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Reversion
Kinds of Reversion Selected AbstractsMORPHOLOGICAL REVERSION OF SPIRULINA (ARTHROSPIRA) PLATENSIS (CYANOPHYTA): FROM LINEAR TO HELICAL,JOURNAL OF PHYCOLOGY, Issue 3 2005Zhi Ping Wang The cyanobacterium Spirulina Turpin is characterized by its regularly coiled trichomes. Under some conditions, its helical filaments can convert to abnormal morphologies, such as irregularly curved and even linear shapes, that had been considered as a permanent degeneration that could not be reversed. However, here we found that the linear filaments of Spirulina platensis Geitler could spontaneously revert to the helical form with the same morphology as the original filaments. Further studies showed that the ultrastructural, physiological, and biochemical characteristics of linear filaments were different from those of the original filaments, whereas they were the same for the reverted and the original filaments. The SDS-PAGE analysis revealed at least four proteins or subunits related to Spirulina morphogenesis: The 21.9-kDa and the 20.3-kDa proteins were highly expressed in the helical filaments, whereas the 52.0-kDa and the 31.8-kDa proteins were highly expressed in the linear filaments. The random amplified polymorphic DNA analysis with 96 random primers showed that the genetic background of the reverted filaments was the same as that of the original filaments but distinct from that of the linear filaments. The results indicated that linear filaments of Spirulina could revert to the original morphology under certain conditions, and their other distinctive traits were regained. [source] MEAN REVERSION OF THE FISCAL CONDUCT IN 24 DEVELOPING COUNTRIESTHE MANCHESTER SCHOOL, Issue 4 2010AHMAD ZUBAIDI BAHARUMSHAH In this paper, we examine the mean reverting behaviour of fiscal deficit by analysing the fiscal position of 24 developing countries. Using annual data over the period 1970,2003 and the series-specific panel unit root test developed by Breuer et al. (Oxford Bulletin of Economics and Statistics, Vol. 64 (2002), pp. 527,546), we found the budget process for most developing countries fails to satisfy the strong-form sustainability condition. Further investigation shows the budget process for a majority of the countries is on a sustainable path (weak form) when a one-time, structural break is allowed in the model. Therefore, our empirical results suggest that the budget process in most of the sample countries is in accordance with the intertemporal budget constraint. [source] Inability of Escherichia coli to resuscitate from the viable but nonculturable stateFEMS MICROBIOLOGY ECOLOGY, Issue 1 2007Inés Arana Abstract After induction of the viable but nonculturable (VBNC) state in Escherichia coli populations, we analysed abiotic and biotic factors suggested to promote the resuscitation process. The response to the stressing conditions implied the formation of three subpopulations, culturable, VBNC and nonviable. In most adverse situations studied, the VBNC subpopulation did not represent the dominant fraction, decreasing with time. This suggests that, in most cases, the VBNC is not a successful phenotype. Combining methods of dilution and inhibition of remaining culturable cells, we designed a working protocol in order to distinguish unequivocally between regrowth and resuscitation. Reversion of abiotic factors inducing nonculturability as well as prevention of additional oxidative stress did not provoke resuscitation. Participation of biotic factors was studied by addition of supernatants from different origin without positive results. These results indicate that the E. coli strain used is not able to resuscitate from the VBNC state. VBNC cells release into the surrounding medium, and could thus aid in the survival of persisting culturable cells. The formation of a VBNC subpopulation could thus be considered as an adaptive process, designed for the benefit of the population as a whole. [source] New Approaches for Validation of Lethal Phenotypes and Genetic Reversion in Helicobacter pyloriHELICOBACTER, Issue 1 2001Timothy K. McDaniel Background. Because of limited genetic tools for use in Helicobacter pylori, tests routinely applied in other bacteria for demonstrating a gene's role in viability and other phenotypes have not been applied to this organism. In a mutational study of putative response regulator genes, we aimed to develop such tools for H. pylori. Materials and Methods. We attempted to mutate five response regulator genes by allelic exchange insertional mutagenesis. For genes that yielded no viable mutants, a second copy of the gene was inserted into the chromosome via a suicide vector, and it was seen if providing the second copy would permit the gene's disruption. For genes that yielded mutants with selectable phenotypes, a strategy was developed for reversion whereby an intact copy of the gene is introduced to the organism by transformation with PCR products. Following this procedure, revertants were selected by phenotypic tests then tested for genetic reversion. Results. After failure to attain transformants upon attempted mutation of genes HP0166 and HP1365, we inserted a second copy of each gene within the H. pylori chromosome. In each case the second copy relieved the block of transformation. Mutation of genes HP0703 and HP1021 gave non-motile and small-colony phenotypes, respectively. Following transformation with PCR products containing intact copies of the genes, both phenotype and genotype had reverted following phenotypic selections. Conclusions. The methods used in this study provide new approaches for confirming suspected genotype/phenotype associations and should be widely applicable in the study of H. pylori. [source] Mean Reversion and the Distribution of United Kingdom Stock Index ReturnsJOURNAL OF BUSINESS FINANCE & ACCOUNTING, Issue 9-10 2006David Ashton Abstract:, Our purpose here is to develop the Pearson Type IV distribution as a candidate for modelling the evolution of short period stock index returns. Here, early work by Praetz (1972 and 1978) and Blattberg and Gonedes (1974) has shown that the scaled ,t' distribution, which is a particular (symmetric) interpretation of the Pearson Type IV, provides a reasonable description of the way stock index returns