Activated polyhydroxyalkanoate meshes prevent bacterial adhesion and biofilm development in regenerative medicine applications

Regenerative medicine has become an extremely valuable tool offering an alternative to conventional therapies for the repair and regeneration of tissues. The re-establishment of tissue and organ functions can be carried out by tissue engineering strategies or by using medical devices such as implants. However, with any material being implanted inside the human body, one of the conundrums that remains is the ease with which these materials can get contaminated by bacteria. Bacterial adhesion leads to the formation of mature, alive and complex three-dimensional biofilm structures, further infection of surrounding tissues and consequent development of complicated chronic infections. Hence, novel tissue engineering strategies delivering biofilm-targeted therapies, while at the same time allowing tissue formation are highly relevant. In this study our aim was to develop surface modified polyhydroxyalkanoate-based fiber meshes with enhanced bacterial anti-adhesive and juvenile biofilm disrupting properties for tissue regeneration purposes. Using reactive and amphiphilic star-shaped macromolecules as an additive to a polyhydroxyalkanoate spinning solution, a synthetic antimicrobial peptide, Amhelin, with strong bactericidal and anti-biofilm properties, and Dispersin B, an enzyme promoting the disruption of exopolysaccharides found in the biofilm matrix, were covalently conjugated to the fibers by addition to the solution before the spinning process. Staphylococcus epidermidis is one of the most problematic pathogens responsible for tissue-related infections. The initial antibacterial screening showed that Amhelin proved to be strongly bactericidal at 12 μg/ml and caused >50% reductions of biofilm formation at 6 μg/ml, while Dispersin B was found to disperse >70% of pre-formed biofilms at 3 μg/ml. Regarding the cytotoxicity of the agents toward L929 murine fibroblasts, a CC50 of 140 and 115 μg/ml was measured for Amhelin and Dispersin B, respectively. Optimization of the electrospinning process resulted in aligned fibers. Surface activated fibers with Amhelin and Dispersin B resulted in 83% reduction of adhered bacteria on the surface of the fibers. Additionally, the materials developed were found to be cytocompatible toward L929 murine fibroblasts. The strategy reported in this preliminary study suggests an alternative approach to prevent bacterial adhesion and, in turn biofilm formation, in materials used in regenerative medicine applications such as tissue engineering

Sensitivity of Southern Ocean overturning to wind stress changes:Role of surface restoring time scales

The influence of different surface restoring time scales on the response of the Southern Ocean overturning circulation to wind stress changes is investigated using an idealised channel model. Regardless of the restoring time scales chosen, the eddy-induced meridional overturning circulation (MOC) is found to compensate for changes of the direct wind-driven Eulerian-mean MOC, rendering the residual MOC less sensitive to wind stress changes. However, the extent of this compensation depends strongly on the restoring time scale: residual MOC sensitivity increases with decreasing restoring time scale. Strong surface restoring is shown to limit the ability of the eddy-induced MOC to change in response to wind stress changes and as such suppresses the eddy compensation effect. These model results are consistent with qualitative arguments derived fromresidual-mean theory andmay have important implications for interpreting past and future observations

Molecular Characterization of the Gastrula in the Turtle Emys orbicularis: An Evolutionary Perspective on Gastrulation

Due to the presence of a blastopore as in amphibians, the turtle has been suggested to exemplify a transition form from an amphibian- to an avian-type gastrulation pattern. In order to test this hypothesis and gain insight into the emergence of the unique characteristics of amniotes during gastrulation, we have performed the first molecular characterization of the gastrula in a reptile, the turtle Emys orbicularis. The study of Brachyury, Lim1, Otx2 and Otx5 expression patterns points to a highly conserved dynamic of expression with amniote model organisms and makes it possible to identify the site of mesoderm internalization, which is a long-standing issue in reptiles. Analysis of Brachyury expression also highlights the presence of two distinct phases, less easily recognizable in model organisms and respectively characterized by an early ring-shaped and a later bilateral symmetrical territory. Systematic comparisons with tetrapod model organisms lead to new insights into the relationships of the blastopore/blastoporal plate system shared by all reptiles, with the blastopore of amphibians and the primitive streak of birds and mammals. The biphasic Brachyury expression pattern is also consistent with recent models of emergence of bilateral symmetry, which raises the question of its evolutionary significance

BMP signals and the transcriptional repressor BLIMP1 during germline segregation in the mammalian embryo

