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Erlangen, Germany

Agency: Cordis | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2014 | Award Amount: 144.00K | Year: 2015

We are proposing a four-year programme of knowledge transfer and networking between Aston University (ASTON, UK), Universitatsklinikum Erlangen (UKER, Germany) and Redoxis AB (Redoxis, Sweden). Our proposal targets an emerging area of biology, i.e. reactive oxygen species (ROS)-mediated regulation of immune responses; it brings together the application of small molecule candidate drugs to generate ROS, with use of innovative approaches to biomarker identification in models of chronic inflammatory disease. This research has significant potential for application in human health and is of particular relevance to the ageing population. Research training, innovation and knowledge exchange for early career researchers, achieved by combining our cutting edge expertise, is important to extend the EUs reach in this emergent area. Interchange in this way will facilitate and promote our early career researchers to develop into tomorrows research leaders of redox biology in chronic inflammation. It will encourage new, cross-European collaboration between academia and industry ensuring that we maintain our leading position world-wide. This tri-partite consortium brings together groups with highly complementary expertise to exchange knowledge and develop staff: ASTON in the biochemical analyses of ROS, the effects of immune cell thiol oxidation in vitro and ex vivo and biomarker identification; UKER - in animal models of chronic diseases such as rheumatoid arthritis; and Redoxis - in development of novel drugs that stimulate production of ROS from the NOX2 enzyme as means to modulate chronic inflammation. The project objectives and challenges present a balanced mix between industrial application and basic science, which is focused on knowledge transfer and drug development. Through future collaborative funding, we anticipate far-reaching applications of redox modulators to manage chronic disease and increases in knowledge of both autoimmunity and ageing of the immune system.

Agency: Cordis | Branch: H2020 | Program: ERC-STG | Phase: ERC-StG-2014 | Award Amount: 1.48M | Year: 2015

During inflammation and infection, we are simultaneously confronted with both self and non-self in form of dying cells and microbes, respectively. Mechanisms that facilitate the non-immunogenic clearance of self-antigens derived from apoptotic and necrotic cells and that, in parallel, allow the initiation of an immune response against invading pathogens are incompletely understood. Recent data from our laboratory show that the immune system actively sorts apoptotic cells (ACs) and bacteria into distinct subspecies of macrophages and dendritic cells thereby enabling a segregated processing of self and non-self as well as a differential immune response against these two entities. Incorrect sorting and aberrant uptake of AC-derived self-antigens by pro-inflammatory and antigen-presenting dendritic cells, however, results in the break of self-tolerance and autoimmunity. Due to technical limitations, the identification and fate-mapping of specific phagocyte subsets that mediate the simultaneous clearance of dying cells and pathogens in vivo has remained largely elusive. We thus plan to develop novel tools that are based on cutting-edge technologies to comprehensively elucidate the sorting of dying cells and pathogens under inflammatory conditions in vivo. We plan to generate TAT-Cre transgenic mice and bacteria that will be used in conjunction with R26-eYFP reporter animals to permanently track phagocytes after ingestion of endogenously accumulated dying cells and pathogens, respectively. These approaches will enable us to characterize the involved phagocytes, study molecular mechanisms underlying the differential processing of self and non-self and follow the phagocytes migratory behaviour and its subsequent differentiation. The obtained data will not only provide insights into the pathogenesis of autoimmune and infectious diseases, but will also foster the development of novel therapeutic strategies for the treatment of such disorders.

University of Duisburg - Essen, Universitaetsklinikum Erlangen, Zentralinstitut Fuer Seelische Gesundheit and Friedrich - Alexander - University, Erlangen - Nuremberg | Date: 2011-04-07

A method of using at least one quantitative ratio of two different amyloid beta-peptides in a sample of a body fluid from a patient for determining the patients probability of contracting Alzheimers disease (AD) or for determining the patients suffering from a precursor of Alzheimers disease includes obtaining the sample of the body fluid from the patient. The at least one quantitative ratio is calculated from the two different amyloid beta-peptides from the sample. The patients probability of contracting Alzheimers disease (AD) or the patients suffering from a precursor of Alzheimers disease is calculated using the at least one quantitative ratio. The two different amyloid beta-peptides are selected from (a) A(1-42), (b) A(2-40) and (c) A(2-42). The at least one quantitative ratio is selected from (a) A(1-42)/(b) A(2-40), (a) A(1-42)/(c) A(2-42), (b) A(2-40)/(a) A(1-42) and (c) A(2-42)/(a) A(1-42).

