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PubMed2002

Iterative database searches demonstrate that glycoside hydrolase families 27, 31, 36 and 66 share a common evolutionary origin with family 13.

Classification of glycoside hydrolases (GHs) into families, along with the structure-based grouping together of families into clans, improve our understanding of the evolution of the large natural variety of these enzymes, help rationalise experimental data and guide further studies. Here we identify triose phosphate isomerase (TIM) barrels in GH families 27, 31, 36 and 66. We further show that iterated sequence database searches provide evidence for their sharing a common evolutionary origin with GH family 13. The catalytic, nucleophilic residue common to all these families is thereby determined and candidate catalytic proton donors identified within each family.

Aspartic Acid↗

PubMed2002

Modeling of the biotransformation of crotonobetaine into L-(-)-carnitine by Escherichia coli strains.

A simple unstructured model, which includes carbon source as the limiting and essential substrate and oxygen as an enhancing substrate for cell growth, has been implemented to depict cell population evolution of two Escherichia coli strains and the expression of their trimethylammonium metabolism in batch and continuous reactors. Although the model is applied to represent the trans-crotonobetaine to L-(-)-carnitine biotransformation, it is also useful for understanding the complete metabolic flow of trimethylammonium compounds in E. coli. Cell growth and biotransformation were studied in both anaerobic and aerobic conditions. For this reason we derived equations to modify the specific growth rate, mu, and the cell yield on the carbon source (glycerol), Y(xg), as oxygen increased the rate of growth. Inhibition functions representing an excess of the glycerol and oxygen were included to depict cell evolution during extreme conditions. As a result, the model fitted experimental data for various growth conditions, including different carbon source concentrations, initial oxygen levels, and the existence of a certain degree of cell death. Moreover, the production of enzymes involved within the E. coli trimethylammonium metabolism and related to trans-crotonobetaine biotransformation was also modeled as a function of both the cell and oxygen concentrations within the system. The model describes all the activities of the different enzymes within the transformed and wild strains, able to produce L-(-)-carnitine from trans-crotonobetaine under both anaerobic and aerobic conditions. Crotonobetaine reductase inhibition by either oxygen or the addition of fumarate as well as its non-reversible catalytic action was taken into consideration. The proposed model was useful for describing the whole set of variables under both growing and resting conditions. Both E. coli strains within membrane high-density reactors were well represented by the model as results matched the experimental data.

Algorithms↗

PubMed1992

Inheritance of the group I rDNA intron in Tetrahymena pigmentosa.

We have previously argued from phylogenetic sequence data that the group I intron in the rRNA genes of Tetrahymena was acquired by different Tetrahymena species at different times during evolution. We have now approached the question of intron mobility experimentally by crossing intron+ and intron- strains looking for a strong polarity in the inheritance of the intron (intron homing). Based on the genetic analysis we find that the intron in T. pigmentosa is inherited as a neutral character and that intron+ and intron- alleles segregate in a Mendelian fashion with no sign of intron homing. In an analysis of vegetatively growing cells containing intron+ and intron- rDNA, initially in the same macronucleus, we similarly find no evidence of intron homing. During the course of this work, we observed to our surprise that progeny clones from some crosses contained three types of rDNA. One possible explanation is that T. pigmentosa has two rdn loci in contrast to the single locus found in T. thermophila. Some of the progeny clones from the genetic analysis were expanded for several hundred generations, and allelic assortment of the rDNA was demonstrated by subcloning analysis.

Alleles↗

PubMed1999

Experimental acute hematogenous osteomyelitis in mice. II. Influence of Staphylococcus aureus infection on T-cell immunity.

