Induction of deoxyribonucleic acid degradation in Escherichia coli by ozone.

Cell survival and deoxyribonucleic acid (DNA) degradation wave measured for wild-type Escherichia coli B251 cells after exposure to different concentrations of ozone. The results show that extensive breakdown of DNA occurs after ozonation and that the extent of ozone-induced DNA degradation generally correlates with the colony-forming ability of the cells.     

Forecasting time series with outliers

Time-series data are often contaminated with outliers due to the influence of unusual and non-repetitive events. Forecast accuracy in such situations is reduced due to (1) a carry-over effect of the outlier on the point forecast and (2) a bias in the estimates of model parameters. Hillmer (1984) and Ledolter (1989) studied the effect of additive outliers on forecasts. It was found that forecast intervals are quite sensitive to additive outliers, but that point forecasts are largely unaffected unless the outlier occurs near the forecast origin. In such a situation the carry-over effect of the outlier can be quite substantial. In this study, we investigate the issues of forecasting when outliers occur near or at the forecast origin. We propose a strategy which first estimates the model parameters and outlier effects using the procedure of Chen and Liu (1993) to reduce the bias in the parameter estimates, and then uses a lower critical value to detect outliers near the forecast origin in the forecasting stage. One aspect of this study is on the carry-over effects of outliers on forecasts. Four types of outliers are considered: innovational outlier, additive outlier, temporary change, and level shift. The effects due to a misidentification of an outlier type are examined. The performance of the outlier detection procedure is studied for cases where outliers are near the end of the series. In such cases, we demonstrate that statistical procedures may not be able to effectively determine the outlier types due to insufficient information. Some strategies are recommended to reduce potential difficulties caused by incorrectly detected outlier types. These findings may serve as a justification for forecasting in conjunction with judgment. Two real examples are employed to illustrate the issues discussed.     

cAMP signalling in mushroom bodies modulates temperature preference behaviour in Drosophila

Homoiotherms, for example mammals, regulate their body temperature with physiological responses such as a change of metabolic rate and sweating. In contrast, the body temperature of poikilotherms, for example Drosophila, is the result of heat exchange with the surrounding environment as a result of the large ratio of surface area to volume of their bodies. Accordingly, these animals must instinctively move to places with an environmental temperature as close as possible to their genetically determined desired temperature. The temperature that Drosophila instinctively prefers has a function equivalent to the 'set point' temperature in mammals. Although various temperature-gated TRP channels have been discovered, molecular and cellular components in Drosophila brain responsible for determining the desired temperature remain unknown. We identified these components by performing a large-scale genetic screen of temperature preference behaviour (TPB) in Drosophila. In parallel, we mapped areas of the Drosophila brain controlling TPB by targeted inactivation of neurons with tetanus toxin and a potassium channel (Kir2.1) driven with various brain-specific GAL4s. Here we show that mushroom bodies (MBs) and the cyclic AMP-cAMP-dependent protein kinase A (cAMP-PKA) pathway are essential for controlling TPB. Furthermore, targeted expression of cAMP-PKA pathway components in only the MB was sufficient to rescue abnormal TPB of the corresponding mutants. Preferred temperatures were affected by the level of cAMP and PKA activity in the MBs in various PKA pathway mutants.     

Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function

Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.     

Embryonic and extraembryonic stem cell lines derived from single mouse blastomeres

The most basic objection to human embryonic stem (ES) cell research is rooted in the fact that ES cell derivation deprives embryos of any further potential to develop into a complete human being. ES cell lines are conventionally isolated from the inner cell mass of blastocysts and, in a few instances, from cleavage stage embryos. So far, there have been no reports in the literature of stem cell lines derived using an approach that does not require embryo destruction. Here we report an alternative method of establishing ES cell lines-using a technique of single-cell embryo biopsy similar to that used in pre-implantation genetic diagnosis of genetic defects-that does not interfere with the developmental potential of embryos. Five putative ES and seven trophoblast stem (TS) cell lines were produced from single blastomeres, which maintained normal karyotype and markers of pluripotency or TS cells for up to more than 50 passages. The ES cells differentiated into derivatives of all three germ layers in vitro and in teratomas, and showed germ line transmission. Single-blastomere-biopsied embryos developed to term without a reduction in their developmental capacity. The ability to generate human ES cells without the destruction of ex utero embryos would reduce or eliminate the ethical concerns of many.     

