[Possibility of hemoblastic evolution of the vascular endothelium. II. Experimental results, interpretative deductions and conclusions].
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Biological Evolution↗
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Results for “Experimental evolution”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
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[Experimental endolymphatic hydrops. Biochemical data in the guinea pig].
The electrochemical and osmotic composition of the inner ear fluids has been studied during experimental endolymphatic hydrops in guinea pig. The data showed that the modifications of the electrochemical composition of endolymph has been detected only after more than 2 weeks after the hydrops induction. The endocochlear potential, the K and Cl concentrations, and the osmolality progressively decreased between 6 and 9 weeks of hydrops. The longitudinal gradients disappeared. After 24 weeks of hydrops, the endocochlear potential was 50% of the initial value whereas the K and Cl concentrations and the osmolality were higher than that measured at 9 weeks but remained lower than contralateral, normal values. These results suggest that the alterations of the electrochemical and osmotic composition of endolymph that were observed during the evolution of experimental endolymphatic hydrops in guinea pig are related to an alteration of the permeabilities of the Reissner's membrane induced by an increase of hydrostatic pressure.
Animals↗
Divergence in fitness and evolution of drug resistance in experimental populations of Candida albicans.
The dissemination and persistence of drug-resistant organisms in nature depends on the relative fitness of sensitive and resistant genotypes. While resistant genotypes are expected to be at an advantage compared to less resistant genotypes in the presence of drug, resistance may incur a cost; resistant genotypes may be at a disadvantage in the absence of drug. We measured the fitness of replicate experimental populations of the pathogenic yeast Candida albicans founded from a single progenitor cell in a previous study (L. E. Cowen, D. Sanglard, D. Calabrese, C. Sirjusingh, J. B. Anderson, and L. M. Kohn, J. Bacteriol. 182:1515-1522, 2000) and evolved in the presence, and in the absence, of the antifungal agent fluconazole. Fitness was measured both in the presence and in the absence of fluconazole by placing each evolved population in direct competition with the drug-sensitive ancestor and measuring the reproductive output of each competitor in the mixture. Populations evolved in the presence of drug diverged in fitness. Any significant cost of resistance, indicated by reduced fitness in the absence of drug, was eliminated with further evolution. Populations evolved in the absence of drug showed more uniform increases in fitness under both conditions. Fitness in the competition assays was not predicted by measurements of the MICs, doubling times, or stationary-phase cell densities of the competitors in isolation, suggesting the importance of interactions between mixed genotypes in competitions.
Antifungal Agents↗
Chronic renal failure and periodontal disease.
In order to define the effects of chronic renal failure (CRF) in the progress of gingival inflammation, we studied 6 patients (4 male, 2 female) with CRF who were on chronic hemodialysis for 4.25 (range 1-15) years. Six healthy individuals, age and sex matched were used as controls. The protocol which we used comprised of two periods (a) a 40-day duration period of preparation and (b) a 28-day duration experimental period. During the (a) period, all subjects went through: (1) therapy of the chronic gingivitis and (2) complete control of dental plaque by oral hygiene. During the experimental period, all subjects were advised to avoid, for at least 21 days, any mechanical or chemical media of oral hygiene and went through photographing, recording of gingival index (GI), recording of plaque index (PII), and the collection and quantification of gingival crevicular fluid (GCF). On the 21st day, root planning and polishing were performed and subjects were advised to carry out oral hygiene. On the 28th day, all previous examinations (GI, PII, GCF) were repeated. In both patients and controls, GI, PII and GCF were increased on 7th, 14th and 21st day, without significant differences between the groups and returned to normal (close to zero point) on the 28th day. There are no significant differences between patients with CRF and normal controls in the evolution of experimental gingivitis. Therefore, chronic uremia has no effect on the defense of periodontal tissue against microbial plaque.
Adult↗
Dialysable leukocyte extracts modify the course of experimental paracoccidioidomycosis in the Syrian hamster.
The effect of dialysable leukocyte extracts (DLE) obtained from hamsters immunized with Paracoccidioides brasiliensis (immune DLE) and from non-immunized hamsters (non-immune DLE) was studied in hamsters inoculated with P. brasiliensis by the intratesticular route. Treatment with immune or non-immune DLE was started during the third week of infection and was repeated at 7, 11, 15 and 19 weeks. A group of untreated infected animals was used as control. Animals were submitted to the delayed hypersensitivity skin test to P. brasiliensis antigen (PbAg) in vivo and assayed in vitro by the macrophage migration inhibition test in the presence of Phytohemagglutinin (PHA) and PbAg and by immunodiffusion for specific antibody. The animals were sacrificed at 4, 8, 12, 16 and 20 weeks. The morphology and extension of the lesions were studied at the inoculation site, and in lymph nodes, lungs, liver, spleen and kidneys. In contrast to the controls, animals treated with both DLEs maintained a positive cell-mediated immune response throughout the experiment and developed less extensive infection with a significantly lower number of fungi in the lesions. The results suggest that immune and non-immune DLE preparations modified the evolution of experimental paracoccidioidomycosis with equal efficiency. This similarity may be explained by the immunoregulatory activities of both extracts.
