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"Simon, M"
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Cellular adaptation to hypoxia through hypoxia inducible factors and beyond
Molecular oxygen (O2) sustains intracellular bioenergetics and is consumed by numerous biochemical reactions, making it essential for most species on Earth. Accordingly, decreased oxygen concentration (hypoxia) is a major stressor that generally subverts life of aerobic species and is a prominent feature of pathological states encountered in bacterial infection, inflammation, wounds, cardiovascular defects and cancer. Therefore, key adaptive mechanisms to cope with hypoxia have evolved in mammals. Systemically, these adaptations include increased ventilation, cardiac output, blood vessel growth and circulating red blood cell numbers. On a cellular level, ATP-consuming reactions are suppressed, and metabolism is altered until oxygen homeostasis is restored. A critical question is how mammalian cells sense oxygen levels to coordinate diverse biological outputs during hypoxia. The best-studied mechanism of response to hypoxia involves hypoxia inducible factors (HIFs), which are stabilized by low oxygen availability and control the expression of a multitude of genes, including those involved in cell survival, angiogenesis, glycolysis and invasion/metastasis. Importantly, changes in oxygen can also be sensed via other stress pathways as well as changes in metabolite levels and the generation of reactive oxygen species by mitochondria. Collectively, this leads to cellular adaptations of protein synthesis, energy metabolism, mitochondrial respiration, lipid and carbon metabolism as well as nutrient acquisition. These mechanisms are integral inputs into fine-tuning the responses to hypoxic stress.The transcriptional response to hypoxia and the role of hypoxia inducible factors have been extensively studied. Yet, hypoxic cells also adapt to hypoxia by modulating protein synthesis, metabolism and nutrient uptake. Understanding these processes could shed light on pathologies associated with hypoxia, including cardiovascular diseases and cancer, and disease mechanisms, such as inflammation and wound repair.
Journal Article
Depression in primary care : evidence and practice
\"Although depression is a major cause of illness and disability, the quality of care offered is often poor. Research evidence demonstrating how the quality of primary care can be improved is dispersed in different academic journals and written in technical jargon. Depression in Primary Care: Evidence and Practice summarizes this research in a clear and useable format. This collection of high quality reviews of research evidence takes the form of a series of clinical and economic evaluations. Each provides a clear summary of the best evidence from trials and an accessible 'how to do it' guide, written by international experts. Global approaches towards the organization and delivery of primary care for depression are presented, from the UK, North America, Europe and the developing world. An important source of practical guidance about how to implement quality improvement programs in clinical practice, this book will assist practitioners, researchers and policy makers alike. - Combines clear evidence summaries with a simple and practical guide about how to implement quality improvement programmes in practice - Prepared by international experts and of interest and relevance in all countries and healthcare settings - Addresses a major healthcare priority identified by the World Health Organization, US Agency for Healthcare Research and UK National Institute for Clinical Excellence\"--Provided by publisher.
Book
Protein digestion and absorption: the influence of food processing
The rates of dietary protein digestion and absorption can be significantly increased or decreased by food processing treatments such as heating, gelling and enzymatic hydrolysis, with subsequent metabolic impacts, e.g. on muscle synthesis and glucose homeostasis. This review examines in vivo evidence that industrial and domestic food processing modify the kinetics of amino acid release and absorption following a protein-rich meal. It focuses on studies that used compositionally-matched test meals processed in different ways. Food processing at extremely high temperature at alkaline pH and/or in the presence of reducing sugars can modify amino acid sidechains, leading to loss of bioavailability. Some protein-rich food ingredients are deliberately aggregated, gelled or hydrolysed during manufacture. Hydrolysis accelerates protein digestion/absorption and increases splanchnic utilisation. Aggregation and gelation may slow or accelerate proteolysis in the gut, depending on the aggregate/gel microstructure. Milk, beef and eggs are heat processed prior to consumption to eliminate pathogens and improve palatability. The temperature and time of heating affect protein digestion and absorption rates, and effects are sometimes non-linear. In light of a dietary transition away from animal proteins, more research is needed on how food processing affects digestion and absorption of non-animal proteins. Food processing modifies the microstructure of protein-rich foods, and thereby alters protein digestion and absorption kinetics in the stomach and small intestine. Exploiting this principle to optimise metabolic outcomes requires more human clinical trials in which amino acid absorption rates are measured and food microstructure is explicitly considered, measured and manipulated.
