Cell migration on material-driven fibronectin microenvironments

Cell migration is a fundamental process involved in a wide range of biological phenomena. However, how the underlying mechanisms that control migration are orchestrated is not fully understood. In this work, we explore the migratory characteristics of human fibroblasts using different organisations of fibronectin (FN) triggered by two chemically similar surfaces, poly(ethyl acrylate) (PEA) and poly(methyl acrylate) (PMA); cell migration is mediated via an intermediate layer of fibronectin (FN). FN is organised into nanonetworks upon simple adsorption on PEA whereas a globular conformation is observed on PMA. We studied cell speed over the course of 24 h and the morphology of focal adhesions in terms of area and length. Additionally, we analysed the amount of cell-secreted FN as well as FN remodelling. Velocity of human fibroblasts was found to exhibit a biphasic behaviour on PEA, whereas it remained fairly constant on PMA. FA analysis revealed more mature focal adhesions on PEA over time contrary to smaller FAs found on PMA. Finally, human fibroblasts seemed to remodel adsorbed FN more on PMA than on PEA. Overall, these results indicate that the cell–protein–material interface affects cell migratory behaviour. Analysis of FAs together with FN secretion and remodelling were associated with differences in cell velocity providing insights into the factors that can modulate cell motility

Influence of biomaterial nanotopography on the adhesive and elastic properties of Staphylococcus aureus cells

Despite the well-known beneficial effects of biomaterial nanopatterning on host tissue integration, the influence of controlled nanoscale topography on bacterial colonisation and infection remains unknown. Therefore, the aim of the present study was to determine the nanoscale effect of surface nanopatterning on biomaterial colonisation by S. aureus, utilising AFM nanomechanics and single-cell force spectroscopy (SCFS). Nanoindentation of S. aureus bound to planar (PL) and nanopatterned (SQ) polycarbonate (PC) surfaces suggested two distinct areas of mechanical properties, consistent with a central bacterial cell surrounded by a capsullar component. Nevertheless, no differences in elastic moduli were found between bacteria bound to PL and SQ, suggesting a minor role of nanopatterning in bacterial cell elasticity. Furthermore, SCFS demonstrated increased adhesion forces and work between S. aureus and SQ surfaces at 0 s and 1 s contact times. Although WLC modelling showed similarities in contour lengths for attachment to both surfaces, Poisson analysis suggests increased short-range forces for the S. aureus–SQ interactions. In the case of S. aureus–PL, long-range forces were found to not only be dominant but also repulsive in nature, which may help explain the reduced adhesion forces observed during AFM probing. In conclusion, although surface nanopatterning does not significantly influence the elasticity of attached bacterial cells, it was found to promote the early-adhesion of S. aureus cells to the biomaterial surface

Different types of soluble fermentable dietary fibre decrease food intake, body weight gain and adiposity in young adult male rats

We thank Donna Wallace and the Rowett Animal House staff for the daily care of experimental rats, body weight and food intake measurements and MRI scanning, Vivien Buchan and Donna Henderson of the Rowett Analytical Department for proximate analyses and SCFA GC, and Andrew Chappell for conducting the beta-glucan analysis. This research was funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division.Peer reviewedPublisher PD

Influence of biomaterial nanotopography on the adhesive and elastic properties of Staphylococcus aureus cells

Despite the well-known beneficial effects of biomaterial nanopatterning on host tissue integration, the influence of controlled nanoscale topography on bacterial colonisation and infection remains unknown. Therefore, the aim of the present study was to determine the nanoscale effect of surface nanopatterning on biomaterial colonisation by S. aureus, utilising AFM nanomechanics and single-cell force spectroscopy (SCFS). Nanoindentation of S. aureus bound to planar (PL) and nanopatterned (SQ) polycarbonate (PC) surfaces suggested two distinct areas of mechanical properties, consistent with a central bacterial cell surrounded by a capsullar component. Nevertheless, no differences in elastic moduli were found between bacteria bound to PL and SQ, suggesting a minor role of nanopatterning in bacterial cell elasticity. Furthermore, SCFS demonstrated increased adhesion forces and work between S. aureus and SQ surfaces at 0 s and 1 s contact times. Although WLC modelling showed similarities in contour lengths for attachment to both surfaces, Poisson analysis suggests increased short-range forces for the S. aureus–SQ interactions. In the case of S. aureus–PL, long-range forces were found to not only be dominant but also repulsive in nature, which may help explain the reduced adhesion forces observed during AFM probing. In conclusion, although surface nanopatterning does not significantly influence the elasticity of attached bacterial cells, it was found to promote the early-adhesion of S. aureus cells to the biomaterial surface

