Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication
Hulme, Heather ; Meikle, Lynsey M. ; Strittmatter, Nicole ; Hooft, Justin J.J. van der; Swales, John ; Bragg, Ryan A. ; Villar, Victor H. ; Ormsby, Michael J. ; Barnes, Stephanie ; Brown, Sheila L. ; Dexter, Alex ; Kamat, Maya T. ; Komen, Jasper C. ; Walker, Daniel ; Milling, Simon ; Osterweil, Emily K. ; MacDonald, Andrew S. ; Schofield, Chris J. ; Tardito, Saverio ; Bunch, Josephine ; Douce, Gillian ; Edgar, Julia M. ; Edrada-Ebel, Ru Angelie ; Goodwin, Richard J.A. ; Burchmore, Richard ; Wall, Daniel M. - \ 2020
Science Advances 6 (2020)11. - ISSN 2375-2548
Alterations to the gut microbiome are associated with various neurological diseases, yet evidence of causality and identity of microbiome-derived compounds that mediate gut-brain axis interaction remain elusive. Here, we identify two previously unknown bacterial metabolites 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate, structural analogs of carnitine that are present in both gut and brain of specific pathogen-free mice but absent in germ-free mice. We demonstrate that these compounds are produced by anaerobic commensal bacteria from the family Lachnospiraceae (Clostridiales) family, colocalize with carnitine in brain white matter, and inhibit carnitine-mediated fatty acid oxidation in a murine cell culture model of central nervous system white matter. This is the first description of direct molecular inter-kingdom exchange between gut prokaryotes and mammalian brain cells, leading to inhibition of brain cell function.
Changing concepts and values in natural heritage conservation: a view from IUCN and UNESCO
Mallarach, J.M. ; Verschuuren, B. - \ 2019
In: Values in Heritage Management / Avrami, Erica, MacDonald, Susan, Mason, Randall, Myers, David, Los Angeles : The Getty Institute - ISBN 9781606066188 - p. 140 - 156.
New directions in natural heritage conservation acknowledge conflicting relationships between societies andtheir environments, and seek to respond to impending global crises due to overconsumption of resources,climate change, and biodiversity extinction. Methodological changes include advancing more holistic,natural-cultural approaches; recognizing the role of governance in successful management strategies;integrating scientific and traditional knowledge in valuation processes through engagement with Indigenouspeoples and local communities; and promoting rights-based approaches. These shifts have significantlyinfluenced the work of international bodies, and thereby helped to institute values-based policies thatconstitute a radically new context for conceiving, evaluating, and prioritizing heritage conservation.
Effect of dietary replacement of fishmeal by insect meal on growth performance, blood profiles and economics of growing pigs in Kenya
Chia, Shaphan Y. ; Tanga, Chrysantus M. ; Osuga, Isaac M. ; Alaru, Alphonce O. ; Mwangi, David M. ; Githinji, Macdonald ; Subramanian, Sevgan ; Fiaboe, Komi K.M. ; Ekesi, Sunday ; Loon, Joop J.A. van; Dicke, Marcel - \ 2019
Animals 9 (2019)10. - ISSN 2076-2615
Alternative protein - Animal feeds - Blood parameters - Cost benefit analysis - Growing pigs - Insect larval meal - Return on investment
Pig production is one of the fastest growing livestock sectors. Development of this sector is hampered by rapidly increasing costs of fishmeal (FM), which is a common protein source in animal feeds. Here, we explored the potential of substituting FM with black soldier fly larval meal (BSFLM) on growth and blood parameters of pigs as well as economic aspects. At weaning, 40 hybrid pigs, i.e., crossbreeds of purebred Large White and Landrace were randomly assigned to five iso-nitrogenous and iso-energetic dietary treatments: Control (0% BSFLM and 100% FM (T0)), and FM replaced at 25% (T25), 50% (T50), 75% (T75) and 100% (T100) with BSFLM. Average daily feed intake (ADFI), average daily gain (ADG), body weight gain (BWG) and feed conversion ratio (FCR) were calculated for the whole trial. Hematological and serum biochemical parameters, the cost– benefit ratio (CBR) and return on investment (RoI) were evaluated. No significant effect of diet type was observed on feed intake and daily weight gain. Red or white blood cell indices did not differ among diets. Pigs fed T25, T75 and T100, had lower platelet counts compared to T0 and T50. Dietary inclusion of BSFLM did not affect blood total cholesterol, triglycerides, low-density lipoprotein and high-density lipoprotein. CBR and RoI were similar for the various diets. In conclusion, BSFLM is a suitable and cost-effective alternative to fishmeal in feed for growing pigs.
