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The present study investigated the potential of bemegride as a pharmacological activation agent that elicits epileptiform discharges (EDs) in interictal electroencephalogram (EEG) recordings in dogs. Four laboratory dogs with idiopathic epilepsy and four without epilepsy were included. The dogs were anesthetized using sevoflurane during EEG recordings. Bemegride was administered intravenously and repeatedly until EDs were enhanced or induced, or until the maximum dose (20 mg/kg) had been administered. Bemegride activated EDs in all dogs with epilepsy. These EDs predominantly occurred in each dog's spontaneous irritative zones, which were identified without the administration of bemegride. EDs occurred after the administration of bemegride in 50% of dogs without epilepsy. The dose required for activation was significantly lower in dogs with epilepsy (median; 7.3 mg/kg) than in those without (median; 19.7 mg/kg) ( p = 0.0294). The only suspected adverse effect associated with the administration of bemegride was vomiting in two dogs after awakening from anesthesia. There were no other adverse effects, including seizures. The present results demonstrated the potential of bemegride as a safe and effective pharmacological activation agent of EDs in anesthetized dogs with epilepsy and provided more options for the diagnosis and therapeutic planning of epilepsy, including presurgical evaluations, in dogs.

Novel DNA-based structures with the ability to encapsulate nanoscale molecules, such as proteins, can be applied to a wide range of areas, including reaction fields and micro/nano drug carriers. DNA-functionalized nanoparticle (DNA-NP) colloidal crystals have emerged as a new class of programmable DNA-based structures harboring metal nanoparticles with improved mechanical properties. The encapsulation of guest molecules into empty spaces in lattice structures is theoretically possible. However, due to the lack of a strategy for versatile encapsulation of guest molecules, the feasibility of nanoscale encapsulation by DNA-NP crystals is unclear. In this study, we developed DNA-functionalized gold nanoparticle (DNA-AuNP) crystals with tunable interparticle spacing for molecular encapsulation. We demonstrated that the modification of DNA-AuNP crystals with functional moieties, that is, biotin molecules, was effective in retaining molecules in the crystals. The crystallinities before and after encapsulation of the molecules were confirmed using small-angle X-ray scattering. We also succeeded in encapsulating CRISPR/Cas9 ribonucleoproteins into DNA-AuNP crystals by harnessing their affinity for target molecules. These findings demonstrated the potential use of metal-DNA hybrid crystals as carriers for direct protein delivery via biolistic bombardment. Thus, this study provides an attractive strategy for creating a new class of DNA-based structures for macromolecular encapsulation, and an alternative research direction toward colloidal crystal engineering using DNA.

Caregivers of dogs with epilepsy experience severe stress due to unpredictable seizures. Hence, they feel the need for a better management strategy. A seizure detection system (SDS), which can identify seizures and provide notifications to caregivers immediately, is required to address this issue. The current study aimed to establish a wearable automatic SDS using acceleration data and the Mahalanobis distance and to preliminarily investigate its feasibility among dogs. A generalized tonic-clonic seizure (GTCS) was targeted because it is the most common type of seizure and can have serious consequences (i.e., status epilepticus). This study comprised three phases. First, the reference datasets of epileptic and non-epileptic activities were established using acceleration data of GTCSs in 3 dogs and daily activities in 27 dogs. Second, the GTCS-detecting algorithm was created using the reference datasets and was validated using other acceleration data of GTCSs in 4 epileptic dogs and daily activities in 27 dogs. Third, a feasibility test of the SDS prototype was performed in three dogs with epilepsy. The algorithm was effective in identifying all acceleration data of GTCSs as seizures and all acceleration data of daily activities as non-seizure activities. Dogs with epilepsy were monitored with the prototype for 48-72 h, and three GTCSs were identified. The prototype detected all GTCSs accurately. A false positive finding was not obtained unless the accelerometer was displaced. Hence, a method that can detect epileptic seizures, particularly GTCSs, was established. Nevertheless, further large-scale studies must be conducted before the method can be commercialized., Competing Interests: The patent of the seizure detection method and monitoring system in this manuscript has been granted and registered. Japanese Patent No. 6193613. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hirashima, Saito, Kuriyama, Akamatsu and Yokomori.)

Haploinsufficiency of EHMT1 , which encodes histone H3 lysine 9 (H3K9) methyltransferase G9a-like protein (GLP), causes Kleefstra syndrome (KS), a complex disorder of developmental delay and intellectual disability. Here, we examined whether postnatal supply of GLP can reverse the neurological phenotypes seen in Ehmt1 Δ/+ mice as a KS model. Ubiquitous GLP supply from the juvenile stage ameliorated behavioral abnormalities in Ehmt1 Δ/+ mice. Postnatal neuron-specific GLP supply was not sufficient for the improvement of abnormal behaviors but still reversed the reduction of H3K9me2 and spine number in Ehmt1 Δ/+ mice. Interestingly, some inflammatory genes, including IL-1β (Il1b) , were upregulated and activated microglial cells increased in the Ehmt1 Δ/+ brain, and such phenotypes were also reversed by neuron-specific postnatal GLP supply. Il1b inactivation canceled the microglial and spine number phenotypes in the Ehmt1 Δ/+ mice. Thus, H3K9me2 and some neurological phenotypes are reversible, but behavioral abnormalities are more difficult to improve depending on the timing of GLP supply., Competing Interests: The authors declare no conflicts of interest related to this research., (© 2021 The Authors.)