Animals↗
[The significance of animals in biomedical research].
The mission of medicine is maintenance of health, elimination of suffering and prolongation of life. These aims can be achieved by medicine based on experimental determination, because only then it becomes a real science. The nature of human mind has led the man since the beginning of humanity on the earth to the cognition of his environment and himself. Being intellectually superior than other living creatures, the man got power over them. In his endless efforts to expand knowledge about living organisms, including his own, he started to use animals. The man has used animals for cognitive purposes for ages and is still doing it, however his motivation has changed and is still changing. Cognition of functions of living organisms on the basis of observation solely, without any interference into the living body gave a lot of important information, yet, generally, this method was of little use for the development of science. Only the use of animals could give information about this what was earlier unknown and impossible. The long-lasting evolution of experimental studies of living functions of higher organisms resulted in achieving a perfect level in biomedical studies. Vivisection, as it was understood years ago, has become history. For a chronic experiment, an animal is surgically prepared according to the researcher's intention. The surgery and the postoperative period follow the principles used in human surgery. After the convalesce period, the animal is used for further experiments. On such prepared animals, the investigations in experimental cardiology, neurophysiology, gastroenterology and other medical disciplines are performed. The animal prepared for longlasting experiments do not suffer from pain during both the experiments and intervals between them. Another important achievement in chronic experiments is considerable reduction of the number of animals used in experimental medicine. Undoubtedly, the greatest achievements in medicine in the 19th and 20th centuries were possible due to the use of animals. There is a strong relationship between a rapid progress in experiments on animals and evident progress in clinical medicine. In the second half of the 20th century the man left the globe for the first time and reached another planet. Tis unusual event in the history of humanity was possible due to space medicine based on biomedical experiments with the use of animals. Also, the man's ability to reach the depths of oceans cost the lives of many experimental animals. Despite advances that have already been made, we are still in the early stages of understanding the complex workings of the body. This makes the replacement of animal experiments a slow process. At the same time, our increasing knowledge is opening up whole new areas of medical research which in turn give rise to a need for further animal use. While it may be difficult to envisage total replacement, the proposition of work that can be done without animals is increasing all the time. Many efforts are being made to find alternatives to animal experiments, to increase the usefulness of those that already exist, and to refine animal research methods. But at present days biomedicine, with its experiments on animals, reveals the laws of nature which the clinical and his patient can use to improve the life quality, prolong the life span and eliminate suffering. We all want to lead a healthy and enjoyable life. Most of us want the benefits of modern medical research-benefits that we would not have without the contribution of animal research. Yet, the health and well being of animals is important too. Clearly, those involved in this research have a moral and legal obligation to ensure that laboratory animals are well housed and cared for, any distress is kept to a minimum and that as few animals as possible are used. In the end, the question of whether animals should be used in medicines research is one everyone must answer for themselves, but the decision is more c
Animal Welfare↗
Evolution of specialists in an experimental microcosm.
The impact of adaptation on the persistence of a balanced polymorphism was explored using the lactose operon of Escherichia coli as a model system. Competition in chemostats for two substitutable resources, methylgalactoside and lactulose, generates stabilizing frequency-dependent selection when two different naturally isolated lac operons (TD2 and TD10) are used. The fate of this balanced polymorphism was tracked over evolutionary time by monitoring the frequency of fhuA-, a linked neutral genetic marker that confers resistance to the bacteriophage T5. In four out of nine chemostats the lac polymorphism persisted for 400-600 generations when the experiments were terminated. In the other five chemostats the fhuA polymorphism, and consequently the lac operon polymorphism, was lost between 86 and 219 generations. Four of 13 chemostat cultures monomorphic for the lac operon retained the neutral fhuA polymorphism for 450-550 generations until they were terminated; the remainder became monomorphic at fhuA between 63 and 303 generations. Specialists on each galactoside were isolated from chemostats that maintained the fhuA polymorphism, whether polymorphic or monomorphic at the lac operon. Strains isolated from three of four chemostats in which the lac polymorphism was preserved had switched their galactoside preference. Most of the chemostats where the fhuA polymorphism was lost also contained specialists. These results demonstrate that the initial polymorphism at lac was of little consequence to the outcome of long-term adaptive evolution. Instead, the fitnesses of evolved strains were dominated by mutations arising elsewhere in the genome, a fact confirmed by showing that operons isolated from their evolved backgrounds were alone unable to explain the presence of both specialists. Our results suggest that, once stabilized, ecological specialization prevented selective sweeps through the entire population, thereby promoting the maintenance of linked neutral polymorphisms.