PREVIEW study—Influence of a behavior modification intervention (PREMIT) in over 2300 people with pre-diabetes : Intention, self-efficacy and outcome expectancies during the early phase of a lifestyle intervention
Huttunen-Lenz, Maija ; Hansen, Sylvia ; Christensen, Pia ; Larsen, Thomas Meinert ; Sandø-Pedersen, Finn ; Drummen, Mathijs ; Adam, Tanja C. ; Macdonald, Ian A. ; Taylor, Moira A. ; Martinez, J.A. ; Navas-Carretero, Santiago ; Handjiev, Svetoslav ; Poppitt, Sally D. ; Silvestre, Marta P. ; Fogelholm, Mikael ; Pietiläinen, Kirsi H. ; Brand-Miller, Jennie ; Berendsen, Agnes A.M. ; Raben, Anne ; Schlicht, Wolfgang - \ 2018
Psychology Research and Behavior Management 11 (2018). - ISSN 1179-1578 - p. 383 - 394.
Cognition - Diabetes mellitus - Goals - Habits - Weight loss
Purpose: Onset of type 2 diabetes (T2D) is often gradual and preceded by impaired glucose homeostasis. Lifestyle interventions including weight loss and physical activity may reduce the risk of developing T2D, but adherence to a lifestyle change is challenging. As part of an international T2D prevention trial (PREVIEW), a behavior change intervention supported participants in achieving a healthier diet and physically active lifestyle. Here, our aim was to explore the influence of this behavioral program (PREMIT) on social-cognitive variables during an 8-week weight loss phase. Methods: PREVIEW consisted of an initial weight loss, Phase I, followed by a weight-maintenance, Phase II, for those achieving the 8-week weight loss target of ≥ 8% from initial bodyweight. Overweight and obese (BMI ≥25 kg/m2) individuals aged 25 to 70 years with confirmed pre-diabetes were enrolled. Uni-and multivariate statistical methods were deployed to explore differences in intentions, self-efficacy, and outcome expectancies between those who achieved the target weight loss (“achievers”) and those who did not (“non-achievers”). Results: At the beginning of Phase I, no significant differences in intentions, self-efficacy and outcome expectancies between “achievers” (1,857) and “non-achievers” (163) were found. “Non-achievers” tended to be younger, live with child/ren, and attended the PREMIT sessions less frequently. At the end of Phase I, “achievers” reported higher intentions (healthy eating χ2 (1)=2.57; P <0.008, exercising χ2 (1)=0.66; P <0.008), self-efficacy (F(2; 1970)=10.27, P <0.005), and were more positive about the expected outcomes (F(4; 1968)=11.22, P <0.005). Conclusion: Although statistically significant, effect sizes observed between the two groups were small. Behavior change, however, is multi-determined. Over a period of time, even small differences may make a cumulative effect. Being successful in behavior change requires that the “new” behavior is implemented time after time until it becomes a habit. Therefore, having even slightly higher self-efficacy, positive outcome expectancies and intentions may over time result in considerably improved chances to achieve long-term lifestyle changes.
The potential role of gut microbiota and its modulators in the management of propionic and methylmalonic acidemia
Burlina, Alberto ; Tims, Sebastian ; Spronsen, Francjan van; Sperl, Wolfgang ; Burlina, Alessandro P. ; Kuhn, Mirjam ; Knol, Jan ; Rakhshandehroo, Maryam ; Coşkun, Turgay ; Singh, Rani H. ; MacDonald, Anita - \ 2018
Expert Opinion on Orphan Drugs 6 (2018)11. - ISSN 2167-8707 - p. 683 - 692.
methylmalonic acid - microbiota - prebiotic - probiotic - Propionic acid
Introduction: Propionic and methylmalonic acidemia (PA/MMA) are rare inborn errors of metabolism characterized by accumulation of propionyl CoA and/or methylmalonyl CoA, resulting in potentially serious metabolic crises and clinical complications. The gut microbiota contributes a significant proportion of total propionate production and provides a potentially modifiable target. Empiric use of oral antibiotics to reduce propionate production is a common approach but is hampered by possible drug resistance, perturbation of normal gut microbiota, and toxicity. Moreover, constipation, associated with low fiber intake, inadequate fluid intake, low gut motility, and other factors, is a chronic problem in this patient population and may influence propionate production. Newer management techniques that reduce the burden of propionate and address these clinical challenges are needed. Areas covered: This paper summarizes the potential contribution of gut-related factors in PA/MMA and considers modifying gut microbiota as a management approach. Expert opinion: Dietary management of PA/MMA may be improved by specific prebiotics that modify gut microbiota to stabilize or possibly reduce PA production.
