Do pioneer cells exist?

Most mathematical models of collective cell spreading make the standard assumption that the cell diffusivity and cell proliferation rate are constants that do not vary across the cell population. Here we present a combined experimental and mathematical modeling study which aims to investigate how differences in the cell diffusivity and cell proliferation rate amongst a population of cells can impact the collective behavior of the population. We present data from a three–dimensional transwell migration assay which suggests that the cell diffusivity of some groups of cells within the population can be as much as three times higher than the cell diffusivity of other groups of cells within the population. Using this information, we explore the consequences of explicitly representing this variability in a mathematical model of a scratch assay where we treat the total population of cells as two, possibly distinct, subpopulations. Our results show that when we make the standard assumption that all cells within the population behave identically we observe the formation of moving fronts of cells where both subpopulations are well–mixed and indistinguishable. In contrast, when we consider the same system where the two subpopulations are distinct, we observe a very different outcome where the spreading population becomes spatially organized with the more motile subpopulation dominating at the leading edge while the less motile subpopulation is practically absent from the leading edge. These modeling predictions are consistent with previous experimental observations and suggest that standard mathematical approaches, where we treat the cell diffusivity and cell proliferation rate as constants, might not be appropriate.

Hemi-field and full-field form-deprivation induce timing changes in multifocal ERG responses in chick

Purpose: In animal models hemi-field deprivation results in localised, graded vitreous chamber elongation and presumably deprivation induced localised changes in retinal processing. The aim of this research was to determine if there are variations in ERG responses across the retina in normal chick eyes and to examine the effect of hemi-field and full-field deprivation on ERG responses across the retina and at earlier times than have previously been examined electrophysiologically. Methods: Chicks were either untreated, wore monocular full-diffusers or half-diffusers (depriving nasal retina) (n = 6-8 each group) from day 8. mfERG responses were measured using the VERIS mfERG system across the central 18.2º× 16.7º (H × V) field. The stimulus consisted of 61 unscaled hexagons with each hexagon modulated between black and white according to a pseudorandom binary m-sequence. The mfERG was measured on day 12 in untreated chicks, following 4 days of hemi-field diffuser wear, and 2, 48 and 96 h after application of full-field diffusers. Results: The ERG response of untreated chick eyes did not vary across the measured field; there was no effect of retinal location on the N1-P1 amplitude (p = 0.108) or on P1 implicit time (p > 0.05). This finding is consistent with retinal ganglion cell density of the chick varying by only a factor of two across the entire retina. Half-diffusers produced a ramped retina and a graded effect of negative lens correction (p < 0.0001); changes in retinal processing were localized. The untreated retina showed increasing complexity of the ERG waveform with development; form-deprivation prevented the increasing complexity of the response at the 2, 48 and 96 h measurement times and produced alterations in response timing. Conclusions: Form-deprivation and its concomitant loss of image contrast and high spatial frequency images prevented development of the ERG responses, consistent with a disruption of development of retinal feedback systems. The characterisation of ERG responses in normal and deprived chick eyes across the retina allows the assessment of concurrent visual and retinal manipulations in this model. (Ophthalmic & Physiological Optics © 2013 The College of Optometrists.)

Aboriginality and the Northern Territory intervention

Architects and supporters of the Northern Territory Emergency Response (the intervention) mobilised a range of ideas about Aboriginality to introduce and justify the policy program. These representations link Aboriginality to abuse of Aboriginal children, establishing a debate about the nature and future of Aboriginality in a context that limits the discursive authority of Aboriginal people. Aboriginality is represented as savage and in need of settler-imposed control, and also primitive and in need of development. These constructions understand Aboriginality temporally, situating it in the past but providing moral justification for coercing Indigenous people into the settler present. Aboriginality is also constructed spatially in this discourse, with prescribed communities framed as the location of both authentic Aboriginality and of threatening disorder. The intervention is framed as extending settler authority over this troubling terrain, containing and redeeming Aboriginality through inclusion in the settler nation’s moral order.

