Overexpression of Flii during murine embryonic development increases symmetrical division of epidermal progenitor cells

Epidermal progenitor cells divide symmetrically and asymmetrically to form stratified epidermis and hair follicles during late embryonic development. Flightless I (Flii), an actin remodelling protein, is implicated in Wnt/β-cat and integrin signalling pathways that govern cell division. This study investigated the effect of altering Flii on the divisional orientation of epidermal progenitor cells (EpSCs) in the basal layer during late murine embryonic development and early adolescence. The effect of altering Flii expression on asymmetric vs. symmetric division was assessed in vitro in adult human primary keratinocytes and in vivo at late embryonic development stages (E16, E17 and E19) as well as adolescence (P21 day-old) in mice with altered Flii expression (Flii knockdown: Flii(+/-), wild type: WT, transgenic Flii overexpressing: Flii(Tg/Tg)) using Western blot and immunohistochemistry. Flii(+/-) embryonic skin showed increased asymmetrical cell division of EpSCs with an increase in epidermal stratification and elevated talin, activated-Itgb1 and Par3 expression. Flii(Tg/Tg) led to increased symmetrical cell division of EpSCs with increased cell proliferation rate, an elevated epidermal SOX9, Flap1 and β-cat expression, a thinner epidermis, but increased hair follicle number and depth. Flii promotes symmetric division of epidermal progenitor cells during murine embryonic development.Gink N. Yang, Parinaz Ahangar, Xanthe L. Strudwick , Zlatko Kopecki and Allison J. Cowi

Attenuation of flightless I increases human pericyte proliferation, migration and angiogenic functions and improves healing in murine diabetic wounds

Pericytes are peri-vascular mural cells which have an important role in the homeostatic regulation of inflammatory and angiogenic processes. Flightless I (Flii) is a cytoskeletal protein involved in regulating cellular functions, but its involvement in pericyte activities during wound healing is unknown. Exacerbated inflammation and reduced angiogenesis are hallmarks of impaired diabetic healing responses, and strategies aimed at regulating these processes are vital for improving healing outcomes. To determine the effect of altering Flii expression on pericyte function, in vitro and in vivo studies were performed to assess the effect on healing, inflammation and angiogenesis in diabetic wounds. Here, we demonstrated that human diabetic wounds display upregulated expression of the Flii protein in conjunction with a depletion in the number of platelet derived growth factor receptor β (PDGFRβ) +/ neural glial antigen 2 (NG2) + pericytes present in the dermis. Human pericytes were found to be positive for Flii and attenuating its expression in vitro through siRNA knockdown led to enhanced proliferation, migration and angiogenic functions. Genetic knockdown of Flii in a streptozotocin-induced murine model of diabetes led to increased numbers of pericytes within the wound. This was associated with dampened inflammation, an increased rate of angiogenic repair and improved wound healing. Our findings show that Flii expression directly impacts pericyte functions, including proliferation, motility and angiogenic responses. This suggests that Flii regulation of pericyte function may be in part responsible for the changes in pericyte-related processes observed in diabetic wounds.Hannah M Thomas, Parinaz Ahangar, Benjamin R Hofma, Xanthe L Strudwick, Robert Fitridge, Stuart J Mills and Allison J Cowi

Human multipotent adult progenitor cell-conditioned medium improves wound healing through modulating inflammation and angiogenesis in mice

