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At least 361 records · Page 20Linked to original sources
PubMed2000

Subcutaneous administration of brain natriuretic peptide in experimental heart failure.

OBJECTIVES: The objective of this investigation was to define for the first time the cardiorenal and humoral actions of repeated short-term administration of subcutaneous (SQ) brain natriuretic peptide (BNP) administration during the evolution of experimental heart failure. BACKGROUND: The rationale of this study was based on BNP as a vasodilating, natriuretic, renin-inhibiting and lusitropic peptide of cardiac origin. METHODS: First, we defined the cardiorenal and humoral responses to acute low and high dose (5 microg/kg or 25 microg/kg) of SQBNP in experimental heart failure to establish the acute efficacy of an SQ delivery. Second, we characterized the response to 10 days of repeated short-term administration of BNP during the evolution of experimental heart failure produced by rapid ventricular pacing. RESULTS: Plasma BNP and 3',5'-cyclic guanosine monophosphate rapidly increased and peaked at 30 min after acute SQBNP administration with increases in urinary sodium excretion, urine flow and renal blood flow in association with reductions in cardiac filling pressures. After 10 days of repeated short-term administration of SQBNP, cardiac output was increased and systemic vascular resistance and pulmonary capillary wedge pressure were decreased, as compared with untreated dogs with heart failure. CONCLUSIONS: This study demonstrated for the first time that repeated short-term administration of SQ BNP administration for 10 days during the evolution of left ventricular dysfunction in a canine model results in an improvement in cardiovascular hemodynamics. This investigation supports a potential novel strategy for the chronic administration of BNP in the therapeutics of heart failure.

Animals↗
PubMed2003

Evolution of cooperation and conflict in experimental bacterial populations.

A fundamental problem in biology is the evolutionary transition from single cells to multicellular life forms. During this transition the unit of selection shifts from individual cells to groups of cooperating cells. Although there is much theory, there are few empirical studies. Here we describe an evolutionary transition that occurs in experimental populations of Pseudomonas fluorescens propagated in a spatially heterogeneous environment. Cooperating groups are formed by over-production of an adhesive polymer, which causes the interests of individuals to align with those of the group. The costs and benefits of cooperation, plus evolutionary susceptibility to defecting genotypes, were analysed to determine conformation to theory. Cooperation was costly to individuals, but beneficial to the group. Defecting genotypes evolved in populations founded by the cooperating type and were fitter in the presence of this type than in its absence. In the short term, defectors sabotaged the viability of the group; but these findings nevertheless show that transitions to higher orders of complexity are readily achievable, provide insights into the selective conditions, and facilitate experimental analysis of the evolution of individuality.

Bacterial Adhesion↗
PubMed1984

Origin and evolution of plateau waves. Experimental observations and a theoretical model.

Laboratory observations made in cats with fluid-percussion head injuries have suggested that plateau waves or Lundberg "A-waves" are not independent of systemic circulatory events. Four distinct phases in the evolution of the plateau wave have been identified, and each related to a circulatory change in a causal manner. The first phase is the premonitory drift phase where intracranial pressure (ICP) gradually increases prior to the plateau proper. This phase is caused by a slow gradual decline in systemic arterial blood pressure (SABP) which increases ICP by autoregulatory vasodilation and reduces cerebral perfusion pressure (CPP) to a range of 70 to 80 mm Hg. The second phase is the plateau phase initiated at a CPP of about 70 to 80 mm Hg, and is characterized by a rapid increase in ICP as CPP falls further to 40 to 50 mm Hg. The plateau lasts as long as the CPP remains stable and above ischemic levels. The third phase is the ischemic response, characterized by CPP being returned toward normal by increases in SABP in response to very low CPP's. The fourth phase is the resolution, characterized by a rapid decline in the ICP to baseline levels with stabilization of the SABP and CPP, and is best explained by autoregulatory vasoconstriction. Plateau waves appear to occur as the result of intact or mostly intact autoregulation responding to changes in CPP. The series of events that follow are best explained by what is known of normal autoregulation; the various properties of plateau waves are viewed and explained as the expected and logical consequences of an unstable CPP acting upon a generally intact cerebrovascular bed in the face of elevated ICP and decreased compliance.

