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At least 1,117 records · Page 62Linked to original sources
PubMed2000

Long-term evolution of local, proximal and remote astrocyte responses after diverse nucleus basalis lesioning (an experimental Alzheimer model): GFAP immunocytochemical study.

A study on long-term astrocytic responses (from 1 day to 20 months after lesioning in 4-month-old rats, and from 1 day to 6 months in 20-month-old rats) to diverse unilateral damage of the nucleus basalis (nbM) by injection of 40 nmol of ibotenic acid, or 50 or 100 nmols of quisqualic acid was performed using a histochemical method (immunoreactivity against the glial fibrillary acidic protein GFAP). Glial reactivity (i.e., isolated or clustered hypertrophic and/or hyper-reactive astrocytes) was evaluated in several ipsilateral and contralateral brain regions: the 'local response' within the damaged nbM region; the 'proximal response' (a new concept proposed by us) in the non-damaged structures neighbouring the nbM; and the 'remote response' in the ipsilateral brain cortex and in the contralateral cortex and nbM. In 4-month-old animals, the remote cortical glial responses, independent of the involution of cortical cholinergic activity and randomly located in layers I-V of motor and somatosensory cortical regions, were similar in appearance over a long period (13-20 months), with the highest reactivity 45 days after lesioning. The proximal response lasted from 1 day to 13 months and afterwards tended to disappear. Contralateral reactivity and ipsilateral cortical scars were observed. The local (nbM) glial response was maintained throughout the period studied. Subsets of astrocytes of different reactivities were observed, most of their elements being highly intermeshed. In 20-month-old animals, nbM lesions produced less positive, but similar, glial reactive patterns. This glial reactivity was superposed onto the glial reactivity of old age. All these results are discussed. The maintenance of reactive astrocytes many months after lesioning suggests the existence of cellular factors other than those produced by damaged nbM neurons. Taking into account the role of glial cells under pathological conditions, it is possible that these reactive astrocytes in humans could promote neurodegenerative processes, such as amyloid plaque formation and neurodegeneration (Alzheimer's disease). Along this line, nbM cholinergic involution could then originate cortical involution through induced reactive astrocytosis.

Age Factors↗
PubMed1988

Baroreflex sensitivity and its evolution during the first year after myocardial infarction.

Experimental data have indicated that baroreflex sensitivity is often depressed in dogs after myocardial infarction and that this depression correlates strongly with subsequent mortality during episodes of acute myocardial ischemia. This finding has several clinical implications. The present study was undertaken with the objectives of assessing the potential existence of differences in baroreflex sensitivity between men with and without myocardial infarction and the time course during the 1st year after infarction of these potential changes in baroreflex sensitivity. Fifty-three subjects entered the study: 32 postinfarction patients and 21 control subjects. Baroreflex sensitivity was assessed by increasing mean blood pressure by aphenylephrine infusion (70 micrograms/ml) and recording the consequent RR interval changes. Baroreflex sensitivity, expressed as the slope of the regression line relating mean blood pressure to RR interval changes, was evaluated 18 days (n = 32), 3 months (n = 17) and 13 months (n = 10) after infarction. Baroreflex sensitivity was lower in the patients than in the control subjects (8.2 +/- 3.7 versus 12.3 +/- 2.9 ms/mm Hg, p = 0.0001). Moreover, 13 (41%) of 32 patients had a baroreflex slope less than 6.5 ms/mm Hg, which was 2 SD below the mean value of the control subjects. The internal control follow-up study showed that baroreflex sensitivity increased 3 months after infarction to values quite similar to those observed in the control subjects (11.1 +/- 5.3 versus 8.7 +/- 3.5 ms/mm Hg, p = 0.02). No further change was observed between 3 and 13 months after myocardial infarction. These data indicate that baroreflex sensitivity is lower in a proportion of postinfarction patients than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1977

Early chemical evolution of nucleic acids: a theoretical model.

Recent experimental work suggests a possible cyclical pathway for early prebiotic oligonucleotide formation that involves (i) dry-state (nontemplate) synthesis of random copolymers with mixed 2',5' and 3',5' bonds, (ii) passage of these oligomers into solution at low temperatures, and (iii) a preferential hydrolysis of the 2',5' bond in any short helices that have formed. This early system could have selected for complementary sequences that were largely 3',5'-linked, but may not have selected efficiently for a single enantiomer of ribose.

Cold Temperature↗
PubMed1995

Alveolar fibrosis and capillary alteration in experimental pulmonary silicosis in rats.

