245 research outputs found
Collagen loss and impaired wound healing is associated with c-Myb deficiency
No full textData source: Supporting information, http://onlinelibrary.wiley.com.access.library.unisa.edu.au/doi/10.1002/path.2113/abstract#footer-support-infoCollagen type I serves as an abundant structural and signalling component of skin. It is also an established target gene of the transcription factor, c-Myb. When c-myb-/- embryos were examined it was observed that their skin was markedly thinner than normal. Importantly, immunohistochemical investigation showed complete absence of collagen type I. Although these homozygous knock-out embryos fail to develop beyond day 15, fibroblasts established from these embryos (mouse embryonic fibroblasts [MEFs]) show defective proliferative responses. Furthermore, in vitro scratch wound assays demonstrated that these c-myb-/- MEFs also exhibit slower closure than their wild-type counterparts. Embryonic lethality has meant that examination of the role of c-Myb in adult mouse skin has not been reported to date. However, in view of the abundance of collagen type I in normal skin, its role in skin integrity and the in vitro data showing proliferative and migration defects in c-myb-/- MEFs, we investigated the consequences of heterozygous c-myb loss in adult mice on the complex process of skin repair in response to injury. Our studies clearly demonstrate that heterozygous c-myb deficiency has a functional effect on wound repair, collagen type I levels and, in response to wounding, transforming growth factor-β1 (an important collagen stimulating factor) induction expression is aberrantly high. Manipulation of c-Myb may therefore provide new therapeutic opportunities for improving wound repair while uncontrolled expression may underpin some fibrotic disorders.Z Kopecki, MM Luchetti, DH Adams, X Strudwick, T Mantamadiotis, A Stoppacciaro, A Gabrielli, RG Ramsay, AJ Cowi
Systematic Bias between Running Speed and Metabolic Power Data in Elite Soccer Players : Influence of Drill Type
No full textThe aims of the present study were to: i) evaluate the agreement between estimates of highintensity activity during soccer small-sided games (SSGs) based on running speed alone and estimated metabolic power derived from a combination of running speed and acceleration; ii) evaluate whether any bias between the 2 approaches is dependent upon playing position or drill characteristics. 3 types of SSGs (5vs5, 7vs7 and 10vs10) were completed by 26 English Premier League outfield players. A total of 420 individual drill observations were collected over the playing season using portable global positioning system technology. High-intensity activity was estimated using the total distance covered at speeds > 14.4 km · h − 1 (TS) and the equivalent metabolic power threshold of > 20 W · kg − 1 (TP). We selected 0.2 as the minimally important standardised diff erence between methods. High-intensity demands were systematically higher (~100 %, p < 0.001) when expressed as TP vs. TS irrespective of playing position and SSG. The magnitude of this diff erence increased as the size of SSG decreased (p < 0.01) with a difference of ~200 % observed in the 5vs5 SSG. A greater diff erence between TP and TS was also evident in central defenders compared to other positions (p < 0.05) particularly during the 5vs5 SSG (~350 %). We conclude that the high-intensity demands of SSGs in elite soccer players are systematically underestimated by running speed alone particularly during “small” SSGs and especially for central defenders. Estimations of metabolic power provide a more valid estimation as to the true demands of SSGs
Monitoring training in elite soccer players : systematic bias between running speed and metabolic power data
No full textWe compared measurements of high-intensity activity during field-based training sessions in elite soccer players of different playing positions. Agreement was appraised between measurements of running speed alone and predicted metabolic power derived from a combination of running speed and acceleration. Data was collected during a 10-week phase of the competitive season from 26 English Premier League outfield players using global positioning system technology. High-intensity activity was estimated using the total distance covered at speeds >14.4 km · h−1 (TS) and the equivalent metabolic power threshold of >20 W · kg−1 (TP), respectively. We selected 0.2 as the minimally important standardised difference between methods. Mean training session TS was 478±300 m vs. 727±338 m for TP (p<0.001). This difference was greater for central defenders (~ 85%) vs. wide defenders and attackers (~ 60%) (p<0.05). The difference between methods also decreased as the proportion of high-intensity distance within a training session increased (R2=0.43; p<0.001). We conclude that the high-intensity demands of soccer training are underestimated by traditional measurements of running speed alone, especially in training sessions or playing positions associated with less high-intensity activity. Estimations of metabolic power better inform the coach as to the true demands of a training session
Wound Healing from an Actin Cytoskeletal Perspective
No full textWound healing requires a complex cascade of highly controlled and conserved cellular and molecular processes. These involve numerous cell types and extracellular matrix molecules regulated by the actin cytoskeleton. This microscopic network of filaments is present within the cytoplasm of all cells and provides the shape and mechanical support required for cell movement and proliferation. Here, an overview of the processes of wound healing are described from the perspective of the cell in relation to the actin cytoskeleton. Key points of discussion include the role of actin, its binding proteins, signaling pathways, and events that play significant roles in the phases of wound healing. The identification of cytoskeletal targets that can be used to manipulate and improve wound healing is included as an emerging area of focus that may inform future therapeutic approaches to improve healing of complex wounds.Parinaz Ahangar, Xanthe L. Strudwick, and Allison J. Cowi
Multifunctional roles of the actin-binding protein Flightless I in inflammation, cancer and wound healing
No full textFlightless I is an actin-binding member of the gelsolin family of actin-remodeling proteins that inhibits actin polymerization but does not possess actin severing ability. Flightless I functions as a regulator of many cellular processes including proliferation, differentiation, apoptosis, and migration all of which are important for many physiological processes including wound repair, cancer progression and inflammation. More than simply facilitating cytoskeletal rearrangements, Flightless I has other important roles in the regulation of gene transcription within the nucleus where it interacts with nuclear hormone receptors to modulate cellular activities. In conjunction with key binding partners Leucine rich repeat in the Flightless I interaction proteins (LRRFIP)1/2, Flightless I acts both synergistically and competitively to regulate a wide range of cellular signaling including interacting with two of the most important inflammatory pathways, the NLRP3 inflammasome and the MyD88-TLR4 pathways. In this review we outline the current knowledge about this important cytoskeletal protein and describe its many functions across a range of health conditions and pathologies. We provide perspectives for future development of Flightless I as a potential target for clinical translation and insights into potential therapeutic approaches to manipulate Flightless I functions.Xanthe L. Strudwick and Allison J. Cowi
[Photograph 2012.201.B0317.0117]
No full textPhotograph taken for a story in the Oklahoma Times newspaper. Caption: "Shepperd Strudwick and Olive Dunbar in "J. B.