Aboriginality and the Northern Territory intervention

This thesis examines the construction of Aboriginality in recent public policy reasoning through identifying representations deployed by architects and supporters of the Commonwealth’s 2007 Northern Territory Emergency Response (the intervention). Debate about the Northern Territory intervention was explicitly situated in relation to a range of ideas about appropriate Government policy towards Indigenous people, and particularly about the nature, role, status, value and future of Aboriginality and of Aboriginal people and Torres Strait Islanders. This project involves analysis of constructions of Aboriginality deployed in texts created and circulated to explain and justify the policy program. The aim of the project is to identify the ideas about Aboriginality deployed by the intervention’s architects and supporters, and to examine the effects and implications of these discourses for political relationships between Indigenous people and settlers in Australia. This thesis will argue that advocates of the Northern Territory intervention construct Aboriginality in a range of important ways that reassert and reinforce the legitimacy of the settler colonial order and the project of Australian nationhood, and operate to limit Aboriginal claims. Specifically, it is argued that in linking Aboriginality to the abuse of Aboriginal children, the intervention’s advocates and supporters establish a political debate about the nature and future of Aboriginality within a discursive terrain in which the authority and perspectives of Indigenous people are problematised. Aboriginality is constructed in this process as both temporally and spatially separated from settler society, and in need of coercive integration into mainstream economic and political arrangements. Aboriginality is depicted by settler advocates of intervention as an anachronism, with Aboriginal people and cultures understood as primitive and/or savage precursors to settlers who are represented as modern and civilised. As such, the communities seen as the authentic home or location of Aboriginality represent a threat to Aboriginal children as well as to settlers. These constructions function to obscure the violence of the settler order, provide justification or moral rehabilitation for the colonising project, and reassert the sovereignty of the settler state. The resolution offered by the intervention’s advocates is a performance or enactment of settler sovereignty, representing a claim over and through both the territory of Aboriginal people and the discursive terrain of nationhood.

Quantitative proteomic approach to study subcellular localization of membrane proteins

As proteins within cells are spatially organized according to their role, knowledge about protein localization gives insight into protein function. Here, we describe the LOPIT technique (localization of organelle proteins by isotope tagging) developed for the simultaneous and confident determination of the steady-state distribution of hundreds of integral membrane proteins within organelles. The technique uses a partial membrane fractionation strategy in conjunction with quantitative proteomics. Localization of proteins is achieved by measuring their distribution pattern across the density gradient using amine-reactive isotope tagging and comparing these patterns with those of known organelle residents. LOPIT relies on the assumption that proteins belonging to the same organelle will co-fractionate. Multivariate statistical tools are then used to group proteins according to the similarities in their distributions, and hence localization without complete centrifugal separation is achieved. The protocol requires approximately 3 weeks to complete and can be applied in a high-throughput manner to material from many varied sources.

The impact of spatial scales and spatial smoothing on the outcome of Bayesian spatial model

Discretization of a geographical region is quite common in spatial analysis. There have been few studies into the impact of different geographical scales on the outcome of spatial models for different spatial patterns. This study aims to investigate the impact of spatial scales and spatial smoothing on the outcomes of modelling spatial point-based data. Given a spatial point-based dataset (such as occurrence of a disease), we study the geographical variation of residual disease risk using regular grid cells. The individual disease risk is modelled using a logistic model with the inclusion of spatially unstructured and/or spatially structured random effects. Three spatial smoothness priors for the spatially structured component are employed in modelling, namely an intrinsic Gaussian Markov random field, a second-order random walk on a lattice, and a Gaussian field with Matern correlation function. We investigate how changes in grid cell size affect model outcomes under different spatial structures and different smoothness priors for the spatial component. A realistic example (the Humberside data) is analyzed and a simulation study is described. Bayesian computation is carried out using an integrated nested Laplace approximation. The results suggest that the performance and predictive capacity of the spatial models improve as the grid cell size decreases for certain spatial structures. It also appears that different spatial smoothness priors should be applied for different patterns of point data.