Molecular factors and tissue compartments involved in the foundation of the mammalian germline have been mainly described in the mouse so far. To find mechanisms applicable to mammals in general, we analyzed temporal and spatial expression patterns of the transcriptional repressor BLIMP1 (also known as PRDM1) and the signaling molecules BMP2 and BMP4 in perigastrulation and early neurulation embryos of the rabbit using whole-mount in situ hybridization and high-resolution light microscopy. Both BMP2 and BMP4 are expressed in annular domains at the boundary of the embryonic disc, which—in contrast to the situation in the mouse—partly belong to intraembryonic tissues. While BMP2 expression begins at (pregastrulation) stage 1 in the hypoblast, BMP4 expression commences—distinctly delayed compared to the mouse—diffusely at (pregastrulation) stage 2; from stage 3 onwards, BMP4 is expressed peripherally in hypoblast and epiblast and in the mesoderm at the posterior pole of the embryonic disc. BLIMP1 expression begins throughout the hypoblast at stage 1 and emerges in single primordial germ cell (PGC) precursors in the posterior epiblast at stage 2 and then in single mesoderm cells at positions identical to those identified by PGC-specific antibodies. These expression patterns suggest that function and chronology of factors involved in germline segregation are similar in mouse and rabbit, but higher temporal and spatial resolution offered by the rabbit demonstrates a variable role of bone morphogenetic proteins and makes “blimping” a candidate case for lateral inhibition without the need for an allantoic germ cell niche

The role of ocean gateways in the dynamics and sensitivity to wind stress of the early Antarctic Circumpolar Current

The date of inception of the Antarctic Circumpolar Current is debated due to uncertainty in the relative opening times of Drake Passage and the Tasman Seaway. Using an idealized eddy-resolving numerical ocean model, we investigate whether both ocean gateways have to be open to allow for a substantial circumpolar current. We find that overlapping continental barriers do not impede a circumpolar transport in excess of 50Sv, as long as a circumpolar path can be traced around the barriers. However, the presence of overlapping barriers does lead to an increased sensitivity of the current's volume transport to changes in wind stress. This change in sensitivity is interpreted in terms of the role of pressure drops across continental barriers and submerged bathymetry in balancing the momentum input by the surface wind stress. Specifically, when the pressure drop across continents is the main balancing sink of momentum, the zonal volume transport is sensitive to changes in wind stress. Changes in zonal volume transport take place via altering the depth-independent part of the circumpolar transport rather than that arising from thermal wind shear. In such a scenario, isopycnals continue to slope steeply across the model Southern Ocean, implying a strong connection between the deep and surface oceans. This may have consequences for the meridional overturning circulation and its sensitivity to wind stress

Detecting the Collapse of Cooperation in Evolving Networks

The sustainability of biological, social, economic and ecological communities is often determined by the outcome of social conflicts between cooperative and selfish individuals (cheaters). Cheaters avoid the cost of contributing to the community and can occasionally spread in the population leading to the complete collapse of cooperation. Although such collapse often unfolds unexpectedly, it is unclear whether one can detect the risk of cheater’s invasions and loss of cooperation in an evolving community. Here, we combine dynamical networks and evolutionary game theory to study the abrupt loss of cooperation with tools for studying critical transitions. We estimate the risk of cooperation collapse following the introduction of a single cheater under gradually changing conditions. We observe an increase in the average time it takes for cheaters to be eliminated from the community as the risk of collapse increases. We argue that such slow system response resembles slowing down in recovery rates prior to a critical transition. In addition, we show how changes in community structure reflect the risk of cooperation collapse. We find that these changes strongly depend on the mechanism that governs how cheaters evolve in the community. Our results highlight novel directions for detecting abrupt transitions in evolving networks

Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post‐hoc analysis of a randomised controlled trial

Magnesium status and vitamin B6 intake have been linked to mental health and/or quality of life (QoL). In an 8‐week Phase IV randomised controlled study in individuals with low magnesemia and severe/extremely severe stress but who were otherwise healthy, greater stress reduction was achieved with magnesium combined with vitamin B6 than with magnesium alone. We present a previously unreported secondary analysis of the effect of magnesium, with and without vitamin B6, on depression, anxiety, and QoL. Adults with Depression Anxiety Stress Scales (DASS‐42) stress subscale score >18 were randomised 1:1 to magnesium + vitamin B6 combination (Magne B6®; daily dose 300 and 30 mg, respectively) or magnesium alone (Magnespasmyl®; daily dose 300 mg). Outcomes included changes from baseline in DASS‐42 depression and anxiety scores, and QoL (Short Form‐36 Health Survey). DASS‐42 anxiety and depression scores significantly improved from baseline to week 8 with both treatments, particularly during the first 4 weeks. Improvement in QoL continued over 8 weeks. Participants' perceived capacity for physical activity in daily life showed greater improvement with magnesium + vitamin B6 than magnesium alone (Week 4). In conclusion, magnesium supplementation, with or without vitamin B6, could provide a meaningful clinical benefit in daily life for individuals with stress and low magnesemia