Impairment of Dendrodendritic Inhibition in the Olfactory Bulb of APP/PS1 Mice

Olfactory dysfunction is an early event in Alzheimer’s disease (AD). However, the mechanism underlying the AD-related changes in the olfactory bulb (OB) remains unknown. Granule cells (GCs) in the OB regulate the activity of mitral cells (MCs) through reciprocal dendrodendritic synapses, which is crucial for olfactory signal processing and odor discrimination. Nevertheless, the relationships between the morphological and functional changes of dendrodendritic synapses, particularly the local field potentials (LFPs) as a consequence of olfactory disorders in patients with AD have not been investigated. Here, we studied the morphological and functional changes induced by dendrodendritic inhibition in GCs onto MCs in the OB of amyloid precursor protein (APP)/PS1 mice and age-matched control mice during aging, particular, we focused on the effects of olfactory disorder in the dendrodendritic synaptic structures and the LFPs. We found that olfactory disorder was associated with increased amyloid-β (Aβ) deposits in the OB of APP/PS1 mice, and those mice also exhibited abnormal changes in the morphology of GCs and MCs, a decreased density of GC dendritic spines and impairments in the synaptic interface of dendrodendritic synapses between GCs and MCs. In addition, the aberrant enhancements in the γ oscillations and firing rates of MCs in the OB of APP/PS1 mice were recorded by multi-electrode arrays (MEAs). The local application of a GABAAR agonist nearly abolished the aberrant increase in γ oscillations in the external plexiform layer (EPL) at advanced stages of AD, whereas a GABAAR antagonist aggravated the γ oscillations. Based on our findings, we concluded that the altered morphologies of the synaptic structures of GCs, the dysfunction of reciprocal dendrodendritic synapses between MCs and GCs, and the abnormal γ oscillations in the EPL might contribute to olfactory dysfunction in AD

Metasurface-generating high purity narrow linewidth cylindrical vector beams: power scaling and its limitation

1.89 kW cylindrical vector beams (CVBs) at 1,064 nm with the 3 dB linewidth being about 0.08 nm have been generated from a narrow linewidth all-fiber linearly-polarized laser by metasurface extra-cavity conversion. At the maximum output power, the transmission efficiency, mode purity of radially polarized cylindrical vector beams (RP-CVBs) are 97% and 92.7%, respectively. To the best of our knowledge, this is the highest power of narrow linewidth CVBs generated from fiber laser. The temperature of the metasurface is moderate, and the maximum temperature is 75.5°C at 1.89 kW, which means that the system can be further power scaled. The evolution of mode purity has been analyzed numerically, and the influence of high-order modes (HOM) in laser source and thermal effects of metasurface has been calculated, which reveals that the presence of high-order modes and the temperature rise of metasurface degrade the mode purity of the CVBs. Among them, HOM causes a degradation of 1.68%, thermal lensing effect contributes 2.32%, and the microstructure variation of the metasurface contributes the remaining 3.3%

Down-Regulation of MiR-127 Facilitates Hepatocyte Proliferation during Rat Liver Regeneration

Liver regeneration (LR) after partial hepatectomy (PH) involves the proliferation and apoptosis of hepatocytes, and microRNAs have been shown to post-transcriptionally regulate genes involved in the regulation of these processes. To explore the role of miR-127 during LR, the expression patterns of miR-127 and its related proteins were investigated. MiR-127 was introduced into a rat liver cell line to examine its effects on the potential target genes Bcl6 and Setd8, and functional studies were undertaken. We discovered that miR-127 was down-regulated and inversely correlated with the expression of Bcl6 and Setd8 at 24 hours after PH, a time at which hypermethylation of the promoter region of the miR-127 gene was detected. Furthermore, in BRL-3A rat liver cells, we observed that overexpression of miR-127 significantly suppressed cell growth and directly inhibited the expression of Bcl6 and Setd8. The results suggest that down-regulation of miR-127 may be due to the rapid methylation of its promoter during the first 24 h after PH, and this event facilitates hepatocyte proliferation by releasing Bcl6 and Setd8. These findings support a miRNA-mediated negative regulation pattern in LR and implicate an anti-proliferative role for miR-127 in liver cells

Inflammation Amplification by Versican: The First Mediator

Abstract: The effects of inflammation may not always benefit the individual. Its amplifying nature represents a highly regulated biological program, and the inflammatory microenvironment is its essential component. Growing evidence suggests that the ECM (extracellular matrix) is important for the early steps of inflammation. Versican, a ubiquitous component of the ECM, contributes to the formation of the inflammatory response and is highly regulated by cytokines. Certain cytokines exert their initial effects on versican to alter the homeostasis of the inflammatory milieu, and inappropriate production of versican may promote the next inflammatory response. Therefore, versican could be the first step in the amplification of the inflammatory response, and ongoing research of this molecule may help to explain the pathogenesis of inflammation

Robust adaptive constrained backstepping flight controller design for re-entry reusable launch vehicle under input constraint

A nonlinear constrained controller is designed for a reusable launch vehicle during re-entry phase in the presence of model uncertainty, external disturbance, and input constraint, via combining sliding mode control and adaptive backstepping control. Since the complex coupling between the translational and rotational dynamics of reusable launch vehicle, a control-oriented model derived from rotational dynamic is used for controller design. During the virtual control input design procedure, a dynamic robust term is utilized to compensate for the uncertainty. In addition, a filter is applied to handle “explosion of terms” problem during the actual control input design. To reduce the computational burden, adaptive law is used to evaluate the unknown norm bound of the lumped uncertainty. An auxiliary system is constructed to compensate for the input constraint effect. The stability of the closed-loop system is analyzed based on Lyapunov theory. Simulation results demonstrate the validity of the developed controller in providing stable tracking of the guidance command by numerical simulation on the 6-degree-of-freedom model of reusable launch vehicle