Demographic and Social-Cognitive Factors Associated with Weight Loss in Overweight, Pre-diabetic Participants of the PREVIEW Study
Hansen, Sylvia ; Huttunen-Lenz, Maija ; Sluik, Diewertje ; Brand-Miller, Jennie ; Drummen, Mathijs ; Fogelholm, Mikael ; Handjieva-Darlenska, Teodora ; Macdonald, Ian ; Martinez, Alfredo J. ; Larsen, Thomas Meinert ; Poppitt, Sally ; Raben, Anne ; Schlicht, Wolfgang - \ 2018
International Journal of Behavioral Medicine 25 (2018)6. - ISSN 1070-5503 - p. 682 - 692.
Behavioral determination - Lifestyle intervention - Social-cognitive factors - Weight loss
Purpose: Weight loss has been demonstrated to be a successful strategy in diabetes prevention. Although weight loss is greatly influenced by dietary behaviors, social-cognitive factors play an important role in behavioral determination. This study aimed to identify demographic and social-cognitive factors (intention, self-efficacy, outcome expectancies, social support, and motivation with regard to dietary behavior and goal adjustment) associated with weight loss in overweight and obese participants from the PREVIEW study who had pre-diabetes. Method: Prospective correlational data from 1973 adult participants were analyzed. The participants completed psychological questionnaires that assessed social-cognitive variables with regard to dietary behavior. Stepwise multiple regression analyses were performed to identify baseline demographic and social-cognitive factors associated with weight loss. Results: Overall, being male, having a higher baseline BMI, having a higher income, perceiving fewer disadvantages of a healthy diet (outcome expectancies), experiencing less discouragement for healthy eating by family and friends (social support), and lower education were independently linked to greater weight loss. When evaluating females and males separately, education was no longer associated with weight loss. Conclusion: The results indicate that a supportive environment in which family members and friends avoid discouraging healthy eating, with the application of a strategy that uses specific behavior change techniques to emphasize the benefits of outcomes, i.e., the benefits of a healthy diet, may support weight loss efforts. Weight loss programs should therefore always address the social environment of persons who try to lose body weight because family members and friends can be important supporters in reaching a weight loss goal.
A workshop on 'Dietary Sweetness-Is It an Issue?'
Wittekind, Anna ; Higgins, Kelly ; McGale, Lauren ; Schwartz, Camille ; Stamataki, Nikoleta S. ; Beauchamp, Gary K. ; Bonnema, Angela ; Dussort, Pierre ; Gibson, Sigrid ; Graaf, Cees de; Halford, Jason C.G. ; Marsaux, Cyril F.M. ; Mattes, Richard D. ; McLaughlin, John ; Mela, David J. ; Nicklaus, Sophie ; Rogers, Peter J. ; Macdonald, Ian A. - \ 2018
International Journal of Obesity 42 (2018)4. - ISSN 0307-0565 - p. 934 - 938.
This report summarises a workshop convened by ILSI Europe on 3 and 4 April 2017 to discuss the issue of dietary sweetness. The objectives were to understand the roles of sweetness in the diet, establish whether exposure to sweetness affects diet quality and energy intake, and consider whether sweetness per se affects health. Although there may be evidence for tracking of intake of some sweet components of the diet through childhood, evidence for tracking of whole diet sweetness, or through other stages of maturity are lacking. The evidence to date does not support adverse effects of sweetness on diet quality or energy intake, except where sweet food choices increase intake of free sugars. There is some evidence for improvements in diet quality and reduced energy intake where sweetness without calories replaces sweetness with calories. There is a need to understand the physiological and metabolic relevance of sweet taste receptors on the tongue, in the gut and elsewhere in the body, as well as possible differentiation in the effects of sustained consumption of individual sweeteners. Despite a plethora of studies, there is no consistent evidence for an association of sweetness sensitivity/preference with obesity or type 2 diabetes. A multifaceted integrated approach, characterising nutritive and sensory aspects of the whole diet or dietary patterns, may be more valuable in providing contextual insight. The outcomes of the workshop could be used as a scientific basis to inform the expert community and create more useful dialogue among health care professionals.
Objectively measured physical activity and sedentary time are associated with cardiometabolic risk factors in adults with prediabetes : The PREVIEW study
Swindell, Nils ; Mackintosh, Kelly ; Mcnarry, Melitta ; Stephens, Jeffrey W. ; Sluik, Diewertje ; Fogelholm, Mikael ; Drummen, Mathijs ; Macdonald, Ian ; Martinez, J.A. ; Handjieva-Darlenska, Teodora ; Poppitt, Sally D. ; Brand-Miller, Jennie ; Larsen, Thomas M. ; Raben, Anne ; Stratton, Gareth - \ 2018
Diabetes Care 41 (2018)3. - ISSN 0149-5992 - p. 562 - 569.
