The effects of taxol on microtubular arrays: in vivo effects on heliozoan axonemes

The effects of the antitumor drug taxol on the microtubular axonemes of the heliozoon Actinophrys sol have been investigated. The drug induces polymerization of microtubules as shown by a large increase in the length and number of microtubular arrays. The interaction between microtubules and microtubule-associated proteins is also affected, with the result that the normal geometric patterning within the microtubular arrays is disturbed. This is due to the loss or inactivation of long intermicrotubule links. As a result, arms lose their rigidity. Because the drug stabilizes polymerized microtubules, C-shaped profiles and other signs of poor microtubule preservation are absent in taxol-treated cells.     

Physiological effects on demography: a long-term experimental study of testosterone's effects on fitness

Understanding physiological and behavioral mechanisms underlying the diversity of observed life-history strategies is challenging because of difficulties in obtaining long-term measures of fitness and in relating fitness to these mechanisms. We evaluated effects of experimentally elevated testosterone on male fitness in a population of dark-eyed juncos studied over nine breeding seasons using a demographic modeling approach. Elevated levels of testosterone decreased survival rates but increased success of producing extra-pair offspring. Higher overall fitness for testosterone-treated males was unexpected and led us to consider indirect effects of testosterone on offspring and females. Nest success was similar for testosterone-treated and control males, but testosterone-treated males produced smaller offspring, and smaller offspring had lower postfledging survival. Older, more experienced females preferred to mate with older males and realized higher reproductive success when they did so. Treatment of young males increased their ability to attract older females yet resulted in poor reproductive performance. The higher fitness of testosterone-treated males in the absence of a comparable natural phenotype suggests that the natural phenotype may be constrained. If this phenotype were to arise, the negative social effects on offspring and mates suggest that these effects might prevent high-testosterone phenotypes from spreading in the population.     

Consequences of paternally inherited effects on the genetic evaluation of maternal effects

Background

Mixed models are commonly used for the estimation of variance components and genetic evaluation of livestock populations. Some evaluation models include two types of additive genetic effects, direct and maternal. Estimates of variance components obtained with models that account for maternal effects have been the subject of a long-standing controversy about strong negative estimates of the covariance between direct and maternal effects. Genomic imprinting is known to be in some cases statistically confounded with maternal effects. In this study, we analysed the consequences of ignoring paternally inherited effects on the partitioning of genetic variance.

Results

We showed that the existence of paternal parent-of-origin effects can bias the estimation of variance components when maternal effects are included in the evaluation model. Specifically, we demonstrated that adding a constraint on the genetic parameters of a maternal model resulted in correlations between relatives that were the same as those obtained with a model that fits only paternally inherited effects for most pairs of individuals, as in livestock pedigrees. The main consequence is an upward bias in the estimates of the direct and maternal additive genetic variances and a downward bias in the direct-maternal genetic covariance. This was confirmed by a simulation study that investigated five scenarios, with the trait affected by (1) only additive genetic effects, (2) only paternally inherited effects, (3) additive genetic and paternally inherited effects, (4) direct and maternal additive genetic effects and (5) direct and maternal additive genetic plus paternally inherited effects. For each scenario, the existence of a paternally inherited effect not accounted for by the estimation model resulted in a partitioning of the genetic variance according to the predicted pattern. In addition, a model comparison test confirmed that direct and maternal additive models and paternally inherited models provided an equivalent fit.

Conclusions

Ignoring paternally inherited effects in the maternal models for genetic evaluation can lead to a specific pattern of bias in variance component estimates, which may account for the unexpectedly strong negative direct-maternal genetic correlations that are typically reported in the literature.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-015-0141-5) contains supplementary material, which is available to authorized users.     

