G protein-coupled receptor 43 (GPR43) has been identified as a for short-chain fatty acids that include acetate and propionate. A potential involvement of GPR43 in immune inflammatory response previously suggested because its expression is highly enriched cells. also expressed number other tissues including adipocytes; however, the functional consequences activation these are not clear. In this report, we focus on functions adipocytes. We show adipocytes treated with natural ligands,...

Adipic acid is an important building block of polymers, and commercially produced by thermo-catalytic oxidation ketone-alcohol oil (a mixture cyclohexanol cyclohexanone). However, this process heavily relies on the use corrosive nitric while releases nitrous oxide as a potent greenhouse gas. Herein, we report electrocatalytic strategy for cyclohexanone to adipic coupled with H2 production over nickel hydroxide (Ni(OH)2) catalyst modified sodium dodecyl sulfonate (SDS). The intercalated SDS...

AbstractThe serine/threonine kinase PAK4 is a target for the Rho GTPase Cdc42 and has been shown to regulate cell morphology cytoskeletal organization in mammalian cells. To examine physiological developmental functions of PAK4, we have disrupted gene mice. The absence led lethality by embryonic day 11.5, result most likely due defect fetal heart. Striking abnormalities were also evident nervous systems PAK4-deficient embryos. These embryos had dramatic defects neuronal development axonal...

Early-life seizures (ELS) can cause permanent cognitive deficits and network hyperexcitability, but it is unclear whether ELS induce persistent alterations to specific neuronal populations if these changes be targeted mitigate dysfunction. We used the recombination of activated (TRAP) approach genetically label neurons by kainate-induced in immature mice. The ELS-TRAPed were mainly found hippocampal CA1, remained uniquely susceptible reactivation later-life seizures, displayed sustained...

FGF19 subfamily proteins (FGF19, FGF21, and FGF23) are unique members of fibroblast growth factors (FGFs) that regulate energy, bile acid, glucose, lipid, phosphate, vitamin D homeostasis in an endocrine fashion. Their activities require the presence α or βKlotho, two related single-pass transmembrane proteins, as co-receptors relevant target tissues. We previously showed can bind to both whereas FGF21 FGF23 only either βKlotho αKlotho, respectively vitro. To determine mechanism regulating...

FGF19 is a hormone that regulates bile acid and glucose homeostasis. Progress has been made in identifying cofactors for receptor activation. However, several functions of have not yet fully defined, including the actions on target tissues, its FGF specificity, contributions other cofactors, such as heparin. Here, we explore requirements FGF19-FGFR/co-receptor interactions signaling detail. We show betaKlotho was essential interaction with FGFRs 1c, 2c, 3c, but able to interact directly...

Connexin 35/36 is the most widespread neuronal gap junction protein in retina and central nervous system. Electrical and/or tracer coupling a number of circuits that express this connexin are regulated by light adaptation. In many cases, regulation depends on signaling pathways activate kinases such as PKA, Cx35 has been shown to be PKA phosphorylation cell culture systems. To examine whether might regulate Cx35/36 we developed phospho-specific polyclonal antibodies against two regulatory...

Abstract Analysis of trajectories from our rigid‐body dynamics simulation package, BioSimz, is used to find regions on the surface unbound proteins that form frequent and tenacious encounter complexes with their binding partner. Binding partners are significantly more likely sojourn around true than remainder protein surface. This information restrict search space for flexible protein–protein docking using SwarmDock algorithm, reducing computational expense docking, improving or matching...

Considerable evidence suggests that day–night rhythms in the functional expression of subthreshold potassium (K+) channels regulate daily oscillations spontaneous firing rates neurons suprachiasmatic nucleus (SCN), master circadian pacemaker mammals. The K+ conductance(s) driving these repetitive SCN neurons, however, have not been identified. To test hypothesis Kv12.1/Kv12.2-encoded play a role, we obtained current-clamp recordings from slices prepared adult mice harboring targeted...

We examined the evolutionary origins of ether-à-go-go (EAG) family voltage-gated K+ channels, which have a strong influence on excitability neurons. The bilaterian EAG comprises three gene subfamilies (Eag, Erg and Elk) distinguished by sequence conservation functional properties. Searches genome indicate that channels are metazoan specific, appearing first in ctenophores. However, phylogenetic analysis including two from ctenophore Mnemiopsis leidyi indicates diversification Eag, Elk...

