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Although aberrations in the number and function of glutamate AMPA ([alpha]-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors are thought to underlie neuropsychiatric disorders, no methods are currently available for visualizing AMPA receptors in the living human brain. Here we developed a positron emission tomography (PET) tracer for AMPA receptors. A derivative of 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide radiolabeled with .sup.11C ([.sup.11C]K-2) showed specific binding to AMPA receptors. Our clinical trial with healthy human participants confirmed reversible binding of [.sup.11C]K-2 in the brain according to Logan graphical analysis ((https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024205); study design: non-randomized, single arm; primary outcome: dynamics and distribution volumes of [.sup.11C]K-2 in the brain; secondary outcome: adverse events of [.sup.11C]K-2 during the 4-10 d following dosing; this trial met prespecified endpoints). In an exploratory clinical study including patients with epilepsy, we detected increased [.sup.11C]K-2 uptake in the epileptogenic focus of patients with mesial temporal lobe epilepsy, which was closely correlated with the local AMPA receptor protein distribution in surgical specimens from the same individuals ((https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028852); study design: non-randomized, single arm; primary outcome: correlation between [.sup.11C]K-2 uptake measured with PET before surgery and AMPA receptor protein density examined by biochemical study after surgery; secondary outcome: adverse events during the 7 d following PET scan; this trial met prespecified endpoints). Thus, [.sup.11C]K-2 is a potent PET tracer for AMPA receptors, potentially providing a tool to examine the involvement of AMPA receptors in neuropsychiatric disorders. A newly developed PET tracer allows visualization of AMPA receptors in the living human brain, providing a new tool to study their potential involvement in neurological or psychiatric disorders., Author(s): Tomoyuki Miyazaki [sup.1] , Waki Nakajima [sup.1] , Mai Hatano [sup.1] , Yusuke Shibata [sup.1] , Yoko Kuroki [sup.1] , Tetsu Arisawa [sup.1] , Asami Serizawa [sup.1] , Akane [...]

Stressful events during early childhood can have a profound lifelong influence on emotional and cognitive behaviors. However, the mechanisms by which stress affects neonatal brain circuit formation are poorly understood. Here, we show that neonatal social isolation disrupts molecular, cellular, and circuit developmental processes, leading to behavioral dysfunction. Neonatal isolation prevented long-term potentiation and experience-dependent synaptic trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors normally occurring during circuit formation in the rodent barrel cortex. This inhibition of AMPA receptor trafficking was mediated by an increase of the stress glucocorticoid hormone and was associated with reduced calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling, resulting in attenuated whisker sensitivity at the cortex. These effects led to defects in whisker-dependent behavior in juvenile animals. These results indicate that neonatal social isolation alters neuronal plasticity mechanisms and perturbs the initial establishment of a normal cortical circuit, which potentially explains the long-lasting behavioral effects of neonatal stress., Introduction Mental stress can have different effects on the nervous system. While brief mild stress can evoke emotional arousal and enhance learning (1), chronic elevated stress can induce deficits in [...]

As the proportion of elderly in society increases, so do the number of older patients undergoing surgical procedures. This is concerning as exposure to anesthesia has been identified as a risk factor for Alzheimer's disease (AD). However, the causal relationship between clinical AD development and anesthesia remains conjectural. Preclinical studies have demonstrated that anesthesia, such as halothane, isoflurane, and sevoflurane, induces AD-like pathophysiological changes and cognitive impairments in transgenic mouse models of AD. Desflurane does not have these effects and is expected to have more potential for use in elderly patients, yet little is known about its effects, especially on non-cognitive functions, such as motor and emotional functions. Thus, we examined the postanesthetic effects of desflurane and sevoflurane on motor and emotional function in aged AppNL−G−F/NL−G−F (App-KI) mice. This is a recently developed transgenic mouse model of AD exhibiting amyloid β peptide (Aβ) amyloidosis and a neuroinflammatory response in an age-dependent manner without non-physiological amyloid precursor protein (APP) overexpression. Mice were subjected to a short behavioral test battery consisting of an elevated plus maze, a balance beam test, and a tail suspension test seven days after exposure to 8.0% desflurane for 6 h or 2.8% sevoflurane for 2 h. App-KI mice showed significant increments in the percentage of entry and time spent in open arms in the elevated plus maze, increments in the number of slips and latency to traverse for the balance beam test, increments in the limb clasping score, increments in immobile duration, and decrements in latency to first immobile episode for the tail suspension test compared to age-matched wild type (WT) controls. Desflurane- and sevoflurane-exposed App-KI mice showed a delayed decrement in the number of slips for each trial in the balance beam test, while air-treated App-KI mice rapidly improved their performance, and increased their clasping behavior in the tail suspension test. Furthermore, App-KI inhibited the change in membrane GluA3 following exposure to anesthetics in the cerebellum. These results suggest high validity of App-KI mice as an animal model of AD. [ABSTRACT FROM AUTHOR]