Journal Article
Fabrication Methods for Microfluidic Devices: An Overview
Microfluidic devices offer the potential to automate a wide variety of chemical and biological operations that are applicable for diagnostic and therapeutic operations with higher efficiency as well as higher repeatability and reproducibility. Polymer based microfluidic devices offer particular advantages including those of cost and biocompatibility. Here, we describe direct and replication approaches for manufacturing of polymer microfluidic devices. Replications approaches require fabrication of mould or master and we describe different methods of mould manufacture, including mechanical (micro-cutting; ultrasonic machining), energy-assisted methods (electrodischarge machining, micro-electrochemical machining, laser ablation, electron beam machining, focused ion beam (FIB) machining), traditional micro-electromechanical systems (MEMS) processes, as well as mould fabrication approaches for curved surfaces. The approaches for microfluidic device fabrications are described in terms of low volume production (casting, lamination, laser ablation, 3D printing) and high-volume production (hot embossing, injection moulding, and film or sheet operations).
Journal Article
Impressionist France : visions of nation from Le Gray to Monet
\"Between 1850 and 1880, Impressionist landscape painting and early forms of photography flourished within the arts in France. In the context of massive social and political change that also marked this era, painters and photographers composed competing visions of France as modern and industrialized or as rural and anti-modern. Impressionist France explores the resonances between landscape art and national identity as reflected in the paintings and photographs made during this period, examining and illustrating in particular the works of key artists such as âEdouard Baldus, Gustave Le Gray, the Bisson Freres, âEdouard Manet, Jean-Franًcois Millet, Claude Monet, Charles Negre, and Camille Pissarro. This ambitious premise focuses on the whole of France, exploring the relationship between landscape art and the notion of French nationhood across the country's varied and spectacular landscapes in seven geographical sections and four scholarly essays, which provide new information regarding the production and impact of French Impressionism. \"-- Provided by publisher.
Book
Treatment of atherosclerosis by macrophage-biomimetic nanoparticles via targeted pharmacotherapy and sequestration of proinflammatory cytokines
Vascular disease remains the leading cause of death and disability, the etiology of which often involves atherosclerosis. The current treatment of atherosclerosis by pharmacotherapy has limited therapeutic efficacy. Here we report a biomimetic drug delivery system derived from macrophage membrane coated ROS-responsive nanoparticles (NPs). The macrophage membrane not only avoids the clearance of NPs from the reticuloendothelial system, but also leads NPs to the inflammatory tissues, where the ROS-responsiveness of NPs enables specific payload release. Moreover, the macrophage membrane sequesters proinflammatory cytokines to suppress local inflammation. The synergistic effects of pharmacotherapy and inflammatory cytokines sequestration from such a biomimetic drug delivery system lead to improved therapeutic efficacy in atherosclerosis. Comparison to macrophage internalized with ROS-responsive NPs, as a live-cell based drug delivery system for treatment of atherosclerosis, suggests that cell membrane coated drug delivery approach is likely more suitable for dealing with an inflammatory disease than the live-cell approach.
Due to poor specificity, the current pharmacotherapy of atherosclerosis has limited therapeutic efficacy. Here, the authors show that a macrophage-biomimetic nanomedicine effectively alleviates atherosclerosis via targeted pharmacotherapy and sequestration of proinflammatory cytokines and chemokines.
Journal Article
Orogenesis : the making of mountains
\"Orogenesis, the process of mountain building, occurs when two tectonic plates collide--either forcing material upwards to form mountain belts such as the Alps or Himalayas or causing one plate to be subducted below the other, resulting in volcanic mountain chains such as the Andes. Integrating the approaches of structural geology and metamorphism, this book provides an up-to-date overview of orogenic research, and an introduction to the physico-chemical properties of mountain belts. Global examples are explored, the interactioning roles of temperature and deformation in the orogenic process are reviewed, and important new concepts such as channel flow are explained. This book provides a valuable introduction to this fast-moving field for advanced undergraduate and graduate students of structural geology, plate tectonics and geodynamics, and will also provide a vital overview of research for academics and researchers working in related fields including petrology, geochemistry and sedimentology.\"-- Provided by publisher.
Book
“It Defines Who I Am” or “It’s Something I Have”: What Language Do Autistic Australian Adults on the Autism Spectrum Prefer?
There has been a recent shift from person-first to identity-first language to describe autism. In this study, Australian adults who reported having a diagnosis of autism (N = 198) rated and ranked autism-terms for preference and offensiveness, and explained their choice in free-text. ‘Autistic’, ‘Person on the Autism Spectrum’, and ‘Autistic Person’ were rated most preferred and least offensive overall. Ranked-means showed ‘person on the autism spectrum’ was the most preferred term overall. Six qualitative themes reflected (1) autism as core to, or (2) part of one’s identity, (3) ‘spectrum’ reflecting diversity, (4) the rejection of stigmatising and (5) medicalised language, and (6) pragmatics. These findings highlight the importance of inclusive dialogue regarding individual language preference.
Journal Article