University of Leeds

About: University of Leeds is a education organization based out in Leeds, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 43481 authors who have published 101856 publications receiving 3672065 citations. The organization is also known as: Leeds University.

Piezo1 integration of vascular architecture with physiological force

Abstract: The mechanisms by which physical forces regulate endothelial cells to determine the complexities of vascular structure and function are enigmatic. Studies of sensory neurons have suggested Piezo proteins as subunits of Ca(2+)-permeable non-selective cationic channels for detection of noxious mechanical impact. Here we show Piezo1 (Fam38a) channels as sensors of frictional force (shear stress) and determinants of vascular structure in both development and adult physiology. Global or endothelial-specific disruption of mouse Piezo1 profoundly disturbed the developing vasculature and was embryonic lethal within days of the heart beating. Haploinsufficiency was not lethal but endothelial abnormality was detected in mature vessels. The importance of Piezo1 channels as sensors of blood flow was shown by Piezo1 dependence of shear-stress-evoked ionic current and calcium influx in endothelial cells and the ability of exogenous Piezo1 to confer sensitivity to shear stress on otherwise resistant cells. Downstream of this calcium influx there was protease activation and spatial reorganization of endothelial cells to the polarity of the applied force. The data suggest that Piezo1 channels function as pivotal integrators in vascular biology.

Climate variability and vulnerability to climate change: a review.

Abstract: The focus of the great majority of climate change impact studies is on changes in mean climate. In terms of climate model output, these changes are more robust than changes in climate variability. By concentrating on changes in climate means, the full impacts of climate change on biological and human systems are probably being seriously underestimated. Here, we briefly review the possible impacts of changes in climate variability and the frequency of extreme events on biological and food systems, with a focus on the developing world. We present new analysis that tentatively links increases in climate variability with increasing food insecurity in the future. We consider the ways in which people deal with climate variability and extremes and how they may adapt in the future. Key knowledge and data gaps are highlighted. These include the timing and interactions of different climatic stresses on plant growth and development, particularly at higher temperatures, and the impacts on crops, livestock and farming systems of changes in climate variability and extreme events on pest-weed-disease complexes. We highlight the need to reframe research questions in such a way that they can provide decision makers throughout the food system with actionable answers, and the need for investment in climate and environmental monitoring. Improved understanding of the full range of impacts of climate change on biological and food systems is a critical step in being able to address effectively the effects of climate variability and extreme events on human vulnerability and food security, particularly in agriculturally based developing countries facing the challenge of having to feed rapidly growing populations in the coming decades.

Biological reactions to wear debris in total joint replacement.

Abstract: The vast majority of total hip prostheses currently implanted consist of a hard metal or ceramic femoral head articulating against an ultra-high molecular weight polyethylene (UHMWPE) acetabular cup. Over the last 10 years, evidence has accumulated to show that these prostheses are prone to failure due to late aseptic loosening and few survive beyond 25 years. With an increasing need to implant hip prostheses in the younger, more active patient the need to understand the mechanisms of failure and to develop artificial hip joints using alternative materials have become major issues in the orthopaedic community. This review focuses initially on our current understanding of the biological reactions to UHMWPE prosthetic wear debris in vivo and in vitro since this is believed to be the main cause of late aseptic loosening. While the precise mechanisms of osteolysis induced by UHMWPE wear debris have not been elucidated, the major message to emerge is that it is not the wear volume that determines the biological response to the debris, but the concentration of the wear volume that is within the critical size range (0.2-0.8 micron) for macrophage activation. The review then considers whether the problem of wear-debris-induced osteolysis may be overcome with the use of new generation metal-on-metal or ceramic-on-ceramic prostheses. For metal-on-metal prostheses, the prospects for increasing the osteolysis free life of the implant are good but additional biological problems associated with the nanometre size and reactivity of the wear particles in vivo may emerge. For the ceramic-on-ceramic prostheses, although initial prospects are encouraging, more data are needed on the characteristics of the wear particles generated in vivo before predictions can be made. It is concluded that the pre-clinical testing of any new materials for joint replacement must include an analysis of the wear particle characteristics and their biological reactivity in addition to the usual assessment of wear.

Update of EULAR recommendations for the treatment of systemic sclerosis

Abstract: The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.