Non-random distribution of individual genetic diversity along an environmental gradient

Improving our knowledge of the links between ecology and evolution is especially critical in the actual context of global rapid environmental changes. A critical step in that direction is to quantify how variation in ecological factors linked to habitat modifications might shape observed levels of genetic variability in wild populations. Still, little is known on the factors affecting levels and distribution of genetic diversity at the individual level, despite its vital underlying role in evolutionary processes. In this study, we assessed the effects of habitat quality on population structure and individual genetic diversity of tree swallows (Tachycineta bicolor) breeding along a gradient of agricultural intensification in southern Québec, Canada. Using a landscape genetics approach, we found that individual genetic diversity was greater in poorer quality habitats. This counter-intuitive result was partly explained by the settlement patterns of tree swallows across the landscape. Individuals of higher genetic diversity arrived earlier on their breeding grounds and settled in the first available habitats, which correspond to intensive cultures. Our results highlight the importance of investigating the effects of environmental variability on individual genetic diversity, and of integrating information on landscape structure when conducting such studies.     

Aldosterone nuclear receptors in kidneys of chick embryo

We have studied the properties of the nuclear receptors for aldosterone in kidneys of chick embryo. Aliquots of 0.4 M KCl nuclear extracts were incubated with [3H]aldosterone with or without 1 microM RU28362, a potent glucocorticoid analog. Scatchard analyses of binding data revealed two classes of binding sites with Ka of 0.26 and 0.03 X 10(9) M-1 and Nmax of 330 fmol and 620 fmol/mg DNA respectively. In presence of RU28362, however, we observed only a single class of binding sites with a Ka of 1.02 X 10(8) M-1 and a Nmax of 90 fmol/mg DNA. Competition studies performed in presence of RU28362 showed that aldosterone was the more effective competitor followed by corticosterone, progesterone, deoxycorticosterone, dexamethasone, cortisol, triamcinolone acetonide and cortisone. The nuclear complexes had a sedimentation coefficient in the area of 8 S which changed to 4-5 S in the presence of 0.4 M KCl. This effect of KCl was prevented by the addition of 10 mM sodium molybdate. Always in the presence of the glucocorticoid analog, by DEAE-c chromatography we observed a major specific aldosterone-binding fraction which was eluted with 0.2 M KCl. This fraction sedimented at 8.4 S in the absence of sodium molybdate and KCl. In the absence of RU28362, DNA-c columns retained only a small portion of the nuclear complexes which were eluted with KCl. These complexes sedimented, on sucrose gradient, at 4.6 and 3.1 S, whereas those which did not bind to DNA-c had a sedimentation coefficient of 8 S. In the presence of RU28362, the majority of bound [3H]aldosterone remained in the column flow-through fraction; when this fraction was further analyzed on DEAE-c, complexes were eluted with 0.2 and 0.3 M KCl. These data indicate that nuclear receptors for aldosterone are present in small number in kidneys of chick embryo and that they are mostly in the 8 S form.     

A Bayesian A-optimal and model robust design criterion

Summary . Suppose that the true model underlying a set of data is one of a finite set of candidate models, and that parameter estimation for this model is of primary interest. With this goal, optimal design must depend on a loss function across all possible models. A common method that accounts for model uncertainty is to average the loss over all models; this is the basis of what is known as Läuter's criterion. We generalize Läuter's criterion and show that it can be placed in a Bayesian decision theoretic framework, by extending the definition of Bayesian A‐optimality. We use this generalized A‐optimality to find optimal design points in an environmental safety setting. In estimating the smallest detectable trace limit in a water contamination problem, we obtain optimal designs that are quite different from those suggested by standard A‐optimality.     

raf RBD and ubiquitin proteins share similar folds, folding rates and mechanisms despite having unrelated amino acid sequences

Recent experimental and theoretical studies in protein folding suggest that the rates and underlying mechanisms by which proteins attain the native state are largely determined by the topological complexity of a specific fold rather than by the fine details of the amino acid sequences. However, such arguments are based upon the examination of a limited number of protein folds. To test this view, we sought to investigate whether proteins belonging to the ubiquitin superfamily display similar folding behavior. To do so, we compared the folding-unfolding transitions of mammalian ubiquitin (mUbi) with those of its close yeast homologue (yUbi), and to those of the structurally related Ras binding domain (RBD) of the serine/threonine kinase raf that displays no apparent sequence homology with the ubiquitin family members. As demonstrated for mUbi [Krantz, B. A., and Sosnick, T. R. (2000) Biochemistry 39, 11696-11701], we show that a two-state transition model with no burst phase intermediate can describe folding of both yUbi and raf RBD. We further demonstrate that (1) all three proteins refold at rates that are within 1 order of magnitude (1800, 1100, and 370 s(-1) for mUbi, raf RBD, and yUbi, respectively), (2) both mUbi and raf RBD display similar refolding heterogeneity, and (3) the folding free energy barriers of both mUbi and raf RBD display a similar temperature dependence and sensitivity to a stabilizing agent or to mutations of a structurally equivalent central core residue. These findings are consistent with the view that rates and mechanisms for protein folding depend mostly on the complexity of the native structure topology rather than on the fine details of the amino acid sequence.     

