2,229 research outputs found
Caspofungin Treatment of Aspergillus fumigatus Results in ChsG-Dependent Upregulation of Chitin Synthesis and the Formation of Chitin-Rich Microcolonies
Date of Acceptance: 23/07/2015 We thank Gillian Milne for help with electron microscopy, Sophie M. SchƤfer for pilot experiments, and Emilia Mellado for strains. All authors acknowledge financial support of Gilead Sciences through Ph.D. studentships for L.A.W. and K.K.L. We also acknowledge research grants from the Wellcome Trust (080088, 086827, 075470, 099215, and 097377) and the British Society for Antimicrobial Chemotherapy.Peer reviewedPublisher PD
Dental characters used in phylogenetic analyses of mammals show higher rates of evolution, but not reduced independence
Accurate reconstructions of phylogeny are essential for studying the evolution of a clade, and morphological characters are necessarily used for the reconstruction of the relationships of fossil organisms. However, variation in their evolutionary modes (for example rate variation and character non-independence) not accounted for in analyses may be leading to unreliable phylogenies. A recent study suggested that phylogenetic analyses of mammals may be suffering from a dominance of dental characters, which were shown to have lower phylogenetic signal than osteological characters and produced phylogenies less congruent with molecularly-derived benchmarks. Here we build on this previous work by testing five additional morphological partitions for phylogenetic signal and examining what aspects of dental and other character evolution may be affecting this, by fitting models of discrete character evolution to phylogenies inferred and time calibrated using molecular data. Results indicate that the phylogenetic signal of discrete characters correlate most strongly with rates of evolution, with increased rates driving increased homoplasy. In a dataset covering all Mammalia, dental characters have higher rates of evolution than other partitions. They do not, however, fit a model of independent character evolution any worse than other regions. Primates and marsupials show different patterns to other mammal clades, with dental characters evolving at slower rates and being more heavily integrated (less independent). While the dominance of dental characters in analyses of mammals could be leading to inaccurate phylogenies, the issue is not unique to dental characters and the results are not consistent across datasets. Molecular benchmarks (being entirely independent of the character data) provide a framework for examining each dataset individually to assess the evolution of the characters used
Cell wall stress induces alternative fungal cytokinesis and septation strategies
Peer reviewedPublisher PD
PERK/EIF2AK3 integrates endoplasmic reticulum stress-induced apoptosis, oxidative stress and autophagy responses in immortalised retinal pigment epithelial cells
Retinal pigment epithelium (RPE) performs essential functions for ensuring retinal homeostasis and is a key site for pathogenic changes leading to age-related macular degeneration (AMD). Compromised proteostasis in RPE results in ER stress and ER stress-dependent antioxidant, apoptosis and autophagic responses. ER stress induces the unfolded protein response (UPR) in which EIF2AK3, encoding the protein kinase RNA-like ER kinase (PERK), acts as a key regulator. Downregulated EIF2AK3 gene expression has recently been identified in AMD using human donor RPE, however the molecular mechanisms that integrate the various ER-mediated cellular pathways underpinning progressive RPE dysfunction in AMD have not been fully characterised. This study investigated the downstream effects of PERK downregulation in response to Brefeldin A (BFA)-induced ER stress in ARPE-19 cells. PERK downregulation resulted in increased ER stress and impaired apoptosis induction, antioxidant responses and autophagic flux. ARPE-19 cells were unable to efficiently induce autophagy following PERK downregulation and PERK presented a role in regulating the rate of autophagy induction. The findings support PERK downregulation as an integrative event facilitating dysregulation of RPE processes critical to cell survival known to contribute to AMD development and highlight PERK as a potential future therapeutic target for AMD
Non-stochastic lattice structures for novel filter applications fabricated via additive manufacturing
Non-stochastic lattice structures are widely used in a variety of applications such as biomedical implants and heat exchangers. However, the utilisation of these structures for filtration applications is rather new. Additive manufacturing techniques such as selective laser melting allows lattice structures to be bespoke depending on the type of filter and its intended function. This study considers the flow characteristics and structural strength of a disc filter with a layer of repeated 1.8 mm lattice unit cell as the filter mesh. Computational fluid dynamics simulation is used to analyse the pressure and flow velocity across the filter, while finite element analysis is utilised to analyse the structural characteristics of the lattice mesh under fluid load. The results show a minimal decrease in pressure and small increases in velocity, with the mesh capable of withstanding higher loads. The ultimate failure load of the structure is also determined. These findings indicate that more layers of lattice structures could be used as filter mesh and the flexibility of AM allows the filter properties to be tailored as required for a given application
The effects of grouping on speed discrimination thresholds in adults, typically developing children, and children with autism.
