Potential Pathways Associated With Exaggerated T Follicular Helper Response in Human Autoimmune Diseases

Convincing lines of evidence in both mice and humans show that exaggerated T follicular helper (Tfh) responses is pathogenic in autoimmune diseases. However, the cause of exaggerated Tfh response in humans is still much less clear than in mouse models where genetic factors can be manipulated for in vivo testing. Nonetheless, recent advances in our understanding on the mechanisms of human Tfh differentiation and identification of multiple risk loci in genome-wide association studies have revealed several pathways potentially associated with exaggerated Tfh response in human autoimmune diseases. In this review, we will first briefly summarize the differentiation mechanisms of Tfh cells in humans. We describe the features of “Tfh-like” cells recently identified in inflamed tissues of human autoimmune diseases. Then we will discuss how risk loci identified in GWAS are potentially involved in exaggerated Tfh response in human autoimmune diseases

A Comparative Study of the Parker Instability under Three Models of the Galactic Gravity

To examine how non-uniform nature of the Galactic gravity might affect length and time scales of the Parker instability, we took three models of gravity, uniform, linear and realistic ones. To make comparisons of the three gravity models on a common basis, we first fixed the ratio of magnetic pressure to gas pressure at $\alpha$ = 0.25, that of cosmic-ray pressure at $\beta$ = 0.4, and the rms velocity of interstellar clouds at $a_s$ = 6.4 km s$^{-1}$, and then adjusted parameters of the gravity models in such a way that the resulting density scale heights for the three models may all have the same value of 160 pc. Performing linear stability analyses onto equilibrium states under the three models with the typical ISM conditions, we calculate the maximum growth rate and corresponding length scale for each of the gravity models. Under the uniform gravity the Parker instability has the growth time of 1.2$\times10^{8}$ years and the length scale of 1.6 kpc for symmetric mode. Under the realistic gravity it grows in 1.8$\times10^{7}$ years for both symmetric and antisymmetric modes, and develops density condensations at intervals of 400 pc for the symmetric mode and 200 pc for the antisymmetric one. A simple change of the gravity model has thus reduced the growth time by almost an order of magnitude and its length scale by factors of four to eight. These results suggest that an onset of the Parker instability in the ISM may not necessarily be confined to the regions of high $\alpha$ and $\beta$.Comment: Accepted for publication in ApJ, using aaspp4.sty, 18 text pages with 9 figure

School teachers' awareness of internet addiction in elementary school students: a regional survey in Japan

In recent years, concerns about internet addiction (IA) among children have been increasing. This study focused on the awareness of IA in elementary school teachers. A web-based anonymous survey was conducted in November 2021. The participants completed an original questionnaire about their awareness of IA. The participants were divided into three groups based on their positions in the classroom: class teachers, support teachers, and administrative teachers. Out of 283 participants, over 70% had not approached students with IA and had little practical knowledge about the disorder. Support and administrative teachers had more opportunities to interact with students with IA than class teachers (p < 0.001 in both cases). Support teachers had more opportunities to ask their colleagues about IA than class teachers (p < 0.01); similarly, administrative teachers also had more opportunities to discuss IA with colleagues than class teachers (p = 0.04). Preventive interventions are recommended for people who communicate with children with IA. Students with IA might cause anxiety among teachers; therefore, preventive education strategies should be implemented with the cooperation of psychiatrists, psychologists, and public health nurses

Case Report Effects of Adenotonsillectomy on Neurocognitive Function in Pediatric Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea syndrome (OSAS) in children does not only present with symptoms of sleep disturbances but also with associated symptoms such as growth failure, enuresis, academic learning difficulties, and behavioral problems, including attention deficit/hyperactivity disorder-(ADHD-) like symptoms. We evaluated neurocognitive functions before and after adenotonsillectomy in a patient with OSAS. An 11-year-old boy suspected of having ADHD with nocturnal enuresis was referred for evaluation. He was found to have adenotonsillar hypertrophy. Presence of snoring was evident only after detailed medical interview. Polysomnography confirmed the diagnosis of OSAS, which was subsequently treated by adenotonsillectomy. The apnea/hypopnea index decreased from 21.9 at baseline to 1.8 after surgery, and the frequency of enuresis fell from almost nightly to 2-3 times per month. Neurocognitive and behavioral assessment after the treatment of OSAS showed significant improvement in cognitive functions, especially attention capacity and considerable amelioration of behavioral problems including ADHD-like symptoms. As the most common cause of pediatric OSAS is adenotonsillar hypertrophy, medical interview and oropharyngeal examination should always be performed in children suspected of having ADHD. The necessity of sleep evaluation for children with ADHD-like symptoms was also emphasized

Tox2 is required for the maintenance of GC TFH cells and the generation of memory TFH cells

