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Chang L.,Universitatsklinikum Hamburg Eppendorf | Schwarzenbach H.,Universitatsklinikum Hamburg Eppendorf | Meyer-Staeckling S.,Universitatsklinikum Hamburg Eppendorf | Brandt B.,Universitatsklinikum Hamburg Eppendorf | And 3 more authors.
Molecular Cancer Research | Year: 2011

Under physiologic conditions, the inositol-1,4,5-trisphosphate (InsP3)-metabolizing, F-actin-bundling InsP3- kinase-A (ITPKA) is expressed only in neurons. Tumor cells that have gained the ability to express ITPKA show an increased metastatic potential due to the migration-promoting properties of ITPKA. Here we investigated the mechanism how tumor cells have gained the ability to reexpress ITPKA by using a breast cancer cell line (T47D) with no expression and a lung carcinoma cell line (H1299) with ectopic ITPKA expression. Cloning of a 1,250-bp ITPKA promoter fragment revealed that methylation of CpG islands was reduced in H1299 as compared with T47D cells, but DNA demethylation did not alter the expression of ITPKA. Instead, we showed that the repressor-element-1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), which suppresses expression of neuronal genes in nonneuronal tissues, regulates expression of ITPKA. Knockdown of REST/NRSF induced expression of ITPKA in T47D cells, whereas its overexpression in H1299 cells strongly reduced the level of ITPKA. In T47D cells, REST/NRSF was bound to the RE-1 site of the ITPKA promoter and strongly reduced its activity. In H1299 cells, in contrast, expressing comparable REST/NRSF levels as T47D cells, REST/NRSF only slightly reduced ITPKA promoter activity. This reduced suppressor activity most likely results from expression of a dominant-negative isoform of REST/NRSF, REST4, which impairs binding of REST/NRSF to the RE-1 site. Thus, ITPKA may belong to the neuronal metastasis-promoting proteins whose ectopic reexpression in tumor cells is associated with impaired REST/NRSF activity. Mol Cancer Res; 9(4); 497-506. © 2011 American Association for Cancer Research.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: KBBE.2010.4-01 | Award Amount: 1.25M | Year: 2011

By integrating the key European teams in genomics, bioinformatics, animal health and animal models, EADGENE has enabled: - the gathering of a critical mass of scientists and a unique access of complementary resources across host and pathogen models - the development of innovative functional genomics so that it has become a powerful tool in veterinary molecular medicine and has contributed to a better understanding of host-pathogen interactions, for the improvement of animal health and food safety, Building from these benefits, EADGENE_S will ensure a long-term integration of the European resources in animal disease genomics grouping together the leading institutions. It will strengthen durably the creation of a core group of European research centres of excellence highly committed to integrating their resources and national facilities. To achieve this, EADGENE_S will: (1) Expend, share and upgrade common research tools and platforms for joint research projects (2) Further develop common research methods, standards and protocols (3) Maintain, consolidate and further develop high quality common research projects on animal genomics and genetics in Europe (4) Support strategies for durable integration, particularly by providing opportunities for further funding (5) Consolidate the skills and expertise throughout the partnership with a programme of workshops, training courses, short-term missions, internships and studentships (6) Provide platforms for the development, management and dissemination of knowledge (7) Ensure efficient technology transfer to the industry to ensure timely commercialisation newest developments This integration will be fulfilled under the framework of the European Research Group EADGENE (EADGENE ERG), a co-operation instrument composed of the EADGENE members as represented by their respective participating research departments.


