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Regulating general mutation rates: examination of the hypermutable state model for Cairnsian adaptive mutation.

In the lac adaptive mutation system of Cairns, selected mutant colonies but not unselected mutant types appear to arise from a nongrowing population of Escherichia coli. The general mutagenesis suffered by the selected mutants has been interpreted as support for the idea that E. coli possesses an evolved (and therefore beneficial) mechanism that increases the mutation rate in response to stress (the hypermutable state model, HSM). This mechanism is proposed to allow faster genetic adaptation to stressful conditions and to explain why mutations appear directed to useful sites. Analysis of the HSM reveals that it requires implausibly intense mutagenesis (10(5) times the unselected rate) and even then cannot account for the behavior of the Cairns system. The assumptions of the HSM predict that selected revertants will carry an average of eight deleterious null mutations and thus seem unlikely to be successful in long-term evolution. The experimentally observed 35-fold increase in the level of general mutagenesis cannot account for even one Lac(+) revertant from a mutagenized subpopulation of 10(5) cells (the number proposed to enter the hypermutable state). We conclude that temporary general mutagenesis during stress is unlikely to provide a long-term selective advantage in this or any similar genetic system.

Adaptation, Biological↗

Vascular and microvascular changes--key factors in the development of acetic acid-induced gastric ulcers in rats.

The present study examined the time sequence and histologic and ultrastructural features of the formation and evolution of experimental, acetic acid-induced gastric ulcerations in rats. One hundred percent acetic acid was applied to the gastric serosa of 140 fasted male Sprague-Dawley rats through a polyethylene tube for 30 s. Gastric mucosal changes were evaluated at 1, 5, 15, and 30 min, 1 and 3 h, and 1, 2, 3, 5, 8, and 11 days after acetic acid application by visual inspection, by quantitative and qualitative light microscopy, and by transmission electron microscopy. Following exposure to acetic acid, the earliest morphologic changes occurred at 1 min and consisted of dilatation of large submucosal veins and arteries and mucosal collecting venules. Five to 15 minutes after injury, thrombi developed in submucosal veins and collecting venules, leading to microvascular stasis and mucosal necrosis. By 3 h, necrotic masses started to detach. By 24-48 h, necrotic changes penetrated the submucosa. By 72 h, most ulcers underwent transition into a "chronic" stage characterized histologically by the presence of granulation tissue at the bottom, and the appearance of a transitional healing zone at the margins. By 5 days, an increased amount of granulation tissue was observed and the gastric glands in transitional zones at the ulcer margin displayed cystic dilatation. Based on this study, we conclude that a key feature of acetic acid-induced ulcer formation is the early vascular and microvascular injury, which precedes glandular cell necrosis.

Acetates↗

Endovascular treatment of aneurysms: gene expression of neointimal cells recruited on the embolic agent and evolution with recurrence in an experimental model.

PURPOSE: The authors attempted to identify genes associated with healing or recurrence after embolization in an aneurysm model in which neointima formation at the neck varies according to flow zones. A better understanding of the relationship between blood flow, molecular events, and healing or recurrence may provide future avenues to improve results of endovascular treatment of aneurysms. METHODS: Bilateral carotid venous pouch aneurysms were constructed in 36 dogs and embolized with gelatin sponges. Angiography and pathological studies were performed at T0 and/or 3 weeks (n=22). Angiographic results and neointima formation were scored using a qualitative index applied to the distal (inflow) and proximal (outflow) zones of the neck. In 14 animals, mRNA expression 1 to 14 days after embolization at the proximal or distal segment of the sponge was analyzed by RT-PCR, attempting to correlate flow zones, gene expression, and neointima formation. RESULTS: Aneurysms recurred at 3 weeks, as shown by significantly worse angiographic scores as compared to T0 (P<.01). Neointimal scores differed at pathology, with a more complete neointima at the proximal as compared to the distal aspect of the sponge at 3 weeks (P=.027). Embolization was followed by migration of CD31+, CD14+, smooth muscle alpha-actin+ (SMA+) cells that progressively expressed metalloproteinases (MMP-9,-12,-14), but stable or lesser, retarded expression of inhibitors (TIMP1-4). Growth factors (PDGF-BB, TGF-beta1, TNF-alpha, MCP-1 and Ang-1) were expressed at increasing levels, maximal at 7 to 14 days. Differences between distal and proximal zones were limited to increased expression of MMP-2 proximally (P<.035). CONCLUSION: Gene expression after embolization is compatible with patterns associated with neointima formation. The authors have not identified key factors involved in recurrence.

Actins↗

Quantitative phase-field model of alloy solidification.

