A family case of fertile human 45,X,psu dic(15;Y) males

We report on a familial case including four male probands from three generations with a 45,X,psu dic(15;Y)(p11.2;q12) karyotype. 45,X is usually associated with a female phenotype and only rarely with maleness, due to translocation of small Y chromosomal fragments to autosomes. These male patients are commonly infertile because of missing azoospermia factor regions from the Y long arm. In our familial case we found a pseudodicentric translocation chromosome, that contains almost the entire chromosomes 15 and Y. The translocation took place in an unknown male ancestor of our probands and has no apparent effect on fertility and phenotype of the carrier. FISH analysis demonstrated the deletion of the pseudoautosomal region 2 (PAR2) from the Y chromosome and the loss of the nucleolus organizing region (NOR) from chromosome 15. The formation of the psu dic(15;Y) chromosome is a reciprocal event to the formation of the satellited Y chromosome (Yqs). Statistically, the formation of 45,X,psu dic(15;Y) (p11.2;q12) is as likely as the formation of Yqs. Nevertheless, it has not been described yet. This can be explained by the dicentricity of this translocation chromosome that usually leads to mitotic instability and meiotic imbalances. A second event, a stable inactivation of one of the two centromeres is obligatory to enable the transmission of the translocation chromosome and thus a stably reduced chromosome number from father to every son in this family

Cell shape analysis of random tessellations based on Minkowski tensors

To which degree are shape indices of individual cells of a tessellation characteristic for the stochastic process that generates them? Within the context of stochastic geometry and the physics of disordered materials, this corresponds to the question of relationships between different stochastic models. In the context of image analysis of synthetic and biological materials, this question is central to the problem of inferring information about formation processes from spatial measurements of resulting random structures. We address this question by a theory-based simulation study of shape indices derived from Minkowski tensors for a variety of tessellation models. We focus on the relationship between two indices: an isoperimetric ratio of the empirical averages of cell volume and area and the cell elongation quantified by eigenvalue ratios of interfacial Minkowski tensors. Simulation data for these quantities, as well as for distributions thereof and for correlations of cell shape and volume, are presented for Voronoi mosaics of the Poisson point process, determinantal and permanental point processes, and Gibbs hard-core and random sequential absorption processes as well as for Laguerre tessellations of polydisperse spheres and STIT- and Poisson hyperplane tessellations. These data are complemented by mechanically stable crystalline sphere and disordered ellipsoid packings and area-minimising foam models. We find that shape indices of individual cells are not sufficient to unambiguously identify the generating process even amongst this limited set of processes. However, we identify significant differences of the shape indices between many of these tessellation models. Given a realization of a tessellation, these shape indices can narrow the choice of possible generating processes, providing a powerful tool which can be further strengthened by density-resolved volume-shape correlations.Comment: Chapter of the forthcoming book "Tensor Valuations and their Applications in Stochastic Geometry and Imaging" in Lecture Notes in Mathematics edited by Markus Kiderlen and Eva B. Vedel Jense

Low Density Lipoproteins as Circulating Fast Temperature Sensors

Background: The potential physiological significance of the nanophase transition of neutral lipids in the core of low density lipoprotein (LDL) particles is dependent on whether the rate is fast enough to integrate small (62uC) temperature changes in the blood circulation. Methodology/Principal Findings: Using sub-second, time-resolved small-angle X-ray scattering technology with synchrotron radiation, we have monitored the dynamics of structural changes within LDL, which were triggered by temperature-jumps and-drops, respectively. Our findings reveal that the melting transition is complete within less than 10 milliseconds. The freezing transition proceeds slowly with a half-time of approximately two seconds. Thus, the time period over which LDL particles reside in cooler regions of the body readily facilitates structural reorientation of the apolar core lipids. Conclusions/Significance: Low density lipoproteins, the biological nanoparticles responsible for the transport of cholesterol in blood, are shown to act as intrinsic nano-thermometers, which can follow the periodic temperature changes during blood circulation. Our results demonstrate that the lipid core in LDL changes from a liquid crystalline to an oily state within fractions of seconds. This may, through the coupling to the protein structure of LDL, have important repercussions o

The shared socioeconomic pathways and their energy, land use, and greenhouse gas emissions implications: An overview

This paper presents the overview of the Shared Socioeconomic Pathways (SSPs) and their energy, land use, and emissions implications. The SSPs are part of a new scenario framework, established by the climate change research community in order to facilitate the integrated analysis of future climate impacts, vulnerabilities, adaptation, and mitigation. The pathways were developed over the last years as a joint community effort and describe plausible major global developments that together would lead in the future to different challenges for mitigation and adaptation to climate change. The SSPs are based on five narratives describing alternative socio-economic developments, including sustainable development, regional rivalry, inequality, fossil-fueled development, and a middle-of-the-road development. The long-term demographic and economic projections of the SSPs depict a wide uncertainty range consistent with the scenario literature. A multi-model approach was used for the elaboration of the energy, land-use and the emissions trajectories of SSP-based scenarios. The baseline scenarios lead to global energy consumption of 500-1100 EJ in 2100, and feature vastly different land-use dynamics, ranging from a possible reduction in cropland area up to a massive expansion by more than 700 million hectares by 2100. The associated annual CO2 emissions of the baseline scenarios range from about 25 GtCO2 to more than 120 GtCO2 per year by 2100. With respect to mitigation, we find that associated costs strongly depend on three factors: 1) the policy assumptions, 2) the socio-economic narrative, and 3) the stringency of the target. The carbon price for reaching the target of 2.6 W/m2 differs in our analysis thus by about a factor of three across the SSP scenarios. Moreover, many models could not reach this target from the SSPs with high mitigation challenges. While the SSPs were designed to represent different mitigation and adaptation challenges, the resulting narratives and quantifications span a wide range of different futures broadly representative of the current literature. This allows their subsequent use and development in new assessments and research projects. Critical next steps for the community scenario process will, among others, involve regional and sectorial extensions, further elaboration of the adaptation and impacts dimension, as well as employing the SSP scenarios with the new generation of earth system models as part of the 6th climate model intercomparison project (CMIP6)

p53 Gene Repair with Zinc Finger Nucleases Optimised by Yeast 1-Hybrid and Validated by Solexa Sequencing

The tumor suppressor gene p53 is mutated or deleted in over 50% of human tumors. As functional p53 plays a pivotal role in protecting against cancer development, several strategies for restoring wild-type (wt) p53 function have been investigated. In this study, we applied an approach using gene repair with zinc finger nucleases (ZFNs). We adapted a commercially-available yeast one-hybrid (Y1H) selection kit to allow rapid building and optimization of 4-finger constructs from randomized PCR libraries. We thus generated novel functional zinc finger nucleases against two DNA sites in the human p53 gene, near cancer mutation ‘hotspots’. The ZFNs were first validated using in vitro cleavage assays and in vivo episomal gene repair assays in HEK293T cells. Subsequently, the ZFNs were used to restore wt-p53 status in the SF268 human cancer cell line, via ZFN-induced homologous recombination. The frequency of gene repair and mutation by non-homologous end-joining was then ascertained in several cancer cell lines, using a deep sequencing strategy. Our Y1H system facilitates the generation and optimisation of novel, sequence-specific four- to six-finger peptides, and the p53-specific ZFN described here can be used to mutate or repair p53 in genomic loci