Heat-Induced Structural Changes Affect OVA-Antigen Processing and Reduce Allergic Response in Mouse Model of Food Allergy

BACKGROUND AND AIMS: The egg protein ovalbumin (OVA) belongs to six most frequent food allergens. We investigated how thermal processing influences its ability to induce allergic symptoms and immune responses in mouse model of food allergy. METHODOLOGY/PRINCIPAL FINDINGS: Effect of increased temperature (70°C and 95°C) on OVA secondary structure was characterized by circular dichroism and by the kinetics of pepsin digestion with subsequent HPLC. BALB/c mice were sensitized intraperitoneally and challenged with repeated gavages of OVA or OVA heated to 70°C (h-OVA). Levels of allergen-specific serum antibodies were determined by ELISA (IgA and IgGs) or by β-hexosaminidase release test (IgE). Specific activities of digestive enzymes were determined in brush border membrane vesicles of jejunal enterocytes. Cytokine production and changes in regulatory T cells in mesenteric lymph nodes and spleen were assessed by ELISA and FACS. Heating of OVA to 70°C caused mild irreversible changes in secondary structure compared to boiling to 95°C (b-OVA), but both OVA treatments led to markedly different digestion kinetics and Tregs induction ability in vitro, compared to native OVA. Heating of OVA significantly decreased clinical symptoms (allergic diarrhea) and immune allergic response on the level of IgE, IL-4, IL-5, IL-13. Furthermore, h-OVA induced lower activities of serum mast cell protease-1 and enterocyte brush border membrane alkaline phosphatase as compared to native OVA. On the other hand h-OVA stimulated higher IgG2a in sera and IFN-γ secretion by splenocytes. CONCLUSIONS: Minor irreversible changes in OVA secondary structure caused by thermal processing changes both its digestion and antigenic epitopes formation, which leads to activation of different T cell subpopulations, induces shift towards Th1 response and ultimately reduces its allergenicity

Palaeoecological data indicates land-use changes across Europe linked to spatial heterogeneity in mortality during the Black Death pandemic

The Black Death (1347–1352 CE) is the most renowned pandemic in human history, believed by many to have killed half of Europe’s population. However, despite advances in ancient DNA research that conclusively identified the pandemic’s causative agent (bacterium Yersinia pestis), our knowledge of the Black Death remains limited, based primarily on qualitative remarks in medieval written sources available for some areas of Western Europe. Here, we remedy this situation by applying a pioneering new approach, ‘big data palaeoecology’, which, starting from palynological data, evaluates the scale of the Black Death’s mortality on a regional scale across Europe. We collected pollen data on landscape change from 261 radiocarbon-dated coring sites (lakes and wetlands) located across 19 modern-day European countries. We used two independent methods of analysis to evaluate whether the changes we see in the landscape at the time of the Black Death agree with the hypothesis that a large portion of the population, upwards of half, died within a few years in the 21 historical regions we studied. While we can confirm that the Black Death had a devastating impact in some regions, we found that it had negligible or no impact in others. These inter-regional differences in the Black Death’s mortality across Europe demonstrate the significance of cultural, ecological, economic, societal and climatic factors that mediated the dissemination and impact of the disease. The complex interplay of these factors, along with the historical ecology of plague, should be a focus of future research on historical pandemics.The authors acknowledge the following funding sources: Max Planck Independent Research Group, Palaeo-Science and History Group (A.I., A.M. and C.V.); Estonian Research Council #PRG323, PUT1173 (A.Pos., T.R., N.S. and S.V.); European Research Council #FP7 263735 (A.Bro. and A.Plu.), #MSC 655659 (A.E.); Georgetown Environmental Initiative (T.N.); Latvian Council of Science #LZP-2020/2-0060 (N.S. and N.J.); LLNL-JRNL-820941 (I.T.); NSF award #GSS-1228126 (S.M.); Polish-Swiss Research Programme #013/2010 CLIMPEAT (M.Lam.), #086/2010 CLIMPOL (A.W.); Polish Ministry of Science and Higher Education #N N306 275635 (M.K.); Polish National Science Centre #2019/03/X/ST10/00849 (M.Lam.), #2015/17/B/ST10/01656 (M.Lam.), #2015/17/B/ST10/03430 (M.Sło.), #2018/31/B/ST10/02498 (M.Sło.), #N N304 319636 (A.W.); SCIEX #12.286 (K.Mar.); Spanish Ministry of Economy and Competitiveness #REDISCO-HAR2017-88035-P (J.A.L.S.); Spanish Ministry of Education, Culture and Sports #FPU16/00676 (R.L.L.); Swedish Research Council #421-2010-1570 (P.L.), #2018-01272 (F.C.L. and A.S.); Volkswagen Foundation Freigeist Fellowship Dantean Anomaly (M.B.), Spanish Ministry of Science and Innovation #RTI2018-101714-B-I00 (F.A.S. and D.A.S.), OP RDE, MEYS project #CZ.02.1.01/0.0/0.0/16_019/0000728 (P.P.)Peer reviewe

Initial characterization of human DHRS1 (SDR19C1), a member of the short chain dehydrogenase/reductase superfamily.