Highly ordered arrangement of single neurons in orientation pinwheels

In the visual cortex of higher mammals, neurons are arranged across the cortical surface in an orderly map of preferred stimulus orientations. This map contains 'orientation pinwheels', structures that are arranged like the spokes of a wheel such that orientation changes continuously around a centre. Conventional optical imaging first demonstrated these pinwheels, but the technique lacked the spatial resolution to determine the response properties and arrangement of cells near pinwheel centres. Electrophysiological recordings later demonstrated sharply selective neurons near pinwheel centres, but it remained unclear whether they were arranged randomly or in an orderly fashion. Here we use two-photon calcium imaging in vivo to determine the microstructure of pinwheel centres in cat visual cortex with single-cell resolution. We find that pinwheel centres are highly ordered: neurons selective to different orientations are clearly segregated even in the very centre. Thus, pinwheel centres truly represent singularities in the cortical map. This highly ordered arrangement at the level of single cells suggests great precision in the development of cortical circuits underlying orientation selectivity.     

互花米草盐沼矿质元素的迁移变化

互花米草盐沼中矿质元素的季节变动较明显春季以植物吸收为主：夏季有部分吸收，开始释放烈季、冬季以释放为主，冬季部分转移并贮存在根茎中．深秋至初冬的盐沼土壤和海水中矿质的元素的含量略高于春季．１９９０年春夏之交互花米草所含Ｃａ．Ｍｇ．Ｓｒ．Ｍｎ．Ｋ．Ｎａ等元素的总量与互花米草生物量呈正相关关系．     

Complex haplotypes, copy number polymorphisms and coding variation in two recently divergent mouse strains

Inbred mouse strains provide the foundation for mouse genetics. By selecting for phenotypic features of interest, inbreeding drives genomic evolution and eliminates individual variation, while fixing certain sets of alleles that are responsible for the trait characteristics of the strain. Mouse strains 129Sv (129S5) and C57BL/6J, two of the most widely used inbred lines, diverged from common ancestors within the last century, yet very little is known about the genomic differences between them. By comparative genomic hybridization and sequence analysis of 129S5 short insert libraries, we identified substantial structural variation, a complex fine-scale haplotype pattern with a continuous distribution of diversity blocks, and extensive nucleotide variation, including nonsynonymous coding SNPs and stop codons. Collectively, these genomic changes denote the level and direction of allele fixation that has occurred during inbreeding and provide a basis for defining what makes these mouse strains unique.     

A radioimmunoassay for deoxycorticosterone in human peripheral plasma using sephadex LH-20 chromatography

Resumen Se reporta un nuevo método para medir desoxicorticosterona en plasma, usando cromatografía de columna LH-20 y radioinmunoensayo. Las cantidades de plasma necesarios para dicho ensayo son mínimas (2 ml) comparadas con otros métodos en la literatura, es un método practico, sensillo y rápido. Resultados así obtenidos han sido comparados con otros métodos, dichos resultados son más precisos y sensitivos para medir valores de desoxicorticosterona en plasma humano.     

Aldose reductase structures: implications for mechanism and inhibition

During chronic hyperglycaemia, elevated vascular glucose level causes increased flux through the polyol pathway, which induces functional and morphological changes associated with secondary diabetic complications. Inhibitors of aldose reductase (ARIs) have been widely investigated as potential therapeutic agents, but to date only epalrestat is successfully marketed for treatment of diabetic neuropathy, in Japan. Promising compounds during in vitro studies or in trials with animal models have failed to proceed beyond clinical trials and to everyday use, due to a lack of efficacy or adverse side effects attributed to lack of inhibitor specificity and likely inhibition of the related aldehyde reductase (ALR1). Knowledge of the catalytic mechanism and structures of the current inhibitors complexed with ALR2 are means by which more specific and tightly bound inhibitors can be discovered. This review will provide an overview of the proposed catalytic mechanism and the current state of structure-based drug design.