SEARCH · PubMed Health

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,477 records · Page 82Linked to original sources

PubMed2005

Comprehensive evaluation of protein structure alignment methods: scoring by geometric measures.

We report the largest and most comprehensive comparison of protein structural alignment methods. Specifically, we evaluate six publicly available structure alignment programs: SSAP, STRUCTAL, DALI, LSQMAN, CE and SSM by aligning all 8,581,970 protein structure pairs in a test set of 2930 protein domains specially selected from CATH v.2.4 to ensure sequence diversity. We consider an alignment good if it matches many residues, and the two substructures are geometrically similar. Even with this definition, evaluating structural alignment methods is not straightforward. At first, we compared the rates of true and false positives using receiver operating characteristic (ROC) curves with the CATH classification taken as a gold standard. This proved unsatisfactory in that the quality of the alignments is not taken into account: sometimes a method that finds less good alignments scores better than a method that finds better alignments. We correct this intrinsic limitation by using four different geometric match measures (SI, MI, SAS, and GSAS) to evaluate the quality of each structural alignment. With this improved analysis we show that there is a wide variation in the performance of different methods; the main reason for this is that it can be difficult to find a good structural alignment between two proteins even when such an alignment exists. We find that STRUCTAL and SSM perform best, followed by LSQMAN and CE. Our focus on the intrinsic quality of each alignment allows us to propose a new method, called "Best-of-All" that combines the best results of all methods. Many commonly used methods miss 10-50% of the good Best-of-All alignments. By putting existing structural alignments into proper perspective, our study allows better comparison of protein structures. By highlighting limitations of existing methods, it will spur the further development of better structural alignment methods. This will have significant biological implications now that structural comparison has come to play a central role in the analysis of experimental work on protein structure, protein function and protein evolution.

Computational Biology↗

PubMed2003

Long-term evaluation of the replacement of the trachea with an autologous aortic graft.

BACKGROUND: Tracheal reconstruction after extensive resection remains a challenge in thoracic surgery. The goal of this experimental study was to analyze the long-term evolution of tracheal replacement using an autologous aortic graft. METHODS: In 21 sheep, a 5-cm segment of the cervical trachea was replaced by a segment of the descending thoracic aorta that was reconstructed to a prosthetic graft. Because of the airway collapse reported in a previous series, a permanent (n = 13) or temporary (n = 8) stent was systematically placed in the lumen of the graft. Clinical, bronchoscopic, and histologic examinations were performed up to 3 years after implantation. RESULTS: All animals survived the operation with no paraplegia. In the group with a permanent stent, three complications occurred: one stent displacement, one laryngeal edema, and one infection. Stent removal was tolerated after 6 months in the group with a temporary stent. Histologic examination showed a progressive transformation of the arterial segment into first extensive inflammatory tissue with a squamous epithelium, and after 6 to 36 months well-differentiated tracheal tissue including a continuous mucociliary epithelium and regular rings of newly formed cartilage. CONCLUSIONS: An autologous aortic graft used as a substitute for extensive tracheal replacement in sheep remained functional for periods up to 3 years. The progressive transformation of the graft into a structure resembling tracheal tissue seems to be a key factor in long-term patency. The mechanism of this regenerative process and the possibility of using arterial homografts, which would make clinical application easier, remain to be evaluated.

Animals↗

PubMed2002

Phage display technology: clinical applications and recent innovations.

Phage display is a molecular diversity technology that allows the presentation of large peptide and protein libraries on the surface of filamentous phage. Phage display libraries permit the selection of peptides and proteins, including antibodies, with high affinity and specificity for almost any target. A crucial advantage of this technology is the direct link that exists between the experimental phenotype and its encapsulated genotype, which allows the evolution of the selected binders into optimized molecules. Phage display facilitates engineering of antibodies with regard to their size, valency, affinity, and effector functions. The selection of antibodies and peptides from libraries displayed on the surface of filamentous phage has proven significant for routine isolation of peptides and antibodies for diagnostic and therapeutic applications. This review serves as an introduction to phage display, antibody engineering, the development of phage-displayed peptides and antibody fragments into viable diagnostic reagents, and recent trends in display technology.

Animals↗

PubMed2003

Cardiac mast cell- and chymase-mediated matrix metalloproteinase activity and left ventricular remodeling in mitral regurgitation in the dog.

