Highlights We performed dynamic glucose enhanced (DGE) 2 H-MRS in mouse GBM tumors. Marchenko-Pastur PCA denoising of 2 H-MRS spectra improved kinetic quantification. Metabolic kinetics revealed differential glucose pathway fluxes in non-necrotic tumors. Modulation of glucose metabolism reflected tumor heterogeneity (proliferation).

studies from other species 12,13 , we have freely released all data and the generated code.

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows comparison with invasive or terminal procedures. To date, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. We introduce StandardRat, a consensus rat functional MRI acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired in rats from 46 centers. We developed a reproducible pipeline for the analysis of rat data acquired with diverse protocols and determined experimental and processing parameters associated with a more robust functional connectivity detection. We show that the standardized protocol enhances biologically plausible functional connectivity patterns, relative to pre-existing acquisitions. The protocol and processing pipeline described here are openly shared with the neuroimaging community to promote interoperability and cooperation towards tackling the most important challenges in neuroscience.

have equally contributed.Abbreviations: ATP, adenosine triphosphate; BiFC, bimolecular fluorescence complementation; BRET, bioluminescence resonance energy transfer; DIC, differential interference contrast; DelCT, deletion of the C-terminus; EGFP, enhanced green fluorescent protein; FRET, fluorescence resonance energy transfer; LIF, leukemia inhibitory factor; PCR, polymerase chain reaction; PTMs, post-translational modifications; SDS, sodium dodecyl sulfate; STAT3, signal transducer and activator of transcription-3; V1, Venus 1 (amino acids 1-158); V2, Venus 2 (amino acids 159-238). AbstractSignal transducer and activator of transcription 3 (STAT3) is a ubiquitous and pleiotropic transcription factor that plays essential roles in normal development, immunity, response to tissue damage and cancer. We have developed a Venus-STAT3 bimolecular fluorescence complementation assay that allows the visualization and study of STAT3 dimerization and protein-protein interactions in living cells. Inactivating mutations on residues susceptible to post-translational modifications (PTMs) (K49R, K140R, K685R, Y705F and S727A) changed significantly the intracellular distribution of unstimulated STAT3 dimers when the dimers were formed by STAT3 molecules that carried different mutations (ie they were "asymmetric"). Some of these asymmetric dimers changed the proliferation rate of HeLa cells. Our results indicate that asymmetric PTMs on STAT3 dimers could constitute a new level of regulation of STAT3 signaling. We put forward these observations as a working hypothesis, since confirming the existence of asymmetric STAT3 homodimers in nature is extremely difficult, and our own experimental setup has technical limitations that we discuss.However, if our hypothesis is confirmed, its conceptual implications go far beyond STAT3, and could advance our understanding and control of signaling pathways. K E Y W O R D Sacetylation, bimolecular fluorescence complementation, dimerization, phosphorylation SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.How to cite this article: Letra-Vilela R, Cardoso B, Silva-Almeida C, et al. Can asymmetric posttranslational modifications regulate the behavior of STAT3 homodimers?. FASEB BioAdvances. 2020;2: 116-125. https ://doi.

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