The requirement for sustainable food production is a global issue to which the EU contributes as a major livestock producer. It is critical to improve animal production efficiency while sustaining environmentally friendly milk production. More profitable dairy production requires increased milk yield, cow health, longevity and fertility; reduced environmental footprint and optimised use of inputs. These are multifactorial problems to achieve. GplusE aims to identify the genotypes controlling biological variation in the important phenotypes of dairy cows, to appreciate how these are influenced by environmental and management factors and thus allow more informed and accurate use of genomic selection. GplusE will link new genomic data in dairy cows to a comprehensive array of phenotypic information going well beyond those existing traits recorded by dairy breeding organisations. It will develop systems that will focus herd and cow management on key time points in production that have a major influence on the rest of the productive cycle including efficiency, environment, physiological status, health, fertility and welfare. This will significantly advance the science, efficiency and management practices in dairy production well beyond the current state-of-the art. The major bioinformatics element of the proposal will illuminate the bovine genome and ensure a reverse flow of information to annotate human and other mammalian genomes; it will ensure training of animal scientists (PhDs & Postdocs) to a high skill level in the use of bioinformatics. The end result of this project will be a comprehensive, integrated identification of genomic-phenotypic associations relevant to dairy production. This information will be translated into benefits for animal breeding and management that will considerably improve sustainable dairy production. It will provide basic biological information into the mechanisms by which genotype, environment and their interaction influence performance.


Henry F.,National Veterinary School of Alfort | Eder S.,Leibniz Institute For Zoo Und Wildtierforschung | Reynaud K.,CNRS Physiology of Reproduction and Behaviors | Schon J.,Leibniz Institute For Nutztierbiologie | And 3 more authors.
Theriogenology | Year: 2015

From many endangered or threatened species which are expected to profit from assisted reproduction techniques, mainly epididymal sperm of dead or freshly castrated males are available. These sperm had contact to epididymal secretion products but not to seminal fluid components. Notably, products of accessory sex glands have been shown in domestic animals to condition sperm for fertilization, in particular by mediating sperm-oviduct interaction. We report for the first time that motile epididymal sperm from domestic cats are able to bind to fresh oviduct epithelial cell explants from preovulatory females (median [min, max] of 10 [8, 16] and 10 [8, 17] sperm per 0.01mm2 explant surface from both isthmic and ampullar regions, respectively). More sperm attach to the explants when epididymal sperm were preincubated for 30minutes with seminal fluid separated from electroejaculates of mature tomcats (median [min, max] of 17 [13, 25] and 16 [12, 21] sperm per 0.01mm2 explant surface from isthmus and ampulla, respectively). The proportion of bound sperm increased from a median of 54% to 62% by seminal fluid treatment. Sperm-oviduct binding could be facilitated by the decelerated sperm motion which was observed in seminal fluid-treated samples or supported by seminal fluid proteins newly attached to the sperm surface. Seminal fluid had no effect on the proportion of sperm with active mitochondria. Extent and pattern of sperm interaction invitro were independent of explant origin from isthmus or ampulla. Sperm were attached to both cilia and microvilli of the main epithelial cell types present in all explants. In contrast to published sperm-binding studies with porcine and bovine oviduct explants where predominantly the anterior head region of sperm was attached to ciliated cells, the tails of some cat sperm were firmly stuck to the oviduct cell surfaces, whereas the heads were wobbling. Whether this response is a preliminary step toward phagocytosis or a precondition to capacitation and fertilization remains to be determined. In conclusion, treatment of epididymal sperm with seminal fluid or particular protein components should be considered in future investigations for its potential to improve the outcome of artificial insemination in felids. © 2015 Elsevier Inc.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.1.3-03 | Award Amount: 7.85M | Year: 2013