IL-5-overexpressing mice exhibit eosinophilia and altered wound healing through mechanisms involving prolonged inflammation
No full textLeucocytes are essential in healing wounds and are predominantly involved in the inflammatory and granulation stages of wound repair. Eosinophils are granulocytic leucocytes and are specifically regulated by interleukin-5 (IL-5), a cytokine produced by T helper 2 (Th2) cells. To characterize more clearly the role of the IL-5 and eosinophils in the wound healing process, IL-5-overexpressing and IL-5-deficient mice were used as models of eosinophilia and eosinophil depletion, respectively. Our results reveal a significantly altered inflammatory response between IL-5-overexpressing and IL-5 knockout mice post-wounding. Healing was significantly delayed in IL-5-overexpressing mice with wounds gaping wider and exhibiting impaired re-epithelialization. A delay in collagen deposition was observed suggesting a direct effect on matrix synthesis. A significant increase in inflammatory cell infiltration, particularly eosinophils and CD4+ cells, one of the main cell types which secrete IL-5, was observed in IL-5-overexpressing mice wounds suggesting that one of the main roles of IL-5 in wound repair may be to promote the infiltration of eosinophils into healing wounds. Healing is delayed in IL-5-overexpressing mice and this corresponds to significantly increased levels of eosinophils and CD4+ cells within the wound site that may contribute to and exacerbate the inflammatory response, resulting in detrimental wound repair.Victoria D Leitch. Xanthe L Strudwick, Klaus I Matthaei, Lindsay A Dent and Allison J Cowin
Investigation of helium plasma jet-treated serum and cell media on the viability of skin cells
No full textThis study compares the differences in the viability of skin cells after culturing in cell medium supplemented with helium (He) plasma jet-treated serum and Dulbecco's Modified Eagle Medium (DMEM). HaCaT and HDFa cells were used as surrogates for the two major cell types of skin, i.e., keratinocytes and fibroblasts, respectively. A reduction in cell viability was observed for cells cultured in cell media supplemented with He plasma jet-treated serum and DMEM; however, cells were more sensitive to the He plasma jet-treated serum. HaCaT cells were more sensitive to He plasma jet-treated serum compared to HDFa cells. The decrease in the viability of HaCaT cells was not directly attributed to excessive oxidative stress (i.e., from reactive oxygen species generated by the He plasma jet). A possible explanation for the decrease in cell viability is that the He plasma jet treatment results in modification of the serum or DMEM, which decreases the bioavailability and/or bioefficacy of their essential components. In response to nutrient-deficiency, the cells may undergo autophagy, which can lead to a different form of cell death compared to apoptosis and necrosis. It will be important in the future to elucidate what essential components in cell media/serum are modified by plasma jets or other plasma sources utilised in biology and medicine research, and how these modifications alter cellular response.Rishabh Bhatia, Xanthe Strudwick, Allison J. Cowin, Endre J. Szil
The development of microfluidic-based western blotting: Technical advances and future perspectives
No full textOver the past two decades significant technical advancement in the field of western blotting has been made possible through the utilization of microfluidic technologies. In this review we provide a critical overview of these advancements, highlighting the advantages and disadvantages of each approach. Particular attention is paid to the development of now commercially available systems, including those for single cell analysis. This review also discusses more recent developments, including algorithms for automation and/or improved quantitation, the utilization of different materials/chemistries, use of projection electrophoresis, and the development of triBlots. Finally, the review includes commentary on future advances in the field based on current developments, and the potential of these systems for use as pointof-care devices in healthcare.Christopher T. Desire, R. Dario Arrua, Xanthe L. Strudwick, Zlatko Kopecki, Allison J. Cowin, Emily F. Hilde
Overexpression of Flii during murine embryonic development increases symmetrical division of epidermal progenitor cells
No full textData source: Supplementary material, https://doi.org/10.3390/ijms22158235Epidermal 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
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