German Federal Institute for Risk Assessment

Berlin, Germany

German Federal Institute for Risk Assessment

Berlin, Germany
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News Article | November 28, 2016

Bekzod Khakimov, from the Department of Food Science at the University of Copenhagen, is the first recipient of the Nils Foss Talent Prize Bekzod Khakimov is one of the most promising young researchers that the Department of Food Science (FOOD) has educated in the last decade. He has published 13 scientific articles in the area of food science, plant science and metabolomics, mostly in highly ranked scientific journals and many more are in the pipeline. He is both proud and pleased to receive the award. "Receiving the first Nils Foss Talent Prize was fabulous and surprising news for me and it is the biggest achievement in my career. It makes me feel that our research goes beyond the Foodomics-lab at FOOD and is important both to science and to the food industry. I want to continue working towards establishing myself as an expert in this area and hope to create a research group in the future," says Bekzod Khakimov, who also cooperates with the Department of Plant and Environmental Sciences (PLEN) at the University of Copenhagen. In order to understand the complexity of food systems, food production and environment, we need reliable analytical systems and efficient data analysis. It is only a matter of time before the methods of Bekzod Khakimov will become standard and lead to considerably more robust and reliable data being produced from the analytical platforms in metabolomics/foodomics. "Foodomics emerged approximately a decade ago as a new field within the biochemical research area. It covers a broad spectrum analysis of foods, food raw materials and ingredients, and attempts to link food to human health and wellbeing. Foodomics also covers sustainable food production, detection of food fraud and food adulteration, as well as food authenticity," explains Bekzod Khakimov. He has already made two fundamental developments to improve the untargeted metabolomics approach using Gas Chromatography-Mass spectrometry (GC-MS). Currently, Bekzod Khakimov is building up a GC-MS database of food and plant metabolites, namely Copenhagen Open Metabolite DatabaSe (COMDAS) with the aim of making future metabolite assignments easier. Inspired by the rigorous standardization currently developed for NMR spectroscopy (Nuclear Magnetic Resonance) in metabolomics, Bekzod Khamimov is also working on establishing GC-MS with thoroughly optimized standard protocols (methods) to enhance data reproducibility and high-throughput analysis. Metabolomics is all about measuring metabolite levels in biological samples to understand their metabolism (synthesis and decomposition in cells) and reveals how internal and external factors (for example the impact of a particular diet) influences the metabolism. The result of a metabolomics study is thus a "fingerprint" of what has happened in the body/biological material. This fingerprint can be used to detect deviations from a given normal state using multivariate data analysis (chemometrics). Three major analytical platforms applied in modern metabolomics are Nuclear Magnetic Resonance (NMR), Liquid Chromatography-Mass Spectrometry (LC-MS), and GC-MS. The application of Bekzod Khakimov's methods has already led to a surprising biomarker that can differentiate people who are on a new Nordic diet from people who are on a traditional Danish diet based on their blood metabolome. He is also working with the German Federal Institute for Risk Assessment with the aim of using his method to detect wine adulteration and food fraud. Bekzod Khakimov has a background in chemistry and received his BSc from National University of Uzbekistan and MSc from Queen Mary University of London. He has received a PhD degree in Metabolomics from the University of Copenhagen (the Chemometrics and Analytical Technology section) in 2013. The Nils Foss Talent Prize of 100,000 DKK (14,000 US dollar) is awarded to a young and promising scientist annually and is the biggest of its kind. Through the Nils Foss Talent Prize, FOSS acknowledges the role of the food and agricultural community in the innovative application of technology for improved value and sustainability in the food supply chain. With the Prize, FOSS wants to further stimulate young and talented researchers in the agricultural and food sector. Read more about the Nils Foss prizes.