Animals↗
PubMed2003

Insights into the evolution of human bipedalism from experimental studies of humans and other primates.

An understanding of the evolution of human bipedalism can provide valuable insights into the biomechanical and physiological characteristics of locomotion in modern humans. The walking gaits of humans, other bipeds and most quadrupedal mammals can best be described by using an inverted-pendulum model, in which there is minimal change in flexion of the limb joints during stance phase. As a result, it seems logical that the evolution of bipedalism in humans involved a simple transition from a relatively stiff-legged quadrupedalism in a terrestrial ancestor to relatively stiff-legged bipedalism in early humans. However, experimental studies of locomotion in humans and nonhuman primates have shown that the evolution of bipedalism involved a much more complex series of transitions, originating with a relatively compliant form of quadrupedalism. These studies show that relatively compliant walking gaits allow primates to achieve fast walking speeds using long strides, low stride frequencies, relatively low peak vertical forces, and relatively high impact shock attenuation ratios. A relatively compliant, ape-like bipedal walking style is consistent with the anatomy of early hominids and may have been an effective gait for a small biped with relatively small and less stabilized joints, which had not yet completely forsaken arboreal locomotion. Laboratory-based studies of primates also suggest that human bipedalism arose not from a terrestrial ancestor but rather from a climbing, arboreal forerunner. Experimental data, in conjunction with anatomical data on early human ancestors, show clearly that a relatively stiff modern human gait and associated physiological and anatomical adaptations are not primitive retentions from a primate ancestor, but are instead recently acquired characters of our genus.

Adaptation, Biological↗
PubMed1999

Evolution of the genetic covariance between male and female components of mate recognition: an experimental test.

The evolution of a positive genetic correlation between male and female components of mate recognition systems will result as a consequence of assortative mating and, in particular, is central to a number of theories of sexual selection. Although the existence of such genetic correlations has been investigated in a number of taxa, it has yet to be shown that such correlations evolve and whether they may evolve as rapidly as suggested by sexual selection models. In this study, I used a hybridization experiment to disrupt natural mate recognition systems and then observed the subsequent evolutionary dynamics of the genetic correlation between male and female components for 56 generations in hybrids between Drosophila serrata and Drosophila birchii. The genetic correlation between male and female components evolved from 0.388 at generation 5 to 1.017 at generation 37 and then declined to -0.040 after a further 19 generations. These results indicated that the genetic basis of the mate recognition system in the hybrid populations evolved rapidly. The initial rapid increase in the genetic correlation was consistent with the classic assumption that male and female components will coevolve under sexual selection. The subsequent decline in genetic correlation may be attributable to the fixation of major genes, or, alternatively, may be a result of a cyclic evolutionary change in mate recognition.

Animals↗
PubMed1995

Laser-flash kinetic analysis of the fast electron transfer from plastocyanin and cytochrome c6 to photosystem I. Experimental evidence on the evolution of the reaction mechanism.

The reaction mechanism of electron transfer from the interchangeable metalloproteins plastocyanin (Pc) and cytochrome c6 (Cyt) to photooxidized P700 in photosystem I (PSI) has been studied by laser-flash absorption spectroscopy using a number of evolutionarily differentiated organisms such as cyanobacteria (Anabaena sp. PCC 7119 and Synechocystis sp. PCC 6803), green algae (Monoraphidium braunii), and higher plants (spinach). PSI reduction by Pc or Cyt shows different kinetics depending on the organism from which the photosystem and metalloproteins are isolated. According to the experimental data herein reported, three different kinetic models are proposed by assuming either an oriented collisional reaction mechanism (type I), a minimal two-step mechanism involving complex formation followed by intracomplex electron transfer (type II), or rearrangement of the reaction partners within the complex before electron transfer takes place (type III). Our findings suggest that PSI was able to first optimize its interaction with positively charged Cyt and that the evolutionary replacement of the ancestral Cyt by Pc, as well as the appearance of the fast kinetic phase in the Pc/PSI system of higher plants, would involve structural modifications in both the donor protein and PSI.

