These results suggest that the FP has external, electrostatic pathways capable of quenching fluorescence that are wavelength specific. One mutation to the FP (E222H) showed a voltage-dependent increase in fluorescence when excited at 390 nm, indicating the ability to affect the proton wire from the protonated chromophore to the H222 position. ArcLight-derived sensors may therefore offer a novel way to map how conditions external to the β-can structure can affect the fluorescence of the chromophore and transiently affect those pathways via conformational changes mediated by manipulating membrane potential.A new family of genetically encoded voltage indicators (GEVIs) has been developed based on intermolecular Förster resonance energy transfer (FRET). To test the hypothesis that the GEVI ArcLight functions via interactions between the fluorescent protein (FP) domains of neighboring probes, the FP of ArcLight was replaced with either a FRET donor or acceptor FP. We discovered relatively large FRET signals only when cells were cotransfected with both the FRET donor and acceptor GEVIs. Using a cyan fluorescent protein donor and an RFP acceptor, we were able to observe a voltage-dependent signal with an emission peak separated by over 200 nm from the excitation wavelength. The intermolecular FRET strategy also works for rhodopsin-based probes, potentially improving their flexibility as well. Separating the FRET pair into two distinct proteins has important advantages over intramolecular FRET constructs. The signals are larger because the voltage-induced conformational change moves two FPs independently. The expression of the FRET donor and acceptor can also be restricted independently, enabling greater cell type specificity as well as refined subcellular voltage reporting.The large K+ channel functional diversity in the pulmonary vasculature results from the multitude of genes expressed encoding K+ channels, alternative RNA splicing, the post-transcriptional modifications, the presence of homomeric or heteromeric assemblies of the pore-forming α-subunits and the existence of accessory β-subunits modulating the functional properties of the channel. K+ channels can also be regulated at multiple levels by different factors controlling channel activity, trafficking, recycling and degradation. The activity of these channels is the primary determinant of membrane potential (Em) in pulmonary artery smooth muscle cells (PASMC), providing an essential regulatory mechanism to dilate or contract pulmonary arteries (PA). K+ channels are also expressed in pulmonary artery endothelial cells (PAEC) where they control resting Em, Ca2+ entry and the production of different vasoactive factors. The activity of K+ channels is also important in regulating the population and phenotype of PASMC in the pulmonary vasculature, since they are involved in cell apoptosis, survival and proliferation. Lapatinib Notably, K+ channels play a major role in the development of pulmonary hypertension (PH). Impaired K+ channel activity in PH results from 1) loss of function mutations, 2) downregulation of its expression, which involves transcription factors and microRNAs, or 3) decreased channel current as a result of increased vasoactive factors (e.g., hypoxia, 5-HT, endothelin-1 or thromboxane), exposure to drugs with channel-blocking properties, or by a reduction in factors that positively regulate K+ channel activity (e.g., NO and prostacyclin). Restoring K+ channel expression, its intracellular trafficking and the channel activity is an attractive therapeutic strategy in PH.The primary cilium projects from the surface of most vertebrate cells, where it senses extracellular signals to regulate diverse cellular processes during tissue development and homeostasis. Dysfunction of primary cilia underlies the pathogenesis of severe diseases, commonly referred to as ciliopathies. Primary cilia contain a unique protein repertoire that is distinct from the cell body and the plasma membrane, enabling the spatially controlled transduction of extracellular cues. G-protein coupled receptors (GPCRs) are key in sensing environmental stimuli that are transmitted via second messenger signaling into a cellular response. Here, we will give an overview of the role of GPCR signaling in primary cilia, and how ciliary GPCR signaling can be targeted by pharmacology, chemogenetics, and optogenetics.Interpersonal physiological synchrony is the spontaneous temporal coordination of physiological processes between several individuals. This type of synchrony is critical for human relationships, as it promotes two important outcomes the quality of the relationships between synchronized individuals, and how well synchronized individuals perform together. Nonetheless a clear estimation of the size of the correlations between interpersonal physiological synchrony and relationship or performance outcomes is missing. To address this gap in knowledge was the main goal of the current meta-analysis. We focused on interpersonal physiological synchrony in measures of autonomic nervous system activity, and specifically we examined the distinct branches of the autonomic nervous system. We conducted two meta-analyses (1) Estimating the association between interpersonal physiological synchrony and relationship outcomes (2) Estimating the association between interpersonal physiological synchrony and performance outcomes. Intween different types of physiological synchrony.The aim of the study was to investigate the effectiveness of exogenous recombinant human decoron and an accompanying penetration-enhancing solution in stiffening ex-vivo porcine corneas both transepithelially and after de-epithelialization. Eight porcine paired eyes were treated transepithelially one eye with a pre-treatment solution (Pre-Tx), penetration enhancing solution (PE), and decoron while the fellow eye was treated by the same protocol but without decoron. A second group included 4 de-epithelialized pairs treated identically. The final group included 4 de-epithelialized pairs with one eye treated with Pre-Tx, PE, and decoron while the fellow eye was treated without PE. Uniaxial tensile testing was used to compare the corneal stiffness between the different treatment conditions. Residual tissue underwent immunohistochemistry analysis to evaluate the depth of penetration of decoron into the corneal stroma. There was no stiffening effect exhibited among corneas treated transepithelially with decoron compared to control (P > 0.