ImaGenes GmbH

Berlin, Germany

ImaGenes GmbH

Berlin, Germany
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Nebendahl C.,Leibniz Institute for Farm Animal Biology | Kruger R.,Leibniz Institute for Farm Animal Biology | Gors S.,Leibniz Institute for Farm Animal Biology | Albrecht E.,Leibniz Institute for Farm Animal Biology | And 8 more authors.
PLoS ONE | Year: 2013

Epidemiological and experimental data indicate that caloric restriction in early postnatal life may improve liver lipid metabolism in low birth weight individuals. The present study investigated transcriptional and metabolic responses to low (U) and normal (N) birth weight (d 75, T1) and postnatal feed restriction (R, 60% of controls, d 98, T2) followed by subsequent refeeding until d 131 of age (T3). Liver tissue studies were performed with a total of 42 female pigs which were born by multiparous German landrace sows. Overall, 194 genes were differentially expressed in the liver of U vs. N (T1) animals with roles in lipid metabolism. The total mean area and number of lipid droplets (LD) was about 4.6- and 3.7 times higher in U compared to N. In U, the mean LD size (μm2) was 24.9% higher. 3-week feed restriction reduced total mean area of LDs by 58.3 and 72.7% in U and N, respectively. A functional role of the affected genes in amino acid metabolism was additionally indicated. This was reflected by a 17.0% higher arginine concentration in the liver of UR animals (vs. NR). To evaluate persistency of effects, analyses were also done after refeeding period at T3. Overall, 4 and 22 genes show persistent regulation in U and N animals after 5 weeks of refeeding, respectively. These genes are involved in e.g. processes of lipid and protein metabolism and glucose homeostasis. Moreover, the recovery of total mean LD area in U and N animals back to the previous T1 level was observed. However, when compared to controls, the mean LD size was still reduced by 23.3% in UR, whereas it was increased in NR (+24.7%). The present results suggest that short-term postnatal feed restriction period programmed juvenile U animals for an increased rate of hepatic lipolysis in later life. © 2013 Nebendahl et al.

Seitz V.,Franklin University | Butzhammer P.,University of Regensburg | Hirsch B.,Franklin University | Hecht J.,Charité - Medical University of Berlin | And 10 more authors.
PLoS ONE | Year: 2011

Background: MYC is a key transcription factor involved in central cellular processes such as regulation of the cell cycle, histone acetylation and ribosomal biogenesis. It is overexpressed in the majority of human tumors including aggressive B-cell lymphoma. Especially Burkitt lymphoma (BL) is a highlight example for MYC overexpression due to a chromosomal translocation involving the c-MYC gene. However, no genome-wide analysis of MYC-binding sites by chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-Seq) has been conducted in BL so far. Methodology/Principal Findings: ChIP-Seq was performed on 5 BL cell lines with a MYC-specific antibody giving rise to 7,054 MYC-binding sites after bioinformatics analysis of a total of approx. 19 million sequence reads. In line with previous findings, binding sites accumulate in gene sets known to be involved in the cell cycle, ribosomal biogenesis, histone acetyltransferase and methyltransferase complexes demonstrating a regulatory role of MYC in these processes. Unexpectedly, MYC-binding sites also accumulate in many B-cell relevant genes. To assess the functional consequences of MYC binding, the ChIP-Seq data were supplemented with siRNA- mediated knock-downs of MYC in BL cell lines followed by gene expression profiling. Interestingly, amongst others, genes involved in the B-cell function were up-regulated in response to MYC silencing. Conclusion/Significance: The 7,054 MYC-binding sites identified by our ChIP-Seq approach greatly extend the knowledge regarding MYC binding in BL and shed further light on the enormous complexity of the MYC regulatory network. Especially our observations that (i) many B-cell relevant genes are targeted by MYC and (ii) that MYC down-regulation leads to an up-regulation of B-cell genes highlight an interesting aspect of BL biology. © 2011 Seitz et al.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2011.2.2.1-4 | Award Amount: 3.97M | Year: 2011