Kugler J.,German Federal Institute for Risk Assessment | Luch A.,German Federal Institute for Risk Assessment | Oelgeschlager M.,German Federal Institute for Risk Assessment
Trends in Pharmacological Sciences | Year: 2016

Despite our increasing understanding of molecular mechanisms controlling embryogenesis, the identification and characterization of teratogenic substances still heavily relies on animal testing. Embryonic development depends on cell-autonomous and non-autonomous processes including spatiotemporally regulated extracellular signaling activities. These have been elucidated in transgenic mouse models harboring easily detectable reporter genes under the control of evolutionarily conserved signaling cascades. We propose combining these transgenic mouse models and cells derived thereof with existing alternative toxicological testing strategies. This would enable the plausibility of in vitro data to be verified in light of in vivo data and, ultimately, facilitate regulatory acceptance of in vitro test methods. © 2016 Elsevier Ltd

Tralau T.,German Federal Institute for Risk Assessment | Luch A.,German Federal Institute for Risk Assessment
Expert Opinion on Drug Metabolism and Toxicology | Year: 2013

Introduction: Over the past years, there has been increasing evidence that, at least in vertebrates, cytochrome P450-dependent monooxygenases (CYPs) are governed by a most complex regulation. The respective mechanisms comprise structural features such as domain movements, allostery, enzyme-oligomerization as well as numerous transcription factors, non-coding RNAs and extensive regulatory crosstalk. Areas covered: This review summarizes the recent aspects of structural and molecular CYP regulation and discusses the respective consequences and implications. The authors, further, examine the evolutionary origins of CYP regulation in light of their role as endogenous and xenobiotic enzymes. Finally, the article aims to elucidate the potential of CYP regulation as a pharmaceutical target. Expert opinion: Studies on CYP regulation paint an increasingly complex picture of a layered set of regulatory mechanisms. These start structurally on single molecule level, continue with cooperativity and oligomerization of enzyme complexes and finally include a multifaceted regulation of expression control and crossregulation. The respective regulatory network is a key to cellular plasticity and adaptivity. However, it can also be the cause for pathological conditions as well as resistance to medical treatment. A better understanding of the regulatory aspects of CYP biology is, thus, not only of academic interest but promises to be highly rewarding. Even with the limited knowledge available, CYP regulation and CYP crosstalk are already promising pharmacological targets. © 2013 Informa UK, Ltd.

Andres S.,German Federal Institute for Risk Assessment | Abraham K.,German Federal Institute for Risk Assessment | Appel K.E.,German Federal Institute for Risk Assessment | Lampen A.,German Federal Institute for Risk Assessment
Critical Reviews in Toxicology | Year: 2011

A high intake of fruits and vegetables is associated with a lower risk of cancer. In this context, considerable attention is paid to Asian populations who consume high amounts of soy and soy-derived isoflavones, and have a lower risk for several cancer types such as breast and prostate cancers than populations in Western countries. Hence, interest focuses on soyfoods, soy products, and soy ingredients such as isoflavones with regard to their possible beneficial effects that were observed in numerous experiments and studies. The outcomes of the studies are not always conclusive, are often contradictory depending on the experimental conditions, and are, therefore, difficult to interpret. Isoflavone research revealed not only beneficial but also adverse effects, for instance, on the reproductive system. This is also the case with tumor-promoting effects on, for example, breast tissue. Isoflavone extracts and supplements are often used for the treatment of menopausal symptoms and for the prevention of age-associated conditions such as cardiovascular diseases and osteoporosis in postmenopausal women. In relation to this, questions about the effectiveness and safety of isoflavones have to be clarified. Moreover, there are concerns about the maternal consumption of isoflavones due to the development of leukemia in infants. In contrast, men may benefit from the intake of isoflavones with regard to reducing the risk of prostate cancer. Therefore, this review examines the risks but also the benefits of isoflavones with regard to various kinds of cancer, which can be derived from animal and human studies as well as from in vitro experiments. Copyright © 2011 Informa Healthcare USA, Inc.

