To reveal whether bats serve as an amplifying host for Yokose virus (YOKV), we conducted a serological survey and experimentally infected fruit bats with YOKV isolated from microbats in Japan. YOKV belongs to the Entebbe bat virus group of vector unknown group within the genus Flavivirus and family Flaviviridae. To detect antibodies against YOKV, we developed an enzyme-linked immunosorbent assay (ELISA) using biotinylated anti-bat IgG rabbit sera. Serological surveillance was conducted with samples collected in the Philippines and the sera supplied from Malaysia. One of the 36 samples from the Philippines (2.7%) and 5 of the 26 samples from Malaysia (19%) had detectable ELISA antibodies. In the experimental infections, no clinical signs of disease were observed. Moreover, no significant viral genome amplification was detected. These findings revealed that YOKV replicates poorly in the fruit bat, suggesting that fruit bats do not seem to serve as an amplifying host for YOKV.

The biological function of a nonstructural protein, NSm, of Akabane virus (AKAV) is unknown. In this study, we generated a series of NSm deletion mutant viruses by reverse genetics and compared their phenotypes. The mutant in which the NSm coding region was almost completely deleted could not be rescued, suggesting that NSm plays a role in virus replication. We next generated mutant viruses possessing various partial deletions in NSm and identified several regions critical for virus infectivity. All rescued mutant viruses produced smaller plaques and grew inefficiently in cell culture, compared to the wild-type virus. Interestingly, although the pathogenicity of NSm deletion mutant viruses varied in mice depending on their deletion regions and sizes, more than half the mice died following infection with any mutant virus and the dead mice exhibited encephalitis as in wild-type virus-inoculated mice, indicating their neuroinvasiveness. Abundant viral antigens were detected in the brain tissues of dead mice, whereas appreciable antigen was not observed in those of surviving mice, suggesting a correlation between virus growth rate in the brain and neuropathogenicity in mice. We conclude that NSm affects AKAV replication in vitro as well as in vivo and that it may function as a virulence factor.

Brain-Machine Interface (BMI) has been considered as an effective way to help and support both the disabled rehabilitation and healthy individuals' daily lives to use their brain activity information instead of their bodies. In order to reduce costs and control exoskeleton robots better, we aim to estimate the necessary torque information for a subject from his/her electroencephalography (EEG) signals when using an exoskeleton robot to perform the power assistance of the upper limb without using external torque sensors nor electromyography (EMG) sensors. In this paper, we focus on extracting the motion-relevant EEG signals' features of the shoulder joint, which is the most complex joint in the human's body, to construct a power assistance system using wearable upper limb exoskeleton robots with BMI technology. We extract the characteristic EEG signals when the shoulder joint is doing flexion and extension movement freely which are the main motions of the shoulder joint needed to be assisted. Independent component analysis (ICA) is used to extract the source information of neural components, and then the average method is used to extract the characteristic signals that are fundamental to achieve the control. The proposed approach has been experimentally verified. The results show that EEG signals begin to increase at 300⁻400 ms before the motion and then decrease at the beginning of the generation of EMG signals, and the peaks appear at about one second after the motion. At the same time, we also confirmed the relationship between the change of EMG signals and the EEG signals on the time dimension, and these results also provide a theoretical basis for the delay parameter in the linear model which will be used to estimate the necessary torque information in future. Our results suggest that the estimation of torque information based on EEG signals is feasible, and demonstrate the potential of using EEG signals via the control of brain-machine interface to support human activities continuously.

The endocytic membrane trafficking system is altered in the brains of early-stage Alzheimer disease (AD) patients, and endocytic disturbance affects the metabolism of β-amyloid (Aβ) protein, a key molecule in AD pathogenesis. It is widely accepted that type 2 diabetes mellitus (T2DM) is one of the strongest risk factors for development of AD. Supporting this link, experimentally induced T2DM enhances AD pathology in various animal models. Spontaneous T2DM also enhances Aβ pathology with severe endocytic pathology, even in nonhuman primate brains. However, it remains unclear how T2DM accelerates Aβ pathology. Herein, we demonstrate that cholesterol metabolism-related protein levels are increased and that membrane cholesterol level is elevated in spontaneous T2DM-affected cynomolgus monkey brains. Moreover, in vitro studies that manipulate cellular cholesterol reveal that elevated membrane cholesterol disrupts lysosomal degradation and enhances chemical-induced endocytic disturbance, resulting in great accumulation of Aβ in Neuro2a cells. These findings suggest that an alteration of cerebral cholesterol metabolism may be responsible for augmentation of Aβ pathology in T2DM-affected brains, which, in turn, may increase the risk for developing AD.

Fifty-two bats captured during July 2008 in the Philippines were tested by reverse transcription-PCR to detect bat coronavirus (CoV) RNA. The overall prevalence of virus RNA was 55.8%. We found 2 groups of sequences that belonged to group 1 (genus Alphacoronavirus) and group 2 (genus Betacoronavirus) CoVs. Phylogenetic analysis of the RNA-dependent RNA polymerase gene showed that groups 1 and 2 CoVs were similar to Bat-CoV/China/A515/2005 (95% nt sequence identity) and Bat-CoV/HKU9-1/China/2007 (83% identity), respectively. To propagate group 2 CoVs obtained from a lesser dog-faced fruit bat (Cynopterus brachyotis), we administered intestine samples orally to Leschenault rousette bats (Rousettus leschenaulti) maintained in our laboratory. After virus replication in the bats was confirmed, an additional passage of the virus was made in Leschenault rousette bats, and bat pathogenesis was investigated. Fruit bats infected with virus did not show clinical signs of infection.

Bats are now known as the source of several diseases in humans, but few studies regarding immune responses and factors associated with bats have so far been reported. In this study, we focused on STAT1, one of the critical components in interferon (IFN)-signaling and antiviral activity, which is often targeted by viral proteins to reduce antiviral activity and increase viral replication. We found that Rousettus aegyptiacus STAT1 (bat STAT1) is phosphorylatable and translocates to the nucleus when stimulated with human IFN-alpha (hIFN-alpha). Furthermore, phosphorylation of bat STAT1 and inhibition of nuclear translocation was observed in IFN-stimulated cells infected with the HEP-Flury strain of rabies virus, in the same manner as in other mammals. Additionally, quantitative real-time RT-PCR revealed that bat STAT1 mRNA was highly expressed in the liver, while low in muscle and spleen.

The AIM2 inflammasome is activated by DNA, leading to caspase-1 activation and release of pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-18, which are critical mediators in host innate immune responses against various pathogens. Some viruses employ strategies to counteract inflammasome-mediated induction of pro-inflammatory cytokines, but their in vivo relevance is less well understood. Here we show that the herpes simplex virus 1 (HSV-1) tegument protein VP22 inhibits AIM2-dependent inflammasome activation. VP22 interacts with AIM2 and prevents its oligomerization, an initial step in AIM2 inflammasome activation. A mutant virus lacking VP22 (HSV-1ΔVP22) activates AIM2 and induces IL-1β and IL-18 secretion, but these responses are lost in the absence of AIM2. Additionally, HSV-1ΔVP22 infection results in diminished viral yields in vivo, but HSV-1ΔVP22 replication is largely restored in AIM2-deficient mice. Collectively, these findings reveal a mechanism of HSV-1 evasion of the host immune response that enables efficient viral replication in vivo.