The present study tested the hypothesis that cardiac mast cells and chymase are associated with matrix metalloproteinase (MMP) activation and extracellular matrix (ECM) degradation in the evolution of left ventricular (LV) chamber remodeling secondary to experimental mitral regurgitation (MR) in dogs. LV mast cell density, chymase activity, and angiotensin II (ANG II) levels were significantly increased 2 and 4 weeks post-MR, while an increase in angiotensin-converting enzyme (ACE) activity was not seen prior to the chronic 24 week stage. As early as 2 and 4 weeks, there was a significant decrease in interstitial myocardial collagen content that was associated with an increase in LV end-diastolic diameter (LVEDD) but a normal LVEDD/wall thickness ratio. While mast cell density decreased to normal at 24 weeks, both chymase and MMP-2 activity remained increased throughout the entire 24-week period post-MR. By 24 weeks a transition to an adverse pattern of LV remodeling characterized by a 2-fold increase in the LVEDD/wall thickness ratio had occurred. Thus, this study supports the hypothesis that mast cells and chymase are important modulators of MMP activity and ECM degradation, contributing to adverse LV remodeling in chronic volume overload secondary to MR.

Animals↗

PubMed2000

Morphogenesis of the eggshell in Drosophila.

The Drosophila eggshell is a specialized extracellular matrix that forms between the oocyte and overlaying somatic follicle cells during the latter stages of oogenesis. Largely proteinaceous, the eggshell is a highly organized multilayered structure with regional specializations designed to perform a variety of functions. Production of a functional eggshell features: (1) the differentiation of subsets of follicle cells in response to ovarian signals, (2) directed migrations of the follicle cells within the developing egg chamber, (3) expression of eggshell structural genes by the follicle cells in a defined temporal and spatial order, (4) postdepositional modifications of the eggshell proteins including several temporally regulated proteolytic cleavage events, and (5) regulated trafficking of several eggshell proteins in the assembling structure. By exploiting the genetic advantages of Drosophila and using evolution as a guide, the eggshell provides an excellent experimental system to study, in vivo, molecular mechanisms used to regulate protein-protein interactions throughout the assembly of a complex extracellular architecture in a developing organism.

Amino Acid Sequence↗

PubMed2002

IFN-gamma diagnostic tests in the context of bovine mycobacterial infections in Belgium.

In countries where cattle tuberculosis caused by Mycobacterium bovis (Mbov) and paratuberculosis caused by Mycobacterium avium subsp. paratuberculosis (Mptb) are present, testing strategies for the Mbov eradication have to discriminate between these two infections. Present indirect tests are based on the analysis of the specific cellular immune response (DTH, IFN-gamma) against crude mycobacterial antigens (avian and bovine PPD). In this study, we compared the evolution of the IFN-gamma responses of animals experimentally infected with Mbov, Mptb, or inoculated with Mycobacterium phlei. Mbov inoculation induced a strong IFN-gamma response that allows rapid classification of the status of the animals following interpretation criteria set up by us. Experimental inoculation with M. phlei induced sensitisation to mycobacterial antigens as detected by the IFN-gamma test but these reactions were of short duration, therefore, repeated testing allows us to define these animals as aspecific reactors. IFN-gamma response induced after oral inoculation of calves with Mptb was of low intensity and ratio of responses measured against avian versus bovine PPD did not allow a clear diagnostic at least for the six first month of infection.

Animals↗

PubMed2000

Hepatocyte transplantation. Advancing biology and treating children.

Key advances over the past three decades have allowed the evolution of hepatocyte transplantation from its use as an experimental tool to study liver cell biology to the initial application as a potential treatment modality for patients with liver disease. Although little is known about the cellular and molecular mechanisms regulating the fate of transplanted cells, studies in animal models of liver disease clearly suggest that transplanted hepatocytes have the potential to repopulate diseased livers and correct metabolic defects. Based on these experiments, human hepatocytes have been used in the treatment of children and adults with metabolic disease and liver failure. In initial trials, the improved clinical course following hepatocyte transplantation points to a potential role of the technique as an adjunct to liver transplantation.

Adolescent↗

PubMed1990

Mutation-selection balance and the evolutionary advantage of sex and recombination.

Mutation-selection balance in a multi-locus system is investigated theoretically, using a modification of Bulmer's infinitesimal model of selection on a normally-distributed quantitative character, taking the number of mutations per individual (n) to represent the character value. The logarithm of the fitness of an individual with n mutations is assumed to be a quadratic, decreasing function of n. The equilibrium properties of infinitely large asexual populations, random-mating populations lacking genetic recombination, and random-mating populations with arbitrary recombination frequencies are investigated. With 'synergistic' epistasis on the scale of log fitness, such that log fitness declines more steeply as n increases, it is shown that equilibrium mean fitness is least for asexual populations. In sexual populations, mean fitness increases with the number of chromosomes and with the map length per chromosome. With 'diminishing returns' epistasis, such that log fitness declines less steeply as n increases, mean fitness behaves in the opposite way. Selection on asexual variants and genes affecting the rate of genetic recombination in random-mating populations was also studied. With synergistic epistasis, zero recombination always appears to be disfavoured, but free recombination is disfavoured when the mutation rate per genome is sufficiently small, leading to evolutionary stability of maps of intermediate length. With synergistic epistasis, an asexual mutant is unlikely to invade a sexual population if the mutation rate per diploid genome greatly exceeds unity. Recombination is selectively disadvantageous when there is diminishing returns epistasis. These results are compared with the results of previous theoretical studies of this problem, and with experimental data.