To analyze the evolution of fibrotic and vascular changes in pulmonary silicosis, ultrastructural and immunohistochemical studies were made of the lungs of rats given a single intratracheal injection of silica particles. Early lesions were characterized by accumulations of macrophages and neutrophils in alveolar lumina and interstitium and by damage to alveolar capillaries and epithelial cells. The intraluminal masses of inflammatory cells developed into granulomas and became associated with myofibroblasts that migrated from the interstitium through the damaged epithelial lining. Type II epithelial cells and bronchiolar cuboidal cells proliferated rapidly to line the intraluminal granulomas, incorporating them into the interstitium. This process mediated the transition from intraalveolar fibrosis to interstitial fibrosis. Vascular damage was repaired by proliferation and migration of endothelial cells. Some endothelial cells in alveolar capillaries expressed Factor VIII-related antigen at 2 wk after silica infusion. In normal animals, this feature was present in peribronchiolar but not in alveolar capillaries. Two patterns of endothelial cell migration were shown by staining for proliferating-cell nuclear antigen. The first pattern was characterized by endothelial cells that extended their cytoplasm over preexisting, denuded basement membranes and replaced necrotic cells in alveolar capillaries. At 4 mo after injury, some of these cells had developed fenestrations. The second pattern consisted of budlike sproutings that developed only in peribronchiolar connective tissue. These observations indicate that peribronchiolar vessels are sources for renewal of alveolar capillary endothelium as well as for neovascularization.

Animals↗
PubMed1979

Morphologic observations on experimental corneal vascularization in the rat.

The morphologic evolution of the early events of corneal vascularization in the rat cornea induced by silver nitrate cautery were followed by light and electron microscopy. An initial acute inflammatory response occurred within the first 6 hours after cautery as evidenced by vascular dilation, diapedesis of leukocytes, and an increased vascular permeability, as manifested by distended lymphatics and the presence of extravascular fibrin. At 24 hours after injury, the hypertrophy and the prominence of nucleoli and the presence of abundant polyribosomes were the initial suggestion that vascular endothelial cells and pericytes had entered the mitotic cycle. Nine hours later, at 33 hours after cautery, the first new vessels were observed as sprouts from the capillary arcade and postcapillary venules. The experiments reemphasize the association of acute inflammation and corneal vascularization in this model and underscore the early occurrence of vascular endothelial cell replication.

Animals↗
PubMed2006

Assessing systems properties of yeast mitochondria through an interaction map of the organelle.

Mitochondria carry out specialized functions; compartmentalized, yet integrated into the metabolic and signaling processes of the cell. Although many mitochondrial proteins have been identified, understanding their functional interrelationships has been a challenge. Here we construct a comprehensive network of the mitochondrial system. We integrated genome-wide datasets to generate an accurate and inclusive mitochondrial parts list. Together with benchmarked measures of protein interactions, a network of mitochondria was constructed in their cellular context, including extra-mitochondrial proteins. This network also integrates data from different organisms to expand the known mitochondrial biology beyond the information in the existing databases. Our network brings together annotated and predicted functions into a single framework. This enabled, for the entire system, a survey of mutant phenotypes, gene regulation, evolution, and disease susceptibility. Furthermore, we experimentally validated the localization of several candidate proteins and derived novel functional contexts for hundreds of uncharacterized proteins. Our network thus advances the understanding of the mitochondrial system in yeast and identifies properties of genes underlying human mitochondrial disorders.

Disease Susceptibility↗
PubMed1994

Development and experimental in vivo validation of mathematical modeling of laser coagulation.

Most clinical procedures using the laser are based on thermal laser-tissue interactions. The treatment often consists of inducing damage of given degree and extent by heating the tissue. The aim of this study was to develop a model called HELIOS. The ability of HELIOS to predict thermal coagulation was evaluated by comparison with in vivo experimental results. Conversion of laser light in tissue was studied using the beam-broadening model. Temperature was described by the heat conduction equation solved using the finite difference method. The tissue denaturation was modeled by the Henriques equation leading to the determination of the damage coefficient omega. For a given set of laser and tissue parameters, HELIOS makes a graphic representation of coagulation necrosis and temperature evolution in tissue. HELIOS was validated by experimental studies in vivo on rat liver using a CW Nd:YAG laser, a CO2 laser, and an argon laser. For given sets of laser parameters, temperature measurements were performed using an infrared camera. Histological examinations were carried out on samples to quantify the depth of coagulation necrosis. Experimental data obtained in vivo were compared with those calculated using HELIOS and similar sets of parameters. The difference between the predicted temperature evolution on tissue surface and that measured by the infrared camera was < 5 degrees C in all cases. The difference between the predicted coagulation necrosis depth and the corresponding experimental one was < 10%. In conclusion, HELIOS allows good prediction of tissue temperature and coagulation necrosis.

Animals↗
PubMed1989

Synopsis of French experimental and in situ research on the terrestrial and marine behavior of Tc.

