Novel Tetrahedral Human Phantoms for Space Radiation Dose Assessment

Space radiation remains one of the primary hazards to spaceflight crews. The unique nature of the intravehicular radiation spectrum makes prediction of biological outcomes difficult, with computational simulation-based efforts stymied by lack of computational resources or accurate modeling capabilities. Recent advancements in both Monte Carlo simulations and computational human phantom developments have allowed for complex radiation simulations and dosimetric calculations to be performed for numerous applications. In this work, advanced tetrahedral-type human phantoms were exposed to a simulated spectrum of particles equivalent to a single days exposure in the International Space Station in Low Earth Orbit. 3D Monte Carlo techniques were used to produce and simulate the radiation spectra. Organ absorbed dose, average energy deposition, and the whole-body integral dose was determined for a male and female phantom. Results were then extrapolated for two long-term scenarios: a 6-9 month mission on the International Space Station and a 3-year mission to Mars. The whole-body integral dose for the male and female models were found to be 0.2985 +- 0.0002 mGy/day 0.3050 +- 0.0002 mGy/day, respectively, which is within 10% of recorded dose values from the International Space Station. This work presents a novel approach to assess absorbed dose from space-like radiation fields using high-fidelity computational phantoms, highlighting the utility of complex models for space radiation research.Comment: 10 pages, 3 figures, 2 table

Translational Regulation of Utrophin by miRNAs

Background Utrophin is the autosomal homolog of dystrophin, the product of the Duchenne Muscular Dystrophy (DMD) locus. Its regulation is of therapeutic interest as its overexpression can compensate for dystrophin's absence in animal models of DMD. The tissue distribution and transcriptional regulation of utrophin have been characterized extensively, and more recently translational control mechanisms that may underlie its complex expression patterns have begun to be identified. Methodology/Principal Findings Using a variety of bioinformatic, molecular and cell biology techniques, we show that the muscle isoform utrophin-A is predominantly suppressed at the translational level in C2C12 myoblasts. The extent of translational inhibition is estimated to be ~99% in C2C12 cells and is mediated by both the 5′- and 3′-UTRs of the utrophin-A mRNA. In this study we identify five miRNAs (let-7c, miR-150, miR-196b, miR-296-5p, miR-133b) that mediate the repression, and confirm repression by the previously identified miR-206. We demonstrate that this translational repression can be overcome by blocking the actions of miRNAs, resulting in an increased level of utrophin protein in C2C12 cells. Conclusions/Significance The present study has identified key inhibitory mechanisms featuring miRNAs that regulate utrophin expression, and demonstrated that these mechanisms can be targeted to increase endogenous utrophin expression in cultured muscle cells. We suggest that miRNA-mediated inhibitory mechanisms could be targeted by methods similar to those described here as a novel strategy to increase utrophin expression as a therapy for DMD

Defining novel functions for cerebrospinal fluid in ALS pathophysiology

Despite the considerable progress made towards understanding ALS pathophysiology, several key features of ALS remain unexplained, from its aetiology to its epidemiological aspects. The glymphatic system, which has recently been recognised as a major clearance pathway for the brain, has received considerable attention in several neurological conditions, particularly Alzheimer's disease. Its significance in ALS has, however, been little addressed. This perspective article therefore aims to assess the possibility of CSF contribution in ALS by considering various lines of evidence, including the abnormal composition of ALS-CSF, its toxicity and the evidence for impaired CSF dynamics in ALS patients. We also describe a potential role for CSF circulation in determining disease spread as well as the importance of CSF dynamics in ALS neurotherapeutics. We propose that a CSF model could potentially offer additional avenues to explore currently unexplained features of ALS, ultimately leading to new treatment options for people with ALS.</p

Wildlife crime : The problems of enforcement

Environmental and wildlife crime appear recently to be benefitting from an increasing profile amongst those agencies tasked with their control, as well as receiving growing criminological attention. Despite this, those with responsibilities in this area report that it remains marginalised, receiving limited resources and suffering from a lack of political impetus to push such problems higher up the agenda. This is particularly so for those agencies, such as the police, that may be seen to have many more pressing objectives. This discussion paper considers the problems of relying on an enforcement approach to controlling such offences, taking, as an example, those activities that may be termed ‘wildlife crime’, focusing on the situation in England and Wales. Firstly, the legislative framework that criminalises harm or exploitation of wildlife is presented, alongside the main enforcement methods used. Next, the problems facing an enforcement approach are critically considered, the key issues being: under-resourcing and marginalisation, the large ‘dark figure’ of wildlife crime, the possibility of corruption, the lack of seriousness with which such crimes are viewed, and the lack of deterrent effect. Finally, responses to the problems of enforcement are presented, categorised as either methods to improve enforcement or, as the author advocates, methods which are alternatives to enforcement (such as adopting a crime prevention approach). The paper concludes with suggestions for future research in this field