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PubMedDate not supplied

Classification of hypotheses on the advantage of amphimixis.

A classification of hypotheses on the advantage of amphimixis over apomixis is presented. According to "Immediate Benefit" hypotheses, amphimixis is advantageous regardless of reciprocal gene exchange, because either it directly increases fitness of the progeny, reduces the deleterious mutation rate, or makes selection more efficient. In contrast, "Variation and Selection" hypotheses attribute the advantage of amphimixis to the reciprocal gene exchange that alters genetic variability and response to selection among the progeny. Most such hypotheses assume that amphimixis increases variability and efficiency of selection, but some claim that amphimixis decreases response to selection. Variation and Selection hypotheses require that some factor, either random drift or epistatic selection, makes distributions of different alleles nonindependent, while another factor, either changes of the genotype fitnesses or deleterious mutations, makes overrepresented genotypes non-optimal. Numerous Variation and Selection hypotheses, dealing with either unstructured or spatially structured populations, are reviewed. Two of them seem most plausible: better responsiveness of the amphimictic population to widely fluctuating selection, and lower mutation load in the amphimictic population under synergistic selection against deleterious mutations. In both cases the large advantage of amphimixis requires rather stringent conditions, which could be falsified by careful experiment. Further progress in understanding the evolution of amphimixis will depend mostly on such experimental work.

Environment↗
PubMed2001

Stroke genomics: approaches to identify, validate, and understand ischemic stroke gene expression.

Sequencing of the human genome is nearing completion and biologists, molecular biologists, and bioinformatics specialists have teamed up to develop global genomic technologies to help decipher the complex nature of pathophysiologic gene function. This review will focus on differential gene expression in ischemic stroke. It will discuss inheritance in the broader stroke population, how experimental models of spontaneous stroke might be applied to humans to identify chromosomal loci of increased risk and ischemic sensitivity, and also how the gene expression induced by stroke is related to the poststroke processes of brain injury, repair, and recovery. In addition, we discuss and summarise the literature of experimental stroke genomics and compare several approaches of differential gene expression analyzes. These include a comparison of representational difference analysis we have provided using an experimental stroke model that is representative of stroke evolution observed most often in man, and a summary of available data on stroke differential gene expression. Issues regarding validation of potential genes as stroke targets, the verification of message translation to protein products, the relevance of the expression of neuroprotective and neurodestructive genes and their specific timings, and the emerging problems of handling novel genes that may be discovered during differential gene expression analyses will also be addressed.

Animals↗
PubMed2004

Reconstruction of the evolutionary history of the LexA-binding sequence.

In recent years, the recognition sequence of the SOS repressor LexA protein has been identified for several bacterial clades, such as the Gram-positive, green non-sulfur bacteria and Cyanobacteria phyla, or the 'Alphaproteobacteria', 'Deltaproteobacteria' and 'Gammaproteobacteria' classes. Nevertheless, the evolutionary relationship among these sequences and the proteins that recognize them has not been analysed. Fibrobacter succinogenes is an anaerobic Gram-negative bacterium that branched from a common bacterial ancestor immediately before the Proteobacteria phylum. Taking advantage of its intermediate position in the phylogenetic tree, and in an effort to reconstruct the evolutionary history of LexA-binding sequences, the F. succinogenes lexA gene has been isolated and its product purified to identify its DNA recognition motif through electrophoretic mobility assays and footprinting experiments. After comparing the available LexA DNA-binding sequences with the F. succinogenes one, reported here, directed mutagenesis of the F. succinogenes LexA-binding sequence and phylogenetic analyses of LexA proteins have revealed the existence of two independent evolutionary lanes for the LexA recognition motif that emerged from the Gram-positive box: one generating the Cyanobacteria and 'Alphaproteobacteria' LexA-binding sequences, and the other giving rise to the F. succinogenes and Myxococcus xanthus ones, in a transitional step towards the current 'Gammaproteobacteria' LexA box. The contrast between the results reported here and the phylogenetic data available in the literature suggests that, some time after its emergence as a distinct bacterial class, the 'Alphaproteobacteria' lost its vertically received lexA gene, but received later through lateral gene transfer a new lexA gene belonging to either a cyanobacterium or a bacterial species closely related to this phylum. This constitutes the first report based on experimental evidence of lateral gene transfer in the evolution of a gene governing such a complex regulatory network as the bacterial SOS system.

Alphaproteobacteria↗
PubMed2001

Position-space description of the cosmic microwave background and its temperature correlation function.

