@article{KraftSchuhmannGarzetal.2017,
  author    = {Kraft, Peter and Schuhmann, Michael K. and Garz, Cornelia and Jandke, Solveig and Urlaub, Daniela and Mencl, Stine and Zernecke, Alma and Heinze, Hans-Jochen and Carare, Roxana O. and Kleinschnitz, Christoph and Schreiber, Stefanie},
  title     = {Hypercholesterolemia induced cerebral small vessel disease},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0182822},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170493},
  pages     = {e0182822},
  year      = {2017},
  abstract  = {Background While hypercholesterolemia plays a causative role for the development of ischemic stroke in large vessels, its significance for cerebral small vessel disease (CSVD) remains unclear. We thus aimed to understand the detailed relationship between hypercholesterolemia and CSVD using the well described Ldlr\(^{-/-}\) mouse model. Methods We used Ldlr\(^{-/-}\) mice (n = 16) and wild-type (WT) mice (n = 15) at the age of 6 and 12 months. Ldlr\(^{-/-}\) mice develop high plasma cholesterol levels following a high fat diet. We analyzed cerebral capillaries and arterioles for intravascular erythrocyte accumulations, thrombotic vessel occlusions, blood-brain barrier (BBB) dysfunction and microbleeds. Results We found a significant increase in the number of erythrocyte stases in 6 months old Ldlr\(^{-/-}\) mice compared to all other groups (P < 0.05). Ldlr\(^{-/-}\) animals aged 12 months showed the highest number of thrombotic occlusions while in WT animals hardly any occlusions could be observed (P < 0.001). Compared to WT mice, Ldlr\(^{-/-}\) mice did not display significant gray matter BBB breakdown. Microhemorrhages were observed in one Ldlr\(^{-/-}\) mouse that was 6 months old. Results did not differ when considering subcortical and cortical regions. Conclusions In Ldlr\(^{-/-}\) mice, hypercholesterolemia is related to a thrombotic CSVD phenotype, which is different from hypertension-related CSVD that associates with a hemorrhagic CSVD phenotype. Our data demonstrate a relationship between hypercholesterolemia and the development of CSVD. Ldlr\(^{-/-}\) mice appear to be an adequate animal model for research into CSVD.},
  language  = {en}
}
@article{GilPulidoCochainLippertetal.2017,
  author    = {Gil-Pulido, Jesus and Cochain, Clement and Lippert, Malte A. and Schneider, Nicole and Butt, Elke and Am{\´e}zaga, N{\´u}ria and Zernecke, Alma},
  title     = {Deletion of Batf3-dependent antigen-presenting cells does not affect atherosclerotic lesion formation in mice},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0181947},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170535},
  pages     = {e0181947},
  year      = {2017},
  abstract  = {Atherosclerosis is the main underlying cause for cardiovascular events such as myocardial infarction and stroke and its development might be influenced by immune cells. Dendritic cells (DCs) bridge innate and adaptive immune responses by presenting antigens to T cells and releasing a variety of cytokines. Several subsets of DCs can be discriminated that engage specific transcriptional pathways for their development. Basic leucine zipper transcription factor ATF-like 3 (Batf3) is required for the development of classical CD8α\(^{+}\) and CD103\(^{+}\) DCs. By crossing mice deficient in Batf3 with atherosclerosis-prone low density lipoprotein receptor (Ldlr\(^{-/-}\))-deficient mice we here aimed to further address the contribution of Batf3-dependent CD8α\(^{+}\) and CD103\(^{+}\) antigen-presenting cells to atherosclerosis. We demonstrate that deficiency in Batf3 entailed mild effects on the immune response in the spleen but did not alter atherosclerotic lesion formation in the aorta or aortic root, nor affected plaque phenotype in low density lipoprotein receptor-deficient mice fed a high fat diet. We thus provide evidence that Batf3-dependent antigen-presenting cells do not have a prominent role in atherosclerosis.},
  language  = {en}
}
@article{GarciaBetancurGoniMorenoHorgeretal.2017,
  author    = {Garc{\´i}a-Betancur, Juan-Carlos and Go{\~n}i-Moreno, Angel and Horger, Thomas and Schott, Melanie and Sharan, Malvika and Eikmeier, Julian and Wohlmuth, Barbara and Zernecke, Alma and Ohlsen, Knut and Kuttler, Christina and Lopez, Daniel},
  title     = {Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus},
  series = {eLife},
  volume    = {6},
  journal   = {eLife},
  number    = {e28023},
  doi       = {10.7554/eLife.28023},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170346},
  year      = {2017},
  abstract  = {A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureusteichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types.},
  language  = {en}
}