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  • 1
    Language: English
    In: The Quarterly Review of Biology, 01 December 2015, Vol.90(4), pp.381-415
    Description: ABSTRACT Organisms adapt developmental and physiological features to local and transient conditions in part by modulating transcription, translation, and protein functions, usually without changing DNA sequences. Remarkably, these epigenetic changes sometimes endure through meiosis and gametogenesis, thereby affecting phenotypic variation across generations, long after epigenetic changes were triggered. Transgenerational effects challenge our traditional understanding of inheritance. In this review, we focus on patterns of inheritance, molecular features, mechanisms that lead from environmental and genetic perturbations to phenotypic variation in later generations, and issues about study design and replication.
    Keywords: Biology;
    ISSN: 00335770
    E-ISSN: 15397718
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  • 2
    Language: English
    In: Chemosphere, November 2015, Vol.138, pp.856-862
    Description: Equilibrium sampling can be applied to measure freely dissolved concentrations ( ) of hydrophobic organic chemicals (HOCs) that are considered effective concentrations for diffusive uptake and partitioning. It can also yield concentrations in lipids at thermodynamic equilibrium with the sediment ( ) by multiplying concentrations in the equilibrium sampling polymer with lipid to polymer partition coefficients. We have applied silicone coated glass jars for equilibrium sampling of seven ‘indicator’ polychlorinated biphenyls (PCBs) in sediment samples from ten locations along the River Elbe to measure of PCBs and their . For three sites, we then related to lipid-normalized PCB concentrations ( ) that were determined independently by the German Environmental Specimen Bank in common bream, a fish species living in close contact with the sediment: (1) In all cases, were below , (2) there was proportionality between the two parameters with high values (0.92–1.00) and (3) the slopes of the linear regressions were very similar between the three stations (0.297; 0.327; 0.390). These results confirm the close link between PCB bioaccumulation and the thermodynamic potential of sediment-associated HOCs for partitioning into lipids. This novel approach gives clearer and more consistent results compared to conventional approaches that are based on total concentrations in sediment and biota-sediment accumulation factors. We propose to apply equilibrium sampling for determining bioavailability and bioaccumulation potential of HOCs, since this technique can provide a thermodynamic basis for the risk assessment and management of contaminated sediments.
    Keywords: Equilibrium Sampling ; Sediment ; Bioaccumulation ; Polychlorinated Biphenyl (Pcb) ; River Elbe ; Freely Dissolved Concentration (Cfree) ; Chemistry ; Ecology
    ISSN: 0045-6535
    E-ISSN: 1879-1298
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  • 3
    In: PLoS ONE, 2013, Vol.8(8)
    Description: Maintenance and maturation of primordial germ cells is controlled by complex genetic and epigenetic cascades, and disturbances in this network lead to either infertility or malignant aberration. Transcription factor TFAP2C has been described to be essential for primordial germ cell maintenance and to be upregulated in several human germ cell cancers. Using global gene expression profiling, we identified genes deregulated upon loss of Tfap2c in embryonic stem cells and primordial germ cell-like cells. We show that loss of Tfap2c affects many aspects of the genetic network regulating germ cell biology, such as downregulation of maturation markers and induction of markers indicative for somatic differentiation, cell cycle, epigenetic remodeling and pluripotency. Chromatin-immunoprecipitation analyses demonstrated binding of TFAP2C to regulatory regions of deregulated genes ( Sfrp1, Dmrt1 , Nanos3 , c-Kit , Cdk6 , Cdkn1a , Fgf4 , Klf4 , Dnmt3b and Dnmt3l ) suggesting that these genes are direct transcriptional targets of TFAP2C in primordial germ cells. Since Tfap2c deficient primordial germ cell-like cells display cancer related deregulations in epigenetic remodeling, cell cycle and pluripotency control, the Tfap2c -knockout allele was bred onto 129S2/Sv genetic background. There, mice heterozygous for Tfap2c develop with high incidence germ cell cancer resembling human pediatric germ cell tumors. Precursor lesions can be observed as early as E16.5 in developing testes displaying persisting expression of pluripotency markers. We further demonstrate that mice with a heterozygous deletion of the TFAP2C target gene Nanos3 are also prone to develop teratomas. These data highlight TFAP2C as a critical and dose-sensitive regulator of germ cell fate.
