The effect of sterilization on biological, organic geochemical and morphological information in natural samples

The loss of biological, organic geochemical, and morphological science information that may occur should a Mars surface sample be sterilized prior to return to earth is examined. Results of experimental studies are summarized

Productivity and income of New Zealand agriculture 1921-67

Supplement to Research report (Lincoln College (University of Canterbury). Agricultural Economics Research Unit) ; no. 59. Data revised back to 1962/63 in same series / by S.M. Hadfield.This discussion paper updates the data on income and productivity for the New Zealand agricultural sector for the period 1921-1967 in the AERU research report titled: Productivity and income of New Zealand agriculture, 1921-67

Energy-momentum diffusion from spacetime discreteness

We study potentially observable consequences of spatiotemporal discreteness for the motion of massive and massless particles. First we describe some simple intrinsic models for the motion of a massive point particle in a fixed causal set background. At large scales, the microscopic swerves induced by the underlying atomicity manifest themselves as a Lorentz invariant diffusion in energy-momentum governed by a single phenomenological parameter, and we derive in full the corresponding diffusion equation. Inspired by the simplicity of the result, we then derive the most general Lorentz invariant diffusion equation for a massless particle, which turns out to contain two phenomenological parameters describing, respectively, diffusion and drift in the particle's energy. The particles do not leave the light cone however: their worldlines continue to be null geodesics. Finally, we deduce bounds on the drift and diffusion constants for photons from the blackbody nature of the spectrum of the cosmic microwave background radiation.Comment: 13 pages, 4 figures, corrected minor typos and updated to match published versio

Subcellular localisation modulates ubiquitylation and degradation of Ascl1.

The proneural transcription factor Ascl1 is a master regulator of neurogenesis, coordinating proliferation and differentiation in the central nervous system. While its expression is well characterised, post-translational regulation is much less well understood. Here we demonstrate that a population of chromatin-bound Ascl1 can be found associated with short chains of ubiquitin while cytoplasmic Ascl1 harbours much longer ubiquitin chains. Only cytoplasmic ubiquitylation targets Ascl1 for destruction, which occurs by conjugation of ubiquitin to lysines in the basic helix-loop-helix domain of Ascl1 and requires the E3 ligase Huwe1. In contrast, chromatin-bound Ascl1 associated with short ubiquitin-chains, which can occur on lysines within the N-terminal region or the bHLH domain and is not mediated by Huwe1, is not targeted for ubiquitin-mediated destruction. We therefore offer further insights into post-translational regulation of Ascl1, highlighting complex regulation of ubiquitylation and degradation in the cytoplasm and on chromatin.This work was funded by MRC Research Grants (MR/K018329/1 and MR/L021129/1) and received core support from Wellcome Trust and MRC Cambridge Stem Cell Institute

The developmental origin of brain tumours: a cellular and molecular framework.

The development of the nervous system relies on the coordinated regulation of stem cell self-renewal and differentiation. The discovery that brain tumours contain a subpopulation of cells with stem/progenitor characteristics that are capable of sustaining tumour growth has emphasized the importance of understanding the cellular dynamics and the molecular pathways regulating neural stem cell behaviour. By focusing on recent work on glioma and medulloblastoma, we review how lineage tracing contributed to dissecting the embryonic origin of brain tumours and how lineage-specific mechanisms that regulate stem cell behaviour in the embryo may be subverted in cancer to achieve uncontrolled proliferation and suppression of differentiation.This work was funded by MRC Research Grants (MR/K018329/1 (AP/RA), MR/L021129/1 (AP) and Neuroblastoma UK (AP), a Wellcome Trust Senior Investigator Award (098357/Z/12/Z (BDS/RA) and received core support from Wellcome Trust and MRC Cambridge Stem Cell Institute and the Cancer Research UK Cambridge Institute. We are grateful to members of the Philpott and Simons labs for useful discussions

Applications of omega-3 polyunsaturated fatty acid supplementation for sport performance

Omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation has recently been proposed as an ergogenic aid for athletes. This claim is primarily based on mechanistic evidence that n-3PUFA’s exert anti-inflammatory properties and act to change the functional capacity of the muscle cell by modifying the membrane fluidity of proteins and lipids within the cell membrane. In this review, we critically evaluate the scientific literature that examines the efficacy of n-3PUFA supplementation to improve athlete performance within the context of promoting muscle adaptation, energy metabolism, muscle recovery and injury prevention (e.g. muscle loss during immobilisation, or concussion). These findings have applications to athletes competing in strength/power-, endurance- and team-, based sports. Based on available information, there is some scientific evidence that n-3PUFA supplementation may improve endurance capacity by reducing the oxygen cost of exercise. Moreover, several studies report a benefit of n-3PUFA supplementation in promoting recovery from eccentric-based muscle damaging exercise. In contrast, there is insufficient evidence from studies in athletic populations to support the claim that n-3PUFA supplementation facilitates muscle growth during resistance training or preserves muscle mass during catabolic scenarios such as energy restriction or immobilisation. Moving forward, there remains ample scope to investigate context-specific applications of n-3PUFA supplementation for sport performance

Multi-site phosphorylation controls the neurogenic and myogenic activity of E47.

The superfamily of basic-Helix-Loop-Helix (bHLH) transcription factors influence cell fate in all three embryonic germ layers, and the tissue-specific class II factors have received prominent attention for their potent ability to direct differentiation during development and in cellular reprogramming. The activity of many class II bHLH proteins driving differentiation, and the inhibitory class VI bHLH factor Hes1, is controlled by phosphorylation on multiple sites by Cyclin-dependent kinases (Cdks). As class II proteins are generally thought to be active through hetero-dimerisation with the ubiquitously expressed class I E proteins, regulation of class I transcription factors such as E47 may influence the activity of multiple tissue-specific bHLH proteins. Using differentiation of nerve and muscle in Xenopus frog embryos as a model system, we set out to explore whether with the ubiquitously expressed class I E protein E47 that hetero-dimerises with Class II bHLHs to control their activity, is also regulated by multi-site phosphorylation. We demonstrate that E47 can be readily phosphorylated by Cdks on multiple sites in vitro, while ectopically-expressed E47 exists in multiple phosphorylated forms in Xenopus embryos. Preventing multi-site phosphorylation using a phospho-mutant version of E47 enhances the neurogenic and myogenic activity of three different class II bHLH reprogramming factors, and also when E47 acts in hetero-dimerisation with endogenous proteins. Mechanistically, unlike phospho-regulation of class II bHLH factors, we find that preventing phosphorylation of E47 increases the amount of chromatin-bound E47 protein but without affecting its overall protein stability. Thus, multi-site phosphorylation is a conserved regulatory mechanism across the bHLH superfamily that can be manipulated to enhance cellular differentiation.This work was supported by Medical Research Council Research Grants MR/L021129/1 and MR/K018329 and AP receives core funding from Wellcome and MRC at the Wellcome-MRC Cambridge Stem Cell Institute. LH is supported by a Peterhouse Research Fellowship