Timing and source constraints on the relationship between mafic and felsic intrusions in the Emeiashan large igneous province

Several I- and A-type granite, syenite plutons and spatially associated, giant Fe–Ti–V deposit-bearing mafic ultramafic layered intrusions occur in the Pan–Xi(Panzhihua–Xichang) area within the inner zone of the Emeishan large igneous province (ELIP). These complexes are interpreted to be related to the Emeishan mantle plume. We present LA-ICP-MS and SIMS zircon U–Pb ages and Hf–Nd isotopic compositions for the gabbros, syenites and granites from these complexes. The dating shows that the age of the felsic intrusive magmatism (256.2 ± 3.0–259.8 ± 1.6 Ma) is indistinguishable from that of the mafic intrusive magmatism (255.4 ± 3.1–259.5 ± 2.7 Ma) and represents the final phase of a continuous magmatic episode that lasted no more than 10 Myr. The upper gabbros in the mafic–ultramafic intrusions are generally more isotopically enriched (lower eNd and eHf) than the middle and lower gabbros, suggesting that the upper gabbros have experienced a higher level of crustal contamination than the lower gabbros. The significantly positive eHf(t) values of the A-type granites and syenites (+4.9 to +10.8) are higher than those of the upper gabbros of the associated mafic intrusion, which shows that they cannot be derived by fractional crystallization of these bodies. They are however identical to those of the mafic enclaves (+7.0 to +11.4) and middle and lower gabbros, implying that they are cogenetic. We suggest that they were generated by fractionation of large-volume, plume-related basaltic magmas that ponded deep in the crust. The deep-seated magma chamber erupted in two stages: the first near a density minimum in the basaltic fractionation trend and the second during the final stage of fractionation when the magma was a low density Fe-poor, Si-rich felsic magma. The basaltic magmas emplaced in the shallowlevel magma chambers differentiated to form mafic–ultramafic layered intrusions accompanied by a small amount of crustal assimilation through roof melting. Evolved A-type granites (synenites and syenodiorites) were produced dominantly by crystallization in the deep crustal magma chamber. In contrast, the I-type granites have negative eNd(t) [-6.3 to -7.5] and eHf(t) [-1.3 to -6.7] values, with the Nd model ages (T Nd DM2) of 1.63-1.67 Ga and Hf model ages (T Hf DM2) of 1.56-1.58 Ga, suggesting that they were mainly derived from partial melting of Mesoproterozoic crust. In combination with previous studies, this study also shows that plume activity not only gave rise to reworking of ancient crust, but also significant growth of juvenile crust in the center of the ELIP.

Towards bio-inspired place recognition over multiple spatial scales

This paper presents a new multi-scale place recognition system inspired by the recent discovery of overlapping, multi-scale spatial maps stored in the rodent brain. By training a set of Support Vector Machines to recognize places at varying levels of spatial specificity, we are able to validate spatially specific place recognition hypotheses against broader place recognition hypotheses without sacrificing localization accuracy. We evaluate the system in a range of experiments using cameras mounted on a motorbike and a human in two different environments. At 100% precision, the multiscale approach results in a 56% average improvement in recall rate across both datasets. We analyse the results and then discuss future work that may lead to improvements in both robotic mapping and our understanding of sensory processing and encoding in the mammalian brain.