Radiation effects on development

It has been widely reported that prenatal exposure to ionizing radiation can interfere with embryonic and fetal development, depending on dose and gestational age in which exposure occurs. According to several studies on animal models, different well-defined stages during prenatal life can be distinguished in relation to teratogenic effects. During the preimplantation stage, elevated doses of radiation can result in abortion, while lower doses may produce genomic damage that is usually repaired. On the other hand, during the organogenesis stage in mice (embryonic day 6.5 [E6.5] to E13.5), irradiation is associated with increased incidence of malformation and intrauterine growth restriction (IUGR). Later exposure is linked to brain damage. Doses used in animal studies are generally higher than those used for diagnostic procedures in humans. Usually, radiation exposure to diagnostic range (<0.05 Gy = 5 rads) is not associated with an increased risk of congenital anomalies. In human studies, elevated doses produce adverse outcomes, depending on stage of development, as in animal studies. Blastogenesis (up to two weeks) is associated with failure to implant or no significant health effects. An increased risk of malformation and growth retardation can be observed for two to seven weeks exposure (organogenesis stage), while exposure at later stages (fetogenesis) is mainly associated with brain damage. In this review we focus on the relevance of estimating the cumulative dose of radiation to the fetus and the gestational age in which exposure occurs, to provide appropriate counseling to pregnant women.     

Remarks on oxygen effects

Oxygen concentration will influence the alpha- and beta-effect (two-component theory of radiation effects) independently. The beta-effect is reduced by a dose-modifying factor gamma. Oxygen, in competition with enzyme repair actions fortifies a part of the beta-lesions and this model leads to a simple equation for the factor gamma. The alpha-effect is also enhanced by oxygen. Measurements of OER indicate that the reduction of the effect from aerobic to anoxic condition might be about 70%. The functional dependence of oxygen concentration has not been investigated. For small oxygen concentrations of 0.15 to 0.5 muM/l and doses below 1000 R Révész and Littbrand have found that oxygen can protect the irradiated cells and thus increase survivals with about 10%. This is explained as a scavenger action where radical hydrogen atoms are oxidized and hydrated electrons captured by oxygen moelcules. When the oxygen concentration is increased, or with higher doses, the usual sensitizing effect of oxygen exceeds the protection effect. The influence of oxygen on alpha-effects are mainly connected with indirect radiation effects and thus depend on temperature and milieu.     

Shear effects on enzymes

Shear inactivation of enzymes has been found to be associated with flow, pumping and mixing. From data taken in a viscometer, shear inactivation in flow could be calculated. Among the materials experiencing this effect are catalase, rennet, carboxypeptidase A, interferon, heparin, fibrinogen, and phage lysozyme. Turbulent flow has greater losses than would be expected from streamline flow under the same dynamic and geometric conditions. Shear conditions also cause changes in the kinetics of reactions by reducing the reaction rate. It is thought that the shear field causes molecular distortions that result in breaking molecular bonds (inactivation) or stretching without breaking within an elastic limit that permits recovery when the shear field is removed (causing reduction of reaction rate.) There are conflicting data from different laboratories in that shear effects are not observed to the same extent. It may be that the presence of oxygen and metal ions and their reactions with disulphide bonds have an influence.     

Radiation effects on NADH

Summary The decrease of NADH following ionizing irradiation was investigated over a concentration range from 10^–3 to 5 x 10^–8 M. The nonexponential function of the curve was discussed. TheG-values were calculated for different starting concentrations. The results were compared with theG-values for NADH following irradiation under enzymatic equilibrium conditions and with somein vivo investigations reported in the literature.The following abbreviations have been used NMN nicotinamide-mononucleotide - NADH reduced nicotinamide-adenine-dinucleotide - NAD nicotinamide-adenine-dinucleotide - ADH alcohol-dehydrogenase - GlDH glutaminate-dehydrogenase Paper read at the 6th Annual Meeting of the European Society for Radiobiology, Interlaken, 5.–8. June, 1968. Round Table: Radiation Effectsin vitro andin vivo. Correlations and Discrepancies.     

Concordance of effects of medical interventions on hospital admission and readmission rates with effects on mortality

Background:

Many clinical trials examine a composite outcome of admission to hospital and death, or infer a relationship between hospital admission and survival benefit. This assumes concordance of the outcomes “hospital admission” and “death.” However, whether the effects of a treatment on hospital admissions and readmissions correlate to its effect on serious outcomes such as death is unknown. We aimed to assess the correlation and concordance of effects of medical interventions on admission rates and mortality.

Methods:

We searched the Cochrane Database of Systematic Reviews from its inception to January 2012 (issue 1, 2012) for systematic reviews of treatment comparisons that included meta-analyses for both admission and mortality outcomes. For each meta-analysis, we synthesized treatment effects on admissions and death, from respective randomized trials reporting those outcomes, using random-effects models. We then measured the concordance of directions of effect sizes and the correlation of summary estimates for the 2 outcomes.