    Keywords: Research Article ; Biology ; Medicine
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: Marine Environmental Research, 2011, Vol.71(1), pp.70-78
    Description: Female and male individuals of the same species often differ with respect to their susceptibility to toxicant stress. In the present study, sea urchins ( ) of both sexes were exposed to high (150 μg L ) and environmentally relevant (5 μg L ) concentrations of phenanthrene over 10 days. While food intake was significantly decreased following exposure to 150 μg L phenanthrene, histological indices (lipofuscin accumulation, fibrosis, oocyte atresia), energetic status (energy charge, sum adenylates, AMP/ATP ratio) as well as ascorbate levels in the gonads showed either little or no effect upon phenanthrene exposure. However, most parameters (vitamin C, energy charge, sum adenylates, AMP/ATP ratio, ATP and ADP concentrations, lipofuscin content, fibrosis) significantly differed between male and female animals. This study illustrates the difficulties to identify toxic injury in reproductive tissue as it may be superimposed by gametogenesis and spawning of gametes.
    Keywords: Sea Urchin ; Gonad ; Lipofuscin ; Energy Charge ; Phenanthrene ; Ascorbate ; Sex-Specific Differences ; ATP ; ATP/Amp Ratio ; Gametogenesis ; Environmental Sciences ; Biology ; Oceanography ; Ecology
    ISSN: 0141-1136
    E-ISSN: 1879-0291
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  • 5
    In: Thewes, Verena; Orso, Francesca; Jäger, Richard; Eckert, Dawid; Schäfer, Sabine; Kirfel, Gregor; Garbe, Stephan; Taverna, Daniela; Schorle, Hubert (2010). Interference with activator protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation-sensitivity in breast cancer cells. BMC Cancer 10 ,
    Description: Background: Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2 alpha and AP-2 gamma is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo-or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms. Methods: We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant. Results: We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo-and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo-and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network. Conclusions: Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo-and radiation-resistance of tumor cells by impairing the ability to induce apoptosis. Therefore, interference with AP-2 function could increase the sensitivity of tumor cells towards therapeutic intervention.
    Keywords: Tissue Growth-Factor ; Smooth-Muscle-Cells ; Differential Expression ; Mammary-Carcinoma ; Ap-2 Family ; Proliferation ; Overexpression ; Ap-2-Gamma ; Tumor ; Lung
    ISSN: 1471-2407
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  • 6
    Language: English
    In: Environmental Science and Technology, 2016, Vol.50(11), pp.5424-5431
    Description: Mixtures of organic contaminants are ubiquitous ronment. Depending on their persistence and physicochemical properties, individual chemicals that make up the mixture partition and distribute within the environment and might then jointly elicit toxicological...
    Keywords: Engineering And Technology ; Environmental Engineering ; Teknik Och Teknologier ; Naturresursteknik ; Natural Sciences ; Earth And Related Environmental Sciences ; Naturvetenskap ; Geovetenskap Och Miljövetenskap
    ISSN: 0013-936X
    E-ISSN: 15205851
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  • 7
    Language: English
    In: Environmental science & technology, 06 September 2016, Vol.50(17), pp.9708-16
    Description: In chronic toxicity tests with Caenorhabditis elegans, it is necessary to feed the nematode with bacteria, which reduces the freely dissolved concentration (Cfree) of hydrophobic organic chemicals (HOCs), leading to poorly defined exposure with conventional dosing procedures. We examined the efficacy of passive dosing of polycyclic aromatic hydrocarbons (PAHs) using silicone O-rings to control exposure during C. elegans toxicity testing and compared the results to those obtained with solvent spiking. Solid-phase microextraction and liquid-liquid extraction were used to measure Cfree and the chemicals taken up via ingestion. During toxicity testing, Cfree decreased by up to 89% after solvent spiking but remained constant with passive dosing. This led to a higher apparent toxicity on C. elegans exposed by passive dosing than by solvent spiking. With increasing bacterial cell densities, Cfree of solvent-spiked PAHs decreased while being maintained constant with passive dosing. This resulted in lower apparent toxicity under solvent spiking but an increased apparent toxicity with passive dosing, probably as a result of the higher chemical uptake rate via food (CUfood). Our results demonstrate the utility of passive dosing to control Cfree in routine chronic toxicity testing of HOCs. Moreover, both chemical uptake from water or via food ingestion can be controlled, thus enabling the discrimination of different uptake routes in chronic toxicity studies.
    Keywords: Caenorhabditis Elegans ; Toxicity Tests, Chronic
    ISSN: 0013936X
    E-ISSN: 1520-5851
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  • 8
    Language: English
    In: Developmental Dynamics, March 2010, Vol.239(3), pp.1027-1033
    Description: Extensive development of the mammary gland occurs during puberty, when rising levels of ovarian hormones induce the formation of highly proliferative terminal end buds (TEBs) at the tips of mammary ducts. TEBs consist of an outer layer of cap cells and of inner body cells. TEBs invade the adipose stroma and bifurcate while extending the ducts to generate an arborized ductal network. We show that in murine mammary glands transcription factor AP‐2γ is strongly expressed in the cap cell layer and in a subset of body cells of TEBs. To decipher AP‐2γ functions during mammary development we generated AP‐2γ‐deficient mice. Their mammary glands displayed impaired ductal branching and elongation. Cellular proliferation within TEBs was reduced. Although estrogen receptor was expressed, exogenously administered ovarian hormones could not restore normal development. Therefore, AP‐2γ is functionally involved in branching morphogenesis of the mammary epithelium, possibly by controlling genetic processes downstream of ovarian hormones. Developmental Dynamics 239:1027–1033, 2010. © 2010 Wiley‐Liss, Inc.