We present a detailed derivation and thin interface analysis of a phase-field model that can accurately simulate microstructural pattern formation for low-speed directional solidification of a dilute binary alloy. This advance with respect to previous phase-field models is achieved by the addition of a phenomenological "antitrapping" solute current in the mass conservation relation [Phys. Rev. Lett. 87, 115701 (2001)]]. This antitrapping current counterbalances the physical, albeit artificially large, solute trapping effect generated when a mesoscopic interface thickness is used to simulate the interface evolution on experimental length and time scales. Furthermore, it provides additional freedom in the model to suppress other spurious effects that scale with this thickness when the diffusivity is unequal in solid and liquid [SIAM J. Appl. Math. 59, 2086 (1999)]], which include surface diffusion and a curvature correction to the Stefan condition. This freedom can also be exploited to make the kinetic undercooling of the interface arbitrarily small even for mesoscopic values of both the interface thickness and the phase-field relaxation time, as for the solidification of pure melts [Phys. Rev. E 53, R3017 (1996)]]. The performance of the model is demonstrated by calculating accurately within a phase-field approach the Mullins-Sekerka stability spectrum of a planar interface and nonlinear cellular shapes for realistic alloy parameters and growth conditions.

Journal Article↗

A nonparametric statistical method for image segmentation using information theory and curve evolution.

In this paper, we present a new information-theoretic approach to image segmentation. We cast the segmentation problem as the maximization of the mutual information between the region labels and the image pixel intensities, subject to a constraint on the total length of the region boundaries. We assume that the probability densities associated with the image pixel intensities within each region are completely unknown a priori, and we formulate the problem based on nonparametric density estimates. Due to the nonparametric structure, our method does not require the image regions to have a particular type of probability distribution and does not require the extraction and use of a particular statistic. We solve the information-theoretic optimization problem by deriving the associated gradient flows and applying curve evolution techniques. We use level-set methods to implement the resulting evolution. The experimental results based on both synthetic and real images demonstrate that the proposed technique can solve a variety of challenging image segmentation problems. Futhermore, our method, which does not require any training, performs as good as methods based on training.

Algorithms↗

Experimental evidence for the adaptive evolution of growth rate in the garter snake Thamnophis elegans.

The western terrestrial garter snake (Thamnophis elegans) varies significantly in individual growth rates and life-history traits (maturation, reproduction, and survival) among adjacent populations in nature. This study focuses on assessing the genetic and environmental components of the substantial among-population variation in growth rates. Litters of neonates from nine populations inhabiting either mountain meadow or lakeshore habitat were reared for one year in a common-garden experiment with two temperature treatments. Diet, frequency of feeding, light exposure, and daytime temperatures were identical for all individuals. The two different nighttime temperatures (20 degrees C and 25 degrees C) were chosen to mirror field differences in nighttime thermoregulatory constraints for mountain-meadow and lakeshore snakes, respectively. Temperature and source habitat interacted to affect first-year growth rate. Neonates from meadow dams grew fastest in the cooler treatment, whereas those from lakeshore dams grew fastest in the warmer treatment. The observation that naive neonates, which were gestated and raised under identical conditions, grew fastest in environments characteristic of their natal population is evidence both that there are genetic differences among populations for growth and that these differences reflect adaptation to local habitats at a very small geographic scale. In addition, significant directional selection for large birthweight was measured for neonates from all populations. These results are considered in the context of population colonization history, migration and selection, and competing models for growth rate variation.

Adaptation, Physiological↗

Mycetoma.

We have reviewed the outstanding facts about mycetoma, including the history, first reports in India, the different causal agents according to their geographic distribution, mycologic characteristics, pathology, microbiology, behavior, evolution, immunology, experimental inoculations, associated bacterial complications, and osseous lesions. Various drugs available for treatment are mentioned and recommended. Therapeutic results depend on the age of the disease, and, above all, the bony involvement. N. brasiliensis mycetoma is one of the most frequent species and causes the greatest number of mycetoma cases in America, especially in Mexico.

Africa↗

CIRCULATORY ADAPTATION TO DIVING IN THE FRESHWATER TURTLE.

The heart of the freshwater turtle has a functional ventricular septal defect. In ambient air there is some shunting of blood from the left to the right ventricle through the defect. During prolonged diving or N(2) inhalation, the shunt is reversed and blood from the tissues bypasses the lung and enters the aorta directly. This adaptation appears to be based on the exclusive use of anaerobic glycolysis as an energy source during prolonged diving.

Acclimatization↗

CALCIFIED ECTODERMAL COLLAGENS OF SHARK TOOTH ENAMEL AND TELEOST SCALE.

Amino acid analysis of protein from the enamel of shark teeth and from teleost scales shows the presence of collagens which can be classified chemically as ectodermal. This finding, together with results from a histological examination of the development of these tissues, constitutes strong evidence that both proteins are derived from the ectoderm, like the enamel of higher vertebrates. Since both are calcified, calcification cannot be a specific property of collagens of mesodermal origin alone.

Amino Acids↗