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The combination of modern biotechnologies such as DNA synthesis, λ red recombineering, CRISPR-based editing and next-generation high-throughput sequencing increasingly enables precise manipulation of genes and genomes. Beyond rational design, these technologies also enable the targeted, and potentially continuous, introduction of multiple mutations. While this might seem to be merely a return to natural selection, the ability to target evolution greatly reduces fitness burdens and focuses mutation and selection on those genes and traits that best contribute to a desired phenotype, ultimately throwing evolution into fast forward. From unbiased mutagenesis to precision modification, in genes or whole genomes, researchers have a panoply of tools to direct evolution.

The City of Wroclaw, in cooperation with the National Cultural Centre (Warsaw), has asked Andreas Joh. Wiesand to prepare, together with experts from many different countries, a basic handbook which cover all relevant legal questions as well as main political consequences related to human rights and culture. The publication is to be presented in the context of the programme for Wroclaw, European Capital of Culture 2016 -- Source other than Library of Congress.

Across all branches of the immune system, the process of autophagy is fundamentally important in cellular development, function and homeostasis. Strikingly, this evolutionarily ancient pathway for intracellular recycling has been adapted to enable a high degree of functional complexity and specialization. However, although the requirement for autophagy in normal immune cell function is clear, the mechanisms involved are much less so and encompass control of metabolism, selective degradation of substrates and organelles and participation in cell survival decisions. We review here the crucial functions of autophagy in controlling the differentiation and homeostasis of multiple immune cell types and discuss the potential mechanisms involved.

The world is shaped by complexity. In this enlightening book, Nobel Prize winner Giorgio Parisi guides us through his unorthodox yet exhilarating work to show us how. It all starts with investigating the principles of physics by observing the sophisticated flight patterns of starlings. Studying the movements of these birds, he has realized, proves an illuminating way into understanding complex systems of all kinds - collections of everything from atoms to planets to other animals like ourselves. Along the way, Parisi reflects on the lessons he's taken from a life in pursuit of scientific truth - the importance of serendipity to the discovery of new ideas, the surprising kinship between physics and other fields of study and the value of science to a thriving society. In so doing, he removes the practice of science from the confines of the laboratory and into the real world.

The anti–interleukin-1 antibody canakinumab was effective at controlling and preventing recurrence of flares in autoimmune inflammatory diseases: familial Mediterranean fever, mevalonate kinase deficiency, and the TNF receptor–associated periodic syndrome.

Lonely Planet Best of Malaysia & Singapore is your passport to Malaysia and Singapore's top sights and most authentic experiences. Enjoy some of Malaysia's best food in charismatic George Town, hunt out giant rafflesia flowers in Sarawak or sing karaoke at the Jonker Walk Night Market, all with your trusted travel companion.

Key Points Interleukin-1 (IL-1) is a master cytokine in the pathogenesis of several diseases, inducing multiple pathways of inflammation. Inflammation is part of every disease, acute or chronic. Diseases in which monocytes and/or macrophages and neutrophils have a dominant role are called autoinflammatory diseases. By contrast, diseases in which T lymphocytes have a major role are termed autoimmune diseases. Autoimmune diseases are treated with glucocorticoids, immunosuppressive drugs as well as various anti-cytokine-based therapeutics that target the immune system. Autoinflammatory diseases are uniquely responsive to IL-1-blocking therapies and are less responsive to immunosuppressors. There are two forms of IL-1: IL-1α and IL-1β. Both trigger inflammation by binding to the same receptor. The IL-1 receptor antagonist anakinra binds to the IL-1 receptor and blocks the activity of both IL-1α and IL-1β. A broad spectrum of acute and inflammatory diseases are treated with anakinra. Neutralizing monoclonal antibodies to IL-1α, IL-1β and the IL-1 receptor have been developed to decrease the activity of IL-1. An orally active inhibitor of caspase 1, the enzyme that processes IL-1β into an active cytokine, has also been developed. Blocking IL-1 in individuals with rare inherited diseases reverses generalized as well as local inflammation. Common inflammatory diseases such as arthritis, gout, type 2 diabetes, dry eye syndrome and heart failure are also responsive to IL-1 blocking. The future of IL-1 drug development will involve an expansion of disease indications through controlled trials. Blockade of the pro-inflammatory cytokine interleukin-1 (IL-1) is emerging as an effective approach for the treatment of an increasing number of diseases. Here, Dinarello and colleagues discuss the pathogenic roles of IL-1, present therapeutic strategies aimed at modulating the activity of this cytokine and review clinical trial data for multiple indications. Interleukin-1 (IL-1) is a highly active pro-inflammatory cytokine that lowers pain thresholds and damages tissues. Monotherapy blocking IL-1 activity in autoinflammatory syndromes results in a rapid and sustained reduction in disease severity, including reversal of inflammation-mediated loss of sight, hearing and organ function. This approach can therefore be effective in treating common conditions such as post-infarction heart failure, and trials targeting a broad spectrum of new indications are underway. So far, three IL-1-targeted agents have been approved: the IL-1 receptor antagonist anakinra, the soluble decoy receptor rilonacept and the neutralizing monoclonal anti-IL-1β antibody canakinumab. In addition, a monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α antibody are in clinical trials.