A murine model of acute hematogenous osteomyelitis was used to study the immune response following Staphylococcus aureus infection and to examine the hypothesis that the bacteria may modify T-cell responses due to the production of bacterial enterotoxins with mitogenic or superantigenic activity. Lymph-node T cell-receptor expression was assessed with use of flow cytometry and reverse transcription-polymerase chain reaction techniques, and increased apoptosis (programmed cell death) in T-cell subsets was monitored. The expression and levels of circulating cytokines and T-cell cytokines within tissues surrounding the damaged area of the proximal tibia were also investigated. Analysis of T-cell receptors in experimental osteomyelitis revealed two distinct patterns of T-cell evolution during the disease. Certain T-cell subsets (Vbeta2, Vbeta3, Vbeta9, and Vbeta10) were activated and expanded during the first 24 hours after infection; they reached maximum levels 6 days after infection, followed by a return to pre-infection levels. In contrast, other T-cell subsets (Vbeta11, Vbeta12, Vbeta13, Vbeta14, and Vbeta16) contracted during the first 24 hours after infection, followed by expansion to a maximum level 9 days after infection. Activation and proliferation of T-cell subsets (notably Vbeta14 T cells) was followed by apoptosis, suggesting that staphylococcal bone infection caused superantigenic-like effects on the mouse immune system. Analysis of cytokine responses in local tissue revealed that the T-cell cytokines interleukin-2 and interferon-gamma showed a late and relatively short activation pattern compared with the inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha. The results suggest that Staphylococcus aureus bone infection may undermine the antibacterial immune response through downregulation of T-cell immunity and immune-cytokine production, which could increase the severity of the systemic infection and local osseous destruction that occur with acute hematogenous osteomyelitis.

Acute Disease↗

PubMed2002

Empathy leads to fairness.

In the Ultimatum Game, two players are asked to split a prize. The first player, the proposer, makes an offer of how to split the prize. The second player, the responder, either accepts the offer, in which case the prize is split as agreed, or rejects it, in which case neither player receives anything. The rational strategy suggested by classical game theory is for the proposer to offer the smallest possible positive share and for the responder to accept. Humans do not play this way, however, and instead tend to offer 50% of the prize and to reject offers below 20%. Here we study the Ultimatum Game in an evolutionary context and show that empathy can lead to the evolution of fairness. Empathy means that individuals make offers which they themselves would be prepared to accept.

Biological Evolution↗

PubMed2003

Non-invasive imaging methods for the characterization of the pathophysiology of brain ischemia.

Non-invasive imaging methods are increasingly used to study the evolution and therapy of brain diseases under both clinical and experimental conditions. In the animal experiment, these methods can be supplemented by invasive tissue assays to allow precise characterization of the underlying pathophysiology. Based on such an approach, this review evaluates the importance of in vivo nuclear magnetic resonance (NMR) and positron emission tomography (PET) for the understanding of the pathophysiology of brain ischemia.

Animals↗

PubMed1997

[New aspects in the pathophysiology of chronic pancreatitis].

Despite numerous experimental and clinical investigations there is no consensus on the evolution of chronic pancreatitis (CP). In the 1970s and 1980s, Sarles persistently emphasised the de novo evolution of CP due to pancreatolithiasis. In recent years, however, clinical and morphological studies have provided strong evidence for the initial proposal of acute pancreatitis progressing to chronic pancreatitis. The so-called necrosis-fibrosis-sequence theory is supported by immunohistochemical work suggesting that inflammatory mediators primarily contribute to tissue destruction and that infiltration of pancreatic nerves by immune cells is a pathogenetic factor for the generation of pain in CP. While Sarles postulates that acinar hypersecretion and an imbalance of pancreatic stone promoting and inhibiting factors trigger the evaluation of CP, the necrosis-fibrosis-sequence theory also involves other pathomechanisms (e.g. changes in ductal permeability, ischemia, oxidative stress) which have been shown to cause (acute) pancreatic injury. Despite this unifying template, which also lessens the need to identify independent mechanisms for the pathogenesis of acute and chronic alcoholic pancreatitis, there are still open questions, e.g. on genetic factors that (like in hereditary CP) may explain the different susceptibility of the pancreas to injury and the individual immunological response.

Cholelithiasis↗

PubMed1993

Effects of nitrate therapy on ventricular remodeling and function.

The hypothesis that nitrates might effectively limit left ventricular remodeling and improve function after acute myocardial infarction has been tested in experimental and clinical models, with special attention to the pathophysiologic evolution of remodeling. In 1 clinical study, before the thrombolytic era, the effects of low-dose intravenous nitroglycerin infusion for the first 48 hours during acute myocardial infarction was evaluated in a prospective, randomized, single-blinded, placebo-controlled study of 310 patients (154 nitroglycerin; 156 placebo). Nitroglycerin proved to be safe and produced several benefits compared with placebo: (1) smaller infarct size; (2) less left ventricular dysfunction; (3) less infarct expansion and thinning; (4) better functional status; (5) fewer in-hospital complications such as left ventricular failure, left ventricular thrombus, cardiogenic shock, and infarct extension; and (6) fewer deaths up to 1 year. Two subsequent clinical studies in the thrombolytic era, with low-dose intravenous nitroglycerin infusion during infarction over the first 48 hours followed by buccal nitrate (eccentric dose regimen) or placebo during healing over 6 weeks postinfarction, indicated that prolonged nitrate therapy effectively limited left ventricular remodeling and improved function further compared with placebo.