Adult observers show elevated speed discrimination thresholds when comparing the speeds of objects moving across a boundary compared to those moving parallel to a boundary (Verghese & McKee, 2006)-an effect that has been attributed to grouping processes in conjunction with a prior for smooth motion. Here, we extended Verghese and McKee's (2006) paradigm to typically developing children (n = 35) and children with autism (n = 26) and compared their performance with that of typical adults (n = 19). Speed discrimination thresholds were measured in three conditions: (a) with dots moving parallel to a boundary, (b) with dots moving perpendicular to a boundary, and (c) with dots in each stimulus half moving in orthogonal, oblique directions. As expected, participants had higher speed discrimination thresholds when dots appeared to cross a boundary compared to when dots moved parallel to the boundary. However, participants had even higher thresholds when dots moved in oblique, orthogonal directions, where grouping should be minimal. All groups of participants showed a similar pattern of performance across conditions although children had higher thresholds than adult participants overall. We consider various explanations for the pattern of performance obtained, including enhanced sensitivity for shearing motions and reduced sensitivity for discriminating different directions. Our results demonstrate that the speed discrimination judgments of typically developing children and children with autism are similarly affected by spatial configuration as those of typical adults and provide further evidence that speed discrimination is unimpaired in children with autism.</p
Exploring links between early adversities and later outcomes for children adopted from care: Implications for planning post adoption support
This study explored how child maltreatment, alongside a range of other variables, predicted adverse outcomes for children adopted from the foster care system in England. The participants were 319 adoptive parents who completed an in-depth online survey about their most recently adopted child. The mean age of children at placement for adoption was 28 months (range 0ā11 years) and their ages at the time of the survey ranged from 0 years to 17 years (meanĀ¼7 years). Detailed information was collected about childrenās backgrounds, including their experiences in the birth family and the care system before adoption. Adoptive parents also reported on how well children were getting on in a range of areas of functioning and how well they felt the adoption was going overall. Child maltreatment and child adverse outcomes were modeled as two factors in a latent factor structural equation model. The relationship between these two factors was explored alongside a range of covariates. Associated with worse outcomes for children were potentially heritable factors (parental learning disability), the pre-birth environment (exposure to drugs or alcohol in utero) and the period between birth and moving to the adoptive family (higher levels of maltreatment, spending more than a year in care, having two or more foster placements). The childās distress on moving from the foster home to the adoptive family was also highly significant in linking to poorer outcomes, suggesting the detrimental effect of poorly managed transitions. Implications for child welfare practices before and after adoption are discussed
LINEARITY OF THE RATIO OF FORCES-VELOCITY RELATIONSHIP IS NOT RELATED TO INITIAL ACCELERATION PERFORMANCE IN SPRINTING
The relationship between the linearity of the ratio of forces (RF)-horizontal velocity (vH) profile and initial acceleration (IA) performance was investigated in trained sprinters. Ground reaction force data from the IA phase of a maximal sprint from a block start were analysed. The coefficient of determination of the linear trendline fitted to four step-averaged values of RF and vH provided a measure of linearity. Semi-partial correlations (sr) accounting for block phase performance revealed a weak negative relationship between linearity of the RF-vH profile and performance over the first four steps (sr = -0.11), while mean RF displayed a very strong positive relationship with performance (sr = 0.80). Sprinters and coaches should therefore prioritise the production of a high RF during IA above trying to ensure a consistent decline in RF as velocity increases
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