ECO-FCEs objective is to firstly understand the interactions within the monogastric biological system which create diversity, optimise feed use efficiency and reduce greenhouse gas emissions, nitrogen and phosphorus excretion, whilst not adversely affecting animal health, welfare or product quality. Secondly, ECO-FCE will develop industry-ready tools which will facilitate the selection of breeding stock and nutritional strategies for improved gut health and functionality and host performance. ECO-FCE will achieve these objectives through five scientific work packages. Work package 1 involves a systematic literature review which will collate information in the open and grey literature on the effect of nutrition, gut characteristics and host genetics on feed use efficiency, nutrient utilization, greenhouse gas emissions, nitrogen and phosphorus excretion in pigs and poultry. Work package 2 will focus on the effect of nutrition. Aspects including how and when feed is offered and diet ingredients (raw materials and feed additives) will be investigated. Particular focus will be on nutritional strategies to reduce N and P excretion and to accurately determine and reduce GHG emissions. The effect of environment pre birth and nutrition post birth in pigs will also be investigated. Data and samples from WP 2 will then be used in WPs 3 and 4. Initial work in work packages 3 and 4 will specifically focus on common gut and host genetic factors which promote good or poor FCE. Other work in WP 3 will then investigate the feasibility of inoculating pigs and poultry with this good gut microflora. WP 4 will focus on host genomics and will specifically attempt to relate genomic variation to variation in FCE. Further work in this work package will apply omics techniques and will aim to derive biomarkers as tools to improve monogastric FCE. In WP 5 novel, industry-ready tools in the form of models will be developed and tested using data collated throughout the project.


PubMed | Leibniz Institute For Zoo Und Wildtierforschung, CNRS Physiology of Reproduction and Behaviors, Leibniz Institute For Nutztierbiologie and National Veterinary School of Alfort
Type: Journal Article | Journal: Theriogenology | Year: 2015

From many endangered or threatened species which are expected to profit from assisted reproduction techniques, mainly epididymal sperm of dead or freshly castrated males are available. These sperm had contact to epididymal secretion products but not to seminal fluid components. Notably, products of accessory sex glands have been shown in domestic animals to condition sperm for fertilization, in particular by mediating sperm-oviduct interaction. We report for the first time that motile epididymal sperm from domestic cats are able to bind to fresh oviduct epithelial cell explants from preovulatory females (median [min, max] of 10 [8, 16] and 10 [8, 17] sperm per 0.01 mm(2) explant surface from both isthmic and ampullar regions, respectively). More sperm attach to the explants when epididymal sperm were preincubated for 30 minutes with seminal fluid separated from electroejaculates of mature tomcats (median [min, max] of 17 [13, 25] and 16 [12, 21] sperm per 0.01 mm(2) explant surface from isthmus and ampulla, respectively). The proportion of bound sperm increased from a median of 54% to 62% by seminal fluid treatment. Sperm-oviduct binding could be facilitated by the decelerated sperm motion which was observed in seminal fluid-treated samples or supported by seminal fluid proteins newly attached to the sperm surface. Seminal fluid had no effect on the proportion of sperm with active mitochondria. Extent and pattern of sperm interaction in vitro were independent of explant origin from isthmus or ampulla. Sperm were attached to both cilia and microvilli of the main epithelial cell types present in all explants. In contrast to published sperm-binding studies with porcine and bovine oviduct explants where predominantly the anterior head region of sperm was attached to ciliated cells, the tails of some cat sperm were firmly stuck to the oviduct cell surfaces, whereas the heads were wobbling. Whether this response is a preliminary step toward phagocytosis or a precondition to capacitation and fertilization remains to be determined. In conclusion, treatment of epididymal sperm with seminal fluid or particular protein components should be considered in future investigations for its potential to improve the outcome of artificial insemination in felids.


Numberg K.,Leibniz Institute For Nutztierbiologie | Numberg G.,Leibniz Institute For Nutztierbiologie | Dannenberger D.,Leibniz Institute For Nutztierbiologie | Hagemann L.,Landesamt fur Landliche Entwicklung | Paulke T.,Landesamt fur Landliche Entwicklung
Fleischwirtschaft | Year: 2011

The supplementation of extruded linseed on growth and meat and fat quality of castrated male pigs has been investigated in this experiment. Pigs were fed with concentrate pellets without supplement (control), added with 2.5% extruded linseed (experimental group 1) or 4% extruded linseed (experimental group 2) during the finishing period. Growth and, meat and fat quality were not affected by extruded linseed feeding. Fat of muscle and back fat in pigs fed linseed deposited dose dependently more n-3 fatty acids. The ratio n-6 to n-3 was decreased in experimental groups. The processing quality of back fat could be reduced.