Heart Ventricles↗

PubMed1994

Prolonged tolerance, dependence and abstinence following subcutaneous morphine pellet implantation in the rat.

Opiate withdrawal is a common occurrence in human opiate addicts that is no life threatening but is hypothesized to be a significant factor which may contribute to drug taking behavior in these opiate dependent individuals. The purpose of this study was to compare the time course for the development of tolerance, dependence and abstinence using a rat model. Rats were made dependent by implantation of 2 morphine pellets s.c. (75 mg morphine base). Morphine implanted rats exhibited analgesia as measured in a tail-dip assay, for up to 12 h post-implant after which the development of tolerance resulted in tail-flick latencies returning to the level of control rats. Withdrawal was evaluated by injection of the opiate antagonist, naloxone (1 mg/kg s.c.). Rating of the abstinence syndrome revealed significant withdrawal signs by 3 h post-implant which became increasingly intense up to 24 h post-implant. Withdrawal could be precipitated for at least 13 days post-implant, while by 18 days post-implant almost no abstinence signs were observed. Plasma morphine levels following implantation of 2 pellets remained relatively stable from 3-12 days post-implantation. These results further extend the characterization of opiate abstinence following subcutaneous pellet implantation. These results also suggest that opiate abstinence develops within the first 24 h and follows the time course of the development of tolerance. The characterization of the evolution of opiate tolerance, physical dependence and abstinence under similar experimental conditions is critical to the design of future studies to examine the neural bases for these phenomena.

Analgesia↗

PubMed2005

Analysis of potential and free furfural compounds in milk-based formulae by high-performance liquid chromatography. Evolution during storage.

A simple and reproducible HPLC-diode array detection method for the qualitative and quantitative analysis of potential and free furfural compounds (5-hydroxymethyl-2-furaldehyde, HMF; 2-furaldehyde, F; 2-furyl methyl ketone, FMC; and 5-methyl-2-furaldehyde, MF) in milk-based formulae was developed and validated. The method showed good linearity with determination coefficients over 0.999. The limits of detection and quantification were acceptable for all furfurals. The relative standard deviations (RSDs) for repeatability and reproducibility were <4.28. Recoveries in all furfurals were between 94.5 and 98.7%. In addition, we report the evolution over shelf life of furfural compound levels in an experimental powder formula for pregnant women stored at 25 and 37 degrees C from production until 15 months.

Animals↗

PubMed2006

Model for Plateau border drainage of power-law fluid with mobile interface and its application to foam drainage.

A model for drainage of a power-law fluid through a Plateau border is proposed which accounts for the actual Plateau border geometry and interfacial mobility. The non-dimensionalized Navier-Stokes equations have been solved using finite element method to obtain the contours of velocity within the Plateau border cross section and average Plateau border velocity in terms of dimensionless inverse surface viscosity and power-law rheological parameters. The velocity coefficient, the correction for the average velocity through a Plateau border of actual geometry compared to that for a simplified circular geometry of the same area of cross section, was expressed as a function of dimensionless inverse surface viscosity and flow behavior index of the power-law fluid. The results of this improved model for Plateau border drainage were then incorporated in a previously developed foam drainage model [G. Narsimhan, J. Food Eng. 14 (1991) 139] to predict the evolution of liquid holdup profiles in a standing foam. Foam drainage was found to be slower for actual Plateau border cross section compared to circular geometry and faster for higher interfacial mobility and larger bubble size. Evolution of liquid holdup profiles in a standing foam formed by whipping and stabilized by 0.1% beta-lactoglobulin in the presence of xanthan gum when subjected to 16g and 45g centrifugal force fields was measured using magnetic resonance imaging for different xanthan gum concentrations. Drainage resulted in the formation of a separate liquid layer at the bottom at longer times. Measured bubble size, surface shear viscosity of beta-lactoglobulin solutions and literature values of power-law parameters of xanthan gum solution were employed in the current model to predict the evolution of liquid holdup profile which compared well with the experimental data. Newtonian model for foam drainage for zero shear viscosity underpredicted drainage rates and did not agree with the experimental data.

Journal Article↗

PubMed2003

Excitation energy transfer dynamics and excited-state structure in chlorosomes of Chlorobium phaeobacteroides.

