Poetry in motion: Increased chromosomal mobility after DNA damage

Double-strand breaks (DSBs) are among the most lethal DNA lesions, and a variety of pathways have evolved to manage their repair in a timely fashion. One such pathway is homologous recombination (HR), in which information from an undamaged donor site is used as a template for repair. Although many of the biochemical steps of HR are known, the physical movements of chromosomes that must underlie the pairing of homologous sequence during mitotic DSB repair have remained mysterious. Recently, several groups have begun to use a variety of genetic and cell biological tools to study this important question. These studies reveal that both damaged and undamaged loci increase the volume of the nuclear space that they explore after the formation of DSBs. This DSB-induced increase in chromosomal mobility is regulated by many of the same factors that are important during HR, such as ATR-dependent checkpoint activation and the recombinase Rad51, suggesting that this phenomenon may facilitate the search for homology. In this perspective, we review current research into the mobility of chromosomal loci during HR, as well as possible underlying mechanisms, and discuss the critical questions that remain to be answered. Although we focus primarily on recent studies in the budding yeast, Saccharomyces cerevisiae, examples of experiments performed in higher eukaryotes are also included, which reveal that increased mobility of damaged loci is a process conserved throughout evolution.     

Prediction Intervals in Nonlinear Regression

By treating the nonlinear model as if it were linear in the parameterization θ in the neighbourhood of the least squares estimate θ, we construct two-sided nominally-q-prediction intervals by applying the usual linear model theory. The derivation of the truncated series expansion of the expected coverage of the prediction intervals at a feasible value of the parameter vector is described. The quadratic approximation of the expected coverage is then obtained for a two-parameter nonlinear model. Finally we show how we may construct the prediction intervals when a certain type of nonlinear transformation of the parameter vector has been applied.     

WFS1 and non-syndromic low-frequency sensorineural hearing loss: A novel mutation in a Portuguese case

Low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of HL in which frequencies at 2000 Hz and below are predominantly affected. Most of the families with LFSNHL carry missense mutations in WFS1 gene, coding for wolframin.     

On partial local smoothing rules for curve estimation

We compare the performances of local and global rules for smoothingparameter choice, in terms of asymptotic mean squared errorsof the resulting estimators. In some instances there is surprisinglylittle to choose between local and global approaches; our analysisidentifies contexts where the differences are small or large.This work motivates development of smoothing rules that forma ‘half-way house’ between local and global smoothing.There, interpolation provides a basis for partial local smoothing.A key result shows that interpolation on even a coarse gridcan produce a very good approximation to full local smoothing.Our theoretical and numerical results lead us to suggest linearinterpolation of a bandwidth obtained by integral approximationson discrete intervals.     

Unravelling the correlates of species richness and ecological uniqueness in a metacommunity of urban pond insects

City ponds have the potential to harbour a rich biodiversity of aquatic insects despite being located in an urban landscape. However, our current knowledge on the correlates of pond biodiversity is limited and even less is known about the factors that influence the ecological uniqueness of urban ponds. The multiple environmental gradients, at different spatial scales, that may affect biodiversity and ecological uniqueness of urban ponds can thus be seen both as an opportunity and as a challenge for a study. In this study, we aimed to fill this gap by focusing on aquatic insect assemblages in 51 ponds in the Swedish city of Stockholm, using a metacommunity perspective. We found that species richness was primarily determined by the density of aquatic insects, water depth and proportion of buildings around the pond. The uniqueness of ponds was estimated as local contributions to beta diversity (LCBD), and it was primarily related to the proportion of arable land and industry around the ponds. With regard to the metacommunity we found two interesting patterns. First, there was a negative relationship between richness and LCBD. Second, biodiversity was spatially independent, suggesting that spatially-patterned dispersal did not structure species richness or LCBD. These last two patterns are important when considering conservation efforts of biodiversity in city ponds. We hence suggest that the conservation of insect biodiversity in urban pond should consider the surroundings of the ponds, and that high-richness ponds are not necessarily those that require most attention because they are not ecologically the most unique.     