Terrestrial environment studies have been essentially concerned with the evolution of soil deposition and soil-plant transfers. Experimentally determined coefficients of distribution in soils are low: 60-80% of Tc remains hydrosoluble during the first months. Technetium emissions resulting from microbiological activity have been quantified. Antagonistic effects on Mo and Tc retention by soils are dependent on their respective concentrations. Four areas of soil-plant transfers have been studied: 1) root absorption kinetics relative to deposition of Tc, 2) interaction of stable Mo (environmental parameter) with the transfer of Tc to plants, 3) interaction of some long-lived radioisotopes (effluent parameters) with the transfer of Tc to plants, and 4) long-term soil-plant transfer and aging of deposited material. Of aquatic systems, only the marine environment has been studied. Under anoxic conditions in the presence of reducing sediments, the distribution coefficients (Kd) were very high (10(3)). Concentration factors (CF) from water to organisms were generally very low (1 to 10); however, CF greater than 1000 have been observed for some biota such as macrophytic brown algae, worms and lobsters. Biochemical analysis showed that Tc was essentially free and partially bonded to proteins. The transfer factors between sediments and species were very low (TF less than 0.5). The biological half-time was determined in some marine organisms that had accumulated Tc from water, food or sediments; the loss is biphasic. Uptake in edible parts was low. The physiochemical form affects the accumulation and loss of Tc. Analyses have quantified 99Tc in marine fauna and biota in the English Channel in relation with releases of the reprocessing plant of La Hague. Brown algae are the best bioindicators for following 99Tc dispersion in marine ecosystems.

Animals↗
PubMed1999

Systematic changes in gene expression patterns following adaptive evolution in yeast.

Culturing a population of Saccharomyces cerevisiae for many generations under conditions to which it is not optimally adapted selects for fitter genetic variants. This simple experimental design provides a tractable model of adaptive evolution under natural selection. Beginning with a clonal, founding population, independently evolved strains were obtained from three independent cultures after continuous aerobic growth in glucose-limited chemostats for more than 250 generations. DNA microarrays were used to compare genome-wide patterns of gene expression in the evolved strains and the parental strain. Several hundred genes were found to have significantly altered expression in the evolved strains. Many of these genes showed similar alterations in their expression in all three evolved strains. Genes with altered expression in the three evolved strains included genes involved in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, and metabolite transport. These results are consistent with physiological observations and indicate that increased fitness is acquired by altering regulation of central metabolism such that less glucose is fermented and more glucose is completely oxidized.

Adaptation, Physiological↗
PubMed1986

Chemical evolution of iron containing enzymes: mixed ligand complexes of iron as intermediary steps.

Activities of the iron complexes of evolutionary importance like K4[Fe(CN)6], K4[Fe(CN)5(gly)], and K4[Fe(CN)5(trigly)] have been tested towards some redox reactions of biological significance, namely, decomposition of hydrogen peroxide, dehydrogenation of NADH and ascorbic acid both coupled with reduction of methylene blue. It has been observed that the catalytic activities of iron (II) complexes towards the redox reactions studied at pH 9.18 followed the order, K4[Fe(CN)6] less than K4[Fe(CN)5(gly)] less than K4[Fe(CN)5(trigly)]. Decomposition of H2O2 catalysed by cyanocomplexes of iron (II) has been discussed through the formation of an innersphere complex in which loosly bound ligands like, glycine and triglycine are replaced by hydroperoxide ion. A tentative mechanism for the catalysed decomposition of H2O2 has been discussed. Based upon the experimental observations a hypothesis on the evolution of iron containing enzymes has been envisaged as: iron(II) ion----iron(II) cyanide complexes----mixed ligand iron(II) cyanide and amino acid complexes----iron(II) complexes of macromolecules----pŕoenzyme or early enzyme containing iron(II).

Biological Evolution↗
PubMed2006

Rapid evolution of reproductive proteins in abalone and Drosophila.

Observations from different taxa, including plants, protozoa, insects and mammals, indicate that proteins involved in reproduction evolve rapidly. Several models of adaptive evolution have been proposed to explain this phenomenon, such as sexual conflict, sexual selection, self versus non-self recognition and pathogen resistance. Here we discuss the potential role of sexual conflict in the rapid evolution of reproductive genes in two different animal systems, abalone (Haliotis) and Drosophila. In abalone, we reveal how specific interacting sperm-egg proteins were identified and discuss this identification in the light of models for rapid protein evolution and speciation. For Drosophila, we describe the genomic approaches taken to identify male accessory gland proteins and female reproductive tract proteins. Patterns of protein evolution from both abalone and Drosophila support the predicted patterns of rapid protein evolution driven by sexual conflict. We stress however that other selective pressures may contribute to the rapid evolution that is observed. We conclude that the key to distinguishing between sexual conflict and other mechanisms of protein evolution will be an integration of genetic, experimental and theoretical data.

Animals↗
PubMed1998

Initial cash/asset ratio and asset prices: an experimental study.