The excited-state relaxation within bacteriochlorophyll (BChl) e and a in chlorosomes of Chlorobium phaeobacteroides has been studied by femtosecond transient absorption spectroscopy at room temperature. Singlet-singlet annihilation was observed to strongly influence both the isotropic and anisotropic decays. Pump intensities in the order of 10(11) photons x pulse(-1) x cm(-2) were required to obtain annihilation-free conditions. The most important consequence of applied very low excitation doses is an observation of a subpicosecond process within the BChl e manifold (approximately 200-500 fs), manifesting itself as a rise in the red part of the Q(y) absorption band of the BChl e aggregates. The subsequent decay of the kinetics measured in the BChl e region and the corresponding rise in the baseplate BChl a is not single-exponential, and at least two components are necessary to fit the data, corresponding to several BChl e-->BChl a transfer steps. Under annihilation-free conditions, the anisotropic kinetics show a generally slow decay within the BChl e band (10-20 ps) whereas it decays more rapidly in the BChl a region ( approximately 1 ps). Analysis of the experimental data gives a detailed picture of the overall time evolution of the energy relaxation and energy transfer processes within the chlorosome. The results are interpreted within an exciton model based on the proposed structure.

Absorptiometry, Photon↗

PubMed2003

Sperm competition games: sperm selection by females.

We analyse a co-evolutionary sexual conflict game, in which males compete for fertilizations (sperm competition) and females operate sperm selection against unfavourable ejaculates (cryptic female choice). For simplicity, each female mates with two males per reproductive event, and the competing ejaculates are of two types, favourable (having high viability or success) or unfavourable (where progeny are less successful). Over evolutionary time, females can increase their level of sperm selection (measured as the proportion of unfavourable sperm eliminated) by paying a fecundity cost. Males can regulate sperm allocations depending on whether they will be favoured or disfavoured, but increasing sperm allocation reduces their mating rate. The resolution of this game depends on whether males are equal, or unequal. Males could be equal: each is favoured with probability, p, reflecting the proportion of females in the population that favour his ejaculate (the 'random-roles' model); different males are favoured by different sets of females. Alternatively, males could be unequal: given males are perceived consistently by all females as two distinct types, favoured and disfavoured, where p is now the frequency of the favoured male type in the population (the 'constant-types' model). In both cases, the evolutionarily stable strategy (ESS) is for females initially to increase sperm selection from zero as the viability of offspring from unfavourable ejaculates falls below that of favourable ejaculates. But in the random-roles model, sperm selection decreases again towards zero as the unfavourable ejaculates become disastrous (i.e. as their progeny viability decreases towards zero). This occurs because males avoid expenditure in unfavourable matings, to conserve sperm for matings in the favoured role where their offspring have high viability, thus allowing females to relax sperm selection. If sperm selection is costly to females, ESS sperm selection is high across a region of intermediate viabilities. If it is uncostly, there is no ESS in this region unless sperm limitation (i.e. some eggs fail to be fertilized because sperm numbers are too low) is included into the model. In the constant-types model, no relaxation of sperm selection occurs at very low viabilities of disfavoured male progeny. If sperm selection is sufficiently costly, ESS sperm selection increases as progeny viability decreases down towards zero; but if it is uncostly, there is no ESS at the lowest viabilities, and unlike the random-roles model, this cannot be stabilized by including sperm limitation. Sperm allocations in the ESS regions differ between the two models. With random roles, males always allocate more sperm in the favoured role. With constant types, the male type that is favoured allocates less sperm than the disfavoured type. These results suggests that empiricists studying cryptic female choice and sperm allocation patterns need to determine whether sperm selection is applied differently, or consistently, on given males by different females in the same population.

Animals↗

PubMed2003

Flexion-relaxation response to static lumbar flexion in males and females.

