Encoding strategies and mechanisms underpinning adaptation to stimulus statistics in the rat barrel cortex

It is well established that, following adaptation, cells adjust their sensitivity to reflect the global stimulus conditions. Two recent studies in guinea pig inferior colliculus (IC, Dean, Harper & McAlpine 2005) and rat barrel cortex (Garcia-Lazaro, Ho, Nair & Schnupp 2007) found that neural stimulus-response functions were displaced laterally in a manner that was dependent on the mean adapting stimulus. However, the direction of gain change, following adaptation to variance, was in contradiction to Information Theory, which predicts a decrease in gain with increased stimulus variance. On further analysis of the experimental data, presented within this thesis, it was revealed that the adaptive gain changes to global stimulus variance were, in fact, in the direction predicted by Information Theory. However, following adaptation to global mean amplitude, neural threshold was displaced to centre the SRF on inputs that were located on the edge of the stimulus distribution. It was found that adaptation scaled neural output such that the relationship between firing rate and local, as opposed to global, differences in stimulus amplitude was maintained; with the majority of cells responding to large differences in stimulus amplitude, on the 40ms scale. A small majority of cells responded to step-size differences, in amplitude, of either direction and were classed as novelty preferring. Adaptation to global mean was replicated in model neuron with spike-rate adaptation and tonic inhibition, which increased with stimulus mean. Adaptation to stimulus variance was replicated in three models 1: By increasing, in proportion to stimulus variance, background, excitatory and inhibitory firing rates in a balanced manner (Chance, Abbott & Reyes 2002), 2: A model of asymmetric synaptic depression (Chelaru & Dragoi 2008) and 3: a model combining non-linear input with synaptic depression. The results presented, within this thesis, demonstrate that neurons change their coding strategies depending upon the global levels of mean and variance within the sensory input. Under low noise conditions, neurons act as deviation detectors, i.e. are primed to respond to large changes in the stimulus on the tens of millisecond; however, under conditions of increased noise switch their encoding strategy in order to compute the full range of the stimulus distribution through adjusting neural gain.EPSR

Risk of Female Breast Cancer in Lifetime Alcohol Consumption in a Community of Trans Nzoia County, Kenya

Consumption of alcohol increases the risk of Breast cancer as revealed in many studies. In 2008, cancer killed 7.6 million people worldwide. In Kenya, one in every eight women had the disease with 2, 2000 deaths in 2011. A matched hospital case control study was carried out to estimate the risk of breast cancer among drinkers and nondrinkers in TransNzoia County. One hundred and fifty participants, 50 cases and 100 controls were included and matched for age (±2) years and residence (1 case to 2 controls). A questionnaire was administered to participants identified from breast cancer registers. Data was collected and analyzed using SPSS version 20 for descriptive statistics. Chi square was used to test association of alcohol and breast cancer. Alcohol measured as ever versus never with OR of 1.558 (p=0.044, 95% CI). Odds ratios > 0-5 and 5 grams of use per day among drinkers and nondrinkers being 1.8 (p=0.02, 95% CI) and 1.0 (p=0.06, 95% CI) respectively. The OR for the time when an individual began drinking was 1.2 (p=0.06 95% CI) but the risk increased with the period consumed 3.2 (P=0.01, 95% CI).This study demonstrated an association between alcohol consumption and breast cancer among women alcohol drinkers and non drinker. Keywords: Alcohol, Breast cancer, Case control stud

Structural basis of meiotic chromosome synaptic elongation through hierarchical fibrous assembly of SYCE2-TEX12

The synaptonemal complex (SC) is a supramolecular protein assembly that mediates synapsis between homologous chromosomes during meiosis. SC elongation along the chromosome length (up to 24 μm) depends on its midline α-fibrous component SYCE2-TEX12. Here, we report X-ray crystal structures of human SYCE2-TEX12 as an individual building-block and upon assembly within a fibrous lattice. We combine these structures with mutagenesis, biophysics and electron microscopy to reveal the hierarchical mechanism of SYCE2-TEX12 fibre assembly. SYCE2-TEX12’s building-blocks are 2:2 coiled-coils which dimerise into 4:4 hetero-oligomers and interact end-to-end and laterally to form 10-nm fibres, which intertwine within 40-nm bundled micrometre-long fibres that define the SC’s midline structure. This assembly mechanism bears striking resemblance with intermediate filament proteins vimentin, lamin and keratin. Thus, SYCE2-TEX12 exhibits behaviour typical of cytoskeletal proteins to provide an α-fibrous SC backbone that structurally underpins synaptic elongation along meiotic chromosomes

Gendered Perspectives of Research Activity Symposium Report 2016

On the 15th-16th June 2016, The Forum for Research into Equality and Diversity (University of Chester), in partnership with the Centre for Diversity Policy Research and Practice (Oxford Brookes University), hosted the Gendered perspectives of research activity Symposium at the University of Chester, Chester, UK. The Symposium brought 30 representatives and researchers from across Higher Education in the UK, Europe and beyond together with sector bodies and policy drivers in order to workshop the gendered barriers and obstacles to research activity in Higher Education. This report provides a summary of the discussions and findings, as well as the key ideas, themes, questions, challenges and conclusions that came out of the two-day discussion. A further goal of the report is to seek to articulate the participants’ deliberations and considerations in order to contribute to the development of an effective strategy in the UK and beyond seeking to break down gendered barriers in relation to research activity