Significance We examined the origin and evolution of two major families voltage-gated K + channels, Shaker KCNQ, which regulate action potential repolarization, patterning, threshold. family channels evolved in a basal metazoan ancestor ctenophores parahoxozoans (including cnidarians bilaterians), but functional diversification emergence KCNQ occurred specifically within parahoxozoan lineage. Our results suggest that many innovations regulation cellular excitability by are unique to these...

The present study investigates the effects of ginsenosides Rh1 and Rg2 against 6-hydroxydopamine (6-OHDA), a neurotoxin on SH-SY5Y cells PC-12 cells. these two neuronal differentiation are also examined.LDH assay was used to measure cell viability after exposure 6-OHDA ginsenosides. Neuronal evaluated by changes in morphology density neurite outgrowths. Western blotting determine ginsenosides' activation extracellular signal-regulated protein kinases (ERKs).Rh1 attenuated toxicity induced...

Phosphatidylinositol 4,5-bisphosphate (PIP2) regulates Shaker K+ channels and voltage-gated Ca2+ in a bimodal fashion by inhibiting voltage activation while stabilizing open channels. Bimodal regulation is conserved hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, but enhanced the channel state destabilized. The proposed sites of PIP2 these include voltage-sensor domain (VSD) regions proximal cytoplasmic C terminus. Relatively little known about Ether-á-go-go (EAG)...

Significance Activation of G protein-gated inwardly rectifying potassium (GIRK) channels inhibits neuronal activity in the brain, but details are lacking on how this important pathway influences neural circuits reward pathway. Here, we provide an example where control trafficking GIRK by a cytoplasmic protein, sorting nexin 27, determines sensitivity mice to cocaine model addiction known as locomotor sensitization. These results implicate therapeutic target for treating addiction, well other...

The Shaker-like family of voltage-gated K+ channels comprises four functionally independent gene subfamilies, Shaker (Kv1), Shab (Kv2), Shaw (Kv3), and Shal (Kv4), each which regulates distinct aspects neuronal excitability. Subfamily-specific assembly tetrameric is mediated by the N-terminal T1 domain segregates Kv1–4, allowing multiple channel types to function independently in same cell. Typical Kv subunits can form functional as homotetramers, but a group mammalian Kv2-related genes...

Addictive drugs usurp the brain's intrinsic mechanism for reward, leading to compulsive and destructive behaviors. In ventral tegmental area (VTA), center of reward circuit, GABAergic neurons control excitability dopamine (DA) projection are site initial psychostimulant-dependent changes in signaling. Previous work established that cocaine/methamphetamine exposure increases protein phosphatase 2A (PP2A) activity, which dephosphorylates GABA B R2 subunit, promotes internalization receptor...

In this paper, we develop an elastodynamic energy transport theory to form expressions for transmission through a heterogeneous continuum of large extent. A model multiple scattering random elastic is constructed by iterative method based on single thin layer or screen. This available both strong and weak scattering, common-type (P-P S-S) converted (P-S S-P), although here assume high frequencies so that only forward are considered. Numerical results have been obtained in terms the angular...

Abstract In this paper, seismic wave equation is transformed into the Hamiltonian system, and a new symplectic numerical scheme developed, which called optimal algorithm generalized discrete convolutional differentiator (OSGCD). For temporal discretization, OSGCD introduces Lie operators to construct two‐stage second‐order adopts based on minimum error principle. spatial employs convolution approximate differential uses derivative approximation obtain stable operator coefficients. We...

Calmodulin binding is a nearly universal property of gap junction proteins, imparting calcium-dependent uncoupling behavior that can serve in an emergency to decouple stressed cell from its neighbors. However, junctions function as electrical synapses within networks neurons routinely encounter large fluctuations local cytoplasmic calcium concentration; frequent would be impractical and counterproductive. We have studied the properties functional consequences calmodulin synapse protein...

Considerable evidence suggests that day-night rhythms in the functional expression of subthreshold potassium (K