効率よい抗体反応の形成に必要なTリンパ球因子の発見. 京都大学プレスリリース. 2021-10-15.Molecules for building stronger antibodies. 京都大学プレスリリース. 2021-10-15.Memory T follicular helper (TFH) cells play an essential role to induce secondary antibody response by providing help to memory and naïve B cells. Here, we show that the transcription factor Tox2 is vital for the maintenance of TFH cells in germinal centers (GCs) and the generation of memory TFH cells. High Tox2 expression was almost exclusive to GC TFH cells among human tonsillar and blood CD4+ T cell subsets. Tox2 overexpression maintained the expression of TFH-associated genes in T cell receptor–stimulated human GC TFH cells and inhibited their spontaneous conversion into TH1-like cells. Tox2-deficient mice displayed impaired secondary TFH cell expansion upon reimmunization with an antigen and upon secondary infection with a heterologous influenza virus. Collectively, our study shows that Tox2 is highly integrated into establishment of durable GC TFH cell responses and development of memory TFH cells in mice and humans

Magnetic Reconnection Triggered by the Parker Instability in the Galaxy: Two-Dimensional Numerical Magnetohydrodynamic Simulations and Application to the Origin of X-Ray Gas in the Galactic Halo

We propose the Galactic flare model for the origin of the X-ray gas in the Galactic halo. For this purpose, we examine the magnetic reconnection triggered by Parker instability (magnetic buoyancy instability), by performing the two-dimensional resistive numerical magnetohydrodynamic simulations. As a result of numerical simulations, the system evolves as following phases: Parker instability occurs in the Galactic disk. In the nonlinear phase of Parker instability, the magnetic loop inflates from the Galactic disk into the Galactic halo, and collides with the anti-parallel magnetic field, so that the current sheets are created in the Galactic halo. The tearing instability occurs, and creates the plasmoids (magnetic islands). Just after the plasmoid ejection, further current-sheet thinning occurs in the sheet, and the anomalous resistivity sets in. Petschek reconnection starts, and heats the gas quickly in the Galactic halo. It also creates the slow and fast shock regions in the Galactic halo. The magnetic field ($B\sim 3 \mu$G), for example, can heat the gas ($n\sim 10^{-3}$ cm$^{-3}$) to temperature of $\sim 10^6$ K via the reconnection in the Galactic halo. The gas is accelerated to Alfv\'en velocity ($\sim 300$ km s$^{-1}$). Such high velocity jets are the evidence of the Galactic flare model we present in this paper, if the Doppler shift of the bipolar jet is detected in the Galactic halo. Full size figures are available at http://www.kwasan.kyoto-u.ac.jp/~tanuma/study/ApJ2002/ApJ2002.htmlComment: 13 pages, 12 figures, uses emulateapj.sty, accepted by Ap

Steatogenesis in adult-onset type II citrullinemia is associated with down-regulation of PPARα

AbstractSLC25A13 (citrin or aspartate–glutamate carrier 2) is located in the mitochondrial membrane in the liver and its genetic deficiency causes adult-onset type II citrullinemia (CTLN2). CTLN2 is one of the urea cycle disorders characterized by sudden-onset hyperammonemia due to reduced argininosuccinate synthase activity. This disorder is frequently accompanied with hepatosteatosis in the absence of obesity and ethanol consumption. However, the precise mechanism of steatogenesis remains unclear. The expression of genes associated with fatty acid (FA) and triglyceride (TG) metabolism was examined using liver samples obtained from 16 CTLN2 patients and compared with 7 healthy individuals. Although expression of hepatic genes associated with lipogenesis and TG hydrolysis was not changed, the mRNAs encoding enzymes/proteins involved in FA oxidation (carnitine palmitoyl-CoA transferase 1α, medium- and very-long-chain acyl-CoA dehydrogenases, and acyl-CoA oxidase 1), very-low-density lipoprotein secretion (microsomal TG transfer protein), and FA transport (CD36 and FA-binding protein 1), were markedly suppressed in CTLN2 patients. Serum concentrations of ketone bodies were also decreased in these patients, suggesting reduced mitochondrial β-oxidation activity. Consistent with these findings, the expression of peroxisome proliferator-activated receptor α (PPARα), a master regulator of hepatic lipid metabolism, was significantly down-regulated. Hepatic PPARα expression was inversely correlated with severity of steatosis and circulating ammonia and citrulline levels. Additionally, phosphorylation of c-Jun-N-terminal kinase was enhanced in CTLN2 livers, which was likely associated with lower hepatic PPARα. Collectively, down-regulation of PPARα is associated with steatogenesis in CTLN2 patients. These findings provide a novel link between urea cycle disorder, lipid metabolism, and PPARα

Three-dimensional simulations of the Parker instability in a uniformly rotating disk