OBJECTIVE: To determine if creep developed in the lumbar viscoelastic tissues during a period of static flexion elicited changes in the muscular responses of the flexion-relaxation phenomenon. BACKGROUND: Static lumbar flexion is a risk factor in workers, yet the physiological biomechanical and histological processes active in the evolution of the consequent low back disorder were not demonstrated experimentally. Controlled animal studies show that static lumbar flexion develops creep in the associated viscoelastic tissues and elicits spasms and modification of muscle function. Such neuromuscular changes are to be investigated in this study while assessing normal human subjects via the flexion-relaxation phenomenon. METHODS: Male and female subject groups performed three bouts of lumbar flexion-extension before and after a 10 min period of static lumbar flexion. The surface electromyographic from the erector spinae muscles as well as flexion angle were recorded. The angle in which electromyographic diminished during flexion and initiated during extension was determined and subjected to ANOVA with repeated measures to determine any significant changes in the flexion-relaxation response. RESULTS: The erector spinae were active through a significantly larger angle during flexion and initiated activity significantly earlier during extension after static flexion. Females demonstrated more pronounced changes than males. EMG amplitude did not change significantly. Spasms were recorded in more than half of the subjects during the static flexion period. CONCLUSIONS: Creep developed during a short static lumbar flexion elicited significant changes in the muscular activity pattern of the flexion-relaxation phenomenon. The muscles seem to compensate for the loss of tension in the lumbar viscoelastic tissues, while spasms suggest that some micro-damage was incurred to the viscoelastic tissues. RELEVANCE: Static lumbar flexion is shown experimentally as an activity that constitutes an occupational risk factor for the development of low back disorder.

Adult↗

PubMed2003

Combinative multi-scale level set framework for echocardiographic image segmentation.

In the automatic segmentation of echocardiographic images, a priori shape knowledge has been used to compensate for poor features in ultrasound images. This shape knowledge is often learned via an off-line training process, which requires tedious human effort and is highly expertise-dependent. More importantly, a learned shape template can only be used to segment a specific class of images with similar boundary shape. In this paper, we present a multi-scale level set framework for segmentation of endocardial boundaries at each frame in a multiframe echocardiographic image sequence. We point out that the intensity distribution of an ultrasound image at a very coarse scale can be approximately modeled by Gaussian. Then we combine region homogeneity and edge features in a level set approach to extract boundaries automatically at this coarse scale. At finer scale levels, these coarse boundaries are used to both initialize boundary detection and serve as an external constraint to guide contour evolution. This constraint functions similar to a traditional shape prior. Experimental results validate this combinative framework.

Algorithms↗

PubMed2006

Impact of ripening on manganese-doped ZnSe nanocrystals.

We examine the impact of growth kinetics on the incorporation of Mn dopants into ZnSe nanocrystals. We synthesize such particles, also known as colloidal quantum dots, and use optical spectroscopy to extract information about the average number of Mn impurities per nanocrystal as the reaction proceeds. We find that this number increases with particle growth until the Zn and/or Se precursors are depleted in the reaction solution. If the reaction is continued further, then ripening of the colloid begins and the average number of Mn per nanocrystal decreases, even as the particles slowly increase in size. We show that this effect, which is detrimental for enhanced doping, can be avoided if the reactant concentration is maintained by addition of more reactants. We consider several explanations and conclude that intraparticle ripening, in which material is redistributed on the same nanocrystal due to evolution of the particle shape, is the most consistent with experimental observations.

Colloids↗

PubMed1972

What cooks with solar neutrinos?

Two desperate explanations of the solar neutrino puzzle are proposed, one involving experimental nuclear physics and the other theoretical solar structure and evolution.

Journal Article↗

PubMed1990

Platelet-activating factor mediates glycerol-induced acute renal failure in rats.

1. We have studied the effect of inhibiting the interaction of platelet-activating factor with its receptor by using two structurally different antagonists BN-52021 (1 mg/kg, intraperitoneally) and alprazolam (1 and 5 mg/kg, intraperitoneally) on the evolution of glomerular filtration and renal blood flow, in the experimental model of acute renal failure induced by the intramuscular injection of glycerol in rats. 2. We have also measured arteriovenous differences in platelet-activating factor concentration, as well as platelet-activating factor content in glomeruli from rats with glycerol-induced acute renal failure. 3. After glycerol injection, untreated rats showed a marked reduction in inulin clearance which reached 77% in the first 30 min. The reduction was only 27% in the rats treated with BN-52021 and 38% in the rats treated with alprazolam (5 mg/kg), with statistically significant differences between treated and untreated groups. 4. Clearance of p-aminohippuric acid was also improved with BN-52021 or alprazolam treatment. 5. This protective effect of BN-52021 was observed in a more prolonged follow-up (3 days). 6. Glomeruli from rats with acute renal failure, treated or untreated with BN-52021, showed similar amounts of platelet-activating factor, whereas it was undetectable in glomeruli from normal rats. Furthermore, rats with glycerol-induced acute renal failure released greater amounts of platelet-activating factor. 7. These results provide evidence of a role for platelet-activating factor in the genesis of this model of experimental acute renal failure.

Acute Kidney Injury↗