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Schweigel-Rontgen M.,Leibniz Institute for Farm Animal Biology
Current Topics in Membranes

The solute carriers families 30 (SLC30; ZnT), 39 (SLC39; ZIP), and 31 (SLC31; CTR) are involved in the essential maintenance of cellular zinc (Zn2+) and copper (Cu2+) homeostasis, respectively.ZnTs mediate Zn2+ extrusion from cells (SLC30A1) or transport Zn2+ into organelles and secretory vesicles/granules (SLC30A2-SLC30A8). SLC39 family members are predominantly localized to the cell membrane where they perform Zn2+ uptake and increase the availability of cytosolic Zn2+. SLC39A1 is ubiquitously expressed, whereas other ZIP transporters (e.g., SLC39A2 and SLC39A3) show a more tissue-restricted expression consistent with organ-specific functions of these proteins.The members A1 (CTR1) and A2 (CTR2) of the SLC31 family of solute carriers belong to a network of proteins that acts to regulate the intracellular Cu2+ concentration within a certain range. SLC31A1 is predominantly localized to the plasma membrane, whereas SLC31A2 is mainly found in intracellular membranes of the late endosome and lysosome. The specific function of SLC31A2 is not known. SLC31A1 is ubiquitously expressed and has been characterized as a high-affinity importer of reduced copper (Cu+). Cu2+ transport function of CTR proteins is associated with oligomerization; SLC31A1 trimerizes and thereby forms a channel-like structure enabling Cu2+ translocation across the cell membrane.The molecular characteristics and structural details (e.g., membrane topology, conserved Zn2+, and Cu2+ binding sites) and mechanisms of translational and posttranslational regulation of expression and/or activity have been described for SLC30 and SLC39 family members, and for SLC31A1.For SLC31A1, data on tissue-specific functions (e.g., in the intestine, heart, and liver) are also available. A link between SLC31A1, immune function, and disorders such as Alzheimer's disease or cancer makes the protein a candidate therapeutic target.In secretory tissues (e.g., the mammary gland and pancreas), Zn2+ transporters of SLC families 30 and 39 are involved in specific functions such as insulin synthesis and secretion, metallation of digestive proenzymes, and transfer of nutrients into milk. Defective or dysregulated Zn2+ metabolism in these organs is associated with disorders such as diabetes and cancer, and impaired Zn2+ secretion into milk. © 2014 Elsevier Inc. Source

We investigated maze learning in dwarf goats (Capra hircus) and the impact of lateralisation on learning. Lateralisation refers to the collection of phenomena in which external stimuli are perceived and processed differentially on the two sides of the brain and/or certain behaviours are preferentially performed by one side of the body. We trained 29 dwarf goats in a Y-maze, directing them to the opposite alley from that chosen in a free pre-run. In total, 13 goats were trained to the left alley (L-goats) and 16 goats to the right alley (R-goats). Recall of the trained alley was tested three months later. We then analysed reversal learning across 10 reversals. During training, the direction of the alley had an impact on learning. The number of runs required to reach the learning criterion was significantly lower in the L- than the R-goats. The goats recalled the trained alley three months later, with no difference between the L- and the R-goats. During the reversal learning, the reversal only tended to impact learning performance, whereas the directions of the new and the initially trained alley did not. Goats did not adopt a general rule with which to master the maze (e.g., win-stay/lose-shift) across the 10 reversals. Our results indicate a right hemisphere bias in the processing of visuospatial cues in the maze during initial training; however, no such impact was detected during reversal learning. © 2012 Elsevier B.V. Source

Schmelzer C.,Leibniz Institute for Farm Animal Biology | Doring F.,University of Kiel
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Coenzyme Q10 (CoQ10) is an essential component for electron transport in the mitochondrial respiratory chain and serves as cofactor in several biological processes. The reduced form of CoQ10 (ubiquinol, Q10H2) is an effective antioxidant in biological membranes. During the last years, particular interest has been grown on molecular effects of CoQ10 supplementation on mechanisms related to DNA damage prevention. This review describes recent advances in our understanding about the impact of CoQ10 on genomic stability in cells, animals and humans. With regard to several in vitro and in vivo studies, CoQ10 provides protective effects on several markers of oxidative DNA damage and genomic stability. In comparison to the number of studies reporting preventive effects of CoQ10 on oxidative stress biomarkers, CoQ10 intervention studies in humans with a direct focus on markers of DNA damage are limited. Thus, more well-designed studies in healthy and disease populations with long-term follow up results are needed to substantiate the reported beneficial effects of CoQ10 on prevention of DNA damage. © 2011 Elsevier B.V. Source

Gimsa U.,Leibniz Institute for Farm Animal Biology | Mitchison N.A.,University College London | Brunner-Weinzierl M.C.,Otto Von Guericke University of Magdeburg
Mediators of Inflammation

Astrocytes have many functions in the central nervous system (CNS). They support differentiation and homeostasis of neurons and influence synaptic activity. They are responsible for formation of the blood-brain barrier (BBB) and make up the glia limitans. Here, we review their contribution to neuroimmune interactions and in particular to those induced by the invasion of activated T cells. We discuss the mechanisms by which astrocytes regulate pro- and anti-inflammatory aspects of T-cell responses within the CNS. Depending on the microenvironment, they may become potent antigen-presenting cells for T cells and they may contribute to inflammatory processes. They are also able to abrogate or reprogram T-cell responses by inducing apoptosis or secreting inhibitory mediators. We consider apparently contradictory functions of astrocytes in health and disease, particularly in their interaction with lymphocytes, which may either aggravate or suppress neuroinflammation. © 2013 Ulrike Gimsa et al. Source

Spitschak M.,Leibniz Institute for Farm Animal Biology | Vanselow J.,Leibniz Institute for Farm Animal Biology
General and Comparative Endocrinology

Transformation of the estrogen producing large dominant follicle into a functional progesterone producing corpus luteum involves profound and well-orchestrated changes in cell type-specific gene expression profiles, possibly involving epigenetic mechanisms of gene silencing. As an experimental paradigm to examine the involvement of de novo DNA methylation in the process of luteinization, the transcript abundance and promoter-specific DNA methylation levels of CYP19A1, which encodes the key enzyme for estrogen biosynthesis, were analyzed in enzymatically dispersed and purified large granulosa luteal cells of early- to mid-cycle bovine corpora lutea. To characterize the morphology and physiology of isolated corpora lutea, their weights and the respective plasma progesterone levels were analyzed. Transcript abundance of CYP19A1, HSD3B1, GHR, and of LHGCR was quantified by real-time PCR. Methylation levels were analyzed by bisulfite direct sequencing. The data indicated that corpora lutea weights and plasma progesterone levels significantly increased during the early luteal phase (days 3-6 of the cycle). The growth of small and large luteal cells was particularly pronounced between days 3 and 4. Large luteal cells are characterized by high HSD3B1 and GHR, but low LHCGR transcript abundance, whereas CYP19A1 expression was very low or undetectable. The DNA methylation levels of the main ovarian CYP19A1 promoter P2 significantly increased from day 5. In conclusion, the data indicated de novo DNA methylation approximately five days after the luteinizing hormone-induced down-regulation of CYP19A1 expression, suggesting that DNA methylation during the early luteal phase might play a role for permanent silencing of previously down-regulated genes. © 2012 Elsevier Inc. Source

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