We suggest that the cosmic microwave background (CMB) temperature correlation function C(theta) as a function of angle provides a direct connection between experimental data and the fundamental cosmological quantities. The evolution of inhomogeneities in the prerecombination universe is studied using Green's functions in position space. We find that a primordial adiabatic point perturbation propagates as a sharp-edged spherical acoustic wave. Density singularities at its wave fronts create a feature in the CMB correlation function distinguished by a dip at theta approximately 1.2 degrees. Characteristics of the feature are sensitive to the values of cosmological parameters, in particular to the total and the baryon densities.

Journal Article↗
PubMed2003

Bridging simulations and experiments in microstructure evolution.

We demonstrate the importance of anisotropic interface properties in microstructure evolution by comparing computed evolved microstructures to final experimental microstructures of 5170 grains in 19 thin aluminum foil samples. This is the first time that a direct experimental validation of simulation has been performed at the level of individual grains. We observe that simulated microstructures using curvature-driven grain boundary motion and anisotropic interface properties agree well with experimentally evolved microstructures, whereas agreement is poor when isotropic properties are used.

Journal Article↗
PubMed2006

Delayed effects of larval predation risk and food quality on anuran juvenile performance.

Metamorphosis can disrupt the correlation structure between juvenile and adult traits, thus allowing relatively independent evolution in contrasting environments. We used a multiple experimental approach to investigate how diet quality and larval predation risk affected the rates of growth and development in painted frogs (Discoglossus galganoi), and how these changes influence post-metamorphic performance. A high-energy diet entailed growth advantages only if predation risk did not constrain energy acquisition, whereas diet quality affected primarily the extension of the larval period. Predation risk influenced juvenile shape, most likely via the effects on growth and differentiation rates. Juvenile frogs emerging from predator environments had shorter legs and longer bodies than those from the nonpredator tanks. However, these morphological changes did not translate into differences in relative jumping performance. Neither size-adjusted lipid storage nor fluctuating asymmetry was significantly influenced by food quality or predation risk. Our data suggest that the post-metamorphic costs of predator avoidance during the larval phase are mostly a consequence of small size at metamorphosis.

Animals↗
PubMed1996

Construction of a multifunctional pneumococcal murein hydrolase by module assembly.

A chimeric trifunctional pneumococcal peptidoglycan hydrolase (CHL) has been constructed by fusing a choline-binding domain with two catalytic modules that provide lysozyme and amidase activity. The chimeric enzymes behaves as a choline-dependent enzyme and its activity is comparable to that of the parent enzymes. Site-directed mutagenesis of CHL produced a mutated enzyme [D9A,36A]CHL) that only exhibited an amidase activity. Comparative biochemical analyses of CHL and [D9A, E36A]CHL strongly suggest that the lysozyme catalytic module confers 88% of the total activity of CHL, whereas 12% of the activity can be ascribed to the amidase module. Both enzymatic activities are affected by the process of activation or conversion induced by choline suggesting that the conversion process is produced by a conformational change in the choline-binding domain. Our findings demonstrate that the three modules can acquire the proper folding conformation in the-three domain chimeric CHL enzyme. This experimental evidence supports the modular theory of protein evolution, and demonstrates that modular assembly of functional domains can be a rational approach to construct fully active chimeric enzymes with novel biological or biotechnological properties.

Amidohydrolases↗
PubMed2004

Uses and abuses of mathematics in biology.

In the physical sciences, mathematical theory and experimental investigation have always marched together. Mathematics has been less intrusive in the life sciences, possibly because they have until recently been largely descriptive, lacking the invariance principles and fundamental natural constants of physics. Increasingly in recent decades, however, mathematics has become pervasive in biology, taking many different forms: statistics in experimental design; pattern seeking in bioinformatics; models in evolution, ecology, and epidemiology; and much else. I offer an opinionated overview of such uses--and abuses.

Allergy and Immunology↗
PubMed1981

Learning dynamic psychotherapy in psychiatric training.

At a time when psychiatric training is undergoing major shifts in response to social and economic pressures, it is crucial to preserve the trainee's opportunity to learn the techniques of dynamic psychotherapy. The author describes the course of the treatment of a patient to illustrate the way in which the central psychological issue had to be learned by sitting with her through the evolution of its discovery. This process of independent, experimental learning is crucial for the trainee's development of a sound and flexible understanding of the basic principles of psychodynamics.

