Application of Polyethylene Glycol to Promote Cellular Biocompatibility of Polyhydroxybutyrate Films

Polyhydroxybutyrate (PHB) is a biomaterial with potential for applications in biomedical and tissue engineering; however, its brittle nature and high crystallinity limit its potential. Blending PHB with a variety of PEGs produced natural-synthetic composite films composed of FDA-approved polymers with significant reductions in crystallinity, from 70.1% for PHB films to 41.5% for its composite with a 30% (w/w) loading of PEG2000. Blending also enabled manipulation of the material properties, increasing film flexibility with an extension to break of 2.49±1.01% for PHB films and 8.32±1.06% for films containing 30% (w/w) PEG106. Significant changes in the film surface properties, as measured by porosity, contact angles, and water uptake, were also determined as a consequence of the blending process, and these supported greater adhesion and proliferation of neural-associated olfactory ensheathing cells (OECs). A growth rate of 7.2×105 cells per day for PHB films with 30% (w/w) PEG2000 loading compared to 2.5×105 for PHB films was observed. Furthermore, while cytotoxicity of the films as measured by lactate dehydrogenase release was unaffected, biocompatibility, as measured by mitochondrial activity, was found to increase. It is anticipated that fine control of PEG composition in PHB-based composite biomaterials can be utilised to support their applications in medicinal and tissue engineering applications. Copyright © 2011 Rodman T. H. Chan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Manipulation of Polyhydroxybutyrate Properties through Blending with Ethyl-Cellulose for a Composite Biomaterial

Polyhydroxybutyrate (PHB) is widely used as a biomaterial in medical and tissue-engineering applications, a relatively high crystallinity limits its application. Blending PHB with ethyl-cellulose (EtC) was readily achieved to reduce PHB crystallinity and promote its degradation under physiological conditions without undue influence on biocompatibility. Material strength of composite films remained unchanged at 6.5 ± 0.6 MPa with 40% (w/w) EtC loadings. Phase separation between the two biopolymers was determined with PHB crystallinity decreasing from 63% to 47% for films with the same loading. This reduction in crystallinity supported an increase in the degradation rates of composite films from 0.39 to 0.81% wk−1 for PHB and its composite, respectively. No significant change in morphology and proliferation of olfactory ensheathing cells were observed with the composites despite significant increases in average surface roughness (Ra) of the films from 2.90 to 3.65 μm for PHB and blends with 80% (w/w) EtC, respectively. Copyright © 2011 Rodman T. H. Chan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

The impact of heavy-quark loops on LHC dark matter searches

If only tree-level processes are included in the analysis, LHC monojet searches give weak constraints on the dark matter-proton scattering cross section arising from the exchange of a new heavy scalar or pseudoscalar mediator with Yukawa-like couplings to quarks. In this letter we calculate the constraints on these interactions from the CMS 5.0/fb and ATLAS 4.7/fb searches for jets with missing energy including the effects of heavy-quark loops. We find that the inclusion of such contributions leads to a dramatic increase in the predicted cross section and therefore a significant improvement of the bounds from LHC searches.Comment: 12 pages, 1 table, 3 figures, v2: extended discussion and improved relic density calculation - matches published versio

A History of the Molecular Initiating Event

The adverse outcome pathway (AOP) framework provides an alternative to traditional $\textit{in vivo}$ experiments for the risk assessment of chemicals. AOPs consist of a number of key events (KEs) linked by key event relationships across a range of biological organization backed by scientific evidence. The first KE in the pathway is the molecular initiating event (MIE)-the initial chemical trigger that starts an AOP. Over the past 3 years the AOP conceptual framework has gained a large amount of momentum in toxicology as an alternative to animal methods, and so the MIE has come into the spotlight. What is an MIE? How can MIEs be measured or predicted? What research is currently contributing to our understanding of MIEs? In this Perspective we outline answers to these key questions.The authors acknowledge financial support from Unilever

Tie-2 regulates the stemness and metastatic properties of prostate cancer cells.

Ample evidence supports that prostate tumor metastasis originates from a rare population of cancer cells, known as cancer stem cells (CSCs). Unfortunately, little is known about the identity of these cells, making it difficult to target the metastatic prostate tumor. Here, for the first time, we report the identification of a rare population of prostate cancer cells that express the Tie-2 protein. We found that this Tie-2High population exists mainly in prostate cancer cell lines that are capable of metastasizing to the bone. These cells not only express a higher level of CSC markers but also demonstrate enhanced resistance to the chemotherapeutic drug Cabazitaxel. In addition, knockdown of the expression of the Tie-2 ligand angiopoietin (Ang-1) led to suppression of CSC markers, suggesting that the Ang-1/Tie-2 signaling pathway functions as an autocrine loop for the maintenance of prostate CSCs. More importantly, we found that Tie-2High prostate cancer cells are more adhesive than the Tie-2Low population to both osteoblasts and endothelial cells. Moreover, only the Tie-2High, but not the Tie-2Low cells developed tumor metastasis in vivo when injected at a low number. Taken together, our data suggest that Tie-2 may play an important role during the development of prostate tumor metastasis.published_or_final_versio

Using Molecular Initiating Events To Generate 2D Structure-Activity Relationships for Toxicity Screening

Molecular initiating events (MIEs) can be boiled down to chemical interactions. Chemicals that interact must have intrinsic properties that allow them to exhibit this behavior, be these properties stereochemical, electronic, or otherwise. In an attempt to discover some of these chemical characteristics, we have constructed structural alert-style structure-activity relationships (SARs) to computationally predict MIEs. This work utilizes chemical informatics approaches, searching the ChEMBL database for molecules that bind to a number of pharmacologically important human toxicology targets, including G-protein coupled receptors, enzymes, ion channels, nuclear receptors, and transporters. By screening these compounds to find common 2D fragments and combining this approach with a good understanding of the literature, bespoke 2D structural alerts have been written. These SARs form the beginning of a tool for screening novel chemicals to establish the kind of interactions that they may be able to make in humans. These SARs have been run through an internal validation to test their quality, and the results of this are also discussed. MIEs have proven to be difficult to find and characterize, but we believe we have taken a key first step with this work.Unileve

Using Molecular Initiating Events To Generate 2D Structure-Activity Relationships for Toxicity Screening

Molecular initiating events (MIEs) can be boiled down to chemical interactions. Chemicals that interact must have intrinsic properties that allow them to exhibit this behavior, be these properties stereochemical, electronic, or otherwise. In an attempt to discover some of these chemical characteristics, we have constructed structural alert-style structure-activity relationships (SARs) to computationally predict MIEs. This work utilizes chemical informatics approaches, searching the ChEMBL database for molecules that bind to a number of pharmacologically important human toxicology targets, including G-protein coupled receptors, enzymes, ion channels, nuclear receptors, and transporters. By screening these compounds to find common 2D fragments and combining this approach with a good understanding of the literature, bespoke 2D structural alerts have been written. These SARs form the beginning of a tool for screening novel chemicals to establish the kind of interactions that they may be able to make in humans. These SARs have been run through an internal validation to test their quality, and the results of this are also discussed. MIEs have proven to be difficult to find and characterize, but we believe we have taken a key first step with this work.Unileve