OBJECTIVE The aim of the present cross-sectional study was to examine the association among physical activity (PA), sedentary time (ST), and cardiometabolic risk in adults with prediabetes. RESEARCH DESIGN AND METHODS Participants (n = 2,326; 25-70 years old, 67% female) from eight countries, with a BMI >25 kg · m22 and impaired fasting glucose (5.6-6.9 mmol · L21) or impaired glucose tolerance (7.8-11.0 mmol · L21 at 2 h), participated. Seven-day accelerometry objectively assessed PA levels and ST. RESULTS Multiple linear regression revealed that moderate-To-vigorous PA (MVPA) was negatively associated withHOMAof insulin resistance (HOMA-IR) (standardizedb =20.078 [95% CI20.128,20.027]), waist circumference (WC) (b =20.177 [20.122,20.134]), fasting insulin (b = 20.115 [20.158, 20.072]), 2-h glucose (b = 20.069 [20.112, 20.025]), triglycerides (b = 20.091 [20.138, 20.044]), and CRP (b = 20.086 [20.127, 20.045]). ST was positively associated with HOMA-IR (b = 0.175 [0.114, 0.236]), WC (b = 0.215 [0.026, 0.131]), fasting insulin (b = 0.155 [0.092, 0.219]), triglycerides (b = 0.106 [0.052, 0.16]), CRP (b = 0.106 [0.39, 0.172]), systolic blood pressure (BP) (b = 0.078 [0.026, 0.131]), and diastolic BP (b = 0.106 [0.39, 20.172]). Associations reported between total PA (counts · min21), and all risk factors were comparable or stronger than for MVPA: HOMA-IR (b = 20.151 [20.194, 20.107]), WC (b = 20.179 [20.224, 20.134]), fasting insulin (b = 20.139 [20.183, 20.096]), 2-h glucose (b = 20.088 [20.131, 20.045]), triglycerides (b = 20.117 [20.162, 20.071]), and CRP (b = 20.104 [20.146, 20.062]). CONCLUSIONS In adults with prediabetes, objectively measured PA and ST were associated with cardiometabolic risk markers. Total PA was at least as strongly associated with cardiometabolic risk markers as MVPA, which may imply that the accumulation of total PA over the day is as important as achieving the intensity of MVPA.
|Simulation of the progression of yellow spot on wheat using a functional-structural plant model (FSPM) : Model concepts
Streit, K. ; Bahr, C. ; Evers, J.B. ; Renton, M. - \ 2017
In: Proceedings - 22nd International Congress on Modelling and Simulation, MODSIM 2017. - Modelling and Simulation Society of Australia and New Zealand Inc. (MSSANZ) (Proceedings - 22nd International Congress on Modelling and Simulation, MODSIM 2017 ) - ISBN 9780987214379 - p. 271 - 277.
Disease progression - Functional-structural plant model (FSPM) - Wheat - Wind dispersal - Yellow spot
Despite disease control management, each year part of crop harvest is lost due to plant diseases. Yellow spot is an important foliar wheat disease throughout the world. The fungus that causes the disease survives on wheat stubble and this is most commonly the source of primary infection (by ascospores) in a crop canopy in the next season. On infected leaves, lesions are formed, surrounded by yellow halos. After a latency period, conidia, the cause of secondary infection, are produced on lesions and are spread over long distances by wind. The secondary cycle can repeat several times through the season and results in the progression of the disease in the canopy. Weather conditions and the developmental stage of the crop play an important role in the progression and severity of disease in the crop canopy. To study the interactions between pathogen, climatic conditions and growing host crop, we developed an epidemiological model of Pyrenophora tritici-repentis, the fungal pathogen that causes yellow spot, and coupled it with an existing functional-structural plant model (FSPM) for cereal crops. An FSPM simulates mutual interactions between plant architecture (structure) and physiological processes (function) in plants at a (sub)organ scale, affected by environmental conditions. In our model, light interception and temperature determine the development and the growth of the cereal crop. Temperature, rainfall, relative humidity and wind data control the development of yellow spot. The pathogen submodel predicts maturation of ascospores and simulates production and wind dispersal of conidia across the canopy. Conidia are transported inside a virtual cone starting from a sporulating lesion and with the axis following the wind direction. Simulations demonstrated horizontal and vertical progression of the disease in the growing crop canopy. However, the upper leaves grew often away from the disease after the begin of stem elongation. In the future we will perform enhanced sensitivity analysis that should help us to identify the most (least) important parameters and so help in the process of model parameterisation. Epidemiological models coupled to models for plant architecture and growth under different climatic conditions are a promising tool to study the dynamics of plant-pathogen-environment interactions and their effect on crop yield. Furthermore, the coupled model can be used as a simulation tool to study the impact of different disease management approaches and lead to improved disease control. We will test the applicability of the model against field data on disease progression in spring wheat.
