Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation

Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications

Protocol for a pilot randomised controlled clinical trial to compare the effectiveness of a graduated three layer straight tubular bandaging system when compared to a standard short stretch compression bandaging system in the management of people with venous ulceration: 3VSS2008

<p>Abstract</p> <p>Background</p> <p>The incidence of venous ulceration is rising with the increasing age of the general population. Venous ulceration represents the most prevalent form of difficult to heal wounds and these problematic wounds require a significant amount of health care resources for treatment. Based on current knowledge multi-layer high compression system is described as the gold standard for treating venous ulcers. However, to date, despite our advances in venous ulcer therapy, no convincing low cost compression therapy studies have been conducted and there are no clear differences in the effectiveness of different types of high compression.</p> <p>Methods/Design</p> <p>The trial is designed as a pilot multicentre open label parallel group randomised trial. Male and female participants aged greater than 18 years with a venous ulcer confirmed by clinical assessment will be randomised to either the intervention compression bandage which consists of graduated lengths of 3 layers of elastic tubular compression bandage or to the short stretch inelastic compression bandage (control). The primary objective is to assess the percentage wound reduction from baseline compared to week 12 following randomisation. Randomisation will be allocated via a web based central independent randomisation service (nQuery v7) and stratified by study centre and wound size ≤ 10 cm²or >10 cm². Neither participants nor study staff will be blinded to treatment. Outcome assessments will be undertaken by an assessor who is blinded to the randomisation process.</p> <p>Discussion</p> <p>The aim of this study is to evaluate the efficacy and safety of two compression bandages; graduated three layer straight tubular bandaging (3L) when compared to standard short stretch (SS) compression bandaging in healing venous ulcers in patients with chronic venous ulceration. The trial investigates the differences in clinical outcomes of two currently accepted ways of treating people with venous ulcers. This study will help answer the question whether the 3L compression system or the SS compression system is associated with better outcomes.</p> <p>Trial Registration</p> <p>ACTRN12608000599370</p

TWEAK Affects Keratinocyte G2/M Growth Arrest and Induces Apoptosis through the Translocation of the AIF Protein to the Nucleus

The soluble TNF-like weak inducer of apoptosis (TWEAK, TNFSF12) binds to the fibroblast growth factor-inducible 14 receptor (FN14, TNFRSF12A) on the cell membrane and induces multiple biological responses, such as proliferation, migration, differentiation, angiogenesis and apoptosis. Previous reports show that TWEAK, which does not contain a death domain in its cytoplasmic tail, induces the apoptosis of tumor cell lines through the induction of TNFα secretion. TWEAK induces apoptosis in human keratinocytes. Our experiments clearly demonstrate that TWEAK does not induce the secretion of TNFα or TRAIL proteins. The use of specific inhibitors and the absence of procaspase-3 cleavage suggest that the apoptosis of keratinocytes follows a caspase- and cathepsin B-independent pathway. Further investigation showed that TWEAK induces a decrease in the mitochondrial membrane potential of keratinocytes. Confocal microscopy showed that TWEAK induces the cleavage and the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus, thus initiating caspase-independent apoptosis. Moreover, TWEAK induces FOXO3 and GADD45 expression, cdc2 phosphorylation and cdc2 and cyclinB1 degradation, resulting in the arrest of cell growth at the G2/M phase. Finally, we report that TWEAK and FN14 are normally expressed in the basal layer of the physiological epidermis and are greatly enhanced in benign (psoriasis) and malignant (squamous cell carcinoma) skin pathologies that are characterized by an inflammatory component. TWEAK might play an essential role in skin homeostasis and pathology

Climate Change, Habitat Loss, Protected Areas and the Climate Adaptation Potential of Species in Mediterranean Ecosystems Worldwide

Mediterranean climate is found on five continents and supports five global biodiversity hotspots. Based on combined downscaled results from 23 atmosphere-ocean general circulation models (AOGCMs) for three emissions scenarios, we determined the projected spatial shifts in the mediterranean climate extent (MCE) over the next century. Although most AOGCMs project a moderate expansion in the global MCE, regional impacts are large and uneven. The median AOGCM simulation output for the three emissions scenarios project the MCE at the end of the 21st century in Chile will range from 129–153% of its current size, while in Australia, it will contract to only 77–49% of its current size losing an area equivalent to over twice the size of Portugal. Only 4% of the land area within the current MCE worldwide is in protected status (compared to a global average of 12% for all biome types), and, depending on the emissions scenario, only 50–60% of these protected areas are likely to be in the future MCE. To exacerbate the climate impact, nearly one third (29–31%) of the land where the MCE is projected to remain stable has already been converted to human use, limiting the size of the potential climate refuges and diminishing the adaptation potential of native biota. High conversion and low protection in projected stable areas make Australia the highest priority region for investment in climate-adaptation strategies to reduce the threat of climate change to the rich biodiversity of the mediterranean biome

SYK/AdS duality with Yang-Baxter deformations

In this paper, based on the notion of SYK/AdS duality we explore the effects of Yang-Baxter (YB) deformations on the SYK spectrum at strong coupling. In the first part of our analysis, we explore the consequences of YB deformations through the Kaluza-Klein (KK) reduction on $(AdS_2)_{\eta}\times (S^1)/Z_2$. It turns out that the YB effects (on the SYK spectrum) starts showing off at \textit{quadratic} order in $1/J$ expansion. For the rest of the analysis, we provide an interpretation for the YB deformations in terms of bi-local/collective field excitations of the SYK model. Using large $N$ techniques, we evaluate the effective action upto quadratic order in the fluctuations and estimate $1/J^2$ corrections to the correlation function at strong coupling.Comment: Revised version, To Appear in JHE

Particulate air pollution, systemic oxidative stress, inflammation, and atherosclerosis

Air pollution has been associated with significant adverse health effects leading to increased overall morbidity and mortality of worldwide significance. Epidemiological studies have shown that the largest portion of air pollution-related mortality is due to cardiovascular diseases, predominantly those of ischemic nature. Human studies suggest an association with atherosclerosis and increasing experimental animal data support that this association is likely to be causal. While both gasses and particles have been linked to detrimental health effects, more evidence implicates the particulate matter (PM) components as major responsible for a large portion of the proatherogenic effects. Multiple experimental approaches have revealed the ability of PM components to trigger and/or enhance free radical reactions in cells and tissues, both ex vivo as well as in vivo. It appears that exposure to PM leads to the development of systemic prooxidant and proinflammatory effects that may be of great importance in the development of atherosclerotic lesions. This article reviews the epidemiological studies, experimental animal, and cellular data that support the association of air pollutants, especially the particulate components, with systemic oxidative stress, inflammation, and atherosclerosis. It also reviews the use of transcriptomic studies to elucidate molecular pathways of importance in those systemic effects