evolve over time. Our analysis shows this is certainly not the case for the daily stock index returns on which our empirical analysis is based. There is significant skewness in the data and this cannot be captured by symmetric distributions like the scaled ,t' and normal distributions. However, the Pearson Type IV, which is a skewed generalisation of the scaled ,t', is capable of modelling the skewness inherent in our data and in such a way that it satisfies asymptotically efficient goodness of fit criteria. Furthermore, the Pearson Type IV can be derived from a stochastic differential equation with standard Markov properties. This enables one to integrate the distributional and time series properties of the returns process and thereby, facilitates both the interpretation and understanding of the role played by the distribution's parameters in the generation of the underlying stock index returns. [source] Mean Reversion in the Short Horizon Returns of UK PortfoliosJOURNAL OF BUSINESS FINANCE & ACCOUNTING, Issue 1-2 2001Patricia Chelley-Steeley This paper will show that short horizon stock returns for UK portfolios are more predictable than suggested by sample autocorrelation co-efficients. Four capitalisation based portfolios are constructed for the period 1976,1991. It is shown that the first order autocorrelation coefficient of monthly returns can explain no more than 10% of the variation in monthly portfolio returns. Monthly autocorrelation coefficients assume that each weekly return of the previous month contains the same amount of information. However, this will not be the case if short horizon returns contain predictable components which dissipate rapidly. In this case, the return of the most recent week would say a lot more about the future monthly portfolio return than other weeks. This suggests that when predicting future monthly portfolio returns more weight should be given to the most recent weeks of the previous month, because, the most recent weekly returns provide the most information about the subsequent months' performance. We construct a model which exploits the mean reverting characteristics of monthly portfolio returns. Using this model we forecast future monthly portfolio returns. When compared to forecasts that utilise the autocorrelation statistic the model which exploits the mean reverting characteristics of monthlyportfolio returns can forecast future returns better than the autocorrelation statistic, both in and out of sample. [source] Mean Reversion of Interest Rates in the Eurocurrency MarketOXFORD BULLETIN OF ECONOMICS & STATISTICS, Issue 4 2001Jhy-Lin Wu One stylised fact to emerge from the empirical analysis of interest rates is that the unit-root hypothesis in nominal interest rates cannot be rejected. However, using the panel date unit-root test IM, Pesaran and Shin (1997), we find support for the mean-reverting property of Eurocurrency rates. Thus, neither a vector-error-correction model nor a vector autoregressive model in differences is appropriate for modelling Eurocurrency rates. Instead, conventional modelling strategies with level data are appropriate. Furthermore, the finding of stationary interest rates supports uncovered interest parity, and hence the convergence hypothesis of interest rates. This in turn suggests a limited role for a monetary authority to affect domestic interest rates. [source] Reversion and Maintenance of Sinus Rhythm in Patients with Permanent Atrial Fibrillation by Internal Cardioversion Followed by Biatrial PacingPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2002NIKOLAOS FRAGAKIS FRAGAKIS, N., et al.: Reversion and Maintenance of Sinus Rhythm in Patients with Permanent Atrial Fibrillation by Internal Cardioversion Followed by Biatrial Pacing. Patients in atrial fibrillation (AF) who fail external cardioversion are usually regarded as in permanent AF. Internal cardioversion may revert many such patients into sinus rhythm (SR) but the majority relapse rapidly into AF. We investigated whether internal cardioversion followed by biatrial pacing is an effective to restore and subsequently maintain SR in patients with permanent AF. Patients in permanent AF underwent internal cardioversion that was followed by biatrial temporary pacing for 48 hours. Those who remained in SR received a permanent biatrial pacemaker programmed to a rate responsive mode with a lower rate 90 beats/min. Primary end point of the study included maintenance in SR 3 months after internal cardioversion. Sixteen patients (14 men, 57 ± 11 years) were cardioverted. The median duration of AF was 24 months (quartiles, Q1= 8.5 and Q3= 102) and mean left atrium diameter was 48 ± 04 mm. A permanent biatrial pacemaker was implanted in 11 patients. At a mean follow-up of 15 months (range 4 to 24), 8 patients remained in SR for more than 3 months. AF was eliminated in 5 patients, while in two a second internal cardioversion on amiodarone was required. Antiarrhythmic therapy was used in half of our population and did not predict the long-term maintenance of SR. Following internal cardioversion with continuous biatrial pacing, 50% of patients with permanent AF were maintained for prolonged periods in SR. This is a new modality of treatment of permanent AF directed to the maintenance of SR that provides a further therapeutic option in end-stage AF. [source] Orientation and strain cycle effects on the impact performance of polyethylenePOLYMER ENGINEERING & SCIENCE, Issue 4 2005Alexis Paizis The effects of orientation by plastic strain on the impact fracture resistance of a pipe-grade polyethylene have been investigated. Isotropic samples of bulk polymer were subjected, by plane-strain compression, to uniform Hencky strains of up to ±40%. In some samples this strain was reversed to restore the original dimensions. Impact bend specimens were prepared from samples oriented either normal to or within the fracture plane. Plane-strain fracture resistance and transition temperature were measured at 1 m/s by using the ISO 17281 method, and plane stress fracture resistance was measured by using the Reversed Charpy test. Orientation within the fracture plane by plastic compression across it compromises the relatively high plane-stress toughness of this material and increases the brittle-tough transition temperature, while