Buhrke T.,German Federal Institute for Risk Assessment | Kibellus A.,German Federal Institute for Risk Assessment | Lampen A.,German Federal Institute for Risk Assessment
Toxicology Letters | Year: 2013

Perfluorooctanoic acid (PFOA) is in use for the production of fluoropolymers (PFT). Due to its toxic properties it was proposed to replace the substance in its industrial applications by homologous compounds with shorter carbon chain length that were supposed to be less toxic compared to PFOA, however, the smaller PFOA homologs are poorly characterized so far. In this study we have conducted a comparative analysis of the toxicity of perfluorinated carboxylic acids (PFCA) with a carbon chain length ranging from four to twelve carbon atoms. By using the human hepatocarcinoma cell line HepG2 as an in vitro model for human hepatocytes we could show a positive correlation between the carbon chain length of the respective PFCA and its cytotoxicity. There was, however, no indication of an apoptotic mechanism for cytotoxicity. All PFCA under investigation were negative in two independent genotoxicity assays. As PFOA, being a well-known peroxisome proliferator, the other PFCA tested in this study were also shown to activate human peroxisome proliferator-activated receptor alpha (PPARα) with PFOA having the highest potential of PPARα activation. Moreover, the compounds showed weak potential to activate PPARγ and hardly activated PPARδ. Taken together, the in vitro study revealed that PFCA with a shorter carbon chain length seem to be less toxic than PFOA. © 2013 Elsevier Ireland Ltd.

Przyrembel H.,Bolchener Strasse 10 | Przyrembel H.,German Federal Institute for Risk Assessment
Annals of Nutrition and Metabolism | Year: 2012

Complementary food is needed when breast milk (or infant formula) alone is no longer sufficient for both nutritional and developmental reasons. The timing of its introduction, therefore, is an individual decision, although 6 months of exclusive breastfeeding can be recommended for most healthy term infants. The new foods are intended to 'complement' ongoing breastfeeding with those dietary items whose intake has become marginal or insufficient. Both breastfeeding and complementary feeding can have direct or later consequences on health. The evaluation of consequences of both early and late introduction of complementary food can neither disregard the effect of breastfeeding compared to formula feeding nor the composition or quality of the complementary food. Possible short-term health effects concern growth velocity and infections, and possible long-term effects may relate to atopic diseases, type 1 and 2 diabetes, obesity and neuromuscular development. On the basis of the currently available evidence, it is impossible to exactly determine the age when risks related to the start of complementary feeding are lowest or highest for most of these effects, with the possible exception of infections and early growth velocity. The present knowledge on undesirable health effects, however, is mainly based on observational studies, and although some mechanisms have been proposed, further prospective studies have to clarify these unsolved issues. Even less evidence on the consequences of the timing of complementary food introduction is available for formula-fed infants. Copyright © 2012 S. Karger AG, Basel.

Bol G.-F.,German Federal Institute for Risk Assessment
EMBO Reports | Year: 2016

The Ebola outbreak in West Africa is an instructive lesson on the difficulties of risk communication in times of crisis. The most effective strategy to improve communication during a crisis is to build public trust in officials and academics long before disaster strikes. © 2015 The Author.

Peiser M.,German Federal Institute for Risk Assessment
Clinical and Developmental Immunology | Year: 2013

Extending the classical concept considering an imbalance exclusively of T helper(h) 1 and Th2 cells on the bottom of many inflammatory diseases, Th17 cells were recently described. Today, there is sufficient experimental evidence to classify psoriasis and allergic contact dermatitis (ACD) amongst other inflammatory skin disorders as IL-17 associated diseases. In several human studies, T-cell-clones could be isolated from eczema biopsies, and high IL-17 levels were observed after challenge with allergen. In the last years, the phenotype of these IL-17 releasing T cells was in the focus of discussion. It has been suggested that Th17 could be identified by expression of retinoic acid receptor-related orphan receptor (ROR)C (humans) or RORγt (mice) and IL-17, accompanied by the absence of IFN-γ and IL-22. In cells from skin biopsies, contact allergens elevate IL-17A, IL-23, and RORC within the subset of Th cells. The indications for a participation of Th17 in the development of ACD are supported by data from IL-17 deficient mice with reduced contact hypersensitivity (CHS) reactions that could be restored after transplantation of wild type CD4+ T cells. In addition to Th17 cells, subpopulations of CD8+ T cells and regulatory T cells are further sources of IL-17 that play important roles in ACD as well. Finally, the results from Th17 cell research allow today identification of different skin diseases by a specific profile of signature cytokines from Th cells that can be used as a future diagnostic tool. © 2013 Matthias Peiser.

