Monopolelike probes for quantitative magnetic force microscopy: calibration and application

A local magnetization measurement was performed with a Magnetic Force Microscope (MFM) to determine magnetization in domains of an exchange coupled [Co/Pt]/Co/Ru multilayer with predominant perpendicular anisotropy. The quantitative MFM measurements were conducted with an iron filled carbon nanotube tip, which is shown to behave like a monopole. As a result we determined an additional in-plane magnetization component of the multilayer, which is explained by estimating the effective permeability of the sample within the \mu*-method.Comment: 3 pages, 3 figure

Harris lines of the tibia across centuries: a comparison of two populations, medieval and contemporary in Central Europe

Objective: To determine the incidence of Harris lines in two medieval populations which inhabited the Canton of Berne, in Central Switzerland, and to compare the results with those of a contemporary population living in the same geographical area. A simplified method is described for measuring the age of the individual at the time of formation of Harris lines, with possible future applications. Design and patients: Radiographs of 112 well-preserved tibiae of skeletons of two medieval populations from the eighth to fifteenth centuries were reviewed for the incidence of Harris lines. The results were compared with those of 138 current patients living in the same geographic location in Central Switzerland. Age and gender of the medieval individual were determined using known anthropological methods. Age of bone at the time of formation of Harris lines was estimated according to the method of Maat. Results: Harris lines were found in 88 of 112 (80%) of the examined medieval skeletons and in 28 of 138 (20%) of the living individuals. Higher incidences of Harris lines were found at the age of 2years and at ages between 8 and 12years in both populations. No gender difference was found regarding the incidence of Harris lines. In both populations the occurrence of Harris lines was associated with certain diseases such as degenerative bone disease, trauma, osteoporosis, rheumatoid arthritis, peripheral vascular diseases, rickets and bony deformities. Conclusion: A high incidence of Harris lines was found in the medieval population, perhaps reflecting difficult living and hygienic conditions, but also the poor care and neglect of the children population. Measuring the age of the individual at the time of formation of Harris lines is simple and may have future clinical applications in the paediatric population for medico-legal purposes. The application of Harris lines as a marker in follow-up of osteoporosis may need further evaluatio

How to run a brain bank. A report from the Austro-German brain bank

The sophisticated analysis of and growing information on the human brain requires that acquisition, dissection, storage and distribution of rare material are managed in a professional way. In this publication we present the concept and practice of our brain bank. Both brain tissue and information are handled by standardized procedures and flow in parallel from pathology to neuropathology and neurochemistry. Data concerning brain material are updated with clinical information gained by standardized procedures

Virtopsy: Zukunftsträchtige Forschung in der Rechtsmedizin

Computed tomography techniques have been developed over the last 10 years and have found various applications in the forensic field. The most recent development is multislice computed tomography combined with photogrammetry-based surface optical scanning and image rendering techniques. This combination of techniques can be used to produce 3-dimensional images of injury patterns for comparison with suspect weapons and also to screen for pathological conditions in the living or deceased. This technology provides a minimally invasive procedure for capturing forensically relevant images which can be produced in the courtroom. The rapid developments in imaging techniques could provide an alternative to conventional autopsy procedures in the futur

Calibration of multi-layered probes with low/high magnetic moments

We present a comprehensive method for visualisation and quantification of the magnetic stray field of magnetic force microscopy (MFM) probes, applied to the particular case of custom-made multi-layered probes with controllable high/low magnetic moment states. The probes consist of two decoupled magnetic layers separated by a non-magnetic interlayer, which results in four stable magnetic states: ±ferromagnetic (FM) and ±antiferromagnetic (A-FM). Direct visualisation of the stray field surrounding the probe apex using electron holography convincingly demonstrates a striking difference in the spatial distribution and strength of the magnetic flux in FM and A-FM states. In situ MFM studies of reference samples are used to determine the probe switching fields and spatial resolution. Furthermore, quantitative values of the probe magnetic moments are obtained by determining their real space tip transfer function (RSTTF). We also map the local Hall voltage in graphene Hall nanosensors induced by the probes in different states. The measured transport properties of nanosensors and RSTTF outcomes are introduced as an input in a numerical model of Hall devices to verify the probe magnetic moments. The modelling results fully match the experimental measurements, outlining an all-inclusive method for the calibration of complex magnetic probes with a controllable low/high magnetic moment

