The role of polyamines in protein-dependent hypoxic tolerance of Drosophila

<p>Abstract</p> <p>Background</p> <p>Chronic hypoxia is a major component of ischemic diseases such as stroke or myocardial infarction. <it>Drosophila </it>is more tolerant to hypoxia than most mammalian species. It is considered as a useful model organism to identify new mechanisms of hypoxic tolerance. The hypoxic tolerance of flies has previously been reported to be enhanced by low protein diets. This study analyses the mechanisms involved.</p> <p>Results</p> <p>Feeding adult <it>Drosophila </it>on a yeast diet dramatically reduced their longevities under chronic hypoxic conditions (5% O₂). Mean and maximum longevities became close to the values observed for starving flies. The action of dietary yeast was mimicked by a whole casein hydrolysate and by anyone of the 20 natural amino acids that compose proteins. It was mimicked by amino acid intermediates of the urea cycle such as L-citrulline and L-ornithine, and by polyamines (putrescine, spermidine and spermine). α-difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, partially protected hypoxic flies from amino acid toxicity but not from polyamine toxicity. N¹-guanyl-1,7 diaminoheptane, a specific inhibitor of eIF5A hypusination, partially relieved the toxicities of both amino acids and polyamines.</p> <p>Conclusion</p> <p>Dietary amino acids reduced the longevity of chronically hypoxic flies fed on a sucrose diet. Pharmacological evidence suggests that the synthesis of polyamines and the hypusination of eIF5A contributed to the life-shortening effect of dietary amino acids.</p

Hypoxia modifies the feeding preferences of Drosophila. Consequences for diet dependent hypoxic survival

International audienceBACKGROUND: Recent attention has been given to the relationships between diet, longevity, aging and resistance to various forms of stress. Flies do not simply ingest calories. They sense different concentrations of carbohydrate and protein macronutrients and they modify their feeding behavior in response to changes in dietary conditions. Chronic hypoxia is a major consequence of cardiovascular diseases. Dietary proteins have recently been shown to decrease the survival of chronically hypoxic Drosophila. Whether flies modify their feeding behavior in response to hypoxia is not currently known. This study uses the recently developed capillary feeding assay to analyze the feeding behavior of normoxic and chronically hypoxic Drosophila melanogaster. RESULTS: The intakes rates of sucrose and yeast by normoxic or chronically hypoxic flies (5% O2) were analyzed under self selecting and "no choice" conditions. Chronically hypoxic flies fed on pure yeast diets or mixed diets under self selection conditions stopped feeding on yeast. Flies fed on mixed diets under "no choice" conditions reduced their food intakes. Hypoxia did not modify the adaptation of flies to diluted diets or to imbalanced diets. Mortality was assessed in parallel experiments. Dietary yeast had two distinct effects on hypoxic flies (i) a repellent action which eventually led to starvation and which was best observed in the absence of dietary sucrose and (ii) a toxic action which led to premature death. Finally we determined that hypoxic survivals were correlated to the intakes of sucrose, which suggested that dietary yeast killed flies by reducing their intake of sucrose. The feeding preferences of adult Drosophila were insensitive to NO scavengers, NO donor molecules and inhibitors of phosphodiesterases which are active on Drosophila larvae. CONCLUSION: Chronically hypoxic flies modify their feeding behavior. They avoid dietary yeast which appears to be toxic. Hypoxic survival is dependent on a source of exogenous sucrose. Ultimately, dietary yeast reduces hypoxic survival by reducing the intake of sucrose. The results highlight the importance of behavioral mechanisms in the responses of Drosophila to chronic hypoxic conditions

Strong Dietary Restrictions Protect Drosophila against Anoxia/Reoxygenation Injuries