Background: Stem cell therapies have been widely investigated for their healing effects. However, the translation of these therapies has been hampered by the requirement to deliver live allogeneic or autologous cells directly to the wound in a clinical setting. Multipotent adult progenitor cells (MAPC® cells) are a subpopulation of bone marrow-derived adherent stem cells that secrete a wide range of factors known to accelerate the wound healing process. The aim of this study was to determine the impact of MAPC cells secretome on healing outcomes without the presence of MAPC cells. Methods: The effect of MAPC-conditioned medium (MAPC-CM) on the capacity of keratinocytes, fibroblasts and endothelial cells to migrate and proliferate was determined in vitro using scratch wound closure and WST1 assay, respectively. The effect of MAPC-CM on collagen deposition and angiogenesis was also assessed using in vitro methods. Additionally, two excisional wounds were created on the dorsal surface of mice (n = 8/group) and 100 μL of 20× MAPC-CM were intradermally injected to the wound margins. Wound tissues were collected at 3, 7 and 14 days post-wounding and stained with H&E for microscopic analysis. Immunohistochemistry was performed to investigate inflammation, angiogenesis and collagen deposition in the wounds. Results: Skin fibroblasts, keratinocytes and endothelial cells treated with MAPC-CM all showed improved rates of scratch closure and increased cellular proliferation. Moreover, fibroblasts treated with MAPC-CM deposited more collagens I and III and endothelial cells treated with MAPC-CM showed increased capillary tube formation. Murine excisional wounds intradermally injected with MAPC-CM showed a significant reduction in the wound area and an increase in the rate of reepithelialisation. The results also showed that inflammatory cell infiltration was decreased while an increase in angiogenesis, as well as collagens I and III expressions, was observed. Conclusion: These findings suggest that factors produced by MAPC cells can have an important effect on cutaneous wound healing by affecting skin cell proliferation and migration, balancing inflammation and improving the formation of extracellular matrix and angiogenesis. Development of stem cell-free therapy for the treatment of wounds may be a more clinically translatable approach for improving healing outcomes.Parinaz Ahangar, Stuart J. Mills, Louise E. Smith, Xanthe L. Strudwick, Anthony E. Ting, Bart Vaes, and Allison J. Cowi

Cognitive Function in Children With Type 1 Diabetes: A meta-analysis

OBJECTIVE—To quantify the magnitude and pattern of cognitive difficulties in pediatric type 1 diabetes as well as the effects associated with earlier disease onset and severe hypoglycemia

Interpreting physical performance in professional soccer match-play: Should we be more pragmatic in our approach?

Academic and practitioner interest in the physical performance of male professional soccer players in the competition setting determined via time-motion analyses has grown substantially over the last four decades leading to a substantial body of published research and aiding development of a more systematic evidence-based framework for physical conditioning. Findings have forcibly shaped contemporary opinions in the sport with researchers and practitioners frequently emphasising the important role that physical performance plays in match outcomes. Time-motion analyses have also influenced practice as player conditioning programmes can be tailored according to the different physical demands identified across individual playing positions. Yet despite a more systematic approach to physical conditioning, data indicate that even at the very highest standards of competition, the contemporary player is still susceptible to transient and end-game fatigue. Over the course of this article, the author suggests that a more pragmatic approach to interpreting the current body of time-motion analysis data and its application in the practical setting is nevertheless required. Examples of this are addressed using findings in the literature to examine: a) the association between competitive physical performance and ‘success’ in professional soccer, b) current approaches to interpreting differences in time-motion analysis data across playing positions and, c) whether data can realistically be used to demonstrate the occurrence of fatigue in match-play. Gaps in the current literature and directions for future research are also identified

Physiological factors facilitating the persistence of Pocillopora aliciae and Plesiastrea versipora in temperate reefs of south-eastern Australia under ocean warming

High-latitude reefs are suboptimal coral habitats, but such habitats are increasingly considered to be potential refugia from climate change for range-shifting coral reef species. Notably, tropical reef fish have been observed along the south-east coast of Australia, but their establishment on temperate rocky reefs is currently limited by winter minimum temperatures and other resource needs, such as structurally complex habitats typical of tropical reefs. Recent expansion of the branching subtropical coral Pocillopora aliciae in rocky reefs near Sydney (34° S) could diversify the architectural structure of temperate marine environments, thereby providing potential shelter for tropical reef taxa in warming seas. Here, we investigated whether future environmental conditions (i.e. temperature increase) can influence the dominance of the subtropical branching coral P. aliciae over the resident encrusting coral Plesiastrea versipora in coastal Sydney by characterising physiological (e.g. metabolic stability) and behavioural (e.g. interspecific competitive hierarchy) traits that contribute to their competitive fitness. Our results suggest that a metabolic response, mediated by sterol and lipid metabolic pathways and provision of antioxidants, allows P. aliciae to reduce cellular stress and withstand exposure to short-term increased temperature. Conversely, P. versipora was more susceptible to heat exposure with no metabolic mediation observed. While P. versipora displayed greater aggressive behaviour when in direct contact with P. aliciae under all temperature conditions, the superior physiological and metabolic flexibility under increased temperatures of P. aliciae suggests that this species will likely outperform P. versipora under future increased temperatures. Such contrasting responses to environmental change would facilitate shifts in coral community and functional composition that could support further tropicalisation of coastal New South Wales