|Global operational data services for storm surge and fluvial flood forecasting
Kleermaeker, S. de; Twigt, D. ; Weerts, A. ; Verlaan, M. - \ 2017
In: Proceedings - 22nd International Congress on Modelling and Simulation, MODSIM 2017. - Modelling and Simulation Society of Australia and New Zealand Inc. (MSSANZ) (Proceedings - 22nd International Congress on Modelling and Simulation, MODSIM 2017 ) - ISBN 9780987214379 - p. 1048 - 1054.
Fluvial flooding - Global operational forecasting system - Storm surge and tide
Riverine floods and coastal inundation by storm surges are the most frequent of natural disasters, affecting millions of people across the globe every year. The forecasting of floods and storm surge at the global scale is crucial to preparing for severe events and providing early awareness where local models and warning services are lacking. Developments in modelling capabilities, data availability, and computational resources in recent years have made it possible to produce global scale flood forecasts. Operational systems currently have the capability to produce discharge and water level forecasts in the medium-range and disseminate forecasts and early warning products in real time across the globe, in support of national forecasting capabilities. Deltares currently runs two global forecasting systems: Global Flood Forecasting Information System (GLOFFIS) and Global Storm Surge Information System (GLOSSIS). These systems are run from an open experimental information and communications technology facility, IdLab, and are being used to test new ideas around interoperability, hydrological/hydrodynamical predictability, big data, and visualization. GLOFFIS and GLOSSIS produce global flood and storm surge forecasts up to four times per day, with a 10 day forecast horizon (Deltares, 2017). These forecasts can be used for early warning in areas that currently lack adequate local forecasting capabilities. In areas where such capabilities are already available, these systems can provide boundary conditions to regional or local models to further improve these. The underlying hydrodynamic and hydrological models are constantly improved and updated, to further increase their accuracy. With improvements in weather forecasting, future advances may include more seamless hydrological forecasting at the global scale alongside a move towards multi-model forecasts and grand ensemble techniques, responding to the need of developing multi-hazard early warning systems for disaster risk reduction. The global forecasts from GLOFFIS and GLOSSIS are made available through various online channels, like web applications and FTP. A subset of results has been made available free of charge in June 2017 via www.GlobalFloodForecast.com. It is foreseen that the full or higher resolution results will be provided through a service with subscription fee by the end of 2017.
Avoiding pitfalls in interdisciplinary education
Holt, R.E. ; Woods, P.J. ; Ferreira, A.S.A. ; Bardarson, H. ; Bonanomi, S. ; Boonstra, W.J. ; Butler, W.E. ; Diekert, F.K. ; Fouzai, N. ; Holma, M. ; Kokkalis, A. ; Kvile, K. ; Macdonald, J.I. ; Malanski, E. ; Nieminen, E. ; Ottosen, K.M. ; Pedersen, M.W. ; Richter, A. ; Rogers, L. ; Romagnoni, G. ; Snickars, M. ; Törnroos, A. ; Weigel, B. ; Whittington, J.D. ; Yletyinen, J. - \ 2017
Climate Research 74 (2017)2. - ISSN 0936-577X - p. 121 - 129.
Climate change - Education - Interdisciplinarity - Learning mechanisms - Research network
As the world's social-environmental problems increasingly extend across boundaries, both disciplinary and political, there is a growing need for interdisciplinarity, not only in research per se, but also in doctoral education. We present the common pitfalls of interdisciplinary research in doctoral education, illustrating approaches towards solutions using the Nordic Centre for Research on Marine Ecosystems and Resources under Climate Change (NorMER) research network as a case study. We provide insights and detailed examples of how to overcome some of the challenges of conducting interdisciplinary research within doctoral studies that can be applied within any doctoral/postdoctoral education programme, and beyond. Results from a selfevaluation survey indicate that early-career workshops, annual meetings and research visits to other institutions were the most effective learning mechanisms, whereas single discipline-focused courses and coursework were among the least effective learning mechanisms. By identifying the strengths and weaknesses of components of NorMER, this case study can inform the design of future programmes to enhance interdisciplinarity in doctoral education, as well as be applied to science collaboration and academic research in general.