the opposite is true of plastic extension. Reversion from a state of adverse orientation, by completing a strain cycle, only partially restores the fracture resistance of the isotropic polymer. POLYM. ENG. SCI., 45:596,605, 2005. © 2005 Society of Plastics Engineers [source] Markov-Switching Mean Reversion in Short-Term Interest Rates: Evidence from East Asian Economies,THE ECONOMIC RECORD, Issue 263 2007CHEW LIAN CHUA This paper employs a Markov-switching approach to model the dynamics of East Asian short rates. Regime changes are incorporated in standard unit root test to reveal periodic changes in the stationarity property of interest rates. There is evidence that three of the five short rates follow a random walk process in tranquil and low rates episodes but mean-revert in periods when rates are high and volatile. Singapore short rates are characterised by a random walk process, whereas the Philippines rates behave as a mean-reverting process in both regimes. Factors such as exchange rates, monetary policy and interest rate differentials vis-à-vis US interest rates influence the likelihood of short rates being in a volatile state. The regime switching dynamics of interest rates carry important implications for policy-makers. [source] Human prion strain selection in transgenic mice,ANNALS OF NEUROLOGY, Issue 2 2010Kurt Giles DPhil Objective: Transgenic (Tg) mice expressing chimeras of mouse and human prion proteins (PrPs) have shorter incubation periods for Creutzfeldt-Jakob disease (CJD) prions than mice expressing full-length human PrP. Increasing the sequence similarity of the chimeric PrP to mouse PrP, by reverting human residues to mouse, resulted in a Tg line, denoted Tg22372, which was susceptible to sporadic (s) CJD prions in ,110 days. Methods: Mice expressing chimeric mouse/human PrP transgenes were produced. The mice were inoculated intracerebrally with extracts prepared from the brains of patients who died of CJD. Onset of neurological dysfunction marked the end of the incubation time. After sacrifice of the Tg mice, their brains were analyzed for PrPSc and neuropathological changes. Results: Reversion of 1 additional residue (M111V) resulted in a new Tg line, termed Tg1014, susceptible to sCJD prions in ,75 days. Tg1014 mice also have shorter incubation periods for variant (v) CJD prions, providing a more tractable model for studying this prion strain. Transmission of vCJD prions to Tg1014 mice resulted in 2 different strains, determined by neuropathology and biochemical analysis, which correlated with the length of the incubation time. One strain had the biochemical, neuropathological, and transmission characteristics, including longer incubation times, of the inoculated vCJD strain; the second strain produced a phenotype resembling that of sCJD prions including relatively shorter incubation periods. Mice with intermediate incubation periods for vCJD prions had a mixture of the 2 strains. Both strains were serially transmitted in Tg1014 mice, which led to further reduction in incubation periods. Conversion of vCJD-like to sCJD-like strains was favored in Tg1014 mice more than in the Tg22372 line. The single amino acid difference therefore appears to offer selective pressure for propagation of the sCJD-like strain. Interpretation: These 2 Tg mouse lines provide relatively rapid models to study human prion diseases as well as the evolution of human prion strains. ANN NEUROL 2010;68:151,161 [source] "Setting paint" analogy for the hydrophobic self-association of tropoelastin into elastin-like hydrogelBIOPOLYMERS, Issue 5 2009Christoph Naumann Abstract Alkaline tropoelastin solutions (pH 11) were optically clear at low temperatures, but a firm gel formed when the temperature was raised to 37°C. Reversion to a clear solution took place if the temperature was lowered to below 20°C within less than 2 h, but not if 37°C was maintained for several hours. The precipitated elastin-like hydrogel thus formed did not visually redissolve at low temperatures. Tropoelastin hydrogel was stable to subsequent washings with alkaline solution at 37°C, but at 4°C some hydrogel redissolved showing that association is at least partly reversible. Washing the hydrogel with neutral 8M urea solution at 4°C dissolved less than 10% of tropoelastin in 24 h. We characterized this phenomenon by combining temperature-controlled light microscopy analysis, 1H NMR spectroscopy (temperature, diffusion, and relaxation time studies), and UV-absorption-based concentration measurements. The self-association of tropoelastin at pH 11 is due to hydrophobic interactions in an emulsion-like system in which the spherules coalesce in a manner like a water-based latex paint that forms a durable hydrophobic sheet as water and the organic solvent evaporate. In the present case, the sedimentation and entanglement of the tropoelastin porous sheets means that reverse dissolution is a kinetically slow process. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 321,330, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Pinocchio, a novel protein expressed in the antenna, contributes to olfactory behavior in Drosophila melanogasterDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2005Stephanie M. Rollmann Abstract Most organisms depend on chemoreception for survival and reproduction. In Drosophila melanogaster multigene families of chemosensory receptors and putative odorant binding proteins have been identified. Here, we introduce an additional distinct protein, encoded by the CG4710 gene, that contributes to olfactory behavior. Previously, we identified through P[lArB] -element mutagenesis a smell impaired (smi) mutant, smi21F, with odorant-specific defects in avoidance responses. Here, we show that the smi21F mutant also exhibits reduced attractant responses to some, but not all, of a select group of odorants. Furthermore, electroantennogram amplitudes are increased in smi21F flies. Characterization of flanking sequences of the P[lArB] insertion site, complementation mapping, phenotypic reversion through P -element excision, and expression analysis implicate a predicted gene, CG4710, as the candidate smi gene. CG4710 produces two transcripts that encode proteins that contain conserved cysteines and which are reduced in the smi21F mutant. Furthermore, in