Tetrameric assembly of channel subunits in the endoplasmic reticulum (ER) is essential for surface expression and function of K channels, but the molecular mechanism underlying this process remains unclear. In this study, we found through genetic screening that ER-located J-domain-containing chaperone proteins (J-proteins) are critical for the biogenesis and physiological function of ether-a-go-go-related gene (ERG) K channels in both Caenorhabditis elegans and human cells. Human J-proteins DNAJB12 and DNAJB14 promoted tetrameric assembly of ERG (and Kv4.2) K channel subunits through a heat shock protein (HSP) 70-independent mechanism, whereas a mutated DNAJB12 that did not undergo oligomerization itself failed to assemble ERG channel subunits into tetramers in vitro and in C. elegans. Overexpressing DNAJB14 significantly rescued the defective function of human ether-a-go-go-related gene (hERG) mutant channels associated with long QT syndrome (LQTS), a condition that predisposes to life-threatening arrhythmia, by stabilizing the mutated proteins. Thus, chaperone proteins are required for subunit stability and assembly of K channels.

An increasing number of experiments have found anomalies in mitochondria in the brains of psychotics, which suggests that mitochondrial dysfunction or abnormal cerebral energy metabolism might play an important role in the pathophysiology of schizophrenia (SCZ). We adopted a proteomic approach to identify the differential effects on the cerebral cortex and hippocampus mitochondrial protein expression of Sprague-Dawley (SD) rats by comparing exposure to typical and atypical antipsychotic medications. Differential mitochondrial protein expressions were assessed using two-dimensional (2D) gel electrophoresis for three groups with Chlorpromazine (CPZ), Clozapine (CLZ), quetiapine (QTP) and a control group. A total of 14 proteins, of which 6 belong to the respiratory electron transport chain (ETC) of oxidative phosphorylation (OXPHOS), showed significant changes in quantity including NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10 (Ndufa10), NADH dehydrogenase (ubiquinone) flavoprotein 2 (Ndufv2), NADH dehydrogenase (ubiquinone) Fe-S protein 3 (Ndufs3), F1-ATPase beta subunit (Atp5b), ATPase, H+ transporting, lysosomal, beta 56/58 kDa, isoform 2 (Atp6v1b2) and ATPase, H+ transporting, V1 subunit A, isoform 1 (Atp6v1a1). The differential proteins subjected to 2D were assessed for levels of mRNA using quantitative real time PCR (Q-RT-PCR), and we also made partial use of Western blotting for assessing differential expression. The results of our study may help to explain variations in SD rats as well as in human response to antipsychotic drugs. In addition, they should improve our understanding of both the curative effects and side effects of antipsychotics and encourage new directions in SCZ research.

We report an 8-element spectral beam combination of Yb-doped all fiber superfluorescent sources around 1070 nm wavelength. Each source consists of a 60 mW front-end and a 1.5 kW three-stage fiber amplifier chain. The eight output beamlets are spectrally combined using a home-made polarization-independent multilayer dielectric reflective diffraction grating. 10.8 kW output power is achieved with an efficiency of 94%. Besides, both theoretical and experimental studies of dual grating dispersion compensation scheme have been performed, which is proved to be a prospective way for high brightness spectral beam combination.

Background Osteoporosis is a common osteopathy, resulting in fractures, especially in elder people. Sesamin has many pharmacological effects, including supplying calcium. However, how sesamin might prevent osteoporosis is still under study. Material/Methods Bone marrow stromal cells (BMSCs) extracted from rat femur were induced for osteoblastic differentiation. Cell proliferation, alkaline phosphatase (ALP), osterix (OSX), SRY-box 9 (SOX9), runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), β-catenin, low density lipoprotein receptor-related protein 5 (LRP5), and glycogen synthase kinase-3β (GSK-3β) levels in BMSCs were detected in the presence or absence of sesamin (1 μM or 10 μM). In addition, FH535 (1 μM) was used to silence Wnt/β-catenin in vitro . Ovariectomized (OVX) rats were established and intragastrically administrated sesamin (80 mg/kg), and then the rat bones were analyzed by micro-computed tomography. Osteocalcin and collagen type I were measured in the rat femurs. Results Sesamin had no influence on BMSC proliferation. Higher sesamin concentration promoted Wnt/β-catenin activity and enhanced more expressions of ALP, OSX, SOX9, RUNX2, and OCN, gradually and significantly ( P <0.05). Silencing Wnt/β-catenin weakened the enhancement on RUNX2 and OCN expression. Sesamin (80 mg/kg) promoted bone structure in ovariectomized rats, and significantly enhanced osteocalcin and collage type I expression ( P <0.05). Conclusions Sesamin promoted osteoblastic differentiation of rat BMSCs by regulating the Wnt/β-catenin pathway, and improved rat bone structure. Sesamin could have therapeutic and preventive effects on osteoporosis.

There is considerable evidence to suggest that aberrations of synapse connectivity contribute to the pathophysiology of schizophrenia and that N-methyl-D-aspartate (NMDA) receptor-mediated glutamate transmission is especially important. Administration of MK-801 ([1]-5-methyl-10, 11-dihydro-5H-dibenzo-[a, d]-cycloheptene-5, 10-iminehydrogenmaleate) induces hypofunction of NMDA receptors in rats, which are widely used as a model for schizophrenia. We investigated synaptosomal proteome expression profiling of the cerebral cortex of MK-801-treated Sprague-Dawley rats using the 2-dimensional difference gel electrophoresis method, and 49 differentially expression proteins were successfully identified using Matrix-Assisted Laser Desorption/Ionization Timeof-Flight/Time-of-Flight mass spectrometry. We carried out a literature search for further confirmation of subsynaptic locations and to explore the relevance to the diseases of differentially expressed proteins. Ingenuity Pathways Analysis (IPA) was used to further examine the underlying relationship between the changed proteins. The network encompassing ''cell morphology, cell-to-cell signaling and interaction, nervous system development and function'' was found to be significantly altered in the MK-801-treated rats. ''Energy metabolism'' and ''semaphorin signaling in neurons'' are the most significant IPA canonical pathways to be affected by MK-801 treatment. Using western blots, we confirmed the differential expression of Camk2a, Crmp2, Crmp5, Dnm1, and Ndufs3 in both synaptosome proteins and total proteins in the cerebral cortex of the rats. Our study identified the change and/or response of the central nervous transmission system under the stress of NMDA hypofunction, underlining the importance of the synaptic function in schizophrenia.

No abstract

No abstract

An injection-locked fiber laser is introduced to the passive fiber laser coherent beam combination with all-optical feedback loop. A coherent beam combining system with two-dimensional four Yb-doped fiber amplifier chains is established, and the injection-locked fiber laser works as a switchable seed source. The 1064 nm output laser of the injection-locked fiber laser is extinguished automatically as the feedback injection power is high enough, and the injection-locked fiber laser acts as an amplifier for the feedback laser with 7.4 dB gains. We find that the phase-locked far-field interference pattern of our system with seed laser extinguished is stable, and the visibility is up to 91.5%, which is slightly higher than the prevalent method with auxiliary seed laser (88.2%).