Body stories

This research is in the field of arts education. Eisner claims that ‘teachers rarely view themselves as artists’ (Taylor, 1993:21). Situating professional dance artists and teacher-artists (Mc Lean, 2009) in close proximity to classroom dance teachers, spatially, through a shared rehearsal studio and creatively, by engaging them in a co-artistry approach, allows participants to map unique and new creative processes, kinaesthetically and experientially. This pratice encourages teachers to attune and align themselves with artists’ states of mind and enables them to nurture both their teacher-self and their artist-self (Lichtenstein 2009). The research question was: can interactions between professional dance artists, teacher-artists (Mc Lean, 2009) and classroom dance teachers change classroom dance teachers’ self-perceptions? The research found that Artists in Residence projects provide up-skilling in situ for classroom dance teachers, and give credence to the act of art making for classroom dance teachers within their peer context, positively enhancing their self-image and promoting self-identification as ‘teacher-artists’ (Mc Lean, 2009). This project received an Artist in Residence Grant (an Australia Council for the Arts, Education Queensland and Queensland Arts Council partnership). The research findings were chosen for inclusion in the Queensland Performing Arts Complex program, Feet First: an invitation to dance, 2013 and selected for inclusion on the Creative Campus website, http://www.creative-campus.org.uk.

Toward biomimetic materials in bone regeneration : functional behavior of mesenchymal stem cells on a broad spectrum of extracellular matrix components

Bone defect treatments can be augmented by mesenchymal stem cell (MSC) based therapies. MSC interaction with the extracellular matrix (ECM) of the surrounding tissue regulates their functional behavior. Understanding of these specific regulatory mechanisms is essential for the therapeutic stimulation of MSC in vivo. However, these interactions are presently only partially understood. This study examined in parallel, for the first time, the effects on the functional behavior of MSCs of 13 ECM components from bone, cartilage and hematoma compared to a control protein, and hence draws conclusions for rational biomaterial design. ECM components specifically modulated MSC adhesion, migration, proliferation, and osteogenic differentiation, for example, fibronectin facilitated migration, adhesion, and proliferation, but not osteogenic differentiation, whereas fibrinogen enhanced adhesion and proliferation, but not migration. Subsequently, the integrin expression pattern of MSCs was determined and related to the cell behavior on specific ECM components. Finally, on this basis, peptide sequences are reported for the potential stimulation of MSC functions. Based on the results of this study, ECM component coatings could be designed to specifically guide cell functions.

Spatiotemporal patterns of Japanese Encephalitis in China, 2002–2010

OBJECTIVE The aim of the study is to examine the spatiotemporal pattern of Japanese Encephalitis (JE) in mainland China during 2002-2010. Specific objectives of the study were to quantify the temporal variation in incidence of JE cases, to determine if clustering of JE cases exists, to detect high risk spatiotemporal clusters of JE cases and to provide evidence-based preventive suggestions to relevant stakeholders. METHODS Monthly JE cases at the county level in mainland China during 2002-2010 were obtained from the China Information System for Diseases Control and Prevention (CISDCP). For the purpose of the analysis, JE case counts for nine years were aggregated into four temporal periods (2002; 2003-2005; 2006; and 2007-2010). Local Indicators of Spatial Association and spatial scan statistics were performed to detect and evaluate local high risk space-time clusters. RESULTS JE incidence showed a decreasing trend from 2002 to 2005 but peaked in 2006, then fluctuated over the study period. Spatial cluster analysis detected high value clusters, mainly located in Southwestern China. Similarly, we identified a primary spatiotemporal cluster of JE in Southwestern China between July and August, with the geographical range of JE transmission increasing over the past years. CONCLUSION JE in China is geographically clustered and its spatial extent dynamically changed during the last nine years in mainland China. This indicates that risk factors for JE infection are likely to be spatially heterogeneous. The results may assist national and local health authorities in the development/refinement of a better preventive strategy and increase the effectiveness of public health interventions against JE transmission.