situ hybridization reveals CG4710 expression in the third antennal segment. We have named this gene of previously unknown function and its product "Pinocchio (Pino)". © 2005 Wiley Periodicals, Inc. J Neurobiol., 2005 [source] Frameshift mutations induced by four isomeric nitroacridines and their des-nitro counterpart in the lacZ reversion assay in Escherichia coliENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2006George R. Hoffmann Abstract Acridines are well-known as compounds that intercalate noncovalently between DNA base pairs and induce ±1 frameshift mutations at sites of monotonous repeats of a single base. Reactive derivatives of acridines, including acridine mustards and nitroacridines, form covalent adducts in DNA and exhibit mutagenic properties different from the simple intercalators. We compared the frameshift mutagenicity of the cancer chemotherapy drug nitracrine (1-nitro-9-(3,-dimethylaminopropylamino)-acridine), its des-nitro counterpart 9-(3,-dimethylaminopropylamino)-acridine (DAPA), and its 2-, 3-, and 4-nitro isomers (2-, 3-, and 4-nitro-DAPA) in the lacZ reversion assay in Escherichia coli. DAPA is a simple intercalator, much like the widely studied 9-aminoacridine. It most strongly induced ±1 frameshift mutations in runs of guanine residues and more weakly induced ,1 frameshifts in a run of adenine residues. A nitro group in the 1, 3, or 4 position of DAPA reduced the yield of ±1 frameshift mutations. DAPA weakly induced ,2 frameshifts in an alternating CG sequence. In contrast, nitracrine and its 3-nitro isomer resembled the 3-nitroacridine Entozon in effectively inducing ,2 frameshift mutations. The 2- and 4-nitro isomers were less effective than the 1- and 3-nitro compounds in ,2 frameshift mutagenesis. The results are interpreted with respect to intercalation, steric interactions, effects of base strength on DNA binding, enzymatic processing, and a slipped mispairing model of frameshift mutagenesis. Environ. Mol. Mutagen., 2006. © 2005 Wiley-Liss, Inc. [source] Bacterial and mammalian-cell genotoxicity of mixtures of chlorohydroxyfuranones, by-products of water chlorinationENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2004Jorma Mäki-Paakkanen Abstract The genotoxic responses of mixtures of four chlorohydroxyfuranones (CHFs), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA), 3-chloro- 4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), were compared with the genotoxicity of the individual compounds. Genotoxicity was evaluated in the Salmonella reversion assay (Ames test), the in vitro Chinese hamster ovary (CHO) cell Hprt mutation assay, and in the CHO chromosome aberration test. When tested individually, the concentrations of the chemicals that were chosen for the mixtures induced no or only a modest increase in the genotoxic effects, and caused little or no cytotoxicity. In the Ames test, the genotoxic responses caused by the mixtures of CHFs did not follow simple additivity. Synergism was observed with strains TA97 and TA98, and antagonism with strain TA100. In the CHO/Hprt mutation assay, the mutagenic response of the mixtures was inconsistent, with near additivity seen with a mixture of CHFs that resulted in 12% cell survival. In contrast, the four CHFs together consistently caused more structural chromosome damage (mainly chromatid-type breaks and exchanges) compared to the sum of net effects of the four CHFs tested alone. Also, a potentiating effect was consistently seen for the cytotoxicity of the CHF mixtures both in the CHO/Hprt mutation assay and the chromosome aberration test. The present results indicate that the genotoxic effects of CHF mixtures can be greater than additive. Such effects may be worth considering in the cancer risk assessment of chlorinated drinking water. Environ. Mol. Mutagen. 43:217,225, 2004. © 2004 Wiley-Liss, Inc. [source] Effect of deletion of SOS-induced polymerases, pol II, IV, and V, on spontaneous mutagenesis in Escherichia coli mutD5ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2004Anetta Nowosielska Abstract The E. coli dnaQ gene encodes the , subunit of DNA polymerase III (pol III) responsible for the proofreading activity of this polymerase. The mutD5 mutant of dnaQ chronically expresses the SOS response and exhibits a mutator phenotype. In this study we have constructed a set of E. coli AB1157 mutD5 derivatives deleted in genes encoding SOS-induced DNA polymerases, pol II, pol IV, and pol V, and estimated the frequency and specificity of spontaneous argE3,Arg+ reversion in exponentially growing and stationary-phase cells of these strains. We found that pol II exerts a profound effect on the specificity of spontaneous mutation in exponentially growing cells. Analysis of growth-dependent Arg+ revertants in mutD5 polB+ strains revealed that Arg+ revertants were due to tRNA suppressor formation, whereas those in mutD5 ,polB strains arose by back mutation at the argE3 ochre site. In stationary-phase bacteria, Arg+revertants arose mainly by back mutation, regardless of whether they were proficient or deficient in pol II. Our results also indicate that in a mutD5 background, the absence of pol II led to increased frequency of Arg+ growth-dependent revertants, whereas the lack of pol V caused its dramatic decrease, especially in mutD5 ,umuDC and mutD5 ,umuDC ,polB strains. In contrast, the rate of stationary-phase Arg+revertants increased in the absence of pol IV in the mutD5 ,dinB strain. We postulate that the proofreading activity of pol II excises DNA lesions in exponentially growing cells, whereas pol V and pol IV are more active in stationary-phase cultures. Environ. Mol. Mutagen. 