Biological Evolution↗
PubMed1996

Sexually antagonistic male adaptation triggered by experimental arrest of female evolution.

Each sex is part of the environment of the other sex. This may lead to perpetual coevolution between the sexes, when adaptation by one sex reduces fitness of the other. Indirect evidence comes from experiments with Drosophila melanogaster indicating that seminal fluid reduces the competitive ability of sperm from other males, thereby increasing male fitness. It also reduces a female's propensity to remate and increase her egg-laying rate. In contrast to these benefits to males, seminal fluid has substantial toxic side effects in females, with increasing quantity leading to decreasing female survival. Here I show that when female D. melanogaster are experimentally prevented from coevolving with males, males rapidly adapt to the static female phenotype. This male adaptation leads to a reduction in female survivorship, which is mediated by an increased rate of remating and increased toxicity of seminal fluid.

Adaptation, Physiological↗
PubMed2003

Experimental evidence for the evolution of numerous, tiny sperm via sperm competition.

Sperm competition, when sperm from different males compete to fertilize a female's ova, is a widespread and fundamental force in the evolution of animal reproduction. The earliest prediction of sperm competition theory was that sperm competition selected for the evolution of numerous, tiny sperm, and that this force maintained anisogamy. Here, we empirically test this prediction directly by using selective breeding to generate controlled and independent variance in sperm size and number traits in the cricket Gryllus bimaculatus. We find that sperm size and number are male specific and vary independently and significantly. We can therefore noninvasively screen individuals and then run sperm competition experiments between males that differ specifically in sperm size and number traits. Paternity success across 77 two-male sperm competitions (each running over 30-day oviposition periods) shows that males producing both relatively small sperm and relatively numerous sperm win competitions for fertilization. Decreased sperm size and increased sperm number both independently predicted sperm precedence. Our findings provide direct experimental support for the theory that sperm competition selects for maximal numbers of miniaturized sperm. However, our study does not explain why G. bimaculatus sperm length persists naturally at approximately 1 mm; we discuss possibilities for this sperm size maintenance.

Animals↗
PubMed1988

Desmin and actin in the identification of Ito cells and in monitoring their evolution to myofibroblasts in experimental liver fibrosis.

It has been reported that myofibroblasts contain actin and that Ito cells are positive for desmin. The distribution of desmin and actin detected by immunofluorescence, of vitamin A autofluorescence and of Sudan III staining of lipid droplets has been evaluated in sequential stages of experimental liver fibrosis induced in rats by intraperitoneal injections of swine serum. In the normal rat liver Ito cells were positive for desmin and weakly positive for actin. Prior to the development of hepatic fibrosis a clearcut increase in number and desmin staining of lobular Ito cells was observed in treated rats, but the overall actin pattern was unchanged. In the fibrotic rat livers, highly cellular septa contained large numbers of strongly desmin-positive, actin-weakly positive Ito cells and strongly desmin- and actin-positive myofibroblasts. These observations indicate that both Ito cells and myofibroblasts are positive for desmin, but only myofibroblasts contain large amounts of actin. Visualization of actin and desmin using relatively simple techniques, allows the monitoring of Ito cells proliferation, the accumulation of these cells in fibrous septa and their evolution into myofibroblasts as characterized by their increased desmin and actin content; it also allows an indirect evaluation of the process of fibrogenesis.

Actin Cytoskeleton↗
PubMed1993

Step-wise mutation of barnase to binase. A procedure for engineering increased stability of proteins and an experimental analysis of the evolution of protein stability.