The DEM-CHILD project focusses on the main cause for childhood dementia in Europe, the neuronal ceroid lipofuscinoses (NCLs). The NCLs are neurodegenerative diseases characterized by dementia, blindness, epilepsy and physical decline leading to an early death of the patients. Since no cure is currently available, these disorders represent a serious social, medical, and economic challenge. To date, eight NCL genes have been characterised. There is evidence suggesting that further gene loci remain to be identified. NCLs are under-diagnosed in many countries around the world as there is an overall lack of research, early diagnosis, treatment and expert availability. Furthermore, due to their broad genetic heterogeneity it is difficult to collect large numbers of genetically similar patients. As such, large therapeutic studies required for advances in treatment are difficult to initiate. The DEM-CHILD project will combine the expertise of (i) recognized European research teams with (ii) high-technology SMEs, and will (iii) collaborate with Indian experts on the following objectives: (1) High-technology SMEs will develop innovative cost- and time-effective testing and screening methods for all NCLs in order to ensure early diagnosis and thereby prevention. (2) DEM-CHILD will collect the worlds largest, clinically and genetically best characterised set of NCL patients in order to study disease prevalence and precisely describe the natural history of the NCLs leading to the development of an evaluation tool for experimental therapy studies. (3) Novel biomarkers and modifiers of NCL will be identified to support the development of innovative therapies. (4) Focussing on the development of therapies for NCLs caused by mutations in intracellular transmembrane proteins, two complementary therapeutic strategies will be used and compared in eye and brain of mouse models: a) viral-mediated gene transfer and b) neural stem cell-mediated delivery of neuroprotective factors.

Weltmeier F.,Angewandte Pflanzengenetik und Biotechnologie GmbH | Maser A.,Angewandte Pflanzengenetik und Biotechnologie GmbH | Menze A.,SAAT AG | Hennig S.,ImaGenes GmbH | And 6 more authors.
Molecular Plant-Microbe Interactions | Year: 2011

Cercospora leaf spot disease, caused by the fungus Cercospora beticola, is the most destructive foliar disease of sugar beet (Beta vulgaris) worldwide. Despite the great agronomical importance of this disease, little is known about its underlying molecular processes. Technical resources are scarce for analyzing this important crop species. We developed a sugar beet microarray with 44,000 oligonucleotides that represent 17,277 cDNAs. During the four stages of C. beticola-B. vulgaris interactions, we profiled the transcriptional responses of three genotypes: susceptible, polygenic partial resistance, and monogenic resistant. Similar genes were induced in all three genotypes during infection but with striking differences in timing. The monogenic resistant genotype displayed strong defense responses at 1 day postinoculation (dpi). The other genotypes displayed defense responses in a later phase (15 dpi) of the infection cycle. The partially resistant genotype displayed a strong defense response in the late phase of the infection cycle. Furthermore, the partially resistant genotype expressed pathogenrelated transcripts that the susceptible genotype lacked. These results indicate that resistance was achieved by the ability to mount an early defense response, and partial resistance was determined by additional defense and signaling transcripts that allowed effective defense in the late phase of the infection cycle. © 2011 The American Phytopathological Society.

Agency: European Commission | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH.2011.2.4.3-4 | Award Amount: 3.85M | Year: 2012