Priorities for research in soil ecology
Eisenhauer, Nico ; Antunes, Pedro M. ; Bennett, Alison E. ; Birkhofer, Klaus ; Bissett, Andrew ; Bowker, Matthew A. ; Caruso, Tancredi ; Chen, Baodong ; Coleman, David C. ; Boer, Wietse de; Ruiter, Peter de; DeLuca, Thomas H. ; Frati, Francesco ; Griffiths, Bryan S. ; Hart, Miranda M. ; Hättenschwiler, Stephan ; Haimi, Jari ; Heethoff, Michael ; Kaneko, Nobuhiro ; Kelly, Laura C. ; Leinaas, Hans Petter ; Lindo, Zoë ; Macdonald, Catriona ; Rillig, Matthias C. ; Ruess, Liliane ; Scheu, Stefan ; Schmidt, Olaf ; Seastedt, Timothy R. ; Straalen, Nico M. van; Tiunov, Alexei V. ; Zimmer, Martin ; Powell, Jeff R. - \ 2017
Pedobiologia 63 (2017). - ISSN 0031-4056 - p. 1 - 7.
Aboveground-belowground interactions - Biodiversity–ecosystem functioning - Biogeography - Chemical ecology - Climate change - Ecosystem services - Global change - Microbial ecology - Novel environments - Plant-microbe interactions - Soil biodiversity - Soil food web - Soil management - Soil processes
The ecological interactions that occur in and with soil are of consequence in many ecosystems on the planet. These interactions provide numerous essential ecosystem services, and the sustainable management of soils has attracted increasing scientific and public attention. Although soil ecology emerged as an independent field of research many decades ago, and we have gained important insights into the functioning of soils, there still are fundamental aspects that need to be better understood to ensure that the ecosystem services that soils provide are not lost and that soils can be used in a sustainable way. In this perspectives paper, we highlight some of the major knowledge gaps that should be prioritized in soil ecological research. These research priorities were compiled based on an online survey of 32 editors of Pedobiologia – Journal of Soil Ecology. These editors work at universities and research centers in Europe, North America, Asia, and Australia. The questions were categorized into four themes: (1) soil biodiversity and biogeography, (2) interactions and the functioning of ecosystems, (3) global change and soil management, and (4) new directions. The respondents identified priorities that may be achievable in the near future, as well as several that are currently achievable but remain open. While some of the identified barriers to progress were technological in nature, many respondents cited a need for substantial leadership and goodwill among members of the soil ecology research community, including the need for multi-institutional partnerships, and had substantial concerns regarding the loss of taxonomic expertise.
Type I interferon is required for T helper (Th) 2 induction by dendritic cells
Webb, Lauren M. ; Lundie, Rachel J. ; Borger, Jessica G. ; Brown, Sheila L. ; Connor, Lisa M. ; Cartwright, Adam N.R. ; Dougall, Annette M. ; Wilbers, Ruud H.P. ; Cook, Peter C. ; Jackson-Jones, Lucy H. ; Phythian-Adams, Alexander T. ; Johansson, Cecilia ; Davis, Daniel M. ; Dewals, Benjamin G. ; Ronchese, Franca ; Macdonald, Andrew S. - \ 2017
The EMBO Journal 36 (2017)16. - ISSN 0261-4189 - p. 2311 - 2465.
Dendritic cell - Interferon - Priming - Th2
Type 2 inflammation is a defining feature of infection with parasitic worms (helminths), as well as being responsible for widespread suffering in allergies. However, the precise mechanisms involved in T helper (Th) 2 polarization by dendritic cells (DCs) are currently unclear. We have identified a previously unrecognized role for type I IFN (IFN-I) in enabling this process. An IFN-I signature was evident in DCs responding to the helminth Schistosoma mansoni or the allergen house dust mite (HDM). Further, IFN-I signaling was required for optimal DC phenotypic activation in response to helminth antigen (Ag), and efficient migration to, and localization with, T cells in the draining lymph node (dLN). Importantly, DCs generated from Ifnar1-/- mice were incapable of initiating Th2 responses in vivo. These data demonstrate for the first time that the influence of IFN-I is not limited to antiviral or bacterial settings but also has a central role to play in DC initiation of Th2 responses.
