Development and application of experimental software for a 21st century occupational psychophysics research toolbox

In the fields of ergonomics and biomechanics, the use of bio-instrumentation for the purpose of analysing work and reducing work related muskuloskeletal disorders for injury prevention has become a new norm. It is equally important to employ these instruments in ecologically-valid experimental work tasks that use relevant and controllable manipulations of occupational psychophysics. The current thesis attempts to begin design and validation of components for a 21st century occupational psychophysics toolbox that couples relevant bio-instrumentation hardware (vision tracking, motion capture, and force platforms) with custom Matlab based experimental software capable of image processing, assessment of full body kinematics, and analysis of ground reaction force kinetics to study the perceptions and actions at work tasks. I investigated the coupling between visual attention and cueing, pre-handling perceptions, and manual material handling actions, with the ultimate goal of understanding occupational behaviours and preventing injurious occupational behaviours

Studying time and disease using two different cell line models

The scientific approach of modelling uses manipulation of simpler systems in order to understand aspects of more complex ones. This method is extensively used to understand the biology of complex organisms through studying representative cells artificially cultured in vitro. The work presented here uses in vitro cell line model systems to investigate two aspects of cell biology: the coupling between the circadian clock and cell cycle, and the role BEST1 protein localisation in Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC) disease. 1. The circadian clock is an internal time-keeping mechanism that allows organisms to anticipate daily environmental changes. This mechanism operates at an organismal level as well as being intrinsic to each cell through oscillating genetic negative feedback loops. One of the many cellular functions that has been found to be regulated by the circadian clock is cell cycle progression. However, it is still an outstanding question as to whether the circadian clock drives cell cycle progression actively or whether it passively gates particular cell cycle transitions to certain times of day. In the first experimental chapter zebrafish (Danio rerio) cell lines are used to investigate the relationship between the circadian clock mechanism and cell cycle behaviour. This relationship is examined at a population and single cell level to address the question as to the effect of varying the circadian clock period on the timing and average length of the cell cycle output. It is demonstrated that altering the period length of the circadian oscillation affects the timing of cell cycle progression, but not the length of the cell cycle or its phases. This provides strong evidence in support of the gating theory of circadian regulation of the cell cycle. In the second experimental chapter the effects of cell density on this coupling between the circadian clock and cell cycle are considered. It is shown that this coupling is not observed in cell populations that are at low density and that are highly proliferative, providing insight into how the assay conditions used in previously published work on this coupling could be contributing to conflicting results. 2. Bestrophinopathies are a group of retinal dystrophic diseases that share a common cause: mutations in the Bestrophin-1 (BEST1) gene, expressed in the retinal pigmented epithelium (RPE). Epithelial cell models, particularly derived from the kidney, have been used as models to study the function and dysfunction of the BEST1 protein in RPE cells through overexpression of the BEST1 gene. The results of these studies have suggested that in ADVIRC disease mutant BEST1 shows mis-splicing defects. However, this has not been supported by work using induced 5 pluripotent stem cell-derived RPE (iPS-RPE) cell models, raising the question as to whether the model cells used are providing accurate insights into the actual properties of native RPE. In this section human epithelial cell lines are used to investigate the relationship between specific point mutations in the gene Bestrophin1 and the localisation within the cell of the resulting protein product. It is shown that the localisation of an ADVIRC mutant BEST1 protein depends partially on the cell line used to express it, as well as the cell culture conditions used. This suggests that the use of non-RPE model cell lines for investigating Bestrophin-1 may be leading to conclusions that do not apply in vivo

The biology of the sheep blowflies Lucilia caesar and Lucilia sericata (Diptera: Calliphoridae) in relation to their control by trapping

This study was an investigation of aspects of the biology of sheep blowflies in relation to their control by trapping. In order to determine the species composition of blowfly larvae in ovine analysis cases in Scotland, samples of dipteran larvae were collected from live sheep throughout Scotland, reared in the laboratory, and identified once adult flies emerged. Lucilia sericata was found in 77% of samples, and other species in 49%. The most common alternative species were L. caesar, which occurred in 31% of samples, and Protophormia terraenovae, which occurred in 18%. Three other calliphorid species, Calliphora vomitoria, C. vicina, and L. illustris, and the muscid Muscina pabulorum were also found. The proportion of samples containing alternative species was significantly lower in eastern Scotland than in western Scotland. Significantly higher proportions of samples containing alternative species were collected at altitudes of 200 metres and above; from sheep of hills breeds; from rough grazing conditions and moorland; in the absence of trees; and in the presence of bracken. The importance of Lucilia caesar in myiasis cases in Scotland having been confirmed, the capture of this species was investigated using four different trap designs, all baited with beef liver and sodium sulphide solution. A horizontal target coated with a polybutene-based adhesive performed significantly better than a similar vertical target. Both of these adhesive designs demonstrated significantly higher catches of both male and female flies than a water trap and a commercially-produced enclosed trap, Fly City (P<0.05). Subsequent investigations showed that catches on adhesive targets were significantly greater at a height of 0.2m than at ground level (P<0.05), 0.6m, or 0.8m (P<0.01). Catches were also increased on larger targets (P<0.05), but there was no significant increase in catch per unit area with target size

Aerospace medicine and biology: A cumulative index to the continuing bibliography of the 1973 issues

A cumulative index to the abstracts contained in Supplements 112 through 123 of Aerospace Medicine and Biology A Continuing Bibliography is presented. It includes three indexes: subject, personal author, and corporate source

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40

Antioxidant and DPPH-Scavenging Activities of Compounds and Ethanolic Extract of the Leaf and Twigs of Caesalpinia bonduc L. Roxb.

Antioxidant effects of ethanolic extract of Caesalpinia bonduc and its isolated bioactive compounds were evaluated in vitro. The compounds included two new cassanediterpenes, 1α,7α-diacetoxy-5α,6β-dihydroxyl-cass-14(15)-epoxy-16,12-olide (1)and 12α-ethoxyl-1α,14β-diacetoxy-2α,5α-dihydroxyl cass-13(15)-en-16,12-olide(2); and others, bonducellin (3), 7,4’-dihydroxy-3,11-dehydrohomoisoflavanone (4), daucosterol (5), luteolin (6), quercetin-3-methyl ether (7) and kaempferol-3-O-α-L-rhamnopyranosyl-(1Ç2)-β-D-xylopyranoside (8). The antioxidant properties of the extract and compounds were assessed by the measurement of the total phenolic content, ascorbic acid content, total antioxidant capacity and 1-1-diphenyl-2-picryl hydrazyl (DPPH) and hydrogen peroxide radicals scavenging activities.Compounds 3, 6, 7 and ethanolic extract had DPPH scavenging activities with IC50 values of 186, 75, 17 and 102 μg/ml respectively when compared to vitamin C with 15 μg/ml. On the other hand, no significant results were obtained for hydrogen peroxide radical. In addition, compound 7 has the highest phenolic content of 0.81±0.01 mg/ml of gallic acid equivalent while compound 8 showed the highest total antioxidant capacity with 254.31±3.54 and 199.82±2.78 μg/ml gallic and ascorbic acid equivalent respectively. Compound 4 and ethanolic extract showed a high ascorbic acid content of 2.26±0.01 and 6.78±0.03 mg/ml respectively.The results obtained showed the antioxidant activity of the ethanolic extract of C. bonduc and deduced that this activity was mediated by its isolated bioactive compounds