Dunkler D.,McMaster University | Dunkler D.,Universitaetsklinikum Erlangen | Dunkler D.,Medical University of Vienna | Dehghan M.,McMaster University | And 12 more authors.
JAMA Internal Medicine | Year: 2013

Importance Type 2 diabetes mellitus and associated chronic kidney disease (CKD) have become major public health problems. Little is known about the influence of diet on the incidence or progression of CKD among individuals with type 2 diabetes. Objective To examine the association between (healthy) diet, alcohol, protein, and sodium intake, and incidence or progression of CKD among individuals with type 2 diabetes. Design, Setting, And Participants All 6213 individuals with type 2 diabetes without macroalbuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) were included in this observational study. Recruitment spanned from January 2002 to July 2003, with prospective follow-up through January 2008. Main Outcomes And Measures Chronic kidney diseasewas defined as new microalbuminuria or macroalbuminuria or glomerular filtration rate decline of more than 5% per year at 5.5 years of follow-up.We assessed diet using the modified Alternate Healthy Eating Index (mAHEI). The analyses were adjusted for known risk factors, and competing risk of death was considered. Results After 5.5 years of follow-up, 31.7%of participants had developed CKD and 8.3%had died. Compared with participants in the least healthy tertile of mAHEI score, participants in the healthiest tertile had a lower risk of CKD (adjusted odds ratio [OR], 0.74; 95%CI, 0.64-0.84) and lower risk of mortality (OR, 0.61; 95%CI, 0.48-0.78). Participants consuming more than 3 servings of fruits per week had a lower risk of CKD compared with participants consuming these food items less frequently. Participants in the lowest tertile of total and animal protein intake had an increased risk of CKD compared with participants in the highest tertile (total protein OR, 1.16; 95%CI, 1.05-1.30). Sodium intake was not associated with CKD. Moderate alcohol intake reduced the risk of CKD (OR, 0.75; 95%CI, 0.65-0.87) and mortality (OR, 0.69; 95%CI, 0.53-0.89). Conclusions And Relevance A healthy diet and moderate intake of alcohol may decrease the incidence or progression of CKD among individuals with type 2 diabetes. Sodium intake, within a wide range, and normal protein intake are not associated with CKD.

Agency: Cordis | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2015 | Award Amount: 580.50K | Year: 2016

Complications related to infectious diseases have significantly reduced, particularly in the developed countries, due to the availability and use of broad-range antibiotics and wide variety of antimicrobial agents. Excessive use of antibiotics and antimicrobial agents increased significantly the number of multi-drug resistant (MDR) bacteria. This has resulted in a serious threat to public health. The inexorable rise in the incidence of antibiotic resistance in bacterial pathogens, coupled with the low rate of emergence of new clinically useful antibiotics, has refocused attention on finding alternatives to overcome antimicrobial resistance. Novel strategies aiming to reduce the amount of antibiotics, but able to prevent and treat animal and human infections should be investigated, evidenced and approved. Among the various approaches, the use of graphene and its derivatives is currently considered a highly promising strategy to overcome microbial drug resistance. In line with this interest in graphene by the European Commission through the graphene flagship initiatives, we respond in this consortium by exploring the utility of novel graphene based nanocomposites for the management and better understanding of microbial infections. The anti-microbical potential of the novel graphene based nanomaterials, the possibility of using such structures for the development of non-invase therapies together with the understanding of the mechanism of action will be the main focal points of the proposed project entitled PANG, relating to Pathogen and Graphene. We have gathered the essential elements, namely different academic institutions in Europe (France, Germany, and Sweden) and their associated countries (Ukraine) as well as two European companies (Graphenea-Spain and LSO Medical-France) and one company (RS RESEARCH) in one of the associated countries (Turkey). The proposed multidisciplinary project uniquely suits high-level interdisciplinary and cross-border training.

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