Animals↗

PubMed2004

Oscillating fluorescence in an unstable colloidal dispersion of CdSe/ZnS core/shell quantum dots.

Fluorescence oscillation is observed in an ensemble of colloidal CdSe/ZnS core/shell quantum dots (QDs) dispersed in nonpolar solvent under continuous irradiation. The QDs dispersed in toluene gradually aggregate and change their fluorescence intensity, even in the dark. During the aggregation, the QD/toluene suspension is unstable, that is, overdispersed. The fluorescence oscillation is found only in this unstable state before the system reaches steady state. In addition, the aggregation rate is promoted by irradiation and strongly correlates with the oscillation amplitude. Our experimental results indicate that the dispersion instability plays an important role in both linear and nonlinear dynamics of the fluorescence. It is inferred from the experimental results and previous studies that the complex time evolution of fluorescence in the QD/toluene dispersion is possibly due to adsorption and desorption of surface ligand molecules over the course of QD aggregation.

Journal Article↗

PubMed2025

Evolutionary fingerprints of epithelial-to-mesenchymal transition.

Mesenchymal plasticity has been extensively described in advanced epithelial cancers; however, its functional role in malignant progression is controversial1-5. The function of epithelial-to-mesenchymal transition (EMT) and cell plasticity in tumour heterogeneity and clonal evolution is poorly understood. Here we clarify the contribution of EMT to malignant progression in pancreatic cancer. We used somatic mosaic genome engineering technologies to trace and ablate malignant mesenchymal lineages along the EMT continuum. The experimental evidence clarifies the essential contribution of mesenchymal lineages to pancreatic cancer evolution. Spatial genomic analysis, single-cell transcriptomic and epigenomic profiling of EMT clarifies its contribution to the emergence of genomic instability, including events of chromothripsis. Genetic ablation of mesenchymal lineages robustly abolished these mutational processes and evolutionary patterns, as confirmed by cross-species analysis of pancreatic and other human solid tumours. Mechanistically, we identified that malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division. Thus, EMT favours the emergence of genomic-unstable, highly fit tumour cells, which strongly supports the concept of cell-state-restricted patterns of evolution, whereby cancer cell speciation is propagated to progeny within restricted functional compartments. Restraining the evolutionary routes through ablation of clones capable of mesenchymal plasticity, and extinction of the derived lineages, halts the malignant potential of one of the most aggressive forms of human cancer.

Animals↗

PubMed2005

Pressure dependence of the glass temperature in supercooled liquids.

The description of the pressure evolution of the glass temperature Tg(p) based on experimental data for diethyl phtalate is discussed. First, parameterizations of Tg(P) experimental data applied are briefly given. Then a novel relation based on the modified Simon-Glatzel equation is proposed. Its applications may result in the appearance of the asymptotic temperature (theta) and the asymptotic pressure (pi) previously postulated [E. Donth,, Springer Series in Material Sci. II (Springer, Berlin, 1998), Vol. 48, pp. 6, 375]. The asymptotic pressure is hidden in the negative pressure domain. Such asymptotic behavior was absent for parameterizations of Tg(p) data in glassy liquids applied up to now.

Journal Article↗

PubMed2004

Adatom ascending at step edges and faceting on fcc metal (110) surfaces.

Using first-principles total-energy calculations, we show that an adatom can easily climb up at monatomic-layer-high steps on several representative fcc metal (110) surfaces via a place exchange mechanism. Inclusion of such novel adatom ascending processes in kinetic Monte Carlo simulations of Al(110) homoepitaxy as a prototypical model system can lead to the existence of an intriguing faceting instability, whose dynamical evolution and kinetic nature are explored in comparison with experimental observations.

Journal Article↗

PubMed2004

Quantitative phase-amplitude microscopy. III. The effects of noise.

We explore the effect of noise on images obtained using quantitative phase-amplitude microscopy - a new microscopy technique based on the determination of phase from the intensity evolution of propagating radiation. We compare the predictions with experimental results and also propose an approach that allows good-quality quantitative phase retrieval to be obtained even for very noisy data.

Artifacts↗

PubMed2006

Genetic immunity and influenza pandemics.