43:226,234, 2004. © 2004 Wiley-Liss, Inc. [source] Assessment of the sensitivity of the computational programs DEREK, TOPKAT, and MCASE in the prediction of the genotoxicity of pharmaceutical moleculesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2004Ronald D. Snyder Abstract Computational models are currently being used by regulatory agencies and within the pharmaceutical industry to predict the mutagenic potential of new chemical entities. These models rely heavily, although not exclusively, on bacterial mutagenicity data of nonpharmaceutical-type molecules as the primary knowledge base. To what extent, if any, this has limited the ability of these programs to predict genotoxicity of pharmaceuticals is not clear. In order to address this question, a panel of 394 marketed pharmaceuticals with Ames Salmonella reversion assay and other genetic toxicology findings was extracted from the 2000,2002 Physicians' Desk Reference and evaluated using MCASE, TOPKAT, and DEREK, the three most commonly used computational databases. These evaluations indicate a generally poor sensitivity of all systems for predicting Ames positivity (43.4,51.9% sensitivity) and even poorer sensitivity in prediction of other genotoxicities (e.g., in vitro cytogenetics positive; 21.3,31.9%). As might be expected, all three programs were more highly predictive for molecules containing carcinogenicity structural alerts (i.e., the so-called Ashby alerts; 61% ± 14% sensitivity) than for those without such alerts (12% ± 6% sensitivity). Taking all genotoxicity assay findings into consideration, there were 84 instances in which positive genotoxicity results could not be explained in terms of structural alerts, suggesting the possibility of alternative mechanisms of genotoxicity not relating to covalent drug-DNA interaction. These observations suggest that the current computational systems when applied in a traditional global sense do not provide sufficient predictivity of bacterial mutagenicity (and are even less accurate at predicting genotoxicity in tests other than the Salmonella reversion assay) to be of significant value in routine drug safety applications. This relative inability of all three programs to predict the genotoxicity of drugs not carrying obvious DNA-reactive moieties is discussed with respect to the nature of the drugs whose positive responses were not predicted and to expectations of improving the predictivity of these programs. Limitations are primarily a consequence of incomplete understanding of the fundamental genotoxic mechanisms of nonstructurally alerting drugs rather than inherent deficiencies in the computational programs. Irrespective of their predictive power, however, these programs are valuable repositories of structure-activity relationship mutagenicity data that can be useful in directing chemical synthesis in early drug discovery. Environ. Mol. Mutagen. 43:143,158, 2004. © 2004 Wiley-Liss, Inc. [source] Oxidative mutagenicity of polar fractions from polycyclic aromatic hydrocarbon,contaminated soilsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2008Joanna Park Abstract Soils at hazardous waste sites contain complex mixtures of chemicals and often are difficult to characterize in terms of risk to human and ecological health. Over time, biogeochemical processes can decrease the apparent concentrations of pollutants but also can lead to accumulation of new products for which toxicity and behavior in the environment are largely unknown. A bioassay-directed fractionation technique was used to assess the contribution of redox-active bacterial metabolites to the toxicity of soil contaminated with polycyclic aromatic hydrocarbons (PAHs). A reverse mutation assay with Escherichia coli WP2 uvrA/pKM101 (IC188) and E. coli WP2 uvrA oxyR/pKM101 (IC203) was used to screen fractions for genotoxicity. Strain IC203 carries the ,oxyR30 mutation, which prevents the expression of antioxidant proteins in response to oxidative stress and increases its reversion by compounds that generate reactive oxygen species (ROS). Polar fractions of PAH-contaminated soil extracts were mutagenic to strain IC203 but not to strain IC188, suggesting the involvement of ROS in genotoxicity. Genotoxic potencies ranged from 300 to 1,700 revertants per milligram of fraction. Catalase was able to decrease IC203 reversion, implicating the involvement of hydrogen peroxide as a key ROS. Oxidized PAH compounds, including quinones, were identified in the mutagenic fractions but were not by themselves mutagenic. Deasphalted whole extracts and recombined fractions were not mutagenic, indicating that interactions between compounds in different fractions can mitigate genotoxicity. [source] On the Magnet Effect of Price LimitsEUROPEAN FINANCIAL MANAGEMENT, Issue 5 2007David Abad G1; G14; D44 Abstract The ,magnet' or ,gravitational' effect hypothesis asserts that, when trading halts are rule-based, investors concerned with a likely impediment to trade advance trades in time. This behaviour actually pushes prices further towards the limit. Empirical studies about the magnet effect are scarce, most likely because of the unavailability of data on rule-based halts. In this paper, we use a large database from the Spanish Stock Exchange (SSE), which combines intraday stock specific price limits and short-lived rule-based call auctions to stabilise prices, to test this hypothesis. The SSE is particularly well suited to test the magnet effect hypothesis since trading halts are price-triggered and, therefore, predictable to some extent. Still, the SSE microstructure presents two particularities: (i) a limit-hit triggers an automatic switch to an alternative trading mechanism, a call auction, rather than a pure halt; (ii) the trading halt only lasts 5 minutes. We find that, even when prices are within a very short distance to the price limits, the probability of observing a limit-hit is unexpectedly low. Additionally, prices either initiate reversion (non limit-hit days) or slow down gradually (limit-hit days) as they come near the intraday limits. Finally, the most aggressive traders progressively become more patient as prices approach the limits. Therefore, both the price patterns and the trading behaviour reported near the limits do not agree with the price limits acting as magnetic fields. Consequently, we conclude that the switching mechanism implemented in the SSE does not induce traders to advance their trading programs in time. [source] Strain differences in ,1 receptor-mediated behaviours are related to neurosteroid levelsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2002Vân-Ly Phan Abstract The sigma1 (,1) receptor exerts a potent neuromodulatory role in the brain with relevant consequences in memory processes, response to stress, depression and pharmacodependence. Its precise endogenous ligand is not yet identified but the ,1 receptor appears to be one target for the nongenomic rapid effects of neuroactive steroids in