We have chosen two members of the microbial RNase family, barnase and binase, which have 85% identity (17 substitutions and 1 deletion) and almost identical three-dimensional structure, to study the evolution of protein stability. The 17 residues that differ are scattered throughout the molecule. Each of the 17 differing residues has been mutated independently and the effect on protein stability analysed. Each point mutation has an effect on protein stability that ranges from +1.1 to -1.1 kcal mol-1. These changes in energy are additive. There is no clear correlation between the type of mutation and the effect on protein stability. A multiple mutant having six of the single mutations that increase the stability of barnase is 3.3 kcal mol-1 more stable than wild type and has the same activity. There could be selective pressure to maintain proteins at a certain stability and, consequently, mutations that decrease stability tend to be counterbalanced by stabilizing mutations. Alternatively, there could simply be pressure to maintain stability above a certain level, and any further increases in stability need not be maintained during evolution. These results suggest a simple way to improve the stability of proteins: choose two homologous proteins that have high similarity, mutate individually all of the residues that differ between the two, and combine the mutations that increase the stability in a multiple mutant.

Amino Acid Sequence↗
PubMed2005

An experimental test of the evolution of increased competitive ability hypothesis in goldenrod, Solidago gigantea.

The mechanisms that allow introduced plants to become invasive are poorly understood. Here, we present a test of the evolution of increased competitive ability hypothesis, which holds that because specialized natural enemies may be absent from the introduced range, exotic plants may evolve to invest less in anti-herbivore defenses and thereby gain a competitive advantage over native plants. We grew Solidago gigantea plants derived from both the native range (North America) and the invasive range (Europe) in a common garden in the native range for 2 years. Half the plants were treated with insecticide to protect them from insect herbivores and the other half were exposed to insects that colonized the garden from nearby fields. Insect herbivore biomass was significantly higher on European plants than US plants in the first year but not the second. European plants were more heavily attacked by pathogens in both years of the study. When exposed to insect herbivores, US plants produced more seed than European plants, but when plants were protected from herbivores, seed production was equivalent between US plants and European plants. The presence of insect herbivores suppressed seed production of European plants much more than that of US plants, even though the level of herbivory experienced by European and US plants was similar in the second year, suggesting that the ability to tolerate herbivory was diminished in European plants. These results partially support the EICA hypothesis: plants from the introduced range were more susceptible to some natural enemies and benefited more from insect removal than plants from the native range. The prediction that European plants would perform better than US plants in the absence of insect herbivores was not supported.

Adaptation, Physiological↗
PubMed1990

Double loop locking suture: a technique of tendon repair for early active mobilization. Part I: Evolution of technique and experimental study.

This article describes a technique of tendon repair and two variations using double loop locking sutures. Experimental study on human tendon specimens showed that the average tensile strength of tendon junctures was 4400 grams by double loop locking sutures and 2252 grams by Kessler's technique. The study also showed that the weakest point of the tendon juncture by double loop locking sutures was the sutures.

Finger Injuries↗
PubMed2001

Experimental studies on the evolution of antimony-resistant phenotype during the in vitro life cycle of Leishmania infantum: implications for the spread of chemoresistance in endemic areas.

Pentavalent antimonial unresponsiveness is an emerging problem in endemic areas and information on factors which could modulate the transmission of drug-resistant phenotypes and parasites during life cycle are warranted. Using axenic amastigotes resistant to potassium antimonyl tartrate (Sb(III)) we investigated the modulation of antimonyl resistance during the in vitro life cycle. We assessed: (i) the stability of the drug-resistant phenotype during the in vitro life cycle; (ii) the transmission of drug-resistant clones when mixed with a wild-type clone at different susceptible/chemoresistant ratios (50/50,90/10,10/90) after one or two in vitro life cycles. We demonstrate that: (i) mutants which were 12,28,35 and 44 fold more resistant to Sb(III)-antimonial than their parental wild-type, were Glucantime Sb(V)-resistant when growing in THP-1 cells; (ii) the drug-resistant phenotype was partially retained during long-term in vitro culture (3 months) in drug free medium; (iii) the antimonyl-resistant phenotype was retained after one or more in vitro life cycles. However, when drug-resistant parasites were mixed with susceptible, mutants could not be detected in the resulting population, after one or two in vitro life cycles, whatever the initial wild-type/chemoresistant ratio. These results could be explained by the lower capacity of drug-resistant amastigotes to undergo the amastigote-promastigote differentiation process, leading probably to their sequential elimination during life cycle. Taken together, these observations demonstrate that different factors could modulate the transmission of Leishmania drug resistance during the parasite's life cycle.

