Aurora kinase B is required for growth and expansion of medulloblastoma cells in the tissue context.

The impact of the tissue context on tumor growth and drug response in medulloblastoma (MB) is poorly understood. To gain insights into the growth and dissemination behavior of the MB tumor cells under treatment, we combined three-dimensional cell culture screening with ex vivo organotypic cerebellum slice co-culture (OCSC), which allowed the assessment of tumor cell behavior in the tissue context. To identify druggable kinase pathways involved in invasion, we screened a panel of 274 kinase inhibitors and identified aurora kinase B (AURKB) as a potential anti-invasion drug target in MB.

Absence of mitochondrial SLC25A51 enhances PARP1-dependent DNA repair by increasing nuclear NAD+ levels.

Though the effect of the recently identified mitochondrial NAD+ transporter SLC25A51 on glucose metabolism has been described, its contribution to other NAD+-dependent processes throughout the cell such as ADP-ribosylation remains elusive. Here, we report that absence of SLC25A51 leads to increased NAD+ concentration not only in the cytoplasm and but also in the nucleus. The increase is not associated with upregulation of the salvage pathway, implying an accumulation of constitutively synthesized NAD+ in the cytoplasm and nucleus.

Secondary Fast Breakdown in Narrow Bipolar Events.

The physical mechanism of Narrow bipolar events (NBEs) has been studied for decades but it still holds many mysteries. Recent observations indicate that the fast breakdown discharges that produce NBEs sometimes contain a secondary fast breakdown that propagates back in the opposite direction but this has not been fully addressed so far in electromagnetic models. In this study, we investigate fast breakdown using different approaches that employ a Modified Transmission Line with Exponential decay (MTLE) model and propose a new model, named "rebounding MTLE model," which reproduces the secondary fast breakdown current in NBEs.

The Propagation Effects of Lightning Electromagnetic Fields Over Mountainous Terrain in the Earth-Ionosphere Waveguide.

In this paper, a full-wave two-dimensional Finite-Difference-Time-Domain model is developed to evaluate the propagation effects of lightning electromagnetic fields over mountainous terrain in the Earth-ionosphere waveguide. In the model, we investigate the effect of the Earth-ionosphere waveguide structure and medium parameters, including the effect of the ionospheric cold plasma characteristics, the effect of the Earth curvature, and the propagation effects over mountainous terrain. For the first time, the obtained results are validated against simultaneous experimental data consisting of lightning currents measured at the Säntis Tower and electric fields measured in Neudorf, Austria, located at 380-km distance from the tower.

The Rise of the Cartwheel: Seeding the Centriole Organelle.

The cartwheel is a striking structure critical for building the centriole, a microtubule-based organelle fundamental for organizing centrosomes, cilia, and flagella. Over the last 50 years, the cartwheel has been described in many systems using electron microscopy, but the molecular nature of its constituent building blocks and their assembly mechanisms have long remained mysterious. Here, we review discoveries that led to the current understanding of cartwheel structure, assembly, and function.

Intra-Arterial Drug and Light Delivery for Photodynamic Therapy Using Visudyne®: Implication for Atherosclerotic Plaque Treatment.

Unlabelled: Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus, this "intra-arterial" PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions.

What lies beneath? Diffusion EAP-based study of brain tissue microstructure.

Diffusion weighted magnetic resonance signals convey information about tissue microstructure and cytoarchitecture. In the last years, many models have been proposed for recovering the diffusion signal and extracting information to constitute new families of numerical indices. Two main categories of reconstruction models can be identified in diffusion magnetic resonance imaging (DMRI): ensemble average propagator (EAP) models and compartmental models.

Polarity-dependent asymmetric distribution and MEX-5/6-mediated translational activation of the Era-1 mRNA in C. elegans embryos.

The early C. elegans embryo is an attractive model system to investigate fundamental developmental processes. With the exception of mex-3 mRNA, maternally contributed mRNAs are thought to be distributed uniformly in the one-cell embryo.

SAS-1 is a C2 domain protein critical for centriole integrity in C. elegans.

Centrioles are microtubule-based organelles important for the formation of cilia, flagella and centrosomes. Despite progress in understanding the underlying assembly mechanisms, how centriole integrity is ensured is incompletely understood, including in sperm cells, where such integrity is particularly critical. We identified C.

Clathrin regulates centrosome positioning by promoting acto-myosin cortical tension in C. elegans embryos.

Regulation of centrosome and spindle positioning is crucial for spatial cell division control. The one-cell Caenorhabditis elegans embryo has proven attractive for dissecting the mechanisms underlying centrosome and spindle positioning in a metazoan organism. Previous work revealed that these processes rely on an evolutionarily conserved force generator complex located at the cell cortex.

Graph theory reveals dysconnected hubs in 22q11DS and altered nodal efficiency in patients with hallucinations.

Schizophrenia is postulated to be the prototypical dysconnection disorder, in which hallucinations are the core symptom. Due to high heterogeneity in methodology across studies and the clinical phenotype, it remains unclear whether the structural brain dysconnection is global or focal and if clinical symptoms result from this dysconnection. In the present work, we attempt to clarify this issue by studying a population considered as a homogeneous genetic sub-type of schizophrenia, namely the 22q11.

Towards a molecular architecture of centriole assembly.

The centriole is an evolutionarily conserved macromolecular structure that is crucial for the formation of flagella, cilia and centrosomes. The ultrastructure of the centriole was first characterized decades ago with the advent of electron microscopy, revealing a striking ninefold radial arrangement of microtubules. However, it is only recently that the molecular mechanisms governing centriole assembly have begun to emerge, including the elucidation of the crucial role of spindle assembly abnormal 6 (SAS-6) proteins in imparting the ninefold symmetry.

Analysis of centriole elimination during C. elegans oogenesis.

Centrosomes are the principal microtubule organizing centers (MTOCs) of animal cells and comprise a pair of centrioles surrounded by pericentriolar material (PCM). Centriole number must be carefully regulated, notably to ensure bipolar spindle formation and thus faithful chromosome segregation. In the germ line of most metazoan species, centrioles are maintained during spermatogenesis, but eliminated during oogenesis.

Synthesis, structure and surface dynamics of phosphorycholine functional biomimicking polymers.

2-Acryloyloxyethyl phosphorylcholine (APC) was synthesised and copolymerised with methyl methacrylate (MMA) and methyl acrylate (MA) to lead to a PC functional terpolymer. Bulk and solution properties were assessed through elemental analysis, DSC and 1H-NMR. The possibility of chain transfer was discussed.