Propofol suppresses synaptic responsiveness of somatosensory relay neurons to excitatory input by potentiating GABA(A )receptor chloride channels

Propofol is a widely used intravenous general anesthetic. Propofol-induced unconsciousness in humans is associated with inhibition of thalamic activity evoked by somatosensory stimuli. However, the cellular mechanisms underlying the effects of propofol in thalamic circuits are largely unknown. We investigated the influence of propofol on synaptic responsiveness of thalamocortical relay neurons in the ventrobasal complex (VB) to excitatory input in mouse brain slices, using both current- and voltage-clamp recording techniques. Excitatory responses including EPSP temporal summation and action potential firing were evoked in VB neurons by electrical stimulation of corticothalamic fibers or pharmacological activation of glutamate receptors. Propofol (0.6 – 3 μM) suppressed temporal summation and spike firing in a concentration-dependent manner. The thalamocortical suppression was accompanied by a marked decrease in both EPSP amplitude and input resistance, indicating that a shunting mechanism was involved. The propofol-mediated thalamocortical suppression could be blocked by a GABA(A )receptor antagonist or chloride channel blocker, suggesting that postsynaptic GABA(A )receptors in VB neurons were involved in the shunting inhibition. GABA(A )receptor-mediated inhibitory postsynaptic currents (IPSCs) were evoked in VB neurons by electrical stimulation of the reticular thalamic nucleus. Propofol markedly increased amplitude, decay time, and charge transfer of GABA(A )IPSCs. The results demonstrated that shunting inhibition of thalamic somatosensory relay neurons by propofol at clinically relevant concentrations is primarily mediated through the potentiation of the GABA(A )receptor chloride channel-mediated conductance, and such inhibition may contribute to the impaired thalamic responses to sensory stimuli seen during propofol-induced anesthesia

A game-theoretic resource allocation approach for intercell device-to-device communications in cellular networks

Device-to-Device (D2D) communication is a recently emerged disruptive technology for enhancing the performance of current cellular systems. To successfully implement D2D communications underlaying cellular networks, resource allocation to D2D links is a critical issue, which is far from trivial due to the mutual interference between D2D users and cellular users. Most of the existing resource allocation research for D2D communications has primarily focused on the intracell scenario while leaving the intercell settings not considered. In this paper, we investigate the resource allocation issue for intercell scenarios where a D2D link is located in the overlapping area of two neighboring cells. Specifically, We present three intercell D2D scenarios regarding the resource allocation problem. To address the problem, we develop a repeated game model under these scenarios. Distinct from existing works, we characterize the communication infrastructure, namely Base Stations (BSs), as players competing resource allocation quota from D2D demand, and we define the utility of each player as the payoff from both cellular and D2D communications using radio resources. We also propose a resource allocation algorithm and protocol based on the Nash equilibrium derivations. Numerical results indicate that the developed model not only significantly enhances the system performance including sum rate and sum rate gain, but also sheds lights on resource configurations for intercell D2D scenarios

Ablation of Dihydroceramide Desaturase Confers Resistance to Etoposide-Induced Apoptosis In Vitro

10.1371/journal.pone.0044042PLoS ONE79

Soft corrugated channel with synergistic exclusive discrimination gating for CO₂ recognition in gas mixture

二酸化炭素に対してのみゲートを開いて吸着する フレキシブル多孔性材料を開発. 京都大学プレスリリース. 2023-08-02.Interactive networks for capturing gas with high selectivity. 京都大学プレスリリース. 2023-08-02.Developing artificial porous systems with high molecular recognition performance is critical but very challenging to achieve selective uptake of a particular component from a mixture of many similar species, regardless of the size and affinity of these competing species. A porous platform that integrates multiple recognition mechanisms working cooperatively for highly efficient guest identification is desired. Here, we designed a flexible porous coordination polymer (PCP) and realised a corrugated channel system that cooperatively responds to only target gas molecules by taking advantage of its stereochemical shape, location of binding sites, and structural softness. The binding sites and structural deformation act synergistically, exhibiting exclusive discrimination gating (EDG) effect for selective gate-opening adsorption of CO₂ over nine similar gas molecules, including N₂, CH₄, CO, O₂, H₂, Ar, C₂H₆, and even higher-affinity gases such as C₂H₂ and C₂H4. Combining in-situ crystallographic experiments with theoretical studies, it is clear that this unparalleled ability to decipher the CO₂ molecule is achieved through the coordination of framework dynamics, guest diffusion, and interaction energetics. Furthermore, the gas co-adsorption and breakthrough separation performance render the obtained PCP an efficient adsorbent for CO₂ capture from various gas mixtures

3, 4-dihydroxyl-phenyl lactic acid restores NADH dehydrogenase 1 α subunit 10 to ameliorate cardiac reperfusion injury.

The present study aimed to detect the role of 3, 4-dihydroxyl-phenyl lactic acid (DLA) during ischemia/reperfusion (I/R) induced myocardial injury with emphasis on the underlying mechanism of DLA antioxidant. Male Spragu-Dawley (SD) rats were subjected to left descending artery occlusion followed by reperfusion. Treatment with DLA ameliorated myocardial structure and function disorder, blunted the impairment of Complex I activity and mitochondrial function after I/R. The results of 2-D fluorescence difference gel electrophoresis revealed that DLA prevented the decrease in NDUFA10 expression, one of the subunits of Complex I. To find the target of DLA, the binding affinity of Sirtuin 1 (SIRT1) to DLA and DLA derivatives with replaced two phenolic hydroxyls was detected using surface plasmon resonance and bilayer interferometry. The results showed that DLA could activate SIRT1 after I/R probably by binding to this protein, depending on phenolic hydroxyl. Moreover, the importance of SIRT1 to DLA effectiveness was confirmed through siRNA transfection in vitro. These results demonstrated that DLA was able to prevent I/R induced decrease in NDUFA10 expression, improve Complex I activity and mitochondrial function, eventually attenuate cardiac structure and function injury after I/R, which was possibly related to its ability of binding to and activating SIRT1