Reoxygenation of ischemic tissues is a major factor that determines the severity of cardiovascular diseases. This paper describes the consequences of anoxia/reoxygenation (A/R) stresses on Drosophila, a useful, anoxia tolerant, model organism.Newly emerged adult male flies were exposed to anoxic conditions (<1% O2) for 1 to 6 hours, reoxygenated and their survival was monitored.A/R stresses induced a transient increase in mortality which peaked at the time of reoxygenation. Then flies recovered low mortality rates similar to those of control flies. A/R induced mortality was strongly dependent on dietary conditions during the 48 h that preceded anoxia. Well fed flies were anoxia sensitive. Strong dietary restrictions and starvation conditions protected flies against A/R injuries. The tolerance to anoxia was associated to large decreases in glycogen, protein, and ATP contents. During anoxia, anoxia tolerant flies produced more lactate, less phosphate and they maintained more stable ATP levels than anoxia sensitive flies. Moderate dietary restrictions, which increased the longevity of normoxic flies, did not promote resistance to A/R stresses. Diet dependent A/R injuries were still observed in sigma loss of function mutants and they were insensitive to dietary rapamycin or resveratrol. AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribose-furanoside), an activator AMP kinase decreased A/R injuries. Mutants in the insulin signalling pathway were more anoxia tolerant in a fed state.Long A/R stresses induce a transient increase in mortality in Drosophila. This mortality is highly dependent on dietary conditions prior to the stress. Strong dietary restrictions and starvation conditions protect flies against A/R injuries, probably by inducing a major remodelling of energy metabolism. The results also indicate that mechanistically different responses develop in response to dietary restrictions of different strengths. AMP kinase and the insulin signalling pathway are possible mediators of diet dependent anoxic tolerance in Drosophila

IL-36α induces maturation of Th1-inducing human MDDC and synergises with IFN-γ to induce high surface expression of CD14 and CD11c

We show that IL-36α induced maturation of human MDDCs and stimulated differentiation of IFN-γ producing (Type 1) CD3+ lymphocytes but was not as effective as IL-36β in doing so. For the first time, we also show that IL-36α induced expression of CD14 by MDDCs and this was highly potentiated by co-cultured with IFN-γ. In contrast, lipopolysaccharide (LPS) did not increase CD14 expression by MDDCs, suggesting that if MDDCs represent a physiologically relevant population in vivo, they need to be stimulated by relevant inflammatory cytokines prior to CD14 expression and detection of LPS, expressed by Gram negative bacteria. IFN-γ synergised with IL-36α to restore the high levels of CD11c expression by MDDCs, which was reduced by culture with these cytokines in isolation. IL-36α/IFN-γ synergy also correlated with increased binding of the opsonic complement protein (iC3b) to MDDCs. However although IL-36α increased the phagocytic capacity of MDDCs for Salmonella Typhimurium 4/74 this was not synergistically increased by IFN-γ (P > 0.05). In conclusion we report the hitherto unknown effects of IL-36α on the innate cell function of human MDDCs