Results:

We identified 61 meta-analyses including 398 trials reporting mortality and 182 trials reporting admission rates; 125 trials reported both outcomes. In 27.9% of comparisons, the point estimates of treatment effects for the 2 outcomes were in opposite directions; in 8.2% of trials, the 95% confidence intervals did not overlap. We found no significant correlation between effect sizes for admission and death (Pearson r = 0.07, p = 0.6). Our results were similar when we limited our analysis to trials reporting both outcomes.

Interpretation:

In this metaepidemiological study, admission and mortality outcomes did not correlate, and discordances occurred in about one-third of the treatment comparisons included in our analyses. Both outcomes convey useful information and should be reported separately, but extrapolating the benefits of admission to survival is unreliable and should be avoided.Health care decisions often rely on effects of interventions described using rates of admission or readmission to hospital.^1,2 These outcomes are typically regarded as indicators of insufficient quality of care and inefficient spending of health care resources;^1,2 however, whether they can predict other serious clinical outcomes, such as death, is unknown.Although effects on admission or readmission rates are often analyzed using large sets of routinely collected data, such as from administrative databases and electronic health records, many randomized controlled trials (RCTs) also collect data on admission rates, and some RCTs collect mortality data. Moreover, some trials combine death and admission to hospital as the primary composite outcome³ to increase the study’s power to detect significant differences and reduce the required study size.⁴ However, the interpretation of such a combination is difficult when the treatment effects on the 2 components are not concordant,⁵ for example, when more patients survive but rates of admission increase. In such cases, composite outcomes may dilute or obscure clinically significant treatment effects on important individual components,^4,6 and incomplete disclosure of individual effects may mislead the interpretation of the results.⁴We investigated systematic reviews of treatment comparisons that included meta-analyses of RCTs assessing effects on both rates of admission and mortality. We used the reported trial data to assess whether effects on admission rates were concordant with effects on mortality or whether it was possible to identify interventions and diseases in which these 2 outcomes would provide differing pictures of the merits of the tested interventions.     

Profound effects of the general anesthetic etomidate on oxidative phosphorylation without effects on their yield

We investigated the effects of the general anesthetic Etomidate on oxidative phosphorylation in isolated rat liver mitochondria. The study of each electron transfer site shows that there is an inhibition: mainly at complex I but also, to a lesser extent, at complex III. Moreover, with succinate as substrate, the increase in non-phosphorylating respiration is accompanied by a decrease in ΔΨ. However, this effect is not due to classical uncoupling of oxidative phosphorylation, since ADP addition at high Etomidate concentrations restores the transmembrane difference of electrical potential. Also, in the same range of Etomidate concentration, the ATP/O ratio is not significantly affected. In conclusion, the main effect of Etomidate is to decrease the oxidative phosphorylation rate without changing yield. The H⁺ leak which appears under non-phosphorylating conditions becomes negligible in physiological conditions.     

The effects of fungi on bracken

Laboratory experiments on fungal pathogens of the gametophyte generation are described and the possible causative agents associated with disease of bracken colonies in the field discussed.     

The effects of salicylate on bacteria

Salicylate and related compounds, such as aspirin, have a variety of effects in eucaryotic systems and are well known for their medicinal properties. Salicylate also has numerous effects on bacteria, yet only a handful of individuals within the scientific community appreciate these findings. From a bacterial viewpoint, growth in the presence of salicylate can be both beneficial and detrimental. On one hand, growth of certain bacteria in the presence of salicylate can induce an intrinsic multiple antibiotic resistance phenotype. On the other hand, growth in the presence of salicylate can reduce the resistance to some antibiotics and affect virulence factor production in some bacteria. This review provides an overview of the effects salicylate has on various bacterial species.     

The effects of noise on sleep

Man remains sensitive to acoustic stimuli during sleep but his sensitivity depends on his own biological characteristics, his sleep state, and the type of noise. Some of the measurable effects of noise are immediate while others occur afterwards. The global psychophysiological approach of the effects of noise on sleep appears to be satisfactory, although complex.