Many enzymes from the short-chain dehydrogenase/reductase superfamily (SDR) have already been well characterized, particularly those that participate in crucial biochemical reactions in the human body (e.g. 11 beta-hydroxysteroid dehydrogenase 1, 17 beta-hydroxysteroid dehydrogenase 1 or carbonyl reductase 1). Several other SDR enzymes are completely or almost completely uncharacterized, such as DHRS1 (also known as SDR19C1). Based on our in silico and experimental approaches, DHRS1 is described as a likely monotopic protein that interacts with the membrane of the endoplasmic reticulum. The highest expression level of DHRS1 protein was observed in human liver and adrenals. The recombinant form of DHRS1 was purified using the detergent ndodecy1-beta-D-maltoside, and DHRS1 was proven to be an NADPH-dependent reductase that is able to catalyse the in vitro reductive conversion of some steroids (estrone, androstene-3,17-dione and cortisone), as well as other endogenous substances and xenobiotics. The expression pattern and enzyme activities fit to a role in steroid and/or xenobiotic metabolism; however, more research is needed to fully clarify the exact biological function of DHRS1

Rapport final du projet européen PRIMA

Facing structural change, European rural areas still fulfil multiple social, economic and ecological functions. Because of scale interplays and sustainability trade-offs, their future dynamics are still difficult to ascertain. In addition to the inherent difficulties of this undertaking, challenges in actual assessments also depend on external shocks to the economy at large or to particular regions, along with spillover effects among neighbouring regions. PRIMA proposes to improve knowledge in scaling down this assessment. It focuses on agriculture, forestry, tourism, and ecosystem services, with special attention to the structural effects of the European policies at municipality levels. The six case studies of PRIMA, conducted in Germany, United Kingdom, France, Croatia, Czech Republic, and Bulgaria, are important for two main reasons: they provide test cases for the PRIMA approaches, and they have influenced the development of the PRIMA approaches. These case studies have been chosen for their variety of rural dynamics and governance organisation. Because of the bottom-up governance of the European cohesion policy, a large variety has been observed in the priorities and measures, targeted to several pillars of sustainable development. This variety has been narrowed in a pre-modelling stage, where 2 groups of stakeholders were interviewed: those who can assist in scenario and model development (coming from the institutions which implement policy), and the actors who may be affected by the policy and hence whose related behavioural changes should be captured by the model framework. A conceptual model has then been developed. This model focuses on the population dynamics in rural municipalities and on the decision making behaviours observed. The conceptual micro-simulation model was successfully adapted to three of the study regions (France, United Kingdom and Germany). Additionally, the developed agent-based model was adapted for the United Kingdom region; this allowed studying the effects of social aspects that are not captured in the micro-simulation model. For validation purposes, a series of workshops were conducted on the case study areas. The orientation of these workshops depended on the availability of the models for the given case study area. The workshops promoted stakeholder learning about modelling. On the whole, participants recognised models as simplifications of reality. They found explanations about the model components comprehensible, and reacted fairly favourably to the idea of having such a decision-support tool available. However, the lack of good data at a low geographical scale in most case study areas was seen as a severe limitation. Beyond pathways for model revision, some methodological advances in the field of participatory modelling have been identified. Among these is making explicit the role of a model broker, the endorsement of which should improve the various interpretations of participants. Scenario development, though far in advance of their technical skills, has also proved an efficient tool to involve stakeholders in challenging a model. Further conceptual work was identified and undertaken concerning the design of methods to reconstruct commuting network for regions where data was unavailable, to calibrate models with several number of variables and of new approaches to dynamically derive services jobs availability. PRIMA also developed a conceptual work that includes the MAGNET (formerly LEITAP) model for downscaling from world level to the country level, and a downscaling tool from country level towards the NUTS2 level. An interface has been developed for easy downscaling of scenarios. Special attention has been paid to procedures to process data from Eurostat towards a database useful as input for the downscaling model. Last, we progressed towards recommendations enhancing the scope of IA methods, with a review of literature and extensive work between all workpackages