the brain. The aim of the present study was to establish whether differences in ,1 receptor-mediated behaviours could be observed among mouse strains, in relation with differences in either ,1 receptor expression or steroid levels. The ,1 -receptor immunohistochemical distribution appeared similar between Swiss and C57BL/6 strains in all the brain structures examined. The levels of in vivo[3H](+)-SKF-10 047 binding to ,1 receptors were lower in Swiss than in C57BL/6. Adrenalectomy/castration significantly increased [3H](+)-SKF-10 047 binding only in Swiss. The behavioural efficacy of the selective ,1 agonists igmesine and PRE-084 , reversion of the scopolamine-induced amnesia in the passive avoidance test; diminution of the immobility duration in the forced swimming test , were significantly higher in C57BL/6 than in Swiss. Steroid levels were measured in the brain in basal conditions and after stress. C57BL/6 mice presented in both conditions, the lowest progesterone levels, this steroid acting as an endogenous ,1 antagonist. Collectively, the results suggested that strain differences in neuroactive steroid and particularly, progesterone, biosynthesis and sensitivity may contribute to the differential behavioural efficacy of ,1 -receptor ligands. Noteworthy, these observations are coherent with strain differences observed in the intensity of cocaine-induced reward properties, known to critically involve the ,1 receptor. [source] HAPLODIPLOIDY AS AN OUTCOME OF COEVOLUTION BETWEEN MALE-KILLING CYTOPLASMIC ELEMENTS AND THEIR HOSTSEVOLUTION, Issue 4 2004Benjamin B. Normark Abstract Haplodiploidy (encompassing both arrhenotoky and paternal genome elimination) could have originated from coevolution between male-killing endosymbiotic bacteria and their hosts. In insects, haplodiploidy tends to arise in lineages that rely on maternally transmitted bacteria for nutrition and that have gregarious broods in which competition between siblings may occur. When siblings compete, there is strong selection on maternally transmitted elements to kill males. I consider a hypothetical bacterial phenotype that renders male zygotes effectively haploid by preventing chromosome decondensation in male-determining sperm nuclei. By causing high male mortality, such a phenotype can be advantageous to the bacterial lineage. By eliminating paternal genes, it can also be advantageous to the host female. A simple model shows that the host female will benefit under a wide range of values for the efficiency of resource re-allocation, the efficiency of transmission, and the viability of haploid males. This hypothesis helps to explain the ecological correlates of the origins of haplodiploidy, as well as such otherwise puzzling phenomena as obligate cannibalism by male Micromalthus beetles, reversion to diploidy by aposymbiotic male stictococcid scale insects, and the bizarre genomic constitution of scale insect bacteriomes. [source] A Required Yield Theory of Stock Market Valuation and Treasury Yield DeterminationFINANCIAL MARKETS, INSTITUTIONS & INSTRUMENTS, Issue 1 2009Christophe Faugère Stock market valuation and Treasury yield determination are consistent with the Fisher effect (1896) as generalized by Darby (1975) and Feldstein (1976). The U.S. stock market (S&P 500) is priced to yield ex-ante a real after-tax return directly related to real long-term GDP/capita growth (the required yield). Elements of our theory show that: (1) real after-tax Treasury and S&P 500 forward earnings yields are stationary processes around positive means; (2) the stock market is indeed priced as the present value of expected dividends with the proviso that investors are expecting fast mean reversion of the S&P 500 nominal growth opportunities to zero. Moreover, (3) the equity premium is mostly due to business cycle risk and is a direct function of below trend expected productivity, where productivity is measured by the growth in book value of S&P 500 equity per-share. Inflation and fear-based risk premia only have a secondary impact on the premium. The premium is always positive or zero with respect to long-term Treasuries. It may be negative for short-term Treasuries when short-term productivity outpaces medium and long run trends. Consequently: (4) Treasury yields are mostly determined in reference to the required yield and the business cycle risk premium; (5) the yield spread is largely explained by the differential of long-term book value per share growth vs. near term growth, with possible yield curve inversions. Finally, (6) the Fed model is partially validated since both the S&P 500 forward earnings yield and the ten-year Treasury yield are determined by a common factor: the required yield. [source] Nonselective DNA damage induced by a replication inhibitor results in the selective elimination of extrachromosomal double minutes from human cancer cellsGENES, CHROMOSOMES AND CANCER, Issue 10 2007Noriaki Shimizu Gene amplification plays a pivotal role in human malignancy. Highly amplified genes frequently localize to extrachromosomal double minutes (dmin), which usually segregate to daughter cells in association with mitotic chromosomes. We and others had shown that treatment with low-dose hydroxyurea (HU) results in the elimination of dmin and reversion of the cancer cell phenotype. HU treatment in early S-phase, when dmin are replicated, results in their detachment from chromosomes at the next M-phase, leading to the appearance of micronuclei enriched in dmin, followed by their elimination. In this article, we examined the effect of low-dose HU on the behavior of dmin in relation to DNA damage induction by simultaneously monitoring LacO-tagged dmin and phosphorylated histone H2AX (,H2AX). As expected, treatment with low-dose HU induced numerous ,H2AX foci throughout the nucleus in early S-phase, and these rarely coincided with dmin. Most chromosomal ,H2AX foci disappeared by metaphase, whereas, unexpectedly, those that persisted frequently associated with dmin. We found that these dmin aggregated, detached from anaphase chromosomes, and apparently formed micronuclei. Because ,H2AX foci likely represent DNA double strand breaks (DSBs), the response to DSBs sustained by extrachromosomal dmin appears to be different from that sustained by chromosomal loci, which may explain why