The power of comparative and developmental studies for mouse models of Down syndrome

Since the genetic basis for Down syndrome (DS) was described, understanding the causative relationship between genes at dosage imbalance and phenotypes associated with DS has been a principal goal of researchers studying trisomy 21 (Ts21). Though inferences to the gene-phenotype relationship in humans have been made, evidence linking a specific gene or region to a particular congenital phenotype has been limited. To further understand the genetic basis for DS phenotypes, mouse models with three copies of human chromosome 21 (Hsa21) orthologs have been developed. Mouse models offer access to every tissue at each stage of development, opportunity to manipulate genetic content, and ability to precisely quantify phenotypes. Numerous approaches to recreate trisomic composition and analyze phenotypes similar to DS have resulted in diverse trisomic mouse models. A murine intraspecies comparative analysis of different genetic models of Ts21 and specific DS phenotypes reveals the complexity of trisomy and important considerations to understand the etiology of and strategies for amelioration or prevention of trisomic phenotypes. By analyzing individual phenotypes in different mouse models throughout development, such as neurologic, craniofacial, and cardiovascular abnormalities, greater insight into the gene-phenotype relationship has been demonstrated. In this review we discuss how phenotype-based comparisons between DS mouse models have been useful in analyzing the relationship of trisomy and DS phenotypes

Genetically enhanced asynapsis of autosomal chromatin promotes transcriptional dysregulation and meiotic failure

During meiosis, pairing of homologous chromosomes and their synapsis are essential prerequisites for normal male gametogenesis. Even limited autosomal asynapsis often leads to spermatogenic impairment, the mechanism of which is not fully understood. The present study was aimed at deliberately increasing the size of partial autosomal asynapsis and analysis of its impact on male meiosis. For this purpose, we studied the effect of t12 haplotype encompassing four inversions on chromosome 17 on mouse autosomal translocation T(16;17)43H (abbreviated T43H). The T43H/T43H homozygotes were fully fertile in both sexes, while +/T43H heterozygous males, but not females, were sterile with meiotic arrest at late pachynema. Inclusion of the t12 haplotype in trans to the T43H translocation resulted in enhanced asynapsis of the translocated autosome, ectopic phosphorylation of histone H2AX, persistence of RAD51 foci, and increased gene silencing around the translocation break. Increase was also on colocalization of unsynapsed chromatin with sex body. Remarkably, we found that transcriptional silencing of the unsynapsed autosomal chromatin precedes silencing of sex chromosomes. Based on the present knowledge, we conclude that interference of meiotic silencing of unsynapsed autosomes with meiotic sex chromosome inactivation is the most likely cause of asynapsis-related male sterility

Enhanced Growth and Osteogenic Differentiation of Human Osteoblast-Like Cells on Boron-Doped Nanocrystalline Diamond Thin Films

Intrinsic nanocrystalline diamond (NCD) films have been proven to be promising substrates for the adhesion, growth and osteogenic differentiation of bone-derived cells. To understand the role of various degrees of doping (semiconducting to metallic-like), the NCD films were deposited on silicon substrates by a microwave plasma-enhanced CVD process and their boron doping was achieved by adding trimethylboron to the CH4:H2 gas mixture, the B∶C ratio was 133, 1000 and 6700 ppm. The room temperature electrical resistivity of the films decreased from >10 MΩ (undoped films) to 55 kΩ, 0.6 kΩ, and 0.3 kΩ (doped films with 133, 1000 and 6700 ppm of B, respectively). The increase in the number of human osteoblast-like MG 63 cells in 7-day-old cultures on NCD films was most apparent on the NCD films doped with 133 and 1000 ppm of B (153,000±14,000 and 152,000±10,000 cells/cm2, respectively, compared to 113,000±10,000 cells/cm2 on undoped NCD films). As measured by ELISA per mg of total protein, the cells on NCD with 133 and 1000 ppm of B also contained the highest concentrations of collagen I and alkaline phosphatase, respectively. On the NCD films with 6700 ppm of B, the cells contained the highest concentration of focal adhesion protein vinculin, and the highest amount of collagen I was adsorbed. The concentration of osteocalcin also increased with increasing level of B doping. The cell viability on all tested NCD films was almost 100%. Measurements of the concentration of ICAM-1, i.e. an immunoglobuline adhesion molecule binding inflammatory cells, suggested that the cells on the NCD films did not undergo significant immune activation. Thus, the potential of NCD films for bone tissue regeneration can be further enhanced and tailored by B doping and that B doping up to metallic-like levels is not detrimental for cells

