Enzyme-responsive RGD-functionalised substrates to influence mesenchymal stem cells

Regenerative medicine is a rapidly expanding field of science with an exhaustive volume of literature published on the different strategies used to repair diseased or injured tissue. Recently, stem cells have emerged as a promising candidate in this regard owing to their involvement in embryogenesis, homeostatic turnover and normal tissue repair. Despite this potential, stem cell-based therapies have yet to be fully established in a clinical setting owing to complications associated with their limited numbers, immunogenicity, tumour formation and the ethical considerations surrounding their usage. Furthermore, the mechanisms underlying stem cell differentiation are complex and not fully understood, thus expanding stem cell numbers and predictably directing their commitment toward a desired lineage, represent a major challenge for tissue regeneration strategies. In an attempt to circumvent these problems there is currently a rising interest in biomimetic materials that aim to reproduce the physical architecture, chemical composition and plasticity of the in vivo extracellular environment in an in vitro setting. Furthermore, the need to expand stem cells while maintaining the stem cell phenotype has prompted many to look to the stem cell niche for answers. At the centre of most cellular responses to the physical cues embedded within the ECM are integrins. Integrins are mechanosensitive membrane spanning receptors that link the ECM to the cytoskeleton and thus transmit information from outside the cell into the nucleus, affecting gene transcription via a series of intracellular signalling cascades. To that end, many biomimetic systems incorporate integrin- binding ligands such as the tripeptide RGD. In this work glass surfaces functionalised with RGD were used to study changes in mesenchymal stem cell (MSC) responses to increased integrin binding by using an enzymatic ‘switch’ to reveal surface-bound RGD peptides that have been masked by a large chemical cap (Fmoc). The results of this work demonstrated that RGD- functionalised substrates can support MSC growth and influence them to commit to a particular fate. MSCs on surfaces where integrin-ligand binding was blocked developed a fibroblast-like phenotype whereas MSC grown on surfaces that were later enzymatically digested to reveal the underlying RGD ligands developed an osteoblast phenotype similar to RGD controls

The RoboCOS Study : Development of an international core outcome set for the comprehensive evaluation of patient, surgeon, organisational and population level impacts of robotic assisted surgery

ACKNOWLEDGEMENTS We would like to thank sincerely all those who contributed to the interviews, the focus group, the Delphi survey and the consensus meeting, and Paul Manson (Health Services Research Unit, University of Aberdeen) for helping to retrieve full text copies of reports identified by the literature search. We also thank HSRU (Health Services Research Unit) at University of Aberdeen for providing support for this work. Funding: The study was funded from NHS Grampian Endowment Fund and the University of Aberdeen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2023 Robertson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Peer reviewedPublisher PD

Reply to White et al.: Providing perspective on ocean conservation targets

In O’Leary et al. (2016), we undertook a quantitative synthesis (rather than a true statistical meta-analysis) of research to consider how much of the sea should be protected to achieve various conservation and management goals. We aimed to provide perspective on the appropriateness of global marine protected area coverage targets, particularly the United Nations Sustainable Development Goal 14/Convention on Biological Diversity goals to protect >10% of the sea by 2020. White et al. (2017) question the methodology of our approach, and we offer the following response

A Mammoth Task:Identifying Mammoth Ivory Using Raman Spectroscopy

A mammoth tusk contains an inner mineralized protein matrix of dentine and an outer layer of cementum. Enamel is only present on the tips of the tusks of young mammoths, and is worn away in older mammoths. Dentine is a mineralized connective tissue containing the inorganic component of dahlite [Ca10(PO4)6(CO3)H2O]. To determine the species from which ivory originated, often destructive methods are used. Raman spectroscopy is a non-invasive laser-based technique that has proven applications in the chemistry of mineralized tissue. Ivory and bone have similar biochemical properties. The aim of this study is to test the hypothesis that mammoth ivory is identifiable using Raman spectroscopy. Mammoth tusks were kindly loaned from the Natural History Museum, London, UK. All tusks were from the species Mammuthus primigenius discovered either in Lyakhov Islands or next to the Yenisei river, Krasnoyarsk (Siberia, Russia) and span the Pleistocene epoch, Cenerzoic era. The ivory was scanned with an inVia Raman micro spectrometer (Renishaw Ltd) equipped with a x50 objective lens and a 785nm laser. Spectra were acquired using line maps on cross sections of two samples, and individual spectral points were acquired independently at random or at points of interest on all samples. Data was analysed with principal component analysis (PCA) using an in-house Matlab script. To date, the results of this study establishes that well preserved mammoth ivory can be characterized through the comparison of peak intensity ratios between organic v(CH) collagen peaks and inorganic v(PO) hydroxyapatite peaks. Differences were observed in the hydroxyapatite peak from spectra acquired near the medulla of the tusk compared to the cortex. This suggests that the tusk is more mineralized towards the cortex compared to dentine found closer to the medulla. A comparison of the average data from each mammoth tusk demonstrated that the mammoth spectral ‘fingerprint’ remains similar for all samples, though there was some inter-variation in the mineralization of the tusks from mammoths of the same species. Further work in this study aims to compare the Raman spectra between mammoth and elephant ivory. This will have direct applications in archaeology, as the species from which an ivory sample is found could be identified without the need for more traditional, destructive techniques of valuable artefacts. Additionally, international trade regulations require proof of the species from which ivory is obtained. The information obtained in this study will be valuable in developing quick and non-destructive methods for the identification of ivory from an unknown origin

CHoosing Active Role Models to INspire Girls (CHARMING): protocol for a cluster randomised feasibility trial of a school-based, community-linked programme to increase physical activity levels in 9-10-year-old girls.