DSB-inducing agents cause the selective elimination of dmin. © 2007 Wiley-Liss, Inc. [source] Role of the Rap1 GTPase in astrocyte growth regulationGLIA, Issue 3 2003Anthony J. Apicelli Abstract Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome in which affected individuals develop nervous system abnormalities that might reflect astrocyte dysfunction. The TSC2 gene product, tuberin, encodes a GTPase-activating protein (GAP) domain, which regulates the activity of Rap1 in vitro. To determine whether dysregulated Rap1, resulting from TSC2 inactivation, leads to increased astrocyte proliferation in vivo, we generated transgenic mice expressing activated Rap1G12V specifically in astrocytes. We observed no statistically significant difference in the number of astrocytes between wild-type and GFAP-Rap1G12V littermates in vivo; however, during log-phase growth, we observed a 25% increase in GFAP-Rap1G12V astrocyte doubling times compared to wild-type controls. This decreased proliferation was associated with delayed MAP kinase, but not AKT, activation. Lastly, to determine whether constitutive Rap1 activation could reverse the increased astrocyte proliferation observed in transgenic mice expressing oncogenic RasG12V, we generated transgenic mice expressing both RasG12V and Rap1G12V in astrocytes. These double transgenic mice showed a striking reversion of the RasG12V astrocyte growth phenotype. Collectively, these results argue that the tumor suppressor properties of tuberin are unlikely to be related to Rap1 inactivation and that Rap1 inhibits mitogenic Ras pathway signaling in astrocytes. GLIA 42:225,234, 2003. © 2003 Wiley-Liss, Inc. [source] Effects of atmospheric CO2 concentration and defoliation on the growth of Themeda triandraGRASS & FORAGE SCIENCE, Issue 3 2004S. J. E. Wand Abstract The effects of elevated atmospheric carbon dioxide (CO2) concentration (700 ,mol mol,1) on defoliated (three clippings at 3-week intervals) and undefoliated plants were determined for the C4 grass Themeda triandra, Forsk. The elevated CO2 concentration significantly increased leaf regrowth following defoliation, and total leaf production was greatest in this treatment. Shoot biomass of undefoliated plants was also increased under the elevated CO2 concentration treatment. The primary effect of the elevated CO2 concentration in both defoliated and undefoliated plants was an increase in individual leaf length and mass of dry matter, linked to a higher leaf water content and increased photosynthetic rates at the canopy level. Photosynthetic down-regulation at the leaf level occurred, but this was compensated for by increased assimilation rates and greater canopy leaf area at the elevated CO2 concentration. Increases in leaf and sheath growth of defoliated plants in the elevated CO2 concentration treatment were lost following a final 3-week reversion to ambient CO2 concentration, but occurred in plants exposed to the elevated CO2 concentration for the final 3-week period only. In conclusion, elevated atmospheric CO2 concentration increases shoot growth via increased leaf extension, which is directly dependent on stimulation of concurrent photosynthesis. CO2 responsiveness is sustained following moderate defoliation but is reduced when plants experience reduced vigour as a result of maturation or high frequency of defoliation. [source] Gene therapy for haemophilia,yes, but,with non-viral vectors?HAEMOPHILIA, Issue 3 2009A. LIRAS Summary., High-purity plasma-derived and recombinant factors are currently safe and efficient treatment for haemophilia. The mid-term future of haemophilia treatment will involve the use of modified recombinant factors to achieve advantages such as decreased immunogenicity in inhibitor formation and enhanced efficacy as a result of their longer half-life. In the long-term, gene therapy and cell therapy strategies will have to be considered. Achievements in cell therapy to date have been using embryonic stem cells and hepatic sinusoidal endothelial cells. Current gene therapy strategies for haemophilia are based on gene transfer using adeno-associated viruses and non-viral vectors. Gene therapy for haemophilia is justified because it is a chronic disease and because a very regular factor infusion is required that may involve fatal risks and because it is very expensive. Haemophilia is a very good candidate for use of gene therapy protocols because it is a monogenic disease, and even low expression is able to achieve reversion from a severe to a moderate phenotype. The current trends in haemophilia using adeno-associated viral vectors are safe but also involve immunogenicity problems. The other alternatives are non-viral vectors. There have been in recent years relevant advances in non-viral transfection that raise hope for considering this possibility. Several research groups are opting for this experimental alternative. An expression over 5%, representing a moderate phenotype, for a few months with a high safety, regarding vector, transfected cells, and implantation procedure, would already be a great success. This may represent an intermediate protocol in which the expression levels and times obtained are lower and shorter respectively as compared to viral vectors, but which provide a potential greater patient safety. This may more readily win acceptance among both patients and haematologists because fatal events in the past due to HIV/HCV infection may constrain the implementation of viruses as vectors. [source] Behavioral Sleep Modification May Revert Transformed Migraine to Episodic MigraineHEADACHE, Issue 8 2007Anne H. Calhoun MD Background.,Sleep problems have been linked with headaches for more than a century, but whether the headaches are the cause or the result of the disrupted sleep is unknown. Objectives.,We previously reported that nonrestorative sleep and poor sleep habits are almost universal in a referral population of women with transformed migraine (TM). Since cognitive behavioral therapy is effective in improving sleep quality in individuals with poor sleep hygiene, we designed a randomized, placebo-controlled study to assess the impact of such treatment on TM. We hypothesized that behavioral sleep modification (BSM) would be associated with improvement in headache frequency and intensity and with reversion to