Adult↗
PubMedDate not supplied

Methodological analysis in behavioral toxicology: an ethotoxicological approach.

A constraint in the development of laboratory animal models of human disease conditions is their applicability to the natural environment in which a given animal species evolved. The range of behavioral patterns that can be carefully assessed and quantified in the laboratory is sometimes limited. Although field studies reflect behavioral responses in natural settings, they may also have methodological limitations. Laboratory techniques are not applicable to wild species since natural conditions cannot be brought into a laboratory in an inexpensive or reliable way. However, it is possible to create near-natural settings which may not fulfill all the criteria of the actual context of evolution, but which can be controlled by the experimenter. We recommend an integrative style of approach considering laboratory constraints and, at the same time, the ecological niche in which a given behavioral pattern evolved. This type of ethological assessment may be useful when carrying out toxicological studies on both wild and laboratory mammals.

Animals↗
PubMed1990

Cerebral blood flow and edema in perinatal hypoxic-ischemic brain damage.

The relationship between cerebral blood flow (CBF) and the evolution of brain edema was investigated in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-d postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37 degrees C. This insult produces neuronal necrosis and/or infarction only in the cerebral hemisphere ipsilateral to the arterial occlusion in the majority of animals; hypoxia alone produces no damage. CBF, measured by the indicator diffusion technique using iodo[14C]-antipyrine, and tissue water content were determined concurrently in both cerebral hemispheres at specific intervals during recovery from cerebral hypoxia-ischemia. Water contents in the ipsilateral cerebral hemisphere were 89.1, 89.6, 89.7, 91.0, and 88.3% at 30 min, 4 h, 24 h, 3 d, and 6 d, respectively (p less than 0.001); whereas the percent tissue water in the contralateral hemisphere was unchanged from values in nonligated, hypoxic control rats (87.7%). CBF was similar in both cerebral hemispheres at 30 min, 4 h, and 24 h of recovery (50-65 mL/100 g/min) and not different from age-matched controls. At 3 and 6 d, CBF in the ipsilateral cerebral hemisphere was 30 and 26% of the contralateral hemisphere and 23 and 29% of the control animals, respectively (p less than 0.001). No inverse correlation existed between the changes in brain water content and CBF at any interval until 6 d of recovery. Thus, an early hypoperfusion does not follow perinatal cerebral hypoxia-ischemia, as occurs in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Hypoxia-ischemia stimulates hippocampal glutamate efflux in perinatal rat brain: an in vivo microdialysis study.

We used in vivo microdialysis to determine the impact of a focal hypoxic-ischemic insult on hippocampal amino acid efflux in the immature brain. Microdialysis probes were inserted into the right hippocampus of postnatal d 7 rats. To induce hypoxic-ischemic injury, the right carotid artery was ligated and animals were exposed to 8% oxygen for 2 h (n = 6, histologically verified). Ten 20-min dialysis fractions were collected from each animal: three sequential 20-min baseline samples, six samples during hypoxia, and a recovery sample in room air. Eight amino acids were detected in dialysates with a HPLC assay. There was marked intra- and interanimal variation in glutamate efflux; mean glutamate efflux increased from 17 pmol/min in baseline samples to 51 in the 2nd h of hypoxia (p = 0.002, Kruskal Wallis test). There was a concurrent decline in glutamine efflux (310 to 207 pmol/min, p = 0.0005). Alanine efflux doubled during hypoxia (p = 0.015). There were no changes in efflux of the other five amino acids analyzed. In this experimental model of perinatal stroke, during the acute evolution of hypoxic-ischemic brain injury, transient large increases in glutamate efflux and corresponding declines in glutamine efflux were detected. These data support the hypothesis that synaptic concentrations of the endogenous excitatory amino acid glutamate increase during the evolution of hippocampal ischemic injury.

Amino Acids↗
PubMed2006

Offline persistence of memory-related cerebral activity during active wakefulness.

Much remains to be discovered about the fate of recent memories in the human brain. Several studies have reported the reactivation of learning-related cerebral activity during post-training sleep, suggesting that sleep plays a role in the offline processing and consolidation of memory. However, little is known about how new information is maintained and processed during post-training wakefulness before sleep, while the brain is actively engaged in other cognitive activities. We show, using functional magnetic resonance imaging, that brain activity elicited during a new learning episode modulates brain responses to an unrelated cognitive task, during the waking period following the end of training. This post-training activity evolves in learning-related cerebral structures, in which functional connections with other brain regions are gradually established or reinforced. It also correlates with behavioral performance. These processes follow a different time course for hippocampus-dependent and hippocampus-independent memories. Our experimental approach allowed the characterization of the offline evolution of the cerebral correlates of recent memories, without the confounding effect of concurrent practice of the learned material. Results indicate that the human brain has already extensively processed recent memories during the first hours of post-training wakefulness, even when simultaneously coping with unrelated cognitive demands.