Dieckmann R.,German Federal Institute for Risk Assessment | Malorny B.,German Federal Institute for Risk Assessment
Applied and Environmental Microbiology | Year: 2011

Currently, 2,610 different Salmonella serovars have been described according to the White-Kauffmann-Le Minor scheme. They are routinely differentiated by serotyping, which is based on the antigenic variability at lipopolysaccharide moieties (O antigens), flagellar proteins (H1 and H2 antigens), and capsular polysaccharides (Vi antigens). The aim of this study was to evaluate the potential of matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry for rapid screening and identification of epidemiologically important Salmonella enterica subsp. enterica serovars based on specific sets of serovar-identifying biomarker ions. By analyzing 913 Salmonella enterica subsp. enterica strains representing 89 different serovars using MALDI-TOF mass spectrometry, several potentially serovar-identifying biomarker ions were selected. Based on a combination of genus-, species-, subspecies-, and serovar-identifying biomarker ions, a decision tree classification algorithm was derived for the rapid identification of the five most frequently isolated Salmonella enterica serovars, Enteritidis, Typhimurium/4,[5],12:i:-, Virchow, Infantis, and Hadar. Additionally, sets of potentially serovar-identifying biomarker ions were detected for other epidemiologically interesting serovars, such as Choleraesuis, Heidelberg, and Gallinarum. Furthermore, by using a bioinformatic approach, sequence variations corresponding to single or multiple amino acid exchanges in several biomarker proteins were tentatively assigned. The inclusivity and exclusivity of the specific sets of serovar-identifying biomarker ions for the top 5 serovars were almost 100%. This study shows that whole-cell MALDI-TOF mass spectrometry can be a rapid method for prescreening S. enterica subsp. enterica isolates to identify epidemiologically important serovars and to reduce sample numbers that have to be subsequently analyzed using conventional serotyping by slide agglutination techniques. © 2011, American Society for Microbiology.

Beutin L.,German Federal Institute for Risk Assessment | Martin A.,German Federal Institute for Risk Assessment
Journal of Food Protection | Year: 2012

An outbreak that comprised 3,842 cases of human infections with enteroaggregative hemorrhagic Escherichia coli (EAHEC) O104:H4 occurred in Germany in May 2011. The high proportion of adults affected in this outbreak and the unusually high number of patients that developed hemolytic uremic syndrome makes this outbreak the most dramatic since enterohemorrhagic E. coli (EHEC) strains were first identified as agents of human disease. The characteristics of the outbreak strain, the way it spread among humans, and the clinical signs resulting from EAHEC infections have changed the way Shiga toxin-producing E. coli strains are regarded as human pathogens in general. EAHEC O104:H4 is an emerging E. coli pathotype that is endemic in Central Africa and has spread to Europe and Asia. EAHEC strains have evolved from enteroaggregative E. coli by uptake of a Shiga toxin 2a (Stx2a)-encoding bacteriophage. Except for Stx2a, no other EHEC-specific virulence markers including the locus of enterocyte effacement are present in EAHEC strains. EAHEC O104:H4 colonizes humans through aggregative adherence fimbrial pili encoded by the enteroaggregative E. coli plasmid. The aggregative adherence fimbrial colonization mechanism substitutes for the locus of enterocyte effacement functions for bacterial adherence and delivery of Stx2a into the human intestine, resulting clinically in hemolytic uremic syndrome. Humans are the only known natural reservoir known for EAHEC. In contrast, Shiga toxin-producing E. coli and EHEC are associated with animals as natural hosts. Contaminated sprouted fenugreek seeds were suspected as the primary vehicle of transmission of the EAHEC O104:H4 outbreak strain in Germany. During the outbreak, secondary transmission (human to human and human to food) was important. Epidemiological investigations revealed fenugreek seeds as the source of entry of EAHEC O104:H4 into the food chain; however, microbiological analysis of seeds for this pathogen produced negative results. The survival of EAHEC in seeds and the frequency of human carriers of EAHEC should be investigated for a better understanding of EAHEC transmission routes. Copyright ©, International Association for Food Protection.

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