Complete analysis of the H5 hemagglutinin and N8 neuraminidase phylogenetic trees reveals that the H5N8 subtype has been produced by multiple reassortment events

The analysis of the complete H5 hemagglutinin and H8 neuraminidase phylogenetic trees presented in this paper shows that the H5N8 avian influenza has been generated by multiple reassortment events. The H5N8 strain does not have a single origin and is produced when the H5 hemagglutinin and N8 neuraminidase re-assort from other H5 and N8 containing strains. While it was known that there had been a re-assortment to incorporate the Guangdong H5 hemagglutinin at the start of the Korean outbreak, the results show that there have also been multiple reassortment events amongst the non-Korean sequences

Identification of Schistosoma mansoni microRNAs

Background: MicroRNAs (miRNAs) constitute a class of single-stranded RNAs which play a crucial role in regulating development and controlling gene expression by targeting mRNAs and triggering either translation repression or messenger RNA (mRNA) degradation. miRNAs are widespread in eukaryotes and to date over 14,000 miRNAs have been identified by computational and experimental approaches. Several miRNAs are highly conserved across species. In Schistosoma, the full set of miRNAs and their expression patterns during development remain poorly understood. Here we report on the development and implementation of a homology-based detection strategy to search for miRNA genes in Schistosoma mansoni. In addition, we report results on the experimental detection of miRNAs by means of cDNA cloning and sequencing of size-fractionated RNA samples. Results: Homology search using the high-throughput pipeline was performed with all known miRNAs in miRBase. A total of 6,211 mature miRNAs were used as reference sequences and 110 unique S. mansoni sequences were returned by BLASTn analysis. The existing mature miRNAs that produced these hits are reported, as well as the locations of the homologous sequences in the S. mansoni genome. All BLAST hits aligned with at least 95% of the miRNA sequence, resulting in alignment lengths of 19-24 nt. Following several filtering steps, 15 potential miRNA candidates were identified using this approach. By sequencing small RNA cDNA libraries from adult worm pairs, we identified 211 novel miRNA candidates in the S. mansoni genome. Northern blot analysis was used to detect the expression of the 30 most frequent sequenced miRNAs and to compare the expression level of these miRNAs between the lung stage schistosomula and adult worm stages. Expression of 11 novel miRNAs was confirmed by northern blot analysis and some presented a stage-regulated expression pattern. Three miRNAs previously identified from S. japonicum were also present in S. mansoni. Conclusion: Evidence for the presence of miRNAs in S. mansoni is presented. The number of miRNAs detected by homology-based computational methods in S. mansoni is limited due to the lack of close relatives in the miRNA repository. In spite of this, the computational approach described here can likely be applied to the identification of pre-miRNA hairpins in other organisms. Construction and analysis of a small RNA library led to the experimental identification of 14 novel miRNAs from S. mansoni through a combination of molecular cloning, DNA sequencing and expression studies. Our results significantly expand the set of known miRNAs in multicellular parasites and provide a basis for understanding the structural and functional evolution of miRNAs in these metazoan parasites

Diversity, competition, extinction: the ecophysics of language change

As early indicated by Charles Darwin, languages behave and change very much like living species. They display high diversity, differentiate in space and time, emerge and disappear. A large body of literature has explored the role of information exchanges and communicative constraints in groups of agents under selective scenarios. These models have been very helpful in providing a rationale on how complex forms of communication emerge under evolutionary pressures. However, other patterns of large-scale organization can be described using mathematical methods ignoring communicative traits. These approaches consider shorter time scales and have been developed by exploiting both theoretical ecology and statistical physics methods. The models are reviewed here and include extinction, invasion, origination, spatial organization, coexistence and diversity as key concepts and are very simple in their defining rules. Such simplicity is used in order to catch the most fundamental laws of organization and those universal ingredients responsible for qualitative traits. The similarities between observed and predicted patterns indicate that an ecological theory of language is emerging, supporting (on a quantitative basis) its ecological nature, although key differences are also present. Here we critically review some recent advances lying and outline their implications and limitations as well as open problems for future research.Comment: 17 Pages. A review on current models from statistical Physics and Theoretical Ecology applied to study language dynamic