Iwen K.A.,University of Lübeck | Klein J.,University of Lübeck | Hubold C.,University of Lübeck | Lehnert H.,University of Lübeck | Weitzel J.M.,Leibniz Institute For Nutztierbiologie
Experimental and Clinical Endocrinology and Diabetes | Year: 2013

Aim: Hepatocyte nuclear factor 1 alpha (HNF1A) mutations cause maturity-onset diabetes of the young (MODY) type 3. Further extending the phenotypic spectrum, HNF1A mutations are associated with hepatic adenomatosis. A 20-year old lean, female patient with newly diagnosed diabetes mellitus was negative for diabetes-associated autoantibodies and had no relevant family history. Hepatic adenomatosis was diagnosed. Her HNF1A gene was examined and identified alterations further analysed. Methods & Results: Sequencing of her HNF1A gene revealed a previously uncharacterised Q495X nonsense mutation, along with the known A98V polymorphism, both in the heterozygous state. The patient's father was also a carrier of both the mutation and the polymorphism. An oral glucose tolerance test (OGTT) revealed impaired glucose tolerance, whereas imaging of his liver was unremarkable. Wild type HNF1A and HNF1A carrying the Q495X mutation were co-transfected in reporter gene assays. The mutation causes a dominant-negative HNF1A protein variant which blocks HNF1A wild-type-mediated gene expression. Conclusion: The novel Q495X mutation is the likely cause of our patient's diabetes and hepatic adenomatosis. It may also cause her father's impaired glucose tolerance. More generally speaking, if non-autoimmune diabetes is suspected, examination of the liver may provide important diagnostic clues. Furthermore, patients with hepatic adenomatosis without known diabetes should be screened by OGTT. Relatives of patients with HNF1A mutations should also be screened by OGTT to detect potential early-stage diabetes. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart . New York ISSN 0947-7349.


Piatkowski B.,Bernhard Piatkowski | Jentsch W.,Werner Jentsch | Derno M.,Leibniz Institute For Nutztierbiologie
Zuchtungskunde | Year: 2010

The used model equation for prediction of the daily methane production of dairy cows, heifers and fattening young bulls is based on 337 methane measurements in 1500 single metabolism experiments in respiration chambers. The equation is: y = 32.76 - 0.384x (y = g methane per kg DM intake, x = DM intake in g per kg live weight). Accordingly the mean daily methane production of dairy cows fed at maintenance amounts to 198 g and at a milk yield of 4000, 6000, 8000, and 10000 kg to 334, 380 404, and 424 g. These are equivalent to yearly productions (305 days), dry period (16 kg methane) included, of 118, 132, 139, and 145 kg. The established data are the base for an estimation of yearly methane production of German cattle stock in 2006. Methane emission of these 12.7 million cattle amounted to 1.03 million tons, according to 0.22% of worldwide methane output to the atmosphere. For cattle this is lower than assumed hitherto. A realistic possibility for further reducing their methane emission seems to be a moderate increase of production performance. © Verlag Eugen Ulmer, Stuttgart.


Nurnberg K.,Leibniz Institute For Nutztierbiologie | Dannenberger D.,Leibniz Institute For Nutztierbiologie | Nurnberg G.,Leibniz Institute For Nutztierbiologie | Paulke T.,Landesamt fur Landliche Entwickl.
Fleischwirtschaft | Year: 2013

The aim of the study was to characterise the meat and fat quality of heavy female Saddleback pigs in comparison to conventional crossbreeds. The individual variations of carcass traits, meat quality and lipid profile of different tissues of heavy Saddle Back pigs was very high. Because of the reduced growth performance this breed will be only a niche production line for pig breeding in Germany. The good meat quality, the high intramuscular fat content (5.18%) and the high back fat thickness guarantee a perfect eating quality. Monoenoic acids are deposited in different tissues at a high level showing a lower biosynthesis of these MUFA in conventional pig breeds even at high live weight.

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