Synonymous mutations have been viewed as silent mutations, since they only affect the DNA and mRNA, but not the amino acid sequence of the resulting protein. Nonetheless, recent studies suggest their significant impact on splicing, RNA stability, RNA folding, translation or co-translational protein folding. Hence, we compile 659194 synonymous mutations found in human cancer and characterize their properties. We provide the user-friendly, comprehensive resource for synonymous mutations in cancer, SynMICdb ( http://SynMICdb.dkfz.de ), which also contains orthogonal information about gene annotation, recurrence, mutation loads, cancer association, conservation, alternative events, impact on mRNA structure and a SynMICdb score. Notably, synonymous and missense mutations are depleted at the 5'-end of the coding sequence as well as at the ends of internal exons independent of mutational signatures. For patient-derived synonymous mutations in the oncogene KRAS , we indicate that single point mutations can have a relevant impact on expression as well as on mRNA secondary structure.

Cell replacement is a long-standing and realistic goal for the treatment of Parkinsonʼs disease (PD). Cells for transplantation can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, we report analysis by single-cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from human embryonic stem cells (hESCs) and fetal tissue after functional maturation in a pre-clinical rat PD model. We show that neurons and astrocytes are major components in both fetal and stem cell-derived grafts. Additionally, we identify a cell type closely resembling a class of recently identified perivascular-like cells in stem cell-derived grafts. Thus, this study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model.

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Dynamical systems can undergo critical transitions where the system suddenly shifts from one stable state to another at a critical threshold called the tipping point. The decrease in recovery rate to equilibrium (critical slowing down) as the system approaches the tipping point can be used to identify the proximity to a critical transition. Several measures have been adopted to provide early indications of critical transitions that happen in a variety of complex systems. In this study, we use early warning indicators to predict subcritical Hopf bifurcation occurring in a thermoacoustic system by analyzing the observables from experiments and from a theoretical model. We find that the early warning measures perform as robust indicators in the presence and absence of external noise. Thus, we illustrate the applicability of these indicators in an engineering system depicting critical transitions.