In vivo alkaline comet assay: Statistical considerations on historical negative and positive control data

The alkaline comet assay is frequently used as in vivo follow-up test within different regulatory environments to characterize the DNA-damaging potential of different test items. The corresponding OECD Test guideline 489 highlights the importance of statistical analyses and historical control data (HCD) but does not provide detailed procedures. Therefore, the working group “Statistics” of the German-speaking Society for Environmental Mutation Research (GUM) collected HCD from five laboratories and >200 comet assay studies and performed several statistical analyses. Key results included that (I) observed large inter-laboratory effects argue against the use of absolute quality thresholds, (II) > 50% zero values on a slide are considered problematic, due to their influence on slide or animal summary statistics, (III) the type of summarizing measure for single-cell data (e.g., median, arithmetic and geometric mean) may lead to extreme differences in resulting animal tail intensities and study outcome in the HCD. These summarizing values increase the reliability of analysis results by better meeting statistical model assumptions, but at the cost of information loss. Furthermore, the relation between negative and positive control groups in the data set was always satisfactorily (or sufficiently) based on ratio, difference and quantile analyses

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Comparison of reliability of 100 nm AlGaN/GaN HEMTs with T-gate and SAG-gate technology

The effect of gate technology and semiconductor passivation on the switching speed and device reliability has been investigated. By reducing the parasitic capacitances and reducing the passivation induced surface charge density a median lifetime of around 106 h at a channel temperature of 125 °C and a current-gain cut-off frequency of 74 GHz for a T-gate technology has been achieved. By electroluminescence and TEM cross-sectioning of a stressed device a local inhomogeneous pit formation process was found as the major degradation mechanism for the decrease of the saturation current

Acetylcholinesterase measurement in various brain regions and muscles of juvenile, adolescent, and adult rats

<p>Several insecticides, chemicals, and drugs are known to inhibit acetylcholinesterase (AChE) activity, responsible for the cleavage of the neurotransmitter acetylcholine. The administration of AChE inhibitors leads to typical parasympathomimetic (toxic) symptoms in rats. In order to differentiate between compounds acting in various regions of the brain or in peripheral nerves, regulatory authorities demand the measurement of AChE activity in different compartments and the study of potential toxicity at different developmental stages. In the present paper, instructions are given for the necropsy of various regions of the brain depending on rat age. Furthermore, a method validation procedure is described for measuring AChE in these parts of the brain as well as peripheral nerves, serum, and erythrocytes in juvenile, adolescent, and adult rats according to the US EPA method. All investigations were performed within the frame of a regulatory extended one-generation reproductive study (EOGRTS, OECD TG 443). AChE activity increases age dependently in parts of the forebrain (cortex, hippocampus, striatum, but decreases in the mid- and hindbrain (cerebellum, brain stem, medulla oblongata) as well as in peripheral nerves (heart, diaphragm, gastrocnemius muscle). Sex-dependent differences of the AChE activity occur after an age of 11 weeks. The implication of AChE measurement in different brain regions of various age groups is discussed regarding the assessment of AChE inhibitors.</p

Unusual Ratio between Free Thyroxine and Free Triiodothyronine in a Long-Lived Mole-Rat Species with Bimodal Ageing

<div><p>Ansell's mole-rats (<i>Fukomys anselli</i>) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding <i>F. anselli</i> to examine whether <i>a</i>) their thyroid hormone system shows any peculiarities on the genetic level, <i>b</i>) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and <i>c</i>) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell's mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of <i>F. anselli</i> were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.</p></div

Intraspecific fT4 (both scenarios) and fT3 differences in Ansell's mole-rats.

<p>GLM main effects for all four factors alone and a GLM two factor model with reproductive status × age as independent variable. The <i>p</i>-values and the correlation coefficients <i>F</i> are shown.</p><p>* =  significant (<i>p</i><0.05).</p><p>Intraspecific fT4 (both scenarios) and fT3 differences in Ansell's mole-rats.</p

Free T4 and free T3 levels of Ansell's mole-rats (n = 24), rats (n = 4) and guinea pigs (n = 4).

<p>Mean ± SD; all data expressed in pg/ml. One-way ANOVA, fT4: <i>F</i> = 206.38, <i>p</i><0.0001; fT3: <i>F</i> = 0.85, <i>p</i> = 0.44. Significant differences in the Bonferroni post hoc comparisons are indicated by asterisks coupled with the comparison species referred to (mr  =  mole-rat, r =  rat, gp  =  guinea pig) in parenthesis. See “Results” section for statistical details and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113698#pone-0113698-t003" target="_blank">Table 3</a> for TH ratios obtained from these data. Mole-rat fT4 data refer to scenario 1; applying the second scenario (not depicted here) created essentially the same result because mean fT4 values of mole-rats were slightly lower.</p

fT4:tT4 and fT3:tT3 ratios in Ansell's mole-rats (n = 12), rats (n = 7) and guinea pigs (n = 4).

<p>One-way ANOVA, fT4:tT4: <i>F = </i>9.60, <i>p</i> = 0.001; fT3:tT3: <i>F = </i>7.724, <i>p = </i>0.004. Significant differences in the Bonferroni post hoc comparisons are indicated by asterisks coupled with the comparison species referred to (mr  =  mole-rat, r =  rat, gp  =  guinea pig) in parenthesis. See “Results” section for statistical details.</p