    Keywords: Ap‐2 ; Tfap2c ; Mammary ; Branching Morphogenesis ; Transgenic Mice
    ISSN: 1058-8388
    E-ISSN: 1097-0177
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  • 9
    Language: English
    In: Genome biology, 19 June 2014, Vol.15(6), pp.R79
    Description: RNA editing encompasses a post-transcriptional process in which the genomically templated sequence is enzymatically altered and introduces a modified base into the edited transcript. Mammalian C-to-U RNA editing represents a distinct subtype of base modification, whose prototype is intestinal apolipoprotein B mRNA, mediated by the catalytic deaminase Apobec-1. However, the genome-wide identification, tissue-specificity and functional implications of Apobec-1-mediated C-to-U RNA editing remain incompletely explored. Deep sequencing, data filtering and Sanger-sequence validation of intestinal and hepatic RNA from wild-type and Apobec-1-deficient mice revealed 56 novel editing sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs, all within 3' untranslated regions. Eleven of 17 liver RNAs shared editing sites with intestinal RNAs, while 6 sites are unique to liver. Changes in RNA editing lead to corresponding changes in intestinal mRNA and protein levels for 11 genes. Analysis of RNA editing in vivo following tissue-specific Apobec-1 adenoviral or transgenic Apobec-1 overexpression reveals that a subset of targets identified in wild-type mice are restored in Apobec-1-deficient mouse intestine and liver following Apobec-1 rescue. We find distinctive polysome profiles for several RNA editing targets and demonstrate novel exonic editing sites in nuclear preparations from intestine but not hepatic apolipoprotein B RNA. RNA editing is validated using cell-free extracts from wild-type but not Apobec-1-deficient mice, demonstrating that Apobec-1 is required. These studies define selective, tissue-specific targets of Apobec-1-dependent RNA editing and show the functional consequences of editing are both transcript- and tissue-specific.
    Keywords: RNA Editing ; Cytidine Deaminase -- Genetics ; Intestine, Small -- Enzymology ; Liver -- Enzymology
    E-ISSN: 1474-760X
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  • 10
    Language: English
    In: Open Journal of Veterinary Medicine, 2013-02-01, 3卷2期 (Vol.3, Issue 2), pp.121-130
    Description: The effect of Procox® (Bayer, emodepside/toltrazuril suspension for dogs) against natural infections with Isospora spp. was investigated. Two groups were treated either with 0.5 ml suspension/kg of body weight (0.45 mg emodepside and 9 mg toltrazuril/kg of body weight) in the 3^(rd), 5^(th) and 7^(th) week of life (w.o.l.) (Procox® group; n = 28) or with a control anthelminthic (Dewormed Control group; n = 26). Animals were surveyed weekly from the 3^(rd) w.o.l. by coproscopy and clinical examination. Faecal samples were examined microbiologically from the 4^(th) to the 8th w.o.l. and faecal inflammatory markers canine calprotectin and canine S100A12 were measured in the 8th w.o.l. Specific antibody titres were evaluated in serum samples from five litters before and after vaccination against canine distemper virus and canine parvovirus 2. The prevalence of Isospora-positive animals increased to 67% in the Dewormed Control group (n = 15 puppies from four parasite-positive litters), while in the Procox® group (n = 15 puppies) it was less than 34% with significantly lower excretion (p < 0.01). Procox® was easily applied and effective; adverse effects did not occur. The level of seroconversion or titre increase upon vaccination was higher in parasite-free animals (91%) compared to Procox®- treated puppies (30%) and the Control animals (10%). Animals from parasite-free litters showed significantly different excretion patterns for haemolytic Escherichia coli and Clostridium perfringens, while there was no difference between Procox®-treated and Control animals. In some animals kept under poor hygienic conditions diarrhoea was noted in association with C. perfringens, E. coli or Salmonella. Concentrations of inflammatory markers in the faeces did not significantly differ between the Procox® and the Control group. Adequate control of parasitic and bacterial infections in suckling puppies requires both antiparasitic treatment and hygiene. Even when parasites do not cause overt effects treatment is recommended in cases with a history of parasite infections.
    Keywords: Dog ; Emodepside ; Gut Health ; Isospora ; Toltrazuril ; Toxocara ; Vaccination
    ISSN: 2165-3356
    E-ISSN: 21653364
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