Adult↗
PubMed2001

Protein folding: a perspective for biology, medicine and biotechnology.

At the present time, protein folding is an extremely active field of research including aspects of biology, chemistry, biochemistry, computer science and physics. The fundamental principles have practical applications in the exploitation of the advances in genome research, in the understanding of different pathologies and in the design of novel proteins with special functions. Although the detailed mechanisms of folding are not completely known, significant advances have been made in the understanding of this complex process through both experimental and theoretical approaches. In this review, the evolution of concepts from Anfinsen's postulate to the "new view" emphasizing the concept of the energy landscape of folding is presented. The main rules of protein folding have been established from in vitro experiments. It has been long accepted that the in vitro refolding process is a good model for understanding the mechanisms by which a nascent polypeptide chain reaches its native conformation in the cellular environment. Indeed, many denatured proteins, even those whose disulfide bridges have been disrupted, are able to refold spontaneously. Although this assumption was challenged by the discovery of molecular chaperones, from the amount of both structural and functional information now available, it has been clearly established that the main rules of protein folding deduced from in vitro experiments are also valid in the cellular environment. This modern view of protein folding permits a better understanding of the aggregation processes that play a role in several pathologies, including those induced by prions and Alzheimer's disease. Drug design and de novo protein design with the aim of creating proteins with novel functions by application of protein folding rules are making significant progress and offer perspectives for practical applications in the development of pharmaceuticals and medical diagnostics.

Animals↗
PubMed2001

Biological factors influencing the RBE of neutrons: implications for their past, present and future use in radiotherapy.

The recent resurgence of interest in fast-neutron therapy, particularly for the treatment of prostate cancer, warrants a review of the original radiobiological basis for this modality and the evolution of these concepts that resulted from subsequent experimentation with the fast-neutron beams used for randomized clinical trials. It is clear from current radiobiological knowledge that some of the postulates that formed the mechanistic basis for past clinical trials were incorrect. Such discrepancies, along with the inherent physical disadvantages of neutron beams in terms of collimation and intensity modulation, may partially account for the lack of therapeutic benefit observed in many randomized clinical trials. Moreover, it is equally apparent that indiscriminate prescription of fast-neutron therapy is likely to lead to an adverse clinical outcome in a proportion of patients. Hence any renewed efforts to establish a niche for this modality in clinical radiation oncology will necessitate the development of a triage system that can discriminate those patients who might benefit from fast-neutron therapy from those who might be harmed by it. In the future, fast-neutron therapy might be prescribed based upon the relative status of appropriate molecular parameters that have a differential impact upon radiosensitivity to photons compared to fast neutrons.

Animals↗
PubMed2000

Gene Therapy for Coronary Restenosis: A Promising Strategy for the New Millennium?

Gene therapy is an attractive alternative for reducing restenosis after percutaneous coronary interventions. Several approaches, using genes encoding antiproliferative, antimigratory, cytostatic, or cytotoxic proteins have been successfully tested in relevant animal models. Antiproliferative, gene-based strategies also appear to be good candidates for the highly proliferative lesion responsible for in-stent restenosis. However, several key issues, including vector safety and delivery mechanisms, still have to be resolved before percutaneous gene therapy can be widely applied in the clinic. The amount of experimental research in this field indicates a medical evolution that can (and should) not be ignored by cardiologists.

Journal Article↗
PubMed2000

Regional hypothermia with epidural cooling for spinal cord protection during thoracoabdominal aneurysm repair.

Several techniques have been developed and clinically applied to reduce the spinal cord ischemia complications that follow thoracoabdominal aortic aneurysm (TAA) repair. Hypothermia as a protective adjunct is a concept that has been used throughout the evolution of cardiac and central aortic surgery. Because experimental regional hypothermic perfusion delivered directly to the epidural or intrathecal space showed protective effects against cord injury, we developed and applied a method for providing regional cord hypothermia with epidural cooling during TAA repair. This review describes the technical considerations with epidural cooling and the clinical results obtained in our experience.

Adolescent↗