Bacterial Outer Membrane Proteins↗
[Experimental rat deciduoma: histoenzymology].
The modifications of enzymatics activities which involved dehydrogenases (LDH, MDH and G6PDH) alkalines phosphatases (Ph. Alc., ATP/as at Ph 7,2 and Ph 9,4) and hydrolases (Ph Ac. and beta Glu) were studied during the experimental deciduomata evolution in the Rat from the 5th to the 9th day. One the 5th day the uterus were used as control. Dehydrogenases and alkalines phosphatases activites appeared in isolated cells of sub-epithelial and middle antimesometrial stroma on the 5th day. Then, on the 6th day, they distributed themselves in strings of 8 to 10 cells. On the 7th day, they were regulary arranged in the decidual area. The growing decidual tissue was always surrounded by an hydrolysis activity.
Acid Phosphatase↗
Transient gene transfer of IL-12 regulates chemokine expression and disease severity in experimental arthritis.
Murine collagen-induced arthritis (CIA) is characterized by pannus formation, cell infiltration, and cartilage erosion, and shares histologic and immunologic features with rheumatoid arthritis. Numerous cytokines are reportedly associated with RA and/or CIA; however, their mechanistic role is not clear. To determine the role of IL-12 in CIA, DBA/1 LacJ mice were administered 3 x 10(8) plaque-forming units of mIL-12 i.p. in a nonreplicating adenoviral vector (AdIL-12) on day 25 following primary type II collagen immunization. Our studies demonstrated that systemic transient overexpression of IL-12 accelerated disease progression and augmented the arthritis severity relative to mice expressing a replication-deficient, E1-deleted Ad5 construct. A likely mechanism for this increase in pathology was the increase in the expression of cytokines and chemokines known to play a proinflammatory role in disease. In particular, levels of murine IFN-gamma were significantly increased in mice overexpressing AdIL-12 relative to the replication-deficient, E1-deleted Ad5 construct. Interestingly, the C-X-C chemokine murine macrophage inflammatory protein-2, as well as the C-C chemokines murine monocyte chemoattractant protein-1 and murine macrophage inflammatory protein-1alpha were up-regulated by AdIL-12 relative to controls. In an additional set of studies, neutralization of endogenous IL-12 in CIA mice was shown to delay disease onset and attenuate disease severity. IFN-gamma levels in the mice receiving anti-IL-12 were significantly decreased in joint homogenates. These studies demonstrate that IL-12 is an important cytokine involved in controlling the production of chemokines/cytokines leading to the evolution of experimental arthritis.
Adenoviridae↗
Tug-of-war over reproduction in a social bee.
One of the main transitions in evolution is the shift from solitary organisms to societies with reproductive division of labour. Understanding social evolution requires us to determine how ecological, social and genetic factors jointly influence group stability and partitioning of reproduction between group members. Here we test the role of the three key factors predicted to influence social evolution by experimentally manipulating them in a social allodapine bee. We show that increased relatedness between nestmates results in more even reproduction among group members and a greater productivity per individual. By contrast, the degree of reproductive skew is not influenced by the opportunity for solitary breeding or by the potential benefits of cooperation. Relatedness also has a positive effect on group stability and overall productivity. These findings are in line with predictions of the tug-of-war models, in which the degree of reproductive division of labour is determined primarily by selfish competition between group members. The alternative view, where the degree of reproductive skew is the outcome of a social contract between potential breeders, was not supported by the data.
Animals↗
Experimental and clinical standards, and evolution of lasers in neurosurgery.