The beacon signals from a geostationary satellite were observed using three-element very long baseline interferometry (VLBI), and the phase fluctuations along the baselines between three sites were obtained. The atmospheric phase fluctuations at each observation site were derived from the baseline phase fluctuation data. The fluctuations were classified into three time-interval regions based on the dependence of the Allan standard deviation of the fluctuations on the time interval. In the region where the interval was less than a few seconds and in the one where it was greater than one hundred seconds, the curve of the Allan standard deviation was steep and showed the property of white phase noise. In the region between these two regions, the dependence of the Allan standard deviation on the time interval was weak. The magnitude of the Allan standard deviations for the three observation sites showed time variations in the region where the time interval was longer than a few seconds. Comparison with the weather conditions suggested that the time variations of the Allan standard deviation reflected atmospheric instability above the sites. Index Terms--Allan standard deviation, atmospheric stability model, beacon wave, geostationary satellite, observation site atmospheric phase fluctuation, very long baseline interferometer (VLBI).

This paper reports the statistical characteristics of phase fluctuations obtained by a very long baseline interferometry, which received beacon waves from a geostationary satellite. Observations were made in different weather conditions by the 6-m Kagoshima and the 10-m Mizusawa radio telescopes, which were 1284 km apart from one another. Atmospheric phase fluctuations ranging from 0.2 to about 1000 s were detected. To study a variety of statistical characteristics of these phase fluctuations, the Allan standard deviation, [[sigma].sub.y] ([tau]), the temporal structure function, [D.sub.[phi]] ([tau]), and the square root of power spectrum, [D.sub.[phi]] (f), were calculated from the observation results. These qualities were found to depend on the time interval [tau] or the frequency f (f : 1/2[tau]) as follows: [[sigma].sub.y] ([tau]) [infinity] [[tau].sup.0.6] [[tau].sup.0.3], [D.sub.[phi]] ([tau]) [infinity] [[tau].sup.0.9], [[tau].sup.1.3] for 0.2 s < [tau] < 1.5 s and 1.5 s < [tau] < 400 s. [G.sub.[phi]](f) [infinity] [f.sup.-0.8] for 2.5 Hz > f > 0.33 Hz and [G.sub.[phi]](f) [infinity] [f.sup.-1.3] for 0.33 Hz > f > 0.00125 Hz. The curves of [[delta].sub.y] ([tau]) and [D.sub.[phi]]([tau]) exhibited shifts whose magnitudes followed the weather order clear, cloudy, and rainy. For [tau] > 1.5 s (or f < 0.33 Hz), the experimental results were consistent with the theoretical values predicted by Kolmogorov's turbulence theory and a frozen-screen model, but for [tau] < 1.5 s (or f > 0.33 Hz), the model has to be modified to explain the experimental results. Index Terms--Allan standard deviation, atmospheric phase fluctuation, beacon wave from geostationary satellite, temporal structure function, very long baseline interferometer (VLBI).

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). In this study, we report the persistence of nAb responses over 12 months after infection despite their decreasing trend noticed from 6 months. Methods The study included sera from 497 individuals who had been infected with SARS-CoV-2 between January and August 2020. Samples were collected at 6 and 12 months after onset. The titers of immunoglobulin (Ig)G to the viral nucleocapsid protein (NP) and receptor-binding domain (RBD) of the spike protein were measured by chemiluminescence enzyme immunoassay. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus. Results Antibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. Although the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (~30%) was undermined, implying the susceptibility to reinfection with the variants of concerns (VOCs). Conclusions Coronavirus disease 2019 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs. [ABSTRACT FROM AUTHOR]