Homeostasis of the gut barrier and potential biomarkers
Wells, Jerry M. ; Brummer, Robert J. ; Derrien, Muriel ; MacDonald, Thomas T. ; Troost, Freddy ; Cani, Patrice D. ; Theodorou, Vassilia ; Dekker, Jan ; Méheust, Agnes ; Vos, Willem M. De; Mercenier, Annick ; Nauta, Arjen ; Garcia-Rodenas, Clara L. - \ 2017
American Journal of Physiology. Gastrointestinal and Liver Physiology 312 (2017)3. - ISSN 0193-1857 - p. G171 - G193.
Antimicrobial peptides - Epithelial permeability - Gut barrier - Microbiota
The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of micro- bial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overre- action to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the micro- biota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by pro- longed mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell- dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts.
Can probiotics modulate human disease by impacting intestinal barrier function?
Bron, Peter A. ; Kleerebezem, Michiel ; Brummer, Robert Jan ; Cani, Patrice D. ; Mercenier, Annick ; MacDonald, Thomas T. ; Garcia-Ródenas, Clara L. ; Wells, Jerry M. - \ 2017
The British journal of nutrition 117 (2017)1. - ISSN 0007-1145 - p. 93 - 107.
Gastrointestinal disorders - Gut barrier - Gut microbiota - Immunity - Probiotics
Intestinal barrier integrity is a prerequisite for homeostasis of mucosal function, which is balanced to maximise absorptive capacity, while maintaining efficient defensive reactions against chemical and microbial challenges. Evidence is mounting that disruption of epithelial barrier integrity is one of the major aetiological factors associated with several gastrointestinal diseases, including infection by pathogens, obesity and diabetes, necrotising enterocolitis, irritable bowel syndrome and inflammatory bowel disease. The notion that specific probiotic bacterial strains can affect barrier integrity fuelled research in which in vitro cell lines, animal models and clinical trials are used to assess whether probiotics can revert the diseased state back to homeostasis and health. This review catalogues and categorises the lines of evidence available in literature for the role of probiotics in epithelial integrity and, consequently, their beneficial effect for the reduction of gastrointestinal disease symptoms.
Human intestinal barrier function in health and disease
König, Julia ; Wells, Jerry ; Cani, Patrice D. ; García-Ródenas, Clara L. ; MacDonald, Tom ; Mercenier, Annick ; Whyte, Jacqueline ; Troost, Freddy J. ; Brummer, Robert-Jan - \ 2016
Clinical and Translational Gastroenterology 7 (2016)10. - ISSN 2155-384X
The gastrointestinal tract consists of an enormous surface area that is optimized to efficiently absorb nutrients, water, and electrolytes from food. At the same time, it needs to provide a tight barrier against the ingress of harmful substances, and protect against a reaction to omnipresent harmless compounds. A dysfunctional intestinal barrier is associated with various diseases and disorders. In this review, the role of intestinal permeability in common disorders such as infections with intestinal pathogens, inflammatory bowel disease, irritable bowel syndrome, obesity, celiac disease, non-celiac gluten sensitivity, and food allergies will be discussed. In addition, the effect of the frequently prescribed drugs proton pump inhibitors and non-steroidal anti-inflammatory drugs on intestinal permeability, as well as commonly used methods to assess barrier function will be reviewed.
European survey on sterigmatocystin in cereals, cereals-based products, beer and nuts
Mol, H.G.J. ; MacDonald, S.J. ; Anagnostopoulos, C. ; Spanjer, M. ; Bertuzzi, T. ; Pietri, A. - \ 2016
World Mycotoxin Journal 9 (2016)4. - ISSN 1875-0710 - p. 633 - 642.
Beer - Cereals - Nuts - Rice - Sterigmatocystin
Based on the EFSA proposal 'Survey on sterigmatocystin in food' (GP/EFSA/CONTAM/2013/02), this study provides a survey on the occurrence of this mycotoxin. A total of 1,259 samples of cereal grains (429), cereal products (713), beer (53) and nuts (64) were analysed for the presence of sterigmatocystin (STC). Samples were mainly collected at processing plants, storage facilities, wholesale and retail between August 2013 and November 2014, in nine European countries, mostly Greece, Italy, the Netherlands and the United Kingdom. The products originated from 27 European countries and 18 other countries. All samples were analysed by methods based on liquid chromatography coupled with tandem mass spectrometry. The limit of quantification (LOQ) was 0.5 μg/kg and the limit of detection (LOD) was in the range 0.05-0.15 μg/kg (0.005-0.01 μg/l for beer). Overall, STC was identified in 10% of the samples; it was not detected in either beer or nut samples. More than 50% of the contaminated samples contained levels between LOD and LOQ; in the other cases, levels were between 0.5-6 μg/kg with one exception (33 μg/kg in oats). In cereal grains, rice and oats seemed the cereals most prone to STC contamination (100% unprocessed rice, 22% oats grains); however the number of rice samples was limited (n=28) and the samples were collected almost exclusively in Italy and Greece. In cereal products, levels were lower than in cereal grains. The highest incidence was in processed rice (21%) and breakfast cereals (19%), while for the other cereal products this was between 5-7%. In the contaminated cereal products, rice and oats were often present as ingredients.