Gene expression studies using microarrays have provided important insights into understanding the mechanisms of transcriptional regulation in a variety of biological and disease phenomena. In a previous study, we developed Photo-DEAN, a universal-microarray-based RNA quantification method that enabled reverse transcription-free multiplex measurement of the absolute amount of RNA. Photo-DEAN promotes high-throughput and bias-less transcriptome analysis without the need for common controls or additional complicated normalization steps. In this study, we empirically identified two conditions (individual specificity and uniform duplex stability) necessary for in silico design of probe sequences, allowing the Photo-DEAN method to accurately measure the absolute amount of target RNA in total RNA. We then demonstrated that using the modified probe design conditions, the Photo-DEAN method successfully measured the absolute amount of pgi mRNA spiked into E. coli total RNA. The measurement was performed at five different sites in the coding region of pgi mRNA, exhibiting no significant site dependence. Theoretical considerations suggested that probe sequences longer than the previously used 30-bases better satisfy the necessary design conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inhibition of angiotensin-converting enzyme (ACE) is a strategy used worldwide for managing hypertension. In addition to converting angiotensin I to angiotensin II, ACE also converts neurotoxic β-amyloid protein 42 (Aβ42) to Aβ40. Because of its neurotoxicity, Aβ42 is believed to play a causative role in the development of Alzheimer's disease (AD), whereas Aβ40 has neuroprotective effects against Aβ42 aggregation and also against metal-induced oxidative damage. Whether ACE inhibition enhances Aβ42 aggregation or impairs human cognitive ability are very important issues for preventing AD onset and for optimal hypertension management. In an 8-year longitudinal study, we found here that the mean intelligence quotient of male, but not female, hypertensive patients taking ACE inhibitors declined more rapidly than that of others taking no ACE inhibitors. Moreover, the sera of all AD patients exhibited a decrease in Aβ42-to-Aβ40-converting activity compared with sera from age-matched healthy individuals. Using human amyloid precursor protein transgenic mice, we found that a clinical dose of an ACE inhibitor was sufficient to increase brain amyloid deposition. We also generated human amyloid precursor protein/ACE +/- mice and found that a decrease in ACE levels promoted Aβ42 deposition and increased the number of apoptotic neurons. These results suggest that inhibition of ACE activity is a risk factor for impaired human cognition and for triggering AD onset., (© 2019 Liu et al.)

We have developed a highly sensitive microarray-based method that determines the absolute amounts of mRNA in a total RNA sample in a multiplex manner without reverse transcription. This direct mRNA measurement promotes high-throughput testing and reduces bias in transcriptome analyses. Furthermore, quantification of the absolute amount of mRNA allows transcriptome analysis without common controls or additional, complicated normalization. The method, called Photo-DEAN, was validated using chemically synthesized RNAs of known quantities and mouse liver total RNA samples. We found that the absolute amounts of mRNA were successfully measured without the cDNA synthesis step, with a sensitivity of 15 zmol achieved in 7 h., (Copyright © 2017. Published by Elsevier Inc.)

We have developed a system that supports presentations in meetings and conferences. Using computers and a network such as an intranet, it enables users to share conference materials effectively, and manages and delivers them easily. If it is used in conjunction with a videoconferencing system, users can hold a teleconference and participate in presentations from various remote sites. From the viewpoint of information transmission, the requirements for a presentation in a teleconference are similar to those for a remote classroom or lecture. We believe that this conference support system is suitable not only for conferences but also for education and telehealth.

Lately, in our country, daily motorcycling mail deliverers suffered from vibration hazards have been increasing. The vibration level of the handle of motorcycles was measured in order to evaluate its hazardous effects. The tested motorcycle with a 90 cc engine was selected among many motorcycles for daily use. Running test was made on the chasis dynamometer and asphalt roads. Following results were obtained. 1) The direction showing the maximum value of vibrations acceleration is in other directions than, X, Y, Z of ISO (International Organization for Standardization). 2) The maximum vibration acceleration level exceeds the exposure guidelines of ISO and its frequency is an accordance to the engine speed of the motorcycle in running. 3) The levels in the frequency ranges from 6 to 20 Hz and from 50 to 100 Hz are liable to induce vibration hazards. 4) The stronger the gripping power, the more the vibration acceleration level in the frequency range of 6-20 Hz and, on the contrary, the vibration acceleration level decreases in the range of 50-100 Hz. 5) The rubber grips of this motorcycle are not effective for abating the vibration on the frequency spectrum less than 125 Hz or 200 Hz.

The causes of vibration hazards to motorcycle mail deliverers have been considered to be due to the vibrations from the motorcycle, strain on the rider's hands and arms, cold conditions, and duration of the operation and others, and the rider's muscle tone in handling the motorcycle rises as the stability of the motorcycle decreases. In this report, the steering angle and banking of the motorcycle, vibration on the handgrips and EMG on the rider's arms and shoulders were measured during motorcycle operation with weights placed on the front and rear carriers. The relationship between the stability of the motorcycle, vibration on the handgrips and strain on the rider's arms and shoulders measured by EMG are also discussed. The following results were obtained. 1. When weights were placed on the front and rear carriers, the motorcycle became unstable especially at low vehicle speed, and handling became difficult. 2. The acceleration levels of the vibrations on the left handgrip exceeded the 4-8 exposure guideline of ISO when the vehicle speed was 50 km/h with weights. 3. When the weights were placed on the front or rear carrier, the vibration levels on the left grip were generally larger than those without weights. 4. The differences in vibration acceleration levels or vibration levels by weights could not be determined. 5. The EMGs of the musculus extensor digitorum (arms) and musculus trapezius (shoulders) increases with increase of vehicle speed. 6. There were no obvious differences in the EMG on the rider's arm and shoulders under straight-ahead operation by weight loading combinations.(ABSTRACT TRUNCATED AT 250 WORDS)