Label-free segmentation of co-cultured cells on a nanotopographical gradient

The function and fate of cells is influenced by many different factors, one of which is surface topography of the support culture substrate. Systematic studies of nanotopography and cell response have typically been limited to single cell types and a small set of topographical variations. Here, we show a radical expansion of experimental throughput using automated detection, measurement, and classification of co-cultured cells on a nanopillar array where feature height changes continuously from planar to 250 nm over 9 mm. Individual cells are identified and characterized by more than 200 descriptors, which are used to construct a set of rules for label-free segmentation into individual cell types. Using this approach we can achieve label-free segmentation with 84% confidence across large image data sets and suggest optimized surface parameters for nanostructuring of implant devices such as vascular stents

Novel statistical approaches for non-normal censored immunological data: analysis of cytokine and gene expression data

Background: For several immune-mediated diseases, immunological analysis will become more complex in the future with datasets in which cytokine and gene expression data play a major role. These data have certain characteristics that require sophisticated statistical analysis such as strategies for non-normal distribution and censoring. Additionally, complex and multiple immunological relationships need to be adjusted for potential confounding and interaction effects. Objective: We aimed to introduce and apply different methods for statistical analysis of non-normal censored cytokine and gene expression data. Furthermore, we assessed the performance and accuracy of a novel regression approach in order to allow adjusting for covariates and potential confounding. Methods: For non-normally distributed censored data traditional means such as the Kaplan-Meier method or the generalized Wilcoxon test are described. In order to adjust for covariates the novel approach named Tobit regression on ranks was introduced. Its performance and accuracy for analysis of non-normal censored cytokine/gene expression data was evaluated by a simulation study and a statistical experiment applying permutation and bootstrapping. Results: If adjustment for covariates is not necessary traditional statistical methods are adequate for non-normal censored data. Comparable with these and appropriate if additional adjustment is required, Tobit regression on ranks is a valid method. Its power, type-I error rate and accuracy were comparable to the classical Tobit regression. Conclusion: Non-normally distributed censored immunological data require appropriate statistical methods. Tobit regression on ranks meets these requirements and can be used for adjustment for covariates and potential confounding in large and complex immunological datasets

Negotiating the inhuman: Bakhtin, materiality and the instrumentalization of climate change

The article argues that the work of literary theorist Mikhail M. Bakhtin presents a starting point for thinking about the instrumentalization of climate change. Bakhtin’s conceptualization of human–world relationships, encapsulated in the concept of ‘cosmic terror’, places a strong focus on our perception of the ‘inhuman’. Suggesting a link between the perceived alienness and instability of the world and in the exploitation of the resulting fear of change by political and religious forces, Bakhtin asserts that the latter can only be resisted if our desire for a false stability in the world is overcome. The key to this overcoming of fear, for him, lies in recognizing and confronting the worldly relations of the human body. This consciousness represents the beginning of one’s ‘deautomatization’ from following established patterns of reactions to predicted or real changes. In the vein of several theorists and artists of his time who explored similar ‘deautomatization’ strategies – examples include Shklovsky’s ‘ostranenie’, Brecht’s ‘Verfremdung’, Artaud’s emotional ‘cruelty’ and Bataille’s ‘base materialism’ – Bakhtin proposes a more playful and widely accessible experimentation to deconstruct our ‘habitual picture of the world’. Experimentation is envisioned to take place across the material and the textual to increase possibilities for action. Through engaging with Bakhtin’s ideas, this article seeks to draw attention to relations between the imagination of the world and political agency, and the need to include these relations in our own experiments with creating climate change awareness