MAVS O-GlcNAcylation Is Essential for Host Antiviral Immunity against Lethal RNA Viruses.

It is known that lethal viruses profoundly manipulate host metabolism, but how the metabolism alternation affects the immediate host antiviral immunity remains elusive. Here, we report that the O-GlcNAcylation of mitochondrial antiviral-signaling protein (MAVS), a key mediator of interferon signaling, is a critical regulation to activate the host innate immunity against RNA viruses. We show that O-GlcNAcylation depletion in myeloid cells renders the host more susceptible to virus infection both in vitro and in vivo. Mechanistically, we demonstrate that MAVS O-GlcNAcylation is required for virus-induced MAVS K63-linked ubiquitination, thereby facilitating IRF3 activation and IFNß production. We further demonstrate that D-glucosamine, a commonly used dietary supplement, effectively protects mice against a range of lethal RNA viruses, including human influenza virus. Our study highlights a critical role of O-GlcNAcylation in regulating host antiviral immunity and validates D-glucosamine as a potential therapeutic for virus infections.

Adaptive control of Parkinson's state based on a nonlinear computational model with unknown parameters.

The objective here is to explore the use of adaptive input-output feedback linearization method to achieve an improved deep brain stimulation (DBS) algorithm for closed-loop control of Parkinson's state. The control law is based on a highly nonlinear computational model of Parkinson's disease (PD) with unknown parameters. The restoration of thalamic relay reliability is formulated as the desired outcome of the adaptive control methodology, and the DBS waveform is the control input. The control input is adjusted in real time according to estimates of unknown parameters as well as the feedback signal. Simulation results show that the proposed adaptive control algorithm succeeds in restoring the relay reliability of the thalamus, and at the same time achieves accurate estimation of unknown parameters. Our findings point to the potential value of adaptive control approach that could be used to regulate DBS waveform in more effective treatment of PD.

Effect of electroacupuncture stimulation at Zusanli acupoint (ST36) on gastric motility: possible through PKC and MAPK signal transduction pathways.

BACKGROUND: Electroacupuncture (EA) stimulation has been shown to have a great therapeutic potential for treating gastrointestinal motility disorders. However, no evidence has clarified the mechanisms contributing to the effects of EA stimulation at the Zusanli acupoint (ST.36). This study was designed to investigate the regulative effect of EA stimulation at the ST.36 on gastric motility and to explore its possible mechanisms. METHODS: Thirty Sprague-Dawley rats were randomly divided into three groups: the ST.36 group, the non-acupoint group, and the control group. EA stimulation was set at 2 Hz, continuous mode, and 1 V for 30 min. The frequency and average peak amplitude of gastric motility were measured by electrogastrography. The protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) signaling pathways were assessed using real-time polymerase chain reactions. Caldesmon (CaD) and calponin (CaP) protein expression in the gastric antrum were detected on Western blots. A Computed Video Processing System was used to evaluate morphological changes in smooth muscle cells (SMCs) from the gastric antrum. RESULTS: EA stimulation at ST.36 had a dual effect on the frequency and average peak amplitude. Additionally, EA stimulation at ST.36 regulated the expression of some genes in the PKC and MAPK signaling pathways, and it regulated the expression of the CaD and CaP proteins. EA serum induced SMC contractility. Promotion of gastric motility may correlate with up-regulation of MAPK6 (ERK3), MAPK13, and Prostaglandin-endoperoxide synthase 2 (PTGS2) gene expression, and the down-regulation of the collagen, type I, alpha 1 (COL1A1) gene and CaD and CaP protein expression. Inhibition of gastric motility may correlate with down-regulation of the Interleukin-1 receptor type 2 (IL1R2) and Matrix metalloproteinase-9 (MMP9) genes, and up-regulation of CaD and CaP protein expression. CONCLUSIONS: EA stimulation at ST.36 regulated gastric motility, and the effects were both promoting and inhibiting in rats. The possible mechanisms may correlate with the PKC and MAPK signal transduction pathways.

Closed-loop control of the thalamocortical relay neuron's Parkinsonian state based on slow variable.

A novel closed-loop control strategy is proposed to control Parkinsonian state based on a computational model. By modeling thalamocortical relay neurons under external electric field, a slow variable feedback control is applied to restore its relay functionality. Qualitative and quantitative analysis demonstrates the performance of feedback controller based on slow variable is more efficient compared with traditional feedback control based on fast variable. These findings point to the potential value of model-based design of feedback controllers for Parkinson's disease.