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Schramm, L.

Publications and source records attributed to Schramm, L..

2 recordsLinked to original sources

Hidden Talents: Silent Gene Clusters Encoding Magnetic Organelle Biosynthesis in a Non-Magnetotactic Phototrophic Bacterium

Horizontal gene transfer is a powerful source of innovations in prokaryotes that can affect almost any cellular system, including microbial organelles. However, typically rapid loss of non-functional gene acquisitions obscures the mechanisms determining the fate of horizontally transferable genes. Here, we report the first discovery of a horizontally inherited gene cluster encoding biosynthesis of magnetosomes, the organelles used by magnetotactic bacteria for navigation, in a non-magnetotactic phototrophic bacterium Rhodovastum atsumiense. We show that these clusters were inactivated through transcriptional silencing and antisense RNA regulation, but retain functionality, as several genes were able to complement the orthologous deletions in a remotely related magnetotactic bacterium. The laboratory transfer of foreign magnetosome genes to R. atsumiense was found to endow the strain with magnetosome biosynthesis, but strong negative selection led to rapid loss of this trait upon subcultivation. Our results provide insight into the horizontal dissemination of gene clusters encoding complex prokaryotic organelles and illuminate the potential mechanisms of their genomic preservation in a dormant state.

microbiology↗

Pioglitazone improves deficits of Fmr1-KO mouse model of Fragile X syndrome by interfering with excessive diacylglycerol signaling

Fragile X syndrome (FXS), the leading cause of familial intellectual disability, is an uncured disease caused by the absence or loss of function of the FMRP protein. FMRP is an RNA binding protein that controls the translation of specific proteins in neurons. A main target of FMRP in neurons is diacylglycerol kinase kappa (DGKk) and the loss of FMRP leads to a loss of DGK activity causing a diacylglycerol excess in the brain. Excessive diacylglycerol signaling could be a significant contributor to the pathomechanism of FXS. Here we tested the contribution of DAG-signaling in Fmr1-KO mouse model of FXS and we show that pioglitazone, a widely prescribed drug for type 2 diabetes, has ability to correct excessive DAG signaling in the brain and rescue behavioral alterations of the Fmr1-KO mouse. This study highlights the role of lipid signaling homeostasis in FXS and provides arguments to support the testing of pioglitazone for treatment of FXS.

neuroscience↗