Ageing is characterized by a progressive loss of cellular function that leads to a decline in tissue homeostasis, increased vulnerability and adverse health outcomes. Important advances in ageing research have now identified a set of nine candidate hallmarks that are generally considered to contribute to the ageing process and that together determine the ageing phenotype, which is the clinical manifestation of age-related dysfunction in chronic diseases. Although most rheumatic diseases are not yet considered to be age related, available evidence increasingly emphasizes the prevalence of ageing hallmarks in these chronic diseases. On the basis of the current evidence relating to the molecular and cellular ageing pathways involved in rheumatic diseases, we propose that these diseases share a number of features that are observed in ageing, and that they can therefore be considered to be diseases of premature or accelerated ageing. Although more data are needed to clarify whether accelerated ageing drives the development of rheumatic diseases or whether it results from the chronic inflammatory environment, central components of age-related pathways are currently being targeted in clinical trials and may provide a new avenue of therapeutic intervention for patients with rheumatic diseases.In this Review, the authors describe the involvement of characteristic hallmarks of ageing in rheumatic diseases, suggesting that these chronic conditions can be considered to be diseases of premature or accelerated ageing, in which anti-ageing drugs may have therapeutic benefits.

Microalgae offer a nutritionally robust alternative to fishmeal and fish oil, helping reduce pressure on wild stocks and supporting more sustainable aquafeed production. This study explored the potential of replacing fish oil with Tetraselmis ( Tetraselmis chui ) microalgae biomass in the diet of juvenile rainbow trout (89.0 ± 1.10 g) ( Oncorhynchus mykiss ), assessing its effects on the fish’s health. A control diet containing 53% crude protein and fish oil (FO) was modified by replacing FO with Tetraselmis at three graded inclusion levels: 33% (Tetra33), 66% (Tetra66), and 100% (Tetra100). The 84-day feeding trial evaluated key growth parameters, biochemistry, liver and intestinal histo-architectures, and immune-antioxidant gene expression profiles of the experimental fish. Time-series analyses of growth performance revealed no significant treatment effects from day 14 to day 70, except at the 84-day biomass sampling. The FO (7321.65 ± 60.03g) attained a significantly greater final weight (FW) than Tetra33 (6984.70 ± 86.15g) and Tetra100 (6823.93 ± 160.42g), while remaining statistically similar to Tetra66 (7051.77 ± 107.30g). Likewise, weight gain (WG) of the FO group (5519.65 ± 57.16g) exceeded that of the Tetra100 group (5043.93 ± 142.09g) but did not differ significantly from the Tetra33 (5220.70 ± 73.95g) and Tetra66 (5281.77 ± 110.86g). The feed conversion ratios (FCRs) and specific growth rates (SGRs) of the Tetra groups were comparable to the FO control. Dietary variation did not elicit significant changes in leukocyte distribution, biochemical indices, or gene expression patterns across Tetra groups relative to the FO. Similarly, the histological analysis revealed that Tetraselmis dietary inclusions did not trigger inflammatory reactions in hepatic or intestinal tissues in the Tetra groups compared to the FO. Minor but inconsequential histological modifications were noted, such as moderated sinusoid dilation in the liver and slight changes in intestinal villi of Tetra33 fish. Health biomarker analyses indicated that replacing fish oil with Tetraselmis preserved physiological homeostasis, whereas 66% replacement (Tetra66) yielded the best growth performance compared to FO. However, longer feeding trials are necessary to confirm long-term health and nutritional outcomes.