Anatomically-based skeletal coordinate systems for use with impact biomechanics data intended for anthropomorphic test device development

Post-mortem human subjects (PMHS) are frequently used to characterize biomechanical response and injury tolerance of humans to various types of loading by means of instrumentation installed directly on the skeleton. Data extracted from such tests are often used to develop and validate anthropomorphic test devices (ATDs), which function as human surrogates in tests for injury assessment. Given that the location and orientation of installed instrumentation differs between subjects, nominally similar measurements made on different PMHS must be transformed to standardized, skeletal-based local coordinate systems (LCS) before appropriate data comparisons can be made. Standardized PMHS LCS that correspond to ATD instrumentation locations and orientations have not previously been published. This paper introduces anatomically-defined PMHS LCS for body regions in which kinematic measurements are made using ATDs. These LCS include the head, sternum, single vertebrae, pelvis, femurs (distal and proximal), and tibiae (distal and proximal) based upon skeletal landmarks extracted from whole body CT scans. The proposed LCS provide a means to standardize the reporting of PMHS data, and facilitate both the comparison of PMHS impact data across institutions and the application of PMHS data to the development and validation of ATDs.     

Local anaesthetic lidocaine modulates epiphyllous bud differentiation in Kalanchoe pinnata

A single treatment with lidocaine(2-Diethylamino-N-[2,6-dimethylphenyl]-acetamide) – a potent localanaesthetic(LA), caused significant and extensive inhibition of epiphyllous buddifferentiation in Kalanchoe pinnata, in a long –term irreversible manner. These effects were both concentration and treatmentduration dependent, with either variant generating similar and additiveeffects.The growth responses studied had differential sensitivity towards the applieddosage of the anaesthetic. Lidocaine also appears to influence expression oftheorganogenic potential of buds since for all inhibitory doses a significantpercentage produced shoots but not roots.     

CH4 emission with differences in atmospheric CO2 enrichment and rice cultivars in a Japanese paddy soil

A pot experiment was conducted to investigate CH₄ emissions from a sandy paddy soil as influenced by rice cultivars and atmospheric CO₂ elevation. The experiment with two CO₂ levels, 370 μL L⁻¹ (ambient) and 570 μL L⁻¹ (elevated), was performed in a climatron, located at the National Institute for Agro‐Environmental Sciences, Tsukuba, Japan. Four rice cultivars were tested in this experiment, including IR65598, IR72, Dular and Koshihikari. Tiller number, root length and grain yield were clearly larger under elevated CO₂ than under ambient CO₂. IR72 and Dular showed significantly higher tiller number, root length and grain yield than Koshihikari and IR65598. Average daily CH₄ fluxes under elevated CO₂ were significantly larger by 10.9–23.8% than those under ambient CO₂, and varied with the cultivars in the sequence Dular ≧ IR72>IR65598 ≧ Koshihikari. Dissolved organic C (DOC) content in the soil was obviously higher under elevated CO₂ than under ambient CO₂ and differed among the cultivars, in the sequence IR72>Dular>Koshihikari>IR65598. The differences in average daily CH₄ fluxes between CO₂ levels and among the cultivars were related to different root exudation as DOC content, root length and tiller number. This study indicated that Koshihikari should be a potential cultivar for mitigating CH₄ emission and simultaneously keeping stable grain yield, because this cultivar emitted lowest CH₄ emission and produced medium grain yield.     

Contact sensitization: A new approach to risk assessment

The murine local lymph node assay is a novel predictive test for the identification of skin sensitizing chemicals. The method measures sensitization potential of a chemical in mice as a function of proliferative activity induced in lymph nodes draining the site of topical exposure to that test chemical. Here we describe the use of the local lymph node assay for evaluation of the relative potency of skin sensitizing chemicals via derivation of the concentration required to produce a threshold positive reaction. Subsequently, the development of risk assessments based on comparisons with index contact allergens is outlined.