Animals↗
PubMed2004

Xenopus as an experimental model for studying evolution of hsp--immune system interactions.

The frog Xenopus provides a unique model system for studying the evolutionary conservation of the immunological properties of heat shock proteins (hsps). General methods for maintaining and immunizing isogenetic clones of defined MHC genotypes are presented together with more recently developed protocols for exploring hsp-mediated immune responses in vitro (proliferative and cytotoxic assays) and in vivo (adoptive cell transfer and antibody treatment) in adults and in naturally MHC class I-deficient larvae. Finally, techniques to study modalities of expression of the endoplasmic reticulum resident gp96 at the cell surface of tumor and normal lymphocytes are considered.

Animals↗
PubMed2004

Experimental life-history evolution: selection on growth form and its plasticity in a clonal plant.

The growth form along the continuum from compact phalanx plants to more loosely packed guerilla plants is an important life-history trait in clonal plants. Prerequisite for its evolution is heritable genetic variation. Starting with 102 genotypes of the stoloniferous herb Ranunculus reptans, we performed one selection experiment on spatial spread per rosette as measure of guerillaness (broad-sense heritability 0.198) and another on plasticity in this trait in response to competition (broad-sense heritability 0.067). After two generations, spatial spread was 36.9% higher in the high line than in the low line (realized heritability +/- SE 0.149 +/- 0.039). Moreover, compared with the low line genotypes of the high line had fewer rosettes, a lower proportion of flowering rosettes, a higher proportion of rooted rosettes, more branches per rosette, longer internodes and longer leaves. In the second experiment, we found no significant direct response to selection for high and low plasticity in spatial spread (realized heritability +/- SE -0.029 +/- 0.063), despite a significant correlated response in plasticity in the length of the first three stolon internodes. Our study indicates a high potential for further evolution of the clonal growth form in R. reptans, but not for its plasticity, and it demonstrates that the clonal growth form does not evolve independently of other clonal life-history characteristics.

Analysis of Variance↗
PubMed2003

Experimental prediction of the evolution of cefepime resistance from the CMY-2 AmpC beta-lactamase.

Understanding of the evolutionary histories of many genes has not yet allowed us to predict the evolutionary potential of those genes. Intuition suggests that current biochemical activity of gene products should be a good predictor of the potential to evolve related activities; however, we have little evidence to support that intuition. Here we use our in vitro evolution method to evaluate biochemical activity as a predictor of future evolutionary potential. Neither the class C Citrobacter freundii CMY-2 AmpC beta-lactamase nor the class A TEM-1 beta-lactamase confer resistance to the beta-lactam antibiotic cefepime, nor do any of the naturally occurring alleles descended from them. However, the CMY-2 AmpC enzyme and some alleles descended from TEM-1 confer high-level resistance to the structurally similar ceftazidime. On the basis of the comparison of TEM-1 and CMY-2, we asked whether biochemical activity is a good predictor of the evolutionary potential of an enzyme. If it is, then CMY-2 should be more able than the TEMs to evolve the ability to confer higher levels of cefepime resistance. Although we generated CMY-2 evolvants that conferred increased cefepime resistance, we did not recover any CMY-2 evolvants that conferred resistance levels as high as the best cefepime-resistant TEM alleles.

Bacterial Proteins↗