Spatiotemporal patterns of Aedes aegyptipopulations in Cairns, Australia : assessing drivers of dengue transmission

OBJECTIVES To identify the meteorological drivers of dengue vector density and determine high- and low-risk transmission zones for dengue prevention and control in Cairns, Australia. METHODS Weekly adult female Ae. aegypti data were obtained from 79 double sticky ovitraps (SOs) located in Cairns for the period September 2007-May 2012. Maximum temperature, total rainfall and average relative humidity data were obtained from the Australian Bureau of Meteorology for the study period. Time series-distributed lag nonlinear models were used to assess the relationship between meteorological variables and vector density. Spatial autocorrelation was assessed via semivariography, and ordinary kriging was undertaken to predict vector density in Cairns. RESULTS Ae. aegypti density was associated with temperature and rainfall. However, these relationships differed between short (0-6 weeks) and long (0-30 weeks) lag periods. Semivariograms showed that vector distributions were spatially autocorrelated in September 2007-May 2008 and January 2009-May 2009, and vector density maps identified high transmission zones in the most populated parts of Cairns city, as well as Machans Beach. CONCLUSION Spatiotemporal patterns of Ae. aegypti in Cairns are complex, showing spatial autocorrelation and associations with temperature and rainfall. Sticky ovitraps should be placed no more than 1.2 km apart to ensure entomological coverage and efficient use of resources. Vector density maps provide evidence for the targeting of prevention and control activities. Further research is needed to explore the possibility of developing an early warning system of dengue based on meteorological and environmental factors.

Using GPS technology to (re)-examine operational definitions of 'neighbourhood' in place-based health research

BACKGROUND Inconsistencies in research findings on the impact of the built environment on walking across the life course may be methodologically driven. Commonly used methods to define 'neighbourhood', from which built environment variables are measured, may not accurately represent the spatial extent to which the behaviour in question occurs. This paper aims to provide new methods for spatially defining 'neighbourhood' based on how people use their surrounding environment. RESULTS Informed by Global Positioning Systems (GPS) tracking data, several alternative neighbourhood delineation techniques were examined (i.e., variable width, convex hull and standard deviation buffers). Compared with traditionally used buffers (i.e., circular and polygon network), differences were found in built environment characteristics within the newly created 'neighbourhoods'. Model fit statistics indicated that exposure measures derived from alternative buffering techniques provided a better fit when examining the relationship between land-use and walking for transport or leisure. CONCLUSIONS This research identifies how changes in the spatial extent from which built environment measures are derived may influence walking behaviour. Buffer size and orientation influences the relationship between built environment measures and walking for leisure in older adults. The use of GPS data proved suitable for re-examining operational definitions of neighbourhood.

Spatial analysis of community-onset Staphylococcus aureus bacteremia in Queensland, Australia

OBJECTIVES To investigate and describe the relationship between indigenous Australian populations, residential aged care services, and community-onset Staphylococcus aureus bacteremia (SAB) among patients admitted to public hospitals in Queensland, Australia. DESIGN Ecological study. METHODS We used administrative healthcare data linked to microbiology results from patients with SAB admitted to Queensland public hospitals from 2005 through 2010 to identify community-onset infections. Data about indigenous Australian population and residential aged care services at the local government area level were obtained from the Queensland Office of Economic and Statistical Research. Associations between community-onset SAB and indigenous Australian population and residential aged care services were calculated using Poisson regression models in a Bayesian framework. Choropleth maps were used to describe the spatial patterns of SAB risk. RESULTS We observed a 21% increase in relative risk (RR) of bacteremia with methicillin-susceptible S. aureus (MSSA; RR, 1.21 [95% credible interval, 1.15-1.26]) and a 24% increase in RR with nonmultiresistant methicillin-resistant S. aureus (nmMRSA; RR, 1.24 [95% credible interval, 1.13-1.34]) with a 10% increase in the indigenous Australian population proportion. There was no significant association between RR of SAB and the number of residential aged care services. Areas with the highest RR for nmMRSA and MSSA bacteremia were identified in the northern and western regions of Queensland. CONCLUSIONS The RR of community-onset SAB varied spatially across Queensland. There was increased RR of community-onset SAB with nmMRSA and MSSA in areas of Queensland with increased indigenous population proportions. Additional research should be undertaken to understand other factors that increase the risk of infection due to this organism.

The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection

Background Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Results Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. Conclusions We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.