episodic migraine. Methods.,Subjects were 43 women with TM referred to an academic headache center. After obtaining informed consent, patients were randomized to receive either behavioral sleep instructions or placebo behavioral instructions in addition to usual medical care. Subjects recorded headaches in standardized diaries. The first postintervention visit was scheduled at 6 weeks. At that visit, the blind was broken and all subjects received BSM instructions. A final visit was scheduled 6 weeks later. Results.,Compared to the placebo behavioral group, the BSM group reported statistically significant reduction in headache frequency [F (1, 33 = 12.42, P=.001)] and headache intensity [F(1, 33 = 14.39, P= .01)]. They were more likely to revert to episodic migraine ,2 (2, n = 43) = 7.06, P= .029. No member of the control group reverted to episodic migraine by the first postintervention visit. By the final visit, 48.5% of those who had received BSM instructions had reverted to episodic migraine. Conclusions.,In this pilot study of women with TM, we found that a targeted behavioral sleep invention was associated with improvement in headache frequency, headache index, and with reversion to episodic migraine. [source] New Approaches for Validation of Lethal Phenotypes and Genetic Reversion in Helicobacter pyloriHELICOBACTER, Issue 1 2001Timothy K. McDaniel Background. Because of limited genetic tools for use in Helicobacter pylori, tests routinely applied in other bacteria for demonstrating a gene's role in viability and other phenotypes have not been applied to this organism. In a mutational study of putative response regulator genes, we aimed to develop such tools for H. pylori. Materials and Methods. We attempted to mutate five response regulator genes by allelic exchange insertional mutagenesis. For genes that yielded no viable mutants, a second copy of the gene was inserted into the chromosome via a suicide vector, and it was seen if providing the second copy would permit the gene's disruption. For genes that yielded mutants with selectable phenotypes, a strategy was developed for reversion whereby an intact copy of the gene is introduced to the organism by transformation with PCR products. Following this procedure, revertants were selected by phenotypic tests then tested for genetic reversion. Results. After failure to attain transformants upon attempted mutation of genes HP0166 and HP1365, we inserted a second copy of each gene within the H. pylori chromosome. In each case the second copy relieved the block of transformation. Mutation of genes HP0703 and HP1021 gave non-motile and small-colony phenotypes, respectively. Following transformation with PCR products containing intact copies of the genes, both phenotype and genotype had reverted following phenotypic selections. Conclusions. The methods used in this study provide new approaches for confirming suspected genotype/phenotype associations and should be widely applicable in the study of H. pylori. [source] Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4, gene,HEPATOLOGY, Issue 5 2008Chuan Yin Previous studies have shown that hepatocyte nuclear factor-4, (HNF4,) is a central regulator of differentiated hepatocyte phenotype and forced expression of HNF4, could promote reversion of tumors toward a less invasive phenotype. However, the effect of HNF4, on cancer stem cells (CSCs) and the treatment of hepatocellular carcinoma (HCC) with HNF4, have not been reported. In this study, an adenovirus-mediated gene delivery system, which could efficiently transfer and express HNF4,, was generated to determine its effect on hepatoma cells (Hep3B and HepG2) in vitro and investigate the anti-tumor effect of HNF4, in mice. Our results demonstrated that forced re-expression of HNF4, induced the differentiation of hepatoma cells into hepatocytes, dramatically decreased "stemness" gene expression and the percentage of CD133+ and CD90+ cells, which are considered as cancer stem cells in HCC. Meanwhile, HNF4, reduced cell viability through inducing apparent apoptosis in Hep3B, while it induced cell cycle arrest and cellular senescence in HepG2. Moreover, infection of hepatoma cells by HNF4, abolished their tumorigenesis in mice. Most interestingly, systemic administration of adenovirus carrying the HNF4, gene protected mice from liver metastatic tumor formation, and intratumoral injection of HNF4, also displayed significant antitumor effects on transplanted tumor models. Conclusion: The striking suppression effect of HNF4, on tumorigenesis and tumor development is attained by inducing the differentiation of hepatoma cells,especially CSCs,into mature hepatocytes, suggesting that differentiation therapy with HNF4, may be an effective treatment for HCC patients. Our study also implies that differentiation therapy may present as one of the best strategies for cancer treatment through the induction of cell differentiation by key transcription factors. (HEPATOLOGY 2008.) [source] Could exercise be a new strategy to revert some patients with atrial fibrillation?INTERNAL MEDICINE JOURNAL, Issue 1 2010P. Gates Abstract Background: This study is the result of the anecdotal observation that a number of patients with atrial fibrillation (AF) had noted reversion to sinus rhythm (SR) with exercise. We aimed to evaluate the potential role of exercise stress test (EST) for the reversion of AF. Methods: Patients with AF who were scheduled to undergo electrical cardioversion (DCR) underwent EST using a modified Bruce protocol. Results: Eighteen patients (16 male); aged 36,74 years (mean 58 years) were studied. Five patients (27.7%) had successful reversion with exercise (group 1). Thirteen patients remained in AF (group 2). No patient who failed to revert with exercise did so spontaneously before DCR 3 h to 7 months later (median 20 days). Comparison between group 1 and group 2 did not reveal any significant difference Conclusion: This small preliminary study suggests that in some patients it may be possible to revert AF to SR with exercise and avoid DCR and concomitant general anaesthesia. The authors suggest that a larger multicentre randomized trial is warranted to confirm or refute these initial results and if correct identify those who might benefit. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||