We investigate the effects of rotation on the evolution of the Parker instability by carrying out three-dimensional numerical simulations with an isothermal magnetohydrodynamic code. These simulations extend our previous work on the nonlinear evolution of the Parker instability by J. Kim and coworkers. The initial equilibrium system is composed of exponentially stratified gas and a field (along the azimuthal direction) in a uniform gravity (along the downward vertical direction). The computational box, placed at the solar neighborhood, is set to rotate uniformly around the Galactic center with a constant angular speed. The instability has been initialized by random velocity perturbations. In the linear stage, the evolution is not much different from that without rotation, and the mixed (undular + interchange) mode regulates the system. The interchange mode induces alternating dense and rarefied regions with small radial wavelengths, while the undular mode bends the magnetic field lines in the plane of the azimuthal and vertical directions. In the nonlinear stage, flow motion overall becomes chaotic, as in the case without rotation. However, as the gas in higher positions slides down along field lines forming supersonic flows, the Coriolis force becomes important. As oppositely directed flows fall into valleys along both sides of the magnetic field lines, they experience the Coriolis force toward opposite directions, which twists the magnetic field lines there. Hence, we suggest that the Coriolis force plays a role in randomizing the magnetic field. The three-dimensional density structure formed by the instability is still sheetlike with the short dimension along the radial direction, as in the case without rotation. However, the long dimension is now slightly tilted with respect to the mean field direction. The shape of high-density regions is a bit rounder. The maximum enhancement factor of the vertical column density relative to its initial value is about 1.5, which is smaller than that in the case without rotation. We conclude that uniform rotation does not change our point of view that the Parker instability alone is not a viable mechanism for the formation of giant molecular cloudsopen252

The Parker instability under a linear gravity

A linear stability analysis has been done to a magnetized disk under a linear gravity. We have reduced the linearized perturbation equations to a second-order differential equation that resembles the Schrodinger equation with the potential of a harmonic oscillator. Depending on the signs of energy and potential terms, eigensolutions can be classified into ''continuum'' and ''discrete'' families. When the magnetic field is ignored, the continuum family is identified as the convective mode, while the discrete family is identified as acoustic-gravity waves. If the effective adiabatic index gamma is less than unity, the former develops into the convective instability. When a magnetic field is included, the continuum and discrete families further branch into several solutions with different characters. The continuum family is divided into two modes: one is the original Parker mode, which is a slow MHD mode modulated by the gravity, and the other is a stable Alfven mode. The Parker modes can be either stable or unstable depending on gamma. When gamma is smaller than a critical value gamma(cr), the Parker mode becomes unstable. The discrete family is divided into three modes: a stable fast MHD mode modulated by the gravity, a stable slow MHD mode modulated by the gravity, and an unstable mode that is also attributed to a slow MHD mode. The unstable discrete mode does not always exist. Even though the unstable discrete mode exists, the Parker mode dominates it if the Parker mode is unstable. However, if gamma greater than or equal to gamma(cr), then the discrete mode could be the only unstable one. When gamma is equal gamma(cr), the minimum growth time of the unstable discrete mode is 1.3 x 10(8) yr, with a corresponding length scale of 2.4 kpc. It is suggestive that the corrugated features seen in the Galaxy and external galaxies are related to the unstable discrete modeopen131

Three-Dimensional Simulations of Parker, Magneto-Jeans, and Swing Instabilities in Shearing Galactic Gas Disks

We use 3D MHD simulations to investigate nonlinear development of the Parker, magneto-Jeans (MJI), and swing mechanisms in galactic disks. The model disks are local, isothermal, and begin from a vertically-stratified equilibrium. We first construct axisymmetric equilibria and examine their stability. Finite disk thickness reduces the critical Toomre Q parameter below unity; we find Q_c \~ 0.75, 0.72, and 0.57 for \beta=\infty, 10, and 1 cases, respectively. We then pursue fully 3D models. In non-self-gravitating cases, the peak density enhancement from the `pure' Parker instability is less a factor of two. The dominant growing modes have radial wavelengths comparable to the disk scale height H, much shorter than the azimuthal wavelength (~10-20 H). Shearing disks, being more favorable to midplane-symmetric modes, have somewhat different late-time magnetic field profiles from nonshearing disks, but otherwise saturated states are similar. Late-time velocity fluctuations at 10% of the sound speed persist, but no characteristic structural signatures of Parker modes remain in the new equilibria. In self-gravitating cases, the development of density structure is qualitatively similar to our previous results from thin-disk simulations. The Parker instability, although it may help seed structure or tip the balance under marginal conditions, appears to play a secondary role. In shearing disks with Q less than a threshold level ~ 1, swing amplification can produce bound clouds of a few times the local Jeans mass. The most powerful cloud-condensing mechanism appears to be the MJI. Our simulations show that condensations of a local Jeans mass (~3\times 10^7 M_sun) grow very rapidly, supporting the idea that MJI is at least partly responsible for the formation of bound cloud complexes in spiral galaxies.Comment: 36 pages, 15 figures, Accepted for publication in ApJ; better postscript figures available from http://www.astro.umd.edu/~kimwt/FIGURE3/ ; for associated Animated GIF movies, see http://www.astro.umd.edu/~kimwt/MOVIES/3DLoca