Previous studies show that Arg(82) controls the pK(a)s of Asp(85) and the proton release group and is essential for fast light-induced proton release. To further investigate the role of Arg(82) in light-induced proton pumping, we replaced Arg(82) with histidine and studied the resulting pigment and its photochemical properties. The main pK(a) of the purple-to-blue transition (pK(a) of Asp(85)) is unusually low in R82H: 1.0 versus 2.6 in wild type (WT). At pH 3, the pigment is purple and shows light and dark adaptation, but almost no light-induced Schiff base deprotonation (formation of the M intermediate) is observed. As the pH is increased from 3 to 7 the M yield increases with pK(a) 4.5 to a value approximately 40% of that in the WT. A transition with a similar pK(a) is observed in the pH dependence of the rate constant of dark adaptation, k(da). These data can be explained, assuming that some group deprotonates with pK(a) 4.5, causing an increase in the pK(a) of Asp(85) and thus affecting k(da) and the yield of M. As the pH is increased from 7 to 10.5 there is a further 2.5-fold increase in the yield of M and a decrease in its rise time from 200 &mgr;s to 75 &mgr;s with pK(a) 9. 4. The chromophore absorption band undergoes a 4-nm red shift with a similar pK(a). We assume that at high pH, the proton release group deprotonates in the unphotolyzed pigment, causing a transformation of the pigment into a red-shifted "alkaline" form which has a faster rate of light-induced Schiff base deprotonation. The pH dependence of proton release shows that coupling between Asp(85) and the proton release group is weakened in R82H. The pK(a) of the proton release group in M is 7.2 (versus 5.8 in the WT). At pH < 7, most of the proton release occurs during O --> bR transition with tau approximately 45 ms. This transition is slowed in R82H, indicating that Arg(82) is important for the proton transfer from Asp(85) to the proton release group. A model describing the interaction of Asp(85) with two ionizable residues is proposed to describe the pH dependence of light-induced Schiff base deprotonation and proton release.     

Aspergillus penicillioides differentiation and cell division at 0.585 water activity

Water availability acts as the most stringent constraint for life on Earth. Thus, understanding the water relations of microbial extremophiles is imperative to our ability to increase agricultural productivity (e.g., by enhancing the processing and turnover of dead organic matter in soils of arid regions), reduce human exposure to mycotoxins in buildings and our food‐supply chain, prevent the spoilage of foods/animal feeds, books, museum specimens and artworks and better control microbiology of industrial fermentations. Only a small number of microbial systems can retain activity at <0.710 water activity (ISME J 2015 9: 1333–1351). It has long‐been considered that the most resilient of these is Xeromyces bisporus, which inhabits sugar‐rich substrates (Appl Environ Microbiol 1968 16: 1853–1858). The current study focused on germination of Aspergillus penicillioides, a xerophile which is also able to grow under low humidity and saline conditions. Investigations of germination differed from those reported earlier: firstly, aerially borne conidia were harvested, and then used for inoculations, in their dry condition; secondly, cultures were incubated at 24°C, i.e. below optimum germination temperature, to minimize the possibility of water loss from the substrate; thirdly, cultures remained sealed throughout the 73‐day study period (microscopic examination was carried out directly 48 through the Petri plate lid); fourthly, the germination parameters determined were: rates and extent of conidial swelling, production of differentiated germination‐structures and septate germlings, and subsequent development of mycelium and/or sporulation; fifthly, assessments were carried out over a range of water‐activity values and time points to obtain a complete profile of the germination process. Conidia swelled, formed differentiated germination‐structures and then produced septate germlings at a water‐activity of just 0.585 (≡58.5% relative humidity), outside the currently understood thermodynamic window for life. Furthermore, analyses of these data suggest a theoretical water‐activity minimum of 0.565 for germination of A. penicilliodes. In relation to astrobiology, these findings have an application in understanding the limits to life in extraterrestrial environments. In light of current plans for exploration missions to Mars and other places, and the need to safeguard martian scientific sites and potential resources (including water) for future human habitation, a knowledge‐based and effective policy for planetary protection is essential. As it is, Mars‐bound spacecraft may frequently be contaminated with aspergilli (including A. penicillioides) and other organisms which, when transported to other planetary bodies, pose a contamination risk. In crafting countermeasures to offset this, it is important to know as precisely as possible the capabilities of these potential interplanetary visitors.