Fire usage and ancient hominin detoxification genes : Protective ancestral variants dominate while additional derived risk variants appear in modern humans
Aarts, Jac M.M.J.G. ; Alink, Gerrit M. ; Scherjon, Fulco ; MacDonald, Katharine ; Smith, Alison C. ; Nijveen, Harm ; Roebroeks, Wil - \ 2016
PLoS ONE 11 (2016)9. - ISSN 1932-6203
Studies of the defence capacity of ancient hominins against toxic substances may contribute importantly to the reconstruction of their niche, including their diets and use of fire. Fire usage implies frequent exposure to hazardous compounds from smoke and heated food, known to affect general health and fertility, probably resulting in genetic selection for improved detoxification. To investigate whether such genetic selection occurred, we investigated the alleles in Neanderthals, Denisovans and modern humans at gene polymorphisms well-known to be relevant from modern human epidemiological studies of habitual tobacco smoke exposure and mechanistic evidence. We compared these with the alleles in chimpanzees and gorillas. Neanderthal and Denisovan hominins predominantly possess gene variants conferring increased resistance to these toxic compounds. Surprisingly, we observed the same in chimpanzees and gorillas, implying that less efficient variants are derived and mainly evolved in modern humans. Less efficient variants are observable from the first early Upper Palaeolithic hunter-gatherers onwards. While not clarifying the deep history of fire use, our results highlight the long-term stability of the genes under consideration despite major changes in the hominin dietary niche. Specifically for detoxification gene variants characterised as deleterious by epidemiological studies, our results confirm the predominantly recent appearance reported for deleterious human gene variants, suggesting substantial impact of recent human population history, including pre-Holocene expansions.
Big data has big potential for applications to climate change adaptation
Ford, James D. ; Tilleard, Simon E. ; Berrang-Ford, Lea ; Araos, Malcolm ; Biesbroek, Robbert ; Lesnikowski, Alexandra C. ; MacDonald, Graham K. ; Hsu, Angel ; Chen, Chen ; Bizikova, Livia - \ 2016
Proceedings of the National Academy of Sciences of the United States of America 113 (2016)39. - ISSN 0027-8424 - p. 10729 - 10732.
The capacity to collect and analyze massive amounts
of data is transforming research in the natural and social
sciences (1). And yet, the climate change adaptation
community has largely overlooked these developments.
Here, we examine how “big data” can inform adaptation
research and decision-making and outline what’s
needed from the adaptation community to maximize
this opportunity. We contend that careful application
of big data could revolutionize our understanding of
how to manage the risks of climate change.
Large scale pantelleritic ash flow eruptions during the Late Miocene in central Kenya and evidence for significant environmental impact
Claessens, L.F.G. ; Veldkamp, A. ; Schoorl, J.M. ; Wijbrans, J.R. ; Gorp, W. van; MacDonald, R. - \ 2016
Global and Planetary Change 145 (2016). - ISSN 0921-8181 - p. 30 - 41.
In the area south-east of Mount Kenya, four previously unrecorded peralkaline rhyolitic (pantelleritic) ash flow tuffs have been located. These predominantly greyish welded and non-welded tuffs form up to 12 m thick units, which are sometimes characterized by a basal vitrophyre. The four flow units yielded 40Ar/39Ar ages ranging from 6.36 to 8.13 Ma, indicating a period of ~ 1.8 Ma of pantelleritic volcanic activity during the Late Miocene in central Kenya. Tentative compositional and age correlations with other known tuff deposits suggest that the pantelleritic tuffs originally covered 40,000 km2 in central Kenya, extending much further than earlier recorded Pliocene tuffs. This newly identified magmatic phase occurred between the phonolitic flood eruptions (16–8 Ma) and the Pliocene tuff eruptions (6–4 Ma). The occurrence of multiple ash flow tuff deposits up to 150 km away from the inferred eruptive center(s) in the central sector of the Kenya Rift, indicates multi-cyclic peralkaline supereruptions during the Late Miocene. By analogy with more recent pantelleritic eruptions, the tuffs are thought to have been sulfur-rich; during eruption, they formed stratospheric aerosols, with significant environmental impact. The timing of the eruptions coincides with the shift towards more savannah-dominated environments in East Africa.