Coherent control of orbital wavefunctions in the quantum spin liquid Tb2Ti2O7Tb_{2}Ti_{2}O_{7}

Resonant driving of electronic transitions with coherent laser sources creates quantum coherent superpositions of the involved electronic states. Most time-resolved studies have focused on gases or isolated subsystems embedded in insulating solids, aiming for applications in quantum information. Here, we demonstrate coherent control of orbital wavefunctions in pyrochlore $Tb_{2}Ti_{2}O_{7}$, which forms an interacting spin liquid ground state. We show that resonant excitation with a strong THz pulse creates a coherent superposition of the lowest energy Tb 4f states before the magnetic interactions eventually dephase them. The coherence manifests itself as a macroscopic oscillating magnetic dipole, which is detected by ultrafast resonant x-ray diffraction. The induced quantum coherence demonstrates coherent control of orbital wave functions, a new tool for the ultrafast manipulation and investigation of quantum materials

Breast compression – An exploration of problem solving and decision-making in mammography

Objective: Breast compression decreases radiation dose and reduces potential for motion and geometric unsharpness, yet there is variability in applied compression force within and between some centres. This article explores the problem solving process applied to the application of breast compression force from the mammography practitioners' perspective. Methods: A qualitative analysis was undertaken using an existing full data set of transcribed qualitative data collected in a phenomenological study of mammography practitioner values, behaviours and beliefs. The data emerged from focus groups conducted at six NHS breast screening centres in England (participant n = 41), and semi-structured interviews with mammography educators (n = 6). A researcher followed a thematic content analysis process to extract data related to mammography compression problem solving, developing a series of categories, themes and sub-themes. Emerging themes were then peer-validated by two other researchers, and developed into a model of practice. Results: Seven consecutive stages contributed towards compression force problem solving: assessing the request; first impressions; explanations and consent; handling the breast and positioning; applying compression force; final adjustments; feedback. The model captures information gathering, problem framing, problem solving and decision making which inform an ‘ideal’ compression scenario. Behavioural problem solving, heuristics and intuitive decision making are reflected within this model. Conclusion: The application of compression should no longer be considered as one single task within mammography, but is now recognised as a seven stage problem solving continuum. This continuum model is the first to be applied to mammography, and is adaptable and transferable to other radiography practice settings

Association football and the representation of homosexuality by the print media: a case study of Anton Hysén

In March 2011 Anton Hysén (a semi-professional footballer currently playing in the Swedish fourth division) became only the second association football (soccer) player of any professional disposition to publicly declare his homosexuality whilst still playing the game. This article provides a textual analysis of the print media’s reaction to Hysén coming out and examines whether, in 2011, they portray more inclusive notions towards homosexuality than they did in 1990 when British footballer Justin Fashanu came out. The results advance inclusive masculinity theory as a number of print media sources (mostly British) interview Hysén in the weeks immediately after he came out and publish articles that challenge homophobia. Highlighting a change since 1990, a significant number of articles stress the need for the key stakeholders in football (players, fans, clubs, agents, the authorities and the media) to accept gay players

The within-participant correlation between perception of effort and heart rate-based estimations of training load in elite soccer players.

The measurement of relative physiological stress during training is important because this is the stimulus for the long-term adaptive response. Measurements of perceived exertion (RPE) have been reported to correlate with the heart rate during field-based training sessions. Nevertheless, there are few studies on how well RPE tracks with the heart rate over repeated training sessions in elite soccer players. Therefore, we aimed to quantify the within-participant correlations between variability in session-RPE (sRPE) and the heart rate in elite male soccer players, and to determine whether the playing position moderated these correlations. The field-based training of four central defenders, four wide defenders, six central midfielders, two wide midfielders and three attackers from an elite English Premier League squad were monitored over an entire in-season competitive period, giving a total of 1010 individual training sessions for study. Correlations between session-RPE and heart rates were quantified using a within-participant model. The correlation between changes in sRPE and heart rates was r = 0.75 (95% CI: 0.71-0.78). This correlation remained high across the various player positions (wide-defender, r = 0.81; central-defender, r = 0.74; wide midfielder, r = 0.70; central midfielder, r = 0.70; attacker, r = 0.84; P < 0.001). The correlation between changes in RPE and heart rates, measured during a season-long period of field-based training, is high in a sample of elite soccer players