Should symptomatic menopausal women be offered hormone therapy?

Many physicians remain uncertain about prescribing hormone therapy for symptomatic women at the onset of menopause. The American Society for Reproductive Medicine (ASRM) convened a multidisciplinary group of healthcare providers to discuss the efficacy and risks of hormone therapy for symptomatic women, and to determine whether it would be appropriate to treat women at the onset of menopause who were complaining of menopausal symptoms. MAJOR FINDINGS: Numerous controlled clinical trials consistently demonstrate that hormone therapy, administered via oral, transdermal, or vaginal routes, is the most effective treatment for vasomotor symptoms. Topical vaginal formulations of hormone therapy should be preferred when prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy. Data from the Women's Health Initiative indicate that the overall attributable risk of invasive breast cancer in women receiving estrogen plus progestin was 8 more cases per 10,000 women-years. No increased risk for invasive breast cancer was detected for women who never used hormone therapy in the past or for those receiving estrogen only. Hormone therapy is not effective for the treatment of cardiovascular disease and that the risk of cardiovascular disease with hormone therapy is principally in older women who are considerably postmenopause. CONCLUSIONS: Healthy symptomatic women should be offered the option of hormone therapy for menopausal symptoms. Symptom relief with hormone therapy for many younger women (at the onset of menopause) with menopausal symptoms outweighs the risks and may provide an overall improvement in quality of life. Hormone therapy should be individualized for symptomatic women. This involves tailoring the regimen and dose to individual needs.     

Sensitive detection of malaria infection by third harmonic generation imaging

Malaria remains a major health concern worldwide, with 350-500 million cases reported annually in endemic countries. In this study, we report a novel and highly sensitive optical-based detection of malaria-infected blood cells by third harmonic generation (THG) imaging of hemozoin pigment that is naturally deposited by the parasite during its lifecycle. The THG signal from the hemozoin was greater than we have observed in any cell type with signal/noise ratios that reach 1000:1. This method allows a rapid and robust detection of early stage infections of blood cells. The immense nonlinear response of the intrinsic parasitic by-product pigments suggests that automated optical detection by THG could be used for sensitive and rapid screening of parasite infection in blood samples.     

Nonideal nest box selection by tree swallows breeding in farmlands: Evidence for an ecological trap?

Animals are expected to select a breeding habitat using cues that should reflect, directly or not, the fitness outcome of the different habitat options. However, human‐induced environmental changes can alter the relationships between habitat characteristics and their fitness consequences, leading to maladaptive habitat choices. The most severe case of such nonideal habitat selection is the ecological trap, which occurs when individuals prefer to settle in poor‐quality habitats while better ones are available. Here, we studied the adaptiveness of nest box selection in a tree swallow (Tachycineta bicolor) population breeding over a 10‐year period in a network of 400 nest boxes distributed along a gradient of agricultural intensification in southern Québec, Canada. We first examined the effects of multiple environmental and social habitat characteristics on nest box preference to identify potential settlement cues. We then assessed the links between those cues and habitat quality as defined by the reproductive performance of individuals that settled early or late in nest boxes. We found that tree swallows preferred nesting in open habitats with high cover of perennial forage crops, high spring insect biomass, and high density of house sparrows (Passer domesticus), their main competitors for nest sites. They also preferred nesting where the density of breeders and their mean number of fledglings during the previous year were high. However, we detected mismatches between preference and habitat quality for several environmental variables. The density of competitors and conspecific social information showed severe mismatches, as their relationships to preference and breeding success went in opposite direction under certain circumstances. Spring food availability and agricultural landscape context, while related to preferences, were not related to breeding success. Overall, our study emphasizes the complexity of habitat selection behavior and provides evidence that multiple mechanisms may potentially lead to an ecological trap in farmlands.     

On the control of HMG-CoA reductase, a key regulatory enzyme of adrenal cholesterol synthesis

In this study we have determined the effect of ACTH on the activity of HMG-CoA reductase in microsomes of hamster adrenals. Cycloheximide was used to study the dependence of the increased enzyme activity by ACTH on de novo protein synthesis. Microsomes were prepared and preincubated with and without NaF and in the presence or absence of phosphorylase phosphatase in order to differentiate between expressed (McNaF) and total (McPP) activity. ACTH induced (after 120 and 180 min) significant increases in HMG-CoA reductase activity with a latent period of 60 min for both McNaF and McPP preparations. Cycloheximide alone decreased the activity of the reductase and the coadministration of cycloheximide + ACTH caused a greater loss of activity. Also, both treatments produced an accumulation of free cholesterol in adrenals suggesting an increased turnover of the reductase by these substances. Preincubation of microsomes at 37 degrees C enhanced per se HMG-CoA reductase activity, but the relative increase produced by ACTH treatments or endogenous ACTH remained essentially the same. In conclusion, under experimental conditions used, the enhancement of HMG-CoA reductase activity produced by ACTH seem to be due to increased enzyme synthesis.