In addition to the great number of publications focused on the leading role of virus mutations and reassortment in the origin of pandemic influenza, general opinion emphasizes the victim side of the epidemic process. Based on the analysis and integration of relevant ecological, epidemiological, clinical, genetic and experimental data, the present article is focused on the evolution of 'virus - victim' ecological systems resulting in the formation of innate (i.e. genetic, constitutional) immunity in the involved species and populations. This kind of immunity functions today as the greatest natural barrier to the pandemic spread of influenza among humans and ecologically related kinds of animals. Global influenza pandemics can arise when the worldwide population contains at least a minimum number of people susceptible to a known or mutant influenza virus. Special attention is paid in this article to individual tests for the presence of this barrier, including the implications of specific findings for public health policy. Such tests could be based on in vitro observation of the action of relevant virus strains on primary cell cultures or on their cellular or molecular components extracted from individuals. The resources of the Human Genome Project should also be utilized.

Disease Outbreaks↗

PubMed1981

Vinyl chloride-induced hepatic lesions in man and rodents. A comparison.

Histologic sequences in the liver of rodents exposed by inhalation to gaseous vinyl chloride were compared to the lesions in man exposed to the same agent, mainly in vinyl chloride polymerization plants. An identical sequence, starting with circumscribed proliferation of hepatocytes, soon followed by proliferation of a variety of sinusoidal cells and frequently associated with sinusoidal dilatation, progresses to intralobular and more frequently to trabecular angiosarcoma. Predominantly in young animals and rarely in man, hepatocellular carcinoma develops, but never cirrhosis. The sequence represents a dynamic process of competition between proliferating hepatocytes and sinusoidal cells, of hepatocytes with fibroplasia, between perisinusoidal fibrosis and sinusoidal dilatation, and of proliferation of various sinusoidal cells versus angiosarcoma. The great similarity in the evolution in man and rodents, rarely encountered in other experimental models, supports the prediction of human cancer from animal experiments. The precursor nodules differ from the nodules commonly observed in hepatocarcinogenesis by co-proliferation of sinusoidal cells. The differences in the reactions between man and rodents bespeak a strong fibroblastic reactivity in man. Most important, the precursor lesion of mixed hepatocellular and sinusoidal cell proliferation may be of diagnostic value, being superior to conventional hepatic tests in detection of some initial environmental lesions.

Animals↗

PubMed1989

Fish as model systems.

Fish represent the largest and most diverse group of vertebrates. Their evolutionary position relative to other vertebrates and their ability to adapt to a wide variety of environments make them ideal for studying both organismic and molecular evolution. A number of other characteristics make them excellent experimental models for studies in embryology, neurobiology, endocrinology, environmental biology, and other areas. In fact, they have played a critical role in the development of several of these disciplines. Research techniques that enable scientists to make isogenic lines in a single generation, create and maintain mutants, culture cells, and transfer cloned genes into embryos signal an increasing role for fish as experimental models.

Adaptation, Biological↗

PubMed1999

HCP<=>CPH isomerization: caught in the act.

In this overview we discuss the vibrational spectrum of phosphaethyne, HCP, in its electronic ground state, as revealed by complementary experimental and theoretical examinations. The main focus is the evolution of specific spectral patterns from the bottom of the potential well up to excitation energies of approximately 25,000 cm(-1), where large-amplitude, isomerization-type motion from H-CP to CP-H is prominent. Distinct structural and dynamical changes, caused by an abrupt transformation from essentially HC bonding to mainly PH bonding, set in around 13,000 cm(-1). They reflect saddle-node bifurcations in the classical phase space--a phenomenon well known in the nonlinear dynamics literature--and result in characteristic patterns in the spectrum and the quantum-number dependence of the vibrational fine-structure constants. Two polar opposites are employed to elucidate the spectral patterns: the exact solution of the Schrödinger equation, using an accurate potential energy surface and an effective or resonance Hamiltonian (expressed in a harmonic oscillator basis set and block diagonalized into polyads), which is defined by parameters adjusted to fit either the measured or the calculated vibrational energies. The combination of both approaches--together with classical mechanics and semiclassical analyses--provides a detailed spectroscopic picture of the breaking of one bond and the formation of a new one.

Journal Article↗

PubMed1993

The role of hormonal and dietary factors in pancreatic carcinogenesis.

The pancreatic cancer continues to represent an important problem, as a cancer with extremely poor prognosis. To date more than 16 chemicals have been shown to induce pancreatic tumors, in animal models. The tumors developed in rats are essentially of acinar type and those in hamsters mostly of ductal type. Many studies proved the direct or indirect role of hormonal and dietary factors in pancreatic cancer. The development of alternative treatments according to biological and biochemical steps of carcinogenesis is available as adjuvant treatment. We present herein an overview of current experimental and clinical results in order to understand the evolution, histogenesis and biological behaviour of pancreatic cancer.

Adenocarcinoma↗