Crop Updates 1999 - Oilseeds

This article contains eighteen papers INTRODUCTION, Paul Carmody, Agriculture Western Australia PLENARY SESSION Transgenic canola in Western Australia: Outlook and challenges, Phil Salisbury, University of Melbourne Farming system issues for herbicide tolerant canola, Rick Madin, Rick Madin and Associates, David Bowran, Agriculture Western Australia Beating blackleg in 1999, Martin Barbetti, Ravjit Khangura, Paul Carmody, Graham Walton, Agriculture Western Australia The Mustard Industry in Australia – Opportunities for a new oilseed, Phil Parker, NSW Agriculture Management of blackleg with fungicides, Ravjit Khangura and Martin Barbetti, Agriculture Western Australia Effect of aphid feeding damage on canola yields in 1998, Francoise Berlandier and Linnet Cartwright, Agriculture Western Australia Post-anthesis duration and rainfall affect oil content of canola, Ping Si, University of West Australia, Graham Walton, Agriculture Western Australia, Nick Galwey and David Turner, University of West Australia Canola responded to high rates of fertiliser in 1998, Wayne Pluske, CSBP Impact of agronomic practices on canola quality, Graham Walton, Agriculture Western Australia Survey reveals widespread infection with two virus diseases in Western Australian canola crops, Roger Jones and Brenda Coutts, Agriculture Western Australia Calculating canola yields and oil contents as a function of soil and fertiliser nitrogen supply, Bill Bowden and Isabel Arevalo-Vigne, Agriculture Western Australia Canola benchmarks 1997/98 – Central Eastern District, Jeff Russell, Agriculture Western Australia Seeding rate affects the yield and some architectural features of canola, Syed H. Zaheer, Nick W. Galwey and David Turner, University of Western Australia Foliar applied fungicides for blackleg, Andrew Simon and Art Diggle, Agriculture Western Australia Farm based demonstration 1998 canola N – Wheel evaluation, Jeff Russell, Agriculture Western Australia Effect of sowing date on seed yield of canola, Dave Eksteen, Agriculture Western Australia Investigating water use of summer crops on the South Coast of Western Australia, Arjen Ryder, Agriculture Western Australia, Bill Crabtree, Western Australia No Till Farming Association, Serena Wyatt, Catchment Landcare Coordinator, Wellstead, Jim Baily, Subasio Downs, Wellstead INTRODUCTION, Paul Carmody, Agriculture Western Australia PLENARY SESSION Transgenic canola in Western Australia: Outlook and challenges, Phil Salisbury, University of Melbourne Farming system issues for herbicide tolerant canola, Rick Madin, Rick Madin and Associates, David Bowran, Agriculture Western Australia Beating blackleg in 1999, Martin Barbetti, Ravjit Khangura, Paul Carmody, Graham Walton, Agriculture Western Australia The Mustard Industry in Australia – Opportunities for a new oilseed, Phil Parker, NSW Agriculture Management of blackleg with fungicides, Ravjit Khangura and Martin Barbetti, Agriculture Western Australia Effect of aphid feeding damage on canola yields in 1998, Francoise Berlandier and Linnet Cartwright, Agriculture Western Australia Post-anthesis duration and rainfall affect oil content of canola, Ping Si, University of West Australia, Graham Walton, Agriculture Western Australia, Nick Galwey and David Turner, University of West Australia Canola responded to high rates of fertiliser in 1998, Wayne Pluske, CSBP Impact of agronomic practices on canola quality, Graham Walton, Agriculture Western Australia Survey reveals widespread infection with two virus diseases in Western Australian canola crops, Roger Jones and Brenda Coutts, Agriculture Western Australia Calculating canola yields and oil contents as a function of soil and fertiliser nitrogen supply, Bill Bowden and Isabel Arevalo-Vigne, Agriculture Western Australia Canola benchmarks 1997/98 – Central Eastern District, Jeff Russell, Agriculture Western Australi

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought

A Low Protein Diet Increases the Hypoxic Tolerance in Drosophila

Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O(2)) and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses

Are Current Physical Match Performance Metrics in Elite Soccer Fit for Purpose or is the Adoption of an Integrated Approach Needed?

Time-motion analysis is a valuable data-collection technique used to quantify the physical match performance of elite soccer players. For over 40 years researchers have adopted a 'traditional' approach when evaluating match demands by simply reporting the distance covered or time spent along a motion continuum of walking through to sprinting. This methodology quantifies physical metrics in isolation without integrating other factors and this ultimately leads to a one-dimensional insight into match performance. Thus, this commentary proposes a novel 'integrated' approach that focuses on a sensitive physical metric such as high-intensity running but contextualizes this in relation to key tactical activities for each position and collectively for the team. In the example presented, the 'integrated' model clearly unveils the unique high-intensity profile that exists due to distinct tactical roles, rather than one-dimensional 'blind' distances produced by 'traditional' models. Intuitively this innovative concept may aid the coaches understanding of the physical performance in relation to the tactical roles and instructions given to the players. Additionally, it will enable practitioners to more effectively translate match metrics into training and testing protocols. This innovative model may well aid advances in other team sports that incorporate similar intermittent movements with tactical purpose. Evidence of the merits and application of this new concept are needed before the scientific community accepts this model as it may well add complexity to an area that conceivably needs simplicity