From initial experiments of ruby, argon and CO2 lasers on the nervous system so far, dramatic progress was made in delivery systems technology as well as in knowledge of laser-tissue interaction effects and hazards through various animal experiments and clinical experience. Most surgical effects of laser light on neural tissue and the central nervous system (CNS) are thermal lesions. Haemostasis, cutting and vaporization depend on laser emission parameters--wavelength, fluence and mode--and on the exposed tissues optical and thermal properties--water and haemoglobin content, thermal conductivity and specific heat. CO2 and Nd-YAG lasers have today a large place in the neurosurgical armamentarium, while new laser sources such as high power diode lasers will have one in the near future. Current applications of these lasers derive from their respective characteristics, and include CNS tumour and vascular malformation surgery, and stereotactic neurosurgery. Intracranial, spinal cord and intra-orbital meningiomas are the best lesions for laser use for haemostasis, dissection and tissue vaporization. Resection of acoustic neuromas, pituitary tumours, spinal cord neuromas, intracerebral gliomas and metastases may also benefit from lasers as accurate, haemostatic, non-contact instruments which reduce surgical trauma to the brain and eloquent structures such as brain stem and cranial nerves. Coagulative lasers (1.06 microns and 1.32 microns Nd-YAG, argon, or diode laser) will find an application for arteriovenous malformations and cavernomas. Any fiberoptic-guided laser will find a use during stereotactic neurosurgical procedures, including image-guided resection of tumours and vascular malformations and endoscopic tumour resection and cysts or entry into a ventricle. Besides these routine applications of lasers, laser interstitial thermotherapy (LITT) and photodynamic therapy (PDT) of brain tumours are still in the experimental stage. The choice of a laser in a neurosurgical operating room implies an evaluation of the laser use (applications, frequency), of the available budget and costs--including purchase, maintenance and staff training--, and material that will be necessary: unit, peripherals, safety devices and measures, training programme. Future applications of lasers in neurosurgery will come from technological advances and refined experimental applications. The availability of new wavelength, tunable, small sized and "smart" laser units, will enlarge the thermal and non-thermal interactions between laser energy and neural tissue leading to new surgical applications. Tissue photo-ablation, photohynamic therapy using second generation of photosensitizers, updated thermotherapy protocols, are current trends for further use of lasers in neurosurgery.
Animals↗
Model of the TBP-TFIIB complex from Plasmodium falciparum: interface analysis and perspectives as a new target for antimalarial design.
BACKGROUND: Malaria affects 200-300 million individuals per year worldwide. Plasmodium falciparum is the causative agent of the most severe and mortal type of malaria. The need for new antimalarials comes from the widespread resistance to those in current use. New antimalarial targets are required to increase chemical diversity and effectiveness of the drugs. The research for such new targets and drug chemotypes is aided by structure-based drug design. We present a model of the TBP-TFIIB complex from P. falciparum (pfTBP-pfTFIIB) and a detailed study of the interactions at the TBP-TFIIB interface. METHODS: The model was built using standard methodology, optimized energetically and evaluated structurally. We carried out an analysis of the interface considering its evolution, available experimental data on TBP and TFIIB mutants, and the main conserved and non-conserved interactions. To support the perspective of using this complex as a new target for rational antimalarial design, we present the comparison of the pfTBP-pfTFIIB interface with its human homolog. RESULTS: Despite the high residue conservation at the interface, we identified a potential region, composed of species-specific residues that can be used for rational antimalarial design. CONCLUSIONS: Currently there are no antimalarial drugs targeted to stop the nuclear transcription process, a vital event for all replication stages of P. falciparum. Due to its absolute requirement in transcription initiation, we consider the pfTBP-pfTFIIB interface as a new potential target for novel antimalarial chemotypes.
Amino Acid Sequence↗
Evolution of competitive fitness in experimental populations of E. coli: what makes one genotype a better competitor than another?
An important problem in microbial ecology is to identify those phenotypic attributes that are responsible for competitive fitness in a particular environment. Thousands of papers have been published on the physiology, biochemistry, and molecular genetics of Escherichia coli and other bacterial models. Nonetheless, little is known about what makes one genotype a better competitor than another even in such well studied systems. Here, we review experiments to identify the phenotypic bases of improved competitive fitness in twelve E. coli populations that evolved for thousands of generations in a defined environment, in which glucose was the limiting substrate. After 10,000 generations, the average fitness of the derived genotypes had increased by approximately 50% relative to the ancestor, based on competition experiments using marked strains in the same environment. The growth kinetics of the ancestral and derived genotypes showed that the latter have a shorter lag phase upon transfer into fresh medium and a higher maximum growth rate. Competition experiments were also performed in environments where other substrates were substituted for glucose. The derived genotypes are generally more fit in competition for those substrates that use the same mechanism of transport as glucose, which suggests that enhanced transport was an important target of natural selection in the evolutionary environment. All of the derived genotypes produce much larger cells than does the ancestor, even when both types are forced to grow at the same rate. Some but not all, of the derived genotypes also have greatly elevated mutation rates. Efforts are now underway to identify the genetic changes that underlie those phenotypic changes, especially substrate specificity and elevated mutation rate for which there are good candidate loci. Identification and subsequent manipulation of these genes may provide new insights into the reproducibility of adaptive evolution, the importance of co-adapted gene complexes, and the extent to which distinct phenotypes (e.g., substrate specificity and cell size) are affected by the same mutations.