A series of experiments, in which nine participants trade an asset over 15 periods, test the hypothesis that an initial imbalance of asset/cash will influence the trading price over an extended time. Participants know at the outset that the asset or "stock" pays a single dividend with fixed expectation value at the end of the 15th period. In experiments with a greater total value of cash at the start, the mean prices during the trading periods are higher, compared with those with greater amount of asset, with a high degree of statistical significance. The difference is most significant at the outset and gradually tapers near the end of the experiment. The results are very surprising from a rational expectations and classical game theory perspective, because the possession of a large amount of cash does not lead to a simple motivation for a trader to bid excessively on a financial instrument. The gradual erosion of the difference toward the end of trading, however, suggests that fundamental value is approached belatedly, offering some consolation to the rational expectations theory. It also suggests that there is a time scale on which an evolution toward fundamental value occurs. The experimental results are qualitatively compatible with the price dynamics predicted by a system of differential equations based on asset flow. The results have broad implications for the marketing of securities, particularly initial and secondary public offerings, government bonds, etc., where excess supply has been conjectured to suppress prices.

Journal Article↗
PubMed2004

Immunity promotes virulence evolution in a malaria model.

Evolutionary models predict that host immunity will shape the evolution of parasite virulence. While some assumptions of these models have been tested, the actual evolutionary outcome of immune selection on virulence has not. Using the mouse malaria model, Plasmodium chabaudi, we experimentally tested whether immune pressure promotes the evolution of more virulent pathogens by evolving parasite lines in immunized and nonimmunized ("naïve") mice using serial passage. We found that parasite lines evolved in immunized mice became more virulent to both naïve and immune mice than lines evolved in naïve mice. When these evolved lines were transmitted through mosquitoes, there was a general reduction in virulence across all lines. However, the immune-selected lines remained more virulent to naïve mice than the naïve-selected lines, though not to immunized mice. Thus, immune selection accelerated the rate of virulence evolution, rendering parasites more dangerous to naïve hosts. These results argue for further consideration of the evolutionary consequences for pathogen virulence of vaccination.

Animals↗
PubMed2026

Evolution of virulence of a plant RNA virus in developmental stage-structured host populations.

Natural host populations are age-structured, and developmental stages differ in susceptibility and within-host pathogen dynamics, potentially imposing distinct selective pressures on viruses. However, the evolutionary consequences of host age structure remain poorly understood. We experimentally evolved turnip mosaic potyvirus for 5 passages in Arabidopsis thaliana populations spanning 7 demographic regimes, from juvenile- to mature-dominated cohorts. We quantified disease progression, symptom severity, and viral load, cross-inoculated evolved lineages across host stages to construct infection matrices, and performed whole-population sequencing at passages 1 and 5. Disease traits changed markedly with passage, demography, and their interaction. Disease progression evolved faster in older populations, whereas symptom severity was independent of median age, indicating demographic reweighting of virulence components. Viral load increased across passages and positively correlated with severity, linking within-host fitness to symptoms. Cross-inoculation assays revealed a modular infection network: juvenile-evolved lineages specialized on juvenile hosts, whereas lineages from intermediate and older populations were more generalist. Genomically, we detected both parallel and demography-specific adaptations, including recurrent changes in the viral protein VPg (involved in translation, replication, and host interactions) as well as synonymous variants showing consistent or opposing selection across host population stage structures. Overall, host age structure emerges as a major ecological driver of virulence evolution, shaping tradeoffs between disease progression and severity and determining specialization versus generalism. These results integrate phenotypic and genomic responses and suggest that manipulating crop age structure could steer virus evolution toward less damaging outcomes.

Virulence↗
PubMed1998

Experimental models of Parkinson's disease: from the static to the dynamic.

The experimental models of Parkinson's disease (PD) available today can be divided into two categories according to the mode of action of the compound used: transient pharmacological impairment of dopaminergic transmission along the nigrostriatal pathway or selective destruction by a neurotoxic agent of the dopaminergic neurons of the substantia nigra pars compacta. The present article looks at the relative merits of each model, the clinical symptoms and neuronal impairment it induces, and the contribution it could make to the development of a truly dynamic model. It is becoming more and more clear that there is an urgent need for a chronic model integrating all the clinical features of PD including resting tremor, and reproducing the gradual but continuous nigral degeneration observed in the human pathology. Discrepancies have been reported several times between results obtained in classic animal models and those described in PD, and it would seem probable that such contradictions can be ascribed to the fact that animal models do not, as yet, reproduce the continuous evolution of the human disease. Dynamic experimental models which come closer to the progressive neurodegeneration and gradual intensification of motor disability so characteristic of human PD will enable us to investigate crucial aspects of the disease, such as compensatory mechanisms and dyskinesia.

Animals↗