BACKGROUND: In the UK, there is evidence that girls' physical activity tends to decline to a greater extent than boys as they enter adolescence. 'Role models' could play a vital role in inspiring girls to become or remain physically active. The CHARMING Programme is a primary school-based community linked role-model programme, co-developed in 2016, with children, parents, schools and wider stakeholders. It involves different types of physical activity delivered for 1-h each week by a community provider and peer role models (e.g. older girls from secondary schools) joining in with the sessions. The programme ultimately aims to increase and sustain physical activity levels among 9-10-year-old girls. This study aims to assess the feasibility and acceptability of the CHARMING Programme and of evaluating it using a randomised trial. METHODS: This study is a feasibility cluster randomised controlled trial, with embedded process evaluation and health economic evaluation. Approximately 90 Year 5 (i.e. 9-10-year-old) girls will be recruited across six primary schools in Mid-South Wales. Participating schools will be allocated to the programme: control on a 2:1 basis; four intervention schools will run the CHARMING Programme and two will continue with usual practice. A survey and accelerometer will be administered at baseline and repeated at 12 months. Interviews and focus groups will be conducted post-intervention delivery. The primary aim is to assess feasibility of a future randomised trial via the recruitment of schools, participants and role models; randomisation; retention; reach; data collection completion rates; programme adherence; and programme fidelity, views on intervention acceptability and programme barriers and facilitators. Secondary aims are to evaluate established physical activity outcome measures for children plus additional health economic outcomes for inclusion in a future full-scale trial. DISCUSSION: The results of this study will inform decisions on whether and how to proceed to a full-scale evaluation of the effectiveness and cost-effectiveness of the CHARMING Programme to improve or sustain physical activity. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN36223327. Registered March 29, 2021

Can personality close the intention-behavior gap for healthy eating? An examination with the HEXACO personality traits

The aim of this study was to investigate the predictive and moderating effects of HEXACO personality factors, in addition to theory of planned behavior (TPB) variables, on fruit and vegetable consumption. American college students (N = 1036) from 24 institutions were administered the TPB, HEXACO and a self-reported fruit and vegetable consumption measure. The TPB predicted 11–17% of variance in fruit and vegetable consumption, with greater variance accounted for in healthy weight compared to overweight individuals. Personality did not significantly improve the prediction of behavior above TPB constructs; however, conscientiousness was a significant incremental predictor of intention in both healthy weight and overweight/obese groups. While support was found for the TPB as an important predictor of fruit and vegetable consumption in students, little support was found for personality factors. Such findings have implications for interventions designed to target students at risk of chronic disease

Discrimination of ivory from extant and extinct elephant species using Raman spectroscopy : A potential non-destructive technique for combating illegal wildlife trade

The use of elephant ivory as a commodity is a factor in declining elephant populations. Despite recent worldwide elephant ivory trade bans, mammoth ivory trade remains unregulated. This complicates law enforcement efforts, as distinguishing between ivory from extant and extinct species requires costly, destructive and time consuming methods. Elephant and mammoth ivory mainly consists of dentine, a mineralized connective tissue that contains an organic collagenous component and an inorganic component of calcium phosphate minerals, similar in structure to hydroxyapatite crystals. Raman spectroscopy is a non-invasive laser-based technique that has previously been used for the study of bone and mineral chemistry. Ivory and bone have similar biochemical properties, making Raman spectroscopy a promising method for species identification based on ivory. This study aimed to test the hypothesis that it is possible to identify differences in the chemistry of mammoth and elephant ivory using Raman spectroscopy. Mammoth and elephant tusks were obtained from the Natural History Museum in London, UK. Included in this study were eight samples of ivory from Mammuthus primigenius, two samples of carved ivory bangles from Africa (Loxodonta species), and one cross section of a tusk from Elephas maximus. The ivory was scanned using an inVia Raman micro spectrometer equipped with a x50 objective lens and a 785nm laser. Spectra were acquired using line maps and individual spectral points were acquired randomly or at points of interest on all samples. The data was then analysed using principal component analysis (PCA) with use of an in-house MATLAB script. Univariate analysis of peak intensity ratios of phosphate to amide I and III peaks, and carbonate to phosphate peaks showed statistical differences (

Dynamic surfaces for the study Of mesenchymal stem cell growth through adhesion regulation

Out of their niche environment, adult stem cells, such as mesenchymal stem cells (MSCs), spontaneously differentiate. This makes both studying these important regenerative cells and growing large numbers of stem cells for clinical use challenging. Traditional cell culture techniques have fallen short of meeting this challenge, but materials science offers hope. In this study, we have used emerging rules of managing adhesion/cytoskeletal balance to prolong MSC cultures by fabricating controllable nanoscale cell interfaces using immobilized peptides that may be enzymatically activated to change their function. The surfaces can be altered (activated) at will to tip adhesion/cytoskeletal balance and initiate differentiation, hence better informing biological mechanisms of stem cell growth. Tools that are able to investigate the stem cell phenotype are important. While large phenotypical differences, such as the difference between an adipocyte and an osteoblast, are now better understood, the far more subtle differences between fibroblasts and MSCs are much harder to dissect. The development of technologies able to dynamically navigate small differences in adhesion are critical in the race to provide regenerative strategies using stem cells