Heparin-stabilised iron oxide for MR applications : a relaxometric study

Superparamagnetic nanoparticles have strong potential in biomedicine and have seen application as clinical magnetic resonance imaging (MRI) contrast agents, though their popularity has plummeted in recent years, due to low efficacy and safety concerns, including haemagglutination. Using an in situ procedure, we have prepared colloids of magnetite nanoparticles, exploiting the clinically approved anti-coagulant, heparin, as a templating stabiliser. These colloids, stable over several days, produce exceptionally strong MRI contrast capabilities particularly at low fields, as demonstrated by relaxometric investigations using nuclear magnetic resonance dispersion (NMRD) techniques and single field r1 and r2 relaxation measurements. This behaviour is due to interparticle interactions, enhanced by the templating effect of heparin, resulting in strong magnetic anisotropic behaviour which closely maps particle size. The nanocomposites have also reliably prevented protein-adsorption triggered thrombosis typical of non-stabilised nanoparticles, showing great potential for in vivo MRI diagnostics

The effects of PPO activity on the proteome of ingested red clover and implications for improving the nutrition of grazing cattle

AbstractIncreasing the rumen-stable protein content of feed would lead to improved nitrogen utilisation in cattle, and less nitrogenous waste. Red clover (Trifolium pratense L.) is a high protein ruminant feed containing high polyphenol oxidase (PPO) activity. PPO mediated protein-quinone binding has been linked to protecting plant proteins from proteolysis. To explore the mechanism underlying the effect of PPO on protein protection in fresh forage feeds, proteomic components of feed down-boli produced from wild-type red clover and a low PPO mutant, at point of ingestion and after 4h in vitro incubation with rumen inoculum were analysed. Significant differences in proteomic profiles between wild-type and mutant red clover were determined after 4h incubation, with over 50% less spots in mutant than wild-type proteomes, indicating decreased proteolysis in the latter. Protein identifications revealed preferentially retained proteins localised within the chloroplast, suggesting that PPO mediated protection in the wild-type operates due to the proximity of target proteins to the enzyme and substrates, either diffusing into this compartment from the vacuole or are present in the chloroplast. This increased understanding of protein targets of PPO indicates that wider exploitation of the trait could contribute to increased protein use efficiency in grazing cattle.Biological significanceOne of the main challenges for sustainable livestock farming is improving capture of dietary nitrogen by ruminants. Typically up to 70% of ingested protein-N is excreted representing a loss of productivity potential and a serious environmental problem in terms of nitrogenous pollution of lands and water. Identification of key characteristics of rumen-protected protein will deliver target traits for selection in forage breeding programmes. The chloroplastic enzyme PPO catalyzes the oxidation of phenols to quinones, which react with protein. Little is currently known about the intracellular protein targets of the products of PPO activity or the mechanism underlying protein complexing, including whether there is any specificity to the reaction. Here we have determined significant differences in the proteomes of freshly ingested down boli corresponding to the presence or absence of active PPO. These results show that in the presence of PPO the forage protein is less amenable to proteolysis and provide the novel information that the protected proteins are putatively chloroplastically located. These data also contribute to a growing evidence base that a chloroplastic PPO substrate exists in red clover in addition to the currently known vacuolar substrates

Lateral habenula regulates temporal pattern organization of rat exploratory behavior and acute nicotine-induced anxiety in hole board

Nicotine is one of the most addictive drugs of abuse. Tobacco smoking is a major cause of many health problems worldwide, and is the first preventable cause of death. Several findings show that nicotine exerts significant aversive as well as the well-known rewarding motivational effects. Less certain is the anatomical substrate that mediates or enables nicotine aversion. Here we have focused on nicotine-induced anxiety-like behavior in unlesioned and lesioned lateral habenula (LHb) rats. Firstly, we showed that acute nicotine induces anxiogenic effects in rats at the doses investigated (0.1, 0.5, and 1.0 mg/kg, i.p.) as measured by the hole-board apparatus, and manifested in behaviors such as decreased rearing and head-dipping and increased grooming. No changes in locomotor behavior were observed at any of the nicotine doses given. T-pattern analysis of the behavioral outcomes revealed a drastic reduction and disruption of complex behavioral patterns induced by all three nicotine doses, with the maximum effect for 1 mg/kg. Lesion of the LHb induced a significant anxiogenic effect, reduced the mean occurrences of T-patterns detected, and strikingly reverted the nicotine-induced anxiety to an anxiolytic effect. We suggest that LHb is critically involved in emotional behavior states and in nicotine-induced anxiety, most likely through modulating serotonergic/dopaminergic nuclei.peer-reviewe