Migration from Sub-Saharan Africa (SSA) to Europe is increasing. The limited evidence suggests that the risk of type 2 diabetes (T2D) and obesity among SSA migrants is higher than among their SSA peers living in Africa and European host populations. The reasons for these observations are only poorly understood, but may involve migration-related changes in lifestyle, genetic predisposition as well as peculiarities in perceptions and practises. Contrasting the increasing number of African migrants in Europe, the health status and needs of these populations remain largely unexamined, and have only insufficiently been integrated into national plans, policies and strategies. Implementation of tailored intervention programmes among migrants implicitly requires the identification and the disentanglement of environmental, lifestyle and genetic factors modifying T2D and obesity risk. The RODAM project addresses these fundamental health issues among a homogeneous, and one of the largest SSA migrant groups in Europe (i.e. Ghanaians). RODAM thus aims to contribute to the understanding of the complex interplay between environment, lifestyle, (epi)genetic as well as social factors in T2D and obesity among SSA immigrants, and to identify specific risk factors to guide intervention and prevention and to provide a basis for improving diagnosis and treatment. In a multi-centre study, 6,250 Ghanaians aged >25 years will be recruited in rural and urban Ghana, Germany, the Netherlands, and the UK. The differences in prevalence rates within Ghana on the one hand, and three European countries on the other, will allow us to unravel environmental, lifestyle and (epi)genetic as well as social factors in relation to T2D and obesity. The proposed study will generate relevant results that will ultimately guide intervention programmes and will provide a basis for improving diagnosis and treatment among SSA migrants in Europe as well as in their counterparts in Africa and beyond.

Doring F.,University of Kiel | Luersen K.,University of Kiel | Schmelzer C.,Leibniz Institute for Farm Animal Biology | Hennig S.,ImaGenes GmbH | And 5 more authors.
Molecular Nutrition and Food Research | Year: 2013

Epidemiological and experimental evidence indicates that maternal nutrition status contributes to long-term changes in the metabolic phenotype of the offspring, a process known as fetal programming. Methods and results: We have used a swine model (Sus scrofa) to analyze consequences of a maternal low protein diet (about 50% of control) during pregnancy on hepatic lipid metabolism and genome-wide hepatic gene expression profile of juvenile female offspring (mean age 85 days). We found 318 S. scrofa genes to be differentially expressed in the liver at age 85 days. In the low protein offspring group key genes of fatty acid de novo synthesis were downregulated whereas several genes of lipolysis and phospholipid biosynthesis were upregulated. qRT-PCR analysis of selected genes verified microarray data and revealed linear correlations between gene expression levels and slaughter weight. Hepatic cholesterol 7α hydroxylase protein expression tended to be lower in the low protein group. Total lipid and triglyceride content and fatty acid composition of total lipids were not different between groups. Conclusion: A maternal low protein diet during pregnancy induces a distinct hepatic gene expression signature in juvenile female pigs which was not translated into phenotypical changes of liver lipid metabolism. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Giller K.,University of Kiel | Huebbe P.,University of Kiel | Hennig S.,ImaGenes GmbH | Hennig S.,Coastal Research and Management GbR | And 4 more authors.
Free Radical Biology and Medicine | Year: 2013

Dietary restriction (DR) has been shown to exert a number of beneficial effects including the prolongation of life span. One of the mechanisms by which DR leads to these advantages seems to be the induction of endogenous antioxidant defense and stress response mechanisms. However, little is known about the persistence of DR benefits after return to an ad libitum diet. In this study, male C57BL/6 mice were fed 75% of a normal diet for 6 months (DR) followed by 6 months of ad libitum refeeding (RF) and compared to a continuously ad libitum fed control group. To study the impact of DR and RF on the liver transcriptome, a global gene expression profile was generated using microarray technology. In comparison, the DR group showed lower body weight, lower triglyceride and cholesterol levels, reduced lipid peroxidation, and a changed hepatic fatty acid pattern. mRNA transcription and activity of antioxidant and phase II enzymes, as well as metallothionein 1 gene expression, were increased and autophagy was induced. Shifting from long-term DR to RF abolished 96% of the DR-mediated changes in differential gene expression within 2 weeks, and after 6 months of refeeding all of the previously differentially expressed genes were similar in both groups. These results indicate that DR has to be maintained continuously to keep its beneficial effects. © 2013 Elsevier Inc.

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