Variation in the spectrum of new mutations among inbred strains of mice

The mouse serves as a mammalian model for understanding the nature of variation from new mutations, a question that has both evolutionary and medical significance. Previous studies suggest that the rate of single-nucleotide mutations (SNMs) in mice is ∼50% of that in humans. However, information largely comes from studies involving the C57BL/6 strain, and there is little information from other mouse strains. Here, we study the mutations that accumulated in 59 mouse lines derived from four inbred strains that are commonly used in genetics and clinical research (BALB/cAnNRj, C57BL/6JRj, C3H/HeNRj, and FVB/NRj), maintained for eight to nine generations by brother–sister mating. By analyzing Illumina whole-genome sequencing data, we estimate that the average rate of new SNMs in mice is ∼μ = 6.7 × 10−9. However, there is substantial variation in the spectrum of SNMs among strains, so the burden from new mutations also varies among strains. For example, the FVB strain has a spectrum that is markedly skewed toward C→A transversions and is likely to experience a higher deleterious load than other strains, due to an increased frequency of nonsense mutations in glutamic acid codons. Finally, we observe substantial variation in the rate of new SNMs among DNA sequence contexts, CpG sites, and their adjacent nucleotides playing an important role

The rate and spectrum of new mutations in mice inferred by long-read sequencing

All forms of genetic variation originate from new mutations, making it crucial to understand their rates and mechanisms. Here, we use long-read sequencing from Pacific Biosciences (PacBio) to investigate de novo mutations that accumulated in 12 inbred mouse lines derived from three commonly used inbred strains (C3H, C57BL/6, and FVB) maintained for 8 to 15 generations in a mutation accumulation (MA) experiment. We built chromosome-level genome assemblies based on the MA line founders’ genomes and then employed a combination of read and assembly-based methods to call the complete spectrum of new mutations. On average, there are about 45 mutations per haploid genome per generation, about half of which (54%) are insertions and deletions shorter than 50 bp (indels). The remainder are single-nucleotide mutations (SNMs; 44%) and large structural mutations (SMs; 2%). We found that the degree of DNA repetitiveness is positively correlated with SNM and indel rates and that a substantial fraction of SMs can be explained by homology-dependent mechanisms associated with repeat sequences. Most (90%) indels can be attributed to microsatellite contractions and expansions, and there is a marked bias toward 4 bp indels. Among the different types of SMs, tandem repeat mutations have the highest mutation rate, followed by insertions of transposable elements (TEs). We uncover a rich landscape of active TEs, notable differences in their spectrum among MA lines and strains, and a high rate of gene retroposition. Our study offers novel insights into mammalian genome evolution and highlights the importance of repetitive elements in shaping genomic diversity

Discrimination between genotoxicity and cytotoxicity for the induction of DNA double-strand breaks in cells treated with aldehydes and diepoxides

The time-dependent dose-response relationships for the induction of DNA double-strand breaks (DSB) assessed by pulsed-field gel electrophoresis (PFGE) and for viability (evaluated by the MTT cytotoxicity test) were investigated in order to discriminate between genotoxic and cytotoxic mechanisms of DNA fragmentation. Cultured human lung epithelial cells (A549) were treated (i) with the aldehydes formaldehyde or glutaraldehyde and (ii) with the DNA-DNA interstrand crosslinkers melphalan, diepoxybutane or diepoxyoctane. Induction of DSB by formaldehyde and glutaraldehyde was seen only after cell viability was reduced to less than about 60% of the control values, indicating that DSB were the consequence of extragenomic damage and viability loss. Melphalan, diepoxybutane and diepoxyoctane induced DSB by a genotoxic mode with concentrations that did not affect cell survival: 8 h after treatment initiation both heat-labile crosslinks and DSB could be detected. Cells were not able to repair the crosslinks induced by diepoxybutane, the crosslinker with the shortest chain length. In contrast, with melphalan and diepoxyoctane, which have a longer crosslinking property considerable repair of crosslinks was observed. The molecular size distribution of the produced DNA fragments supported this mechanistic distinction. The DNA fragments generated by diepoxides were initially large, their concentration decreasing monotonously from 7 Mbp to less than 1 Mbp and were converted to smaller fragments by 72 h in the course of cell death. In contrast, DNA fragments induced by formaldehyde peaked below 1 Mbp, implicating activation of DNA-degrading enzymes. Copyright (C) 1999 Elsevier Science B.V

A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct emx2 mutant phenotype

<p>Abstract</p> <p>Background</p> <p>The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood.</p> <p>Results</p> <p>To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-<it>tau-lacZ </it>reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs), but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as <it>reeler</it>. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the <it>Emx2 </it>gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development.</p> <p>Conclusions</p> <p>These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the mouse brain, identifying mutant phenotypes at multiple steps of the pathway, and revealing a new aspect of the <it>Emx2 </it>mutant. The phenotypes highlight vulnerable choice points and latent tendencies of TCAs, and will lead to a refined understanding of the elements and interactions required to form the thalamocortical system.</p> <p>See Commentary: <url>http://www.biomedcentral.com/1741-7007/9/1</url></p