Adaptation, Physiological↗
Filamentous cheater phages drive bacterial and phage populations to lower fitness.
Many bacteria carry phage genome(s) in their chromosome, which intertwines the fitness of the bacterium and the phage. Most Pseudomonas aeruginosa strains carry filamentous phages called Pf that establish chronic infections and do not require host lysis to spread. However, spontaneous mutations in the Pf repressor gene (pf5r) can allow extreme phage production that slows bacterial growth and increases cell death, violating an apparent détente between bacterium and phage. We observed this paradoxical outcome in an evolution experiment with P. aeruginosa in media simulating nutrients from the cystic fibrosis airway. Bacteria containing pf5r mutant phage grow to a lower density but directly outcompete their ancestor and convert them into pf5r mutants via phage superinfection. Reduced fitness therefore spreads throughout the bacterial population, driven by weaponized Pf. Yet high intracellular phage replication facilitates another evolutionary conflict: "cheater miniphages" lacking capsid genes and the superinfection exclusion gene (pfsE) invade populations of full-length phages within cells. Although bacteria containing both full-length phages and miniphages are most immune to superinfection by limiting the Pf receptor, this hybrid vigor is extremely unstable, as a classic Tragedy of the Commons scenario ensues that causes complete prophage loss. The entire cycle - from phage hyperactivation to miniphage invasion to prophage loss - can occur within 24h, showcasing rapid coevolution between bacteria and their filamentous phages. This study demonstrates that P. aeruginosa, and potentially many other bacterial species that carry filamentous prophages, risk being exploited by these phages in a runaway process that reduces fitness of both host and virus.
Inoviridae↗
Summary of the Third World Congress on Psychiatric Genetics.
A summary of the proceedings of the third world congress on psychiatric genetics is presented. The meeting was held in New Orleans on October 2-5, 1993 and brought together researchers from around the world. The International Society of Psychiatric Genetics sponsored and organized this meeting. Rapid advances of the last few years were reviewed and discussed in terms of their impact on the evolution of experimental design. The importance of definition of heritable clinical phenotypes, and the need to continue to enhance analytic methods were stressed as a priority for the field.
Animals↗
A COMPARISON OF NEW AND OLD WORLD MONKEY SOCIAL ORGANIZATIONS AND BEHAVIOR.
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Animals↗
Effect of pH on biological phosphorus uptake.
An anaerobic aerobic laboratory scale sequencing batch reactor (SBR) was operated to study the effect of pH on enhanced biological phosphorus removal. Seven steady states were achieved under different operating conditions. In all of them, a slight variation in the pH value was observed during anaerobic phase. However, pH rose significantly during aerobic phase. The increase observed was due to phosphorus uptake and carbon dioxide stripping. When pH was higher than 8.2-8.25 the phosphorus uptake rate clearly decreased. The capability of Activated Sludge Model No. 2d (ASM2d) and Biological Nutrient Removal Model No. 1 (BNRM1) to simulate experimental results was evaluated. Both models successfully characterized the enhanced biological phosphorus removal performance of the SBR. Furthermore, BNRM1 also reproduced the pH variations observed and the decrease in the phosphorus uptake rate. This model includes a switch function in the kinetic expressions to represent the pH inhibition in biological processes. The pH inhibition constants related to polyphosphate storage process were obtained by adjusting model predictions to measured phosphorus concentrations. On the other hand, pH inhibition should be included in ASM2d to accurately simulate experimental phosphorus evolution observed in an A/O SBR.
Aerobiosis↗
Structure of wild-type and mutant repressors and of the control region of the rbt operon of Klebsiella aerogenes.
Pentitol metabolism in Klebsiella aerogenes is encoded by continuous ribitol (rbt) and D-arabitol (dal) operons transcribed in bipolar fashion and sandwiched between long stretches of homologous DNA. The operons are separated by a central control region (2.2 kb) which encodes both the repressors and all the control sequences. The rbt repressor (270 amino acids) shows homology to the Escherichia coli lac repressor and other DNA-binding proteins. It is transcribed from the strand opposite the rbt operon and the intervening control region (254-bp) contains features which reflect the complex regulation. A rbt-constitutive mutant strain used in previous studies of experimental enzyme evolution encodes a truncated rbt-peptide of 133 residues due to a frameshift mutation.
Amino Acid Sequence↗