The axonal transcript Tp53inp2 mediates the development of the sympathetic nervous system

Nerve Growth Factor (NGF) is a neurotrophin essential for the survival of sympathetic and sensory neurons. Localisation of mRNA in axons of NGF- dependent neurons supports growth and maintains axon integrity, however how localised transcripts regulates most axonal functions remains unknown. To characterise the 3’UTR of transcripts localised in sympathetic neuron axons, we performed a 3’end RNA-Seq on mRNA isolated from either axons or cell bodies of neurons cultured in compartmentalised chambers. We identified Tp53inp2 as the most abundant transcripts in axons, accounting for almost one third of the reads. Interestingly, despite the abundance of its RNA, the protein for Tp53inp2 is not detectable within axons of sympathetic neurons. We observe that Tp53inp2 is not actively translated, held in a strictly repressed state mediated by its UTRs. Deletion of Tp53inp2 in sympathetic neurons in vivo and in vitro affects both cell survival and axon growth, suggesting a critical role for Tp53inp2 in neuronal development, despite the lack of translation. That this phenotype can be rescued by transfecting a non- translatable form of the transcript, suggests that instead Tp53inp2 acts as an atypical non-coding RNA, whose function is mediated through interaction with the NGF receptor TrkA. We conclude that Tp53inp2 mRNA regulates sympathetic neuron survival and axon growth in a coding-independent manner by interacting with TrkA receptor and enhancing axonal NGF- dependent signalling

Space, Time and Change: Investigations of Soil Bacterial Diversity and its Drivers in the Mongolian Steppe

Microorganisms are the most diverse life forms on Earth and are the foundation of any ecosystem. As estimates of microbial diversity rapidly increase with advances in sequencing technologies, so does the need to identify the drivers of such overwhelming diversity. This is particularly true in soil—the most biodiverse habitat on the planet and the key component of terrestrial ecosystems, which are being altered by changes in climate and land use. In order to understand the potential consequences of these changes, we conducted a multi-year experiment to test the effects of global change on soil bacterial communities in northern Mongolia, a region where air temperatures have increased by 1.7 °C since 1960, and traditional land-use patterns are shifting with socio-economic changes. Set in the semi-arid steppe, our global change experiment allowed as to evaluate responses to multiple stressors at once over a range of spatial and temporal scales. Over the course of three years, we investigated soil bacterial diversity at two positions (upper and lower) along a south-facing slope and documented the response of these communities to three experimental treatments: a Watering experiment (upper slope only), a Grazing experiment (lower slope only) and a Climate Manipulation experiment (both slopes). We measured diversity using both the number and abundance of distinct bacterial taxa in a soil sample and then correlated these findings with corresponding measurements of biotic and abiotic factors, which included plant richness and biomass, as well as plant available N, pH, soil moisture and soil temperature. We found that temporal and spatial factors explained much of the variation in the bacterial communities. After accounting for temporal and spatial variation, soil moisture content was the primary driver structuring bacterial diversity across the landscape and within experimental treatments. In particular, the effects of climate change on these semi-arid grasslands may act primarily through soil moisture content. Concomitant shifts in key members of the bacterial community may ultimately be bioindicators of a drier future for Mongolia

A non-toxic concentration of telomerase inhibitor BIBR1532 fails to reduce tert expression in a feeder-free induced pluripotent stem cell model of human motor neurogenesis

Several studies have shown that human induced pluripotent stem cell (iPSC)-derivatives are essentially fetal in terms of their maturational status. Inducing ageing in iPSC-motor neuron (MN) models of amyotrophic lateral sclerosis (ALS) has the potential to capture pathology with higher fidelity and consequently improve translational success. We show here that the telomerase inhibitor BIBR1532, hypothesised to recapitulate the telomere attrition hallmark of ageing in iPSC-MNs, was in fact cytotoxic to feeder-free iPSCs when used at doses previously shown to be effective in iPSCs grown on a layer of mouse embryonic fibroblasts. Toxicity in feeder-free cultures was not rescued by co-treatment with Rho Kinase (ROCK) inhibitor (Y-27632). Moreover, the highest concentration of BIBR1532 compatible with continued iPSC culture proved insufficient to induce detectable telomerase inhibition. Our data suggest that direct toxicity by BIBR1532 is the most likely cause of iPSC death observed, and that culture methods may influence enhanced toxicity. Therefore, recapitulation of ageing hallmarks in iPSC-MNs, which might reveal novel and relevant human disease targets in ALS, is not achievable in feeder-free culture through the use of this small molecule telomerase inhibitor

Investigations into the dehulling of pigeon peas and mung beans

Non-Peer ReviewedLegumes provide a rich source of protein for animal and human consumption. They also supply a substantial amount of minerals and vitamins. Currently the world production of legumes is estimated to be 57.5 million metric tonnes. After harvest, pigeon peas (Cajanus cajan L.) and mung beans (Vigna radiata L.) are dehulled to improve cooking and nutritional qualities and to reduce cooking time. Pigeon peas and mung beans can be consumed as dehulled splits, whole, canned, boiled, roasted or ground into flour to make a variety of desserts, snacks and main dishes. These legumes are hard to dehull because of the presence of mucilages and gums which form a strong bond between the hulls and the cotyledons. To improve the dehulling characteristics of these legumes, a tangential abrasive dehulling device (TADD) was used to investigate their dehulling characteristics. Different treatments consisting of heating, soaking and heating, steaming and drying in addition to tempering were investigated. The control samples yielded less dehulled kernels and generated more fines for both pigeon peas and mung beans. Steaming at 98.0oC for 10 min and heating at 120oC for 10 min followed by tempering for 24 h yielded more dehulled kernels for both pigeon peas and mung beans compared to the other treatments

Bad Judgement: An Essay in Vice Epistemology

This thesis provides an account of the nature of intellectual vice. An intellectual vice is an aspect of someone’s character that makes them a bad intellectual agent, or bad knower. Previous accounts of the intellectual vices have tended to identify them with either the disposition to have bad epistemic motivations, or the disposition to produce bad epistemic effects. I argue for a new view that can overcome the difficulties faced by both of these accounts. According to this view, there are two distinct forms of intellectual vice: vices that involve motivations towards bad epistemic ends, and vices that involve some entrenched pattern of bad judgement