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Simultaneous sensing of temperature, pH, serotonin, and dopamine enabled integration of physiological and neurochemical data from individual bioelectronic devices.While the analysis of mitochondrial morphology has emerged as a key tool in the study of mitochondrial function, efficient quantification of mitochondrial microscopy images presents a challenging task and bottleneck for statistically robust conclusions. Here, we present Mitochondrial Segmentation Network (MitoSegNet), a pretrained deep learning segmentation model that enables researchers to easily exploit the power of deep learning for the quantification of mitochondrial morphology. We tested the performance of MitoSegNet against three feature-based segmentation algorithms and the machine-learning segmentation tool Ilastik. MitoSegNet outperformed all other methods in both pixelwise and morphological segmentation accuracy. We successfully applied MitoSegNet to unseen fluorescence microscopy images of mitoGFP expressing mitochondria in wild-type and catp-6ATP13A2 mutant C. elegans adults. Additionally, MitoSegNet was capable of accurately segmenting mitochondria in HeLa cells treated with fragmentation inducing reagents. We provide MitoSegNet in a toolbox for Windows and Linux operating systems that combines segmentation with morphological analysis.Xenopus laevis tolerate dehydration when their environments evaporate during summer months. Protein phosphorylation has previously shown to regulate important adaptations in X. laevis, including the transition to anaerobic metabolism. We therefore performed phosphoproteomic analysis of X. laevis to further elucidate the cellular and metabolic responses to dehydration. Phosphoproteins were enriched in cellular functions and pathways related to glycolysis/gluconeogenesis, the TCA cycle, and protein metabolism, among others. The prominence of phosphoproteins related to glucose metabolism led us to discover that the hypoxia-inducible PFKFB3 enzyme was highly phosphorylated and likely activated during dehydration, a feature of many cancers. Expression of the four transcript variants of the pfkfb3 gene was found all to be upregulated during dehydration, potentially due to the enrichment of hypoxia responsive elements in the pfkfb3 promoter. These results further support the role of anaerobic glycolysis during dehydration in X. laevis and elucidate a potential mechanism for its increased rate.Spermatogonial stem cells (SSCs) both self-renew and give rise to progenitors that initiate spermatogenic differentiation in the mammalian testis. Questions remain regarding the extent to which the SSC and progenitor states are functionally distinct. Here we provide the first multiparametric integrative analysis of mammalian germ cell epigenomes comparable with that done for >100 somatic cell types by the ENCODE Project. Differentially expressed genes distinguishing SSC- and progenitor-enriched spermatogonia showed distinct histone modification patterns, particularly for H3K27ac and H3K27me3. Motif analysis predicted transcription factors that may regulate spermatogonial subtype-specific fate, and immunohistochemistry and gene-specific chromatin immunoprecipitation analyses confirmed subtype-specific differences in target gene binding of a subset of these factors. Taken together, these results show that SSCs and progenitors display distinct epigenetic profiling consistent with these spermatogonial subtypes being differentially programmed to either self-renew and maintain regenerative capacity as SSCs or lose regenerative capacity and initiate lineage commitment as progenitors.MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to target messenger RNAs (mRNAs). Many human miRNAs are intragenic, located within introns of protein-coding sequence (host). Intriguingly, a percentage of intragenic miRNAs downregulate the host transcript forming an incoherent feedforward motif topology. read more Here, we study intragenic miRNA-mediated host gene regulation using a synthetic gene circuit stably integrated within a safe-harbor locus of human cells. When the intragenic miRNA is directed to inhibit the host transcript, we observe a reduction in reporter expression accompanied by output filtering and noise reduction. Specifically, the system operates as a filter with respect to promoter strength, with the threshold being robust to promoter strength and measurement time. Additionally, the intragenic miRNA regulation reduces expression noise compared to splicing-alone architecture. Our results provide a new insight into miRNA-mediated gene expression, with direct implications to gene therapy and synthetic biology applications.Ionic reactions are the most common reactions used in chemical synthesis. In relatively low dielectric constant solvents (e.g., dichloromethane, toluene), ions usually exist as ion pairs. Despite the importance of counterions, a quantitative description of how the paired ‘counterion’ affects the reaction kinetic is still elusive. We introduce a general and quantitative model, namely transition-state expansion (TSE), that describes how the size of a counterion affects the transition-state structure and the kinetics of an ionic reaction. This model could rationalize the counterion effects in nucleophilic substitutions and gold-catalyzed enyne cycloisomerizations.Signaling pathways that promote oligodendrocyte development improve oligodendrocyte regeneration and myelin recovery from demyelinating pathologies. Sox factors critically control myelin gene expression and oligodendroglial fate, but little is known about signaling events underlying Sox-mediated oligodendroglial regeneration. In this study of the SoxF member Sox17, we demonstrate that Sox17-induced oligodendrocyte regeneration in adult myelin lesions occurs by suppressing lesion-induced Wnt/beta-catenin signaling which is inhibitory to oligodendrocyte regeneration and by increasing Sonic Hedgehog/Smoothened/Gli2 activity. Hedgehog signaling through Smoothened critically supports adult oligodendroglial viability and is an upstream regulator of beta-catenin. Gli2 ablation in adult oligodendrocyte progenitor cells indicates that Gli2 regulates beta-catenin differentially in wild-type and Sox17-overexpressing white matter. Myelin lesions in Sox17-deficient mice show beta-catenin hyperactivation, regenerative failure, and loss of oligodendrogenesis, despite exogenous Hedgehog stimulation.