Alzheimer's disease is a devastating neurodegenerative disease eventually leading to dementia. An effective treatment does not yet exist. Here we show that oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally before or after the onset of pathology. At the mechanistic level we provide evidence that anle138b blocks the formation of conducting Aß pores without changing the membrane embedded Aß-oligomer structure. In conclusion, our data suggest that anle138b is a novel and promising compound to treat AD-related pathology that should be investigated further. Overall design: APPdelta9 and Wildtype mouse treated with anle138b or placebo
The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology.
Age, Cell line, Subject
View SamplesThe behavior of yeast cells during industrial processes such as the production of beer, wine and bioethanol has been extensively studied. By contrast, our knowledge about yeast physiology during solid state processes, such as bread dough, cheese or cocoa fermentation remains limited. We investigated changes in the transcriptome of three genetically distinct Saccharomyces cerevisiae strains during bread dough fermentation. Our results show that regardless of the genetic background, all three strains exhibit similar changes in expression patterns. At the onset of fermentation, expression of glucose-regulated genes changes dramatically, and the osmotic stress response is activated. The middle fermentation phase is characterized by the induction of genes involved in amino acid metabolism. Finally, at the latest time point, cells suffer from nutrient depletion and activate pathways associated with starvation and stress response. Further analysis shows that genes regulated by the High Osmolarity Glycerol (HOG) pathway, the major pathway involved in the response to osmotic stress and glycerol homeostasis, are among the most differentially expressed genes at the onset of fermentation. More importantly, deletion of HOG1 and other genes of this pathway significantly reduces fermentation capacity. Together, our results demonstrate that cells embedded in a solid matrix such as bread dough suffer severe osmotic stress, and that a proper induction of the HOG pathway is critical for an optimal fermentation.
Dynamics of the Saccharomyces cerevisiae transcriptome during bread dough fermentation.
No sample metadata fields
View SamplesPHD4 regulates the expression of Hypxia-inducible Factor 2 (HIF-2) alpha in LM8 osteosarcoma cells. PHD4 overexpression inhibits the growth of experimental tumor in syngenic mice but stimulates angiogenesis via Transforming Growth-Factor (TGF)-alpha.
PHD4 stimulates tumor angiogenesis in osteosarcoma cells via TGF-α.
Cell line, Treatment
View SamplesPurpose: The purpose of the study was to investigate the differential expression pattern of genes in Rag2 KO mice spleen compared to its wild type counterpart.
Microarray profiling of miRNA and mRNA expression in Rag2 knockout and wild-type mouse spleens.
No sample metadata fields
View SamplesSelective RAF inhibitors including vemurafenib (PLX4032) have demonstrated clinical efficacy in mutant BRAF driven metastatic melanoma. The clinical effectiveness of RAF inhibitors depends on near complete abolition of the MAPK pathway output in tumors harboring BRAF mutations. However these compounds paradoxically activate the MAPK pathway in cells bearing oncogenic RAS or elevated upstream receptor signaling. This paradox can promote cellular proliferation and can manifest clinically with progression of secondary malignancies such as cutaneous squamous cell carcinomas (cuSCC). We have identified next generation RAF inhibitors (paradox breakers, e.g. PLX7904) that inhibit mutant BRAF cells without activating the MAPK pathway in cells bearing upstream activation.
RAF inhibitors that evade paradoxical MAPK pathway activation.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Recombination activating gene-2<sup>null</sup> severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently.
Specimen part
View SamplesIt contains a disruption of the recombination activating gene 2 (RAG2) and homozygoue mice exhibit total inability to initiate V(D)J rearrangement and fail to generate mature T or B lymphocytes. (https://www.taconic.com)
Recombination activating gene-2<sup>null</sup> severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently.
Specimen part
View SamplesIt contains a disruption of the recombination activating gene 2 (RAG2) and homozygoue mice exhibit total inability to initiate V(D)J rearrangement and fail to generate mature T or B lymphocytes. (https://www.taconic.com)
Recombination activating gene-2<sup>null</sup> severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently.
Specimen part
View SamplesIt contains a disruption of the recombination activating gene 2 (RAG2) and homozygoue mice exhibit total inability to initiate V(D)J rearrangement and fail to generate mature T or B lymphocytes. (https://www.taconic.com)
Recombination activating gene-2<sup>null</sup> severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently.
Specimen part
View SamplesHomeostatic programs maintain equilibrium between immune protection, and selftolerance. Such mechanisms impact autoimmunity and tumor formation, respectively. How tissue homeostasis is maintained, and impacts tumor surveillance is unknown. Here we identify that mononuclear phagocytes share conserved programming during homeostatic differentiation, and entry into tissue. IFN is necessary and sufficient to induce these transcripts, revealing a key instructive role. Remarkably, homeostatic and IFN-dependent programs enrich across primary human tumors, including melanoma, and stratify metastatic melanoma survival. Single-cell RNA-sequencing reveals enrichment of these modules in monocytes and DCs in human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2), a highly conserved transcript in this program is induced by IFN, and expressed in mononuclear phagocytes infiltrating primary melanoma. SOCS2 limits DC adaptive anti-tumoral immunity and T cell priming in vivo, indicating a critical regulatory role. Our findings link homeostasis in peripheral tissue to anti-tumoral immunity and escape, revealing coopting of tissue-specific immune development in the tumor microenvironment.
IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment.
Specimen part, Disease, Disease stage
View Samples