C9orf72 plays a central role in Rab GTPase-dependent regulation of autophagy

A GGGGCC hexanucleotide repeat expansion in the first intron of the C9orf72 gene is the most common genetic defect associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9ALS/FTD). Haploinsufficiency and a resulting loss of C9orf72 protein function has been suggested as a possible pathogenic mechanism in C9ALS/FTD. C9ALS/FTD patients exhibit specific ubiquitin and p62/sequestosome-1 positive but TDP-43 negative inclusions in the cerebellum and hippocampus, indicating possible autophagy deficits in these patients. In a recent study, we investigated this possibility by reducing expression of C9orf72 in cell lines and primary neurons and found that C9orf72 regulates the initiation of autophagy. C9orf72 interacts with Rab1a, preferentially in its GTP-bound state, as well as the ULK1 autophagy initiation complex. As an effector of Rab1a, C9orf72 controls the Rab1a-dependent trafficking of the ULK1 initiation complex prior to autophagosome formation. In line with this function, C9orf72 depletion in cell lines and primary neurons caused the accumulation of p62/sequestosome-1-positive inclusions. In support of a role in disease pathogenesis, C9ALS/FTD patient-derived iNeurons showed markedly reduced levels of autophagy. In this Commentary we summarise recent findings supporting the key role of C9orf72 in Rab GTPase-dependent regulation of autophagy and discuss autophagy dysregulation as a pathogenic mechanism in ALS/FTD

Dynamical density functional theory for the evaporation of droplets of nanoparticle suspension

We develop a lattice gas model for the drying of droplets of a nanoparticle suspension on a planar surface, using dynamical density functional theory (DDFT) to describe the time evolution of the solvent and nanoparticle density profiles. The DDFT assumes a diffusive dynamics but does not include the advective hydrodynamics of the solvent, so the model is relevant to highly viscous or near to equilibrium systems. Nonetheless, we see an equivalent of the coffee-ring stain effect, but in the present model it occurs for thermodynamic rather the fluid-mechanical reasons. The model incorporates the effect of phase separation and vertical density variations within the droplet and the consequence of these on the nanoparticle deposition pattern on the surface. We show how to include the effect of slip or no-slip at the surface and how this is related to the receding contact angle. We also determine how the equilibrium contact angle depends on the microscopic interaction parameters.Comment: 35 pages, 10 figure

Enzootic geophagia of calves and lambs in Northern Cape and Northwest and the possible role of chronic manganese poisoning

(South African J of Animal Science, 2000, 30, Supplement 1: 105-106

A method for isolating and culturing placental cells from failed early equine pregnancies

Early pregnancy loss occurs in 6–10% of equine pregnancies making it the main cause of reproductive wastage. Despite this, reasons for the losses are known in only 16% of cases. Lack of viable conceptus material has inhibited investigations of many potential genetic and pathological causes. We present a method for isolating and culturing placental cells from failed early equine pregnancies. Trophoblast cells from 18/30 (60%) failed equine pregnancies of gestational ages 14–65 days were successfully cultured in three different media, with the greatest growth achieved for cells cultured in AmnioChrome™ Plus. Genomic DNA of a suitable quality for molecular assays was also isolated from 29/30 of these cases. This method will enable future investigations determining pathologies causing EPL

The UKIDSS Galactic Plane Survey

'The definitive version is available at www.blackwell-synergy.com .' Copyright Blackwell Publishing DOI: 10.1111/j.1365-2966.2008.13924.xThe UKIDSS Galactic Plane Survey (GPS) is one of the five near-infrared Public Legacy Surveys that are being undertaken by the UKIDSS consortium, using the Wide Field Camera on the United Kingdom Infrared TelescopePeer reviewe

Electronic and Structural Properties of a 4d-Perovskite: Cubic Phase of SrZrO3_3

First-principles density functional calculations are performed within the local density approximation to study the electronic properties of SrZrO$_3$, an insulating 4d-perovskite, in its high-temperature cubic phase, above 1400 K, as well as the generic 3d-perovskite SrTiO$_3$, which is also a d^0-insulator and cubic above 105 K, for comparison reasons. The energy bands, density of states and charge density distributions are obtained and a detailed comparison between their band structures is presented. The results are discussed also in terms of the existing data in the literature for both oxides.Comment: 5 pages, 2 figure

Sustainable intensification of agriculture for human prosperity and global sustainability

There is an ongoing debate on what constitutes sustainable intensification of agriculture (SIA). In this paper, we propose that a paradigm for sustainable intensification can be defined and translated into an operational framework for agricultural development. We argue that this paradigm must now be defined—at all scales—in the context of rapidly rising global environmental changes in the Anthropocene, while focusing on eradicating poverty and hunger and contributing to human wellbeing. The criteria and approach we propose, for a paradigm shift towards sustainable intensification of agriculture, integrates the dual and interdependent goals of using sustainable practices to meet rising human needs while contributing to resilience and sustainability of landscapes, the biosphere, and the Earth system. Both of these, in turn, are required to sustain the future viability of agriculture. This paradigm shift aims at repositioning world agriculture from its current role as the world’s single largest driver of global environmental change, to becoming a key contributor of a global transition to a sustainable world within a safe operating space on Earth

United classification of cosmic gamma-ray bursts and their counterparts

United classification of gamma-ray bursts and their counterparts is established on the basis of measured characteristics: photon energy E and emission duration T. The founded interrelation between the mentioned characteristics of events consists in that, as the energy increases, the duration decreases (and vice versa). The given interrelation reflects the nature of the phenomenon and forms the E-T diagram, which represents a natural classification of all observed events in the energy range from 10E9 to 10E-6 eV and in the corresponding interval of durations from about 10E-2 up to 10E8 s. The proposed classification results in the consequences, which are principal for the theory and practical study of the phenomenon.Comment: Keywords Gamma rays: burst

Mass Splitting and Production of Σc0\Sigma_c^0 and Σc++\Sigma_c^{++} Measured in 500GeV500 {GeV} π−−\pi^- -N Interactions

From a sample of $2722 \pm 78$ $\Lambda_c^+$ decaying to the $pK^-\pi^+$ final state, we have observed, in the hadroproduction experiment E791 at Fermilab, $143 \pm 20$ $\Sigma_c^0$ and $122 \pm 18$ $\Sigma_c^{++}$ through their decays to $\Lambda_c^+ \pi^{\pm}$. The mass difference $M(\Sigma_c^0) - M(\Lambda_c^+$) is measured to be $(167.38\pm 0.29\pm 0.15) {MeV}$; for $M(\Sigma_c^{++}) - M(\Lambda_c^+)$, we find $(167.76\pm 0.29\pm0.15) {MeV}$. The rate of $\Lambda_c^+$ production from decays of the $\Sigma_c$ triplet is (22\pm 2\pm 3) {%} of the total $\Lambda_c^+$ production assuming equal rate of production from all three, as measured for $\Sigma_c^0$ and $\Sigma_c^{++}$. We do not observe a statistically significant $\Sigma_c$ baryon-antibaryon production asymmetry. The $x_F$ and $p_t^2$ spectra of $\Lambda_c^+$ from $\Sigma_c$ decays are observed to be similar to those for all $\Lambda_c^+$'s produced.Comment: 15 pages, uuencoded postscript 3 figures uuencoded, tar-compressed fil