Current Wildland Fire Patterns and Challenges in Europe: A Synthesis of National Perspectives

Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009–2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action “Fire and the Earth System: Science & Society” funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence

Stand structure and natural regeneration of Taxus baccata at "Stiwollgraben" in Austria

English yew (Taxus baccata L.) is a rare tree species in Austria and gene conservation forests reserves are used to maintain English yew populations by silvicultural treatments. This paper describes the current situation of an English yew population at “Stiwollgraben”in Austria with regard to stand structure, vitality and natural regeneration. The area is one of the most important sites in Austria as it consists of 2236 yews.The vitality condition of the yew is very good, and more than 79% of the yews have been assessed as very vital to vital. The potentiality for natural regeneration (13019 one-year seedlings ha–1) is very high, but not all height classes are represented. This indicates a high survival ability of English yew at this site. Three different treatment strategies are described to maintain the yew population. The future effects of these treatments are discussed in the light of the environmental requirements of English yew

Doping of nuclear tracks with fullerene solution

Latent nuclear tracks in polymers can occasionally be doped with fullerene solution. A new technique Fullerene Tracer Profiling , FTP allows us to verify the success of the doping procedure by determining the fullerene depth distribution along the tracks. The basic principle of FTP is described, and first examples are given. Fullerene solution is found to penetrate into ion tracks in polyimide, but not into tracks in polypropylene, or into unirradiated polyimide or polypropylene foil

Depth profiles of fullerene in ion irradiated polyimide

An analytical experimental technique is described which permits depth profiles of the fundamental molecule fullerene, C60, to be determined in solids for low molecular concentrations. The method combines a procedure for the simultaneous marking and immobilizing of fullerene in organic solids, by means of lithium salt formation, with neutron depth profiling a highly sensitive approach in determining specific depth distributions of 6Li. The new technique fullerene tracer profiling FTP is described in some detail, and results of the first experiments are discussed. Fullerene solutions have been introduced into both pristine and ion irradiated samples of the polymer polyimide PI . The C60 depth distributions were then measured using fullerene tracer profiling. From the shapes of the depth distributions conclusions are drawn concerning the uptake of fullerene solutions by polymers and the mobility of fullerene. Fullerene does not penetrate unirradiated PI, but it does readily fill up latent tracks of energetic ions in this polymer. Depending on the specific ion track density, some 104 to 107 C60 molecules can be identified as being present in a single track. The diffusion coefficient for C60 is estimated to be at least 2 10 amp; 8722;12 to 2 10 amp; 8722;13 cm2s amp; 8722;1, much higher than expected. This may be ascribed in part to the remarkable elastic deformability of the fullerene molecule in both kinetic and dynamic motion, and to the near perfect spherical geometry accompanying elimination of dangling bonds in simultaneously minimising the surface energ

Three dimensional implantation distribution of lithium implanted into pyrographite, as revealed by solid state tomography in combination with neutron depth profiling

We have studied the three dimensional distribution of 2.5 MeV Li implanted into pyrographite at room temperature by means of modified tomography in combination with neutron depth profiling. Our new findings essentially reconfirm earlier results D. Fink et al., J. Appl. Phys. 58 1985 668 [1]; Radiat. Eff. and Def. in Solids 114 1990 21 [2] which indicated the presence of some radiation enhanced mobility of the implanted lithium. This diffusion is anisotropic. It preferentially proceeds into the radial directio