The effects of transcranial static magnetic fields stimulation over the supplementary motor area on anticipatory postural adjustments

We investigated the influence of transcranial static magnetic field stimulation (tSMS) over the supplementary motor area (SMA) on anticipatory postural adjustments (APAs), in which the activation of the postural muscles of the legs and trunk that control standing posture precedes the activation of the prime mover muscles during rapid shoulder flexion movement. Eighteen subjects performed a self-paced rapid shoulder flexion task before, during, and after tSMS. Electromyogram (EMG) activity was recorded from the deltoid anterior (AD) as the prime mover muscle and the biceps femoris (BF) as the postural muscle during the task. The EMG latency difference (ΔEMG onset) between the two muscles was calculated by subtracting the EMG burst onset of the BF from that of the AD. The ΔEMG onset was significantly shortened, but center-of-pressure parameters were not affected after tSMS stimulation. These findings suggest that tSMS applied over the SMA could inhibitively modulate APAs function

Smad1の条件付き遺伝子削除は進行性糸球体腎炎による糸球体傷害を改善する

Matrix expansion and cell proliferation are concomitantly observed in various glomerular injuries. However, the molecular mechanisms responsible for these changes have not been fully elucidated. We have reported that Smad1 is a key signalling molecule that regulates the transcription of type IV collagen (Col4) in mesangial matrix expansion and is thereby involved in glomerular injury in an acute model of glomerulonephritis. In this study, we addressed the role of Smad1 signalling in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis, using conditional deletion of Smad1 in Rosa26CreERT2 mice (Smad1-CKO). Mesangial matrix expansion in the Smad1-CKO mice with NTN was significantly inhibited compared with that in wild type mice with NTN, which was consistent with the decrease in Col4 expression level. On the other hand, STAT3 activation and cell proliferation were not influenced by Smad1 deletion in the NTN model. Therefore, we investigated another factor that activates cell proliferation in the absence of Smad1. Id2 induced VEGF secretion and subsequent STAT3 activation, independently of Smad1 expression in mouse mesangial cells. Here we show that Smad1 plays an important role in the development of glomerular injury without affecting cell proliferation, in progressive glomerulonephritis

Conditional Deletion of Smad1 Ameliorates Glomerular Injury in Progressive Glomerulonephritis

Matrix expansion and cell proliferation are concomitantly observed in various glomerular injuries. However, the molecular mechanisms responsible for these changes have not been fully elucidated. We have reported that Smad1 is a key signalling molecule that regulates the transcription of type IV collagen (Col4) in mesangial matrix expansion and is thereby involved in glomerular injury in an acute model of glomerulonephritis. In this study, we addressed the role of Smad1 signalling in accelerated nephrotoxic nephritis (NTN), a model of progressive glomerulonephritis, using conditional deletion of Smad1 in Rosa26CreERT2 mice (Smad1-CKO). Mesangial matrix expansion in the Smad1-CKO mice with NTN was significantly inhibited compared with that in wild type mice with NTN, which was consistent with the decrease in Col4 expression level. On the other hand, STAT3 activation and cell proliferation were not influenced by Smad1 deletion in the NTN model. Therefore, we investigated another factor that activates cell proliferation in the absence of Smad1. Id2 induced VEGF secretion and subsequent STAT3 activation, independently of Smad1 expression in mouse mesangial cells. Here we show that Smad1 plays an important role in the development of glomerular injury without affecting cell proliferation, in progressive glomerulonephritis

Activation of Src Mediates PDGF-Induced Smad1 Phosphorylation and Contributes to the Progression of Glomerulosclerosis in Glomerulonephritis

Platelet-derived growth factor (PDGF) plays critical roles in mesangial cell (MC) proliferation in mesangial proliferative glomerulonephritis. We showed previously that Smad1 contributes to PDGF-dependent proliferation of MCs, but the mechanism by which Smad1 is activated by PDGF is not precisely known. Here we examined the role of c-Src tyrosine kinase in the proliferative change of MCs. Experimental mesangial proliferative glomerulonephritis (Thy1 GN) was induced by a single intravenous injection of anti-rat Thy-1.1 monoclonal antibody. In Thy1 GN, MC proliferation and type IV collagen (Col4) expression peaked on day 6. Immunohistochemical staining for the expression of phospho-Src (pSrc), phospho-Smad1 (pSmad1), Col4, and smooth muscle α-actin (SMA) revealed that the activation of c-Src and Smad1 signals in glomeruli peaked on day 6, consistent with the peak of mesangial proliferation. When treated with PP2, a Src inhibitor, both mesangial proliferation and sclerosis were significantly reduced. PP2 administration also significantly reduced pSmad1, Col4, and SMA expression. PDGF induced Col4 synthesis in association with increased expression of pSrc and pSmad1 in cultured MCs. In addition, PP2 reduced Col4 synthesis along with decreased pSrc and pSmad1 protein expression in vitro. Moreover, the addition of siRNA against c-Src significantly reduced the phosphorylation of Smad1 and the overproduction of Col4. These results provide new evidence that the activation of Src/Smad1 signaling pathway plays a key role in the development of glomerulosclerosis in experimental glomerulonephritis

Tackling social anxiety with targeted brain stimulation: investigating the effects of transcranial static magnetic field stimulation on self-focused attention

Previous studies suggested that self-focused attention (SFA), implicated in social anxiety disorder (SAD), correlates with heightened activity in the right frontopolar area (rFPA), which is the right prefrontal cortex just behind the forehead. Transcranial static magnetic field stimulation (tSMS) is a non-invasive brain stimulation method capable of temporarily suppressing brain function beneath the magnet. We explored whether tSMS on individuals with tendencies toward SAD elicited (1) suppressing rFPA activation during the resting-state and (2) reducing SFA during a subsequent speech task. Twenty-three university students with social anxiety performed two speech tasks. Between tasks, the tSMS group received neodymium magnet stimulation while the sham group received fake magnet stimulation on the rFPA for 20 min. Resting-state rFPA activities was measured using functional near-infrared spectroscopy (fNIRS), while SFA (body sensations and observer perspective), field perspective, and detached mindfulness (DM) perspective were assessed via questionnaires during both speech tasks. The observer perspective means SFA to self-imagery from others’ viewpoint, while the field and DM perspectives mean appropriately focusing on the external environment. The results indicated that tSMS intervention decreased rFPA activity from pre- to post-intervention rest. Then, tSMS reduced SFA to bodily sensations and increased DM perspective from pre- to post-intervention speech, especially in those with high levels of social anxiety. Furthermore, tSMS enhanced the field perspective regardless of social anxiety tendency. The results suggest that tSMS may suppress overactivity in rFPA, reduce SFA to body sensation, and increase adaptive attention in highly socially anxious individuals. Our study suggests the possibility of the clinical application of tSMS for treating SAD

Expansion of a CD28-Intermediate Subset among CD8 T Cells in Patients with Infectious Mononucleosis

Infectious mononucleosis (IM) is an acute sporadic infection that usually affects young adults, and during infection a massive expansion of CD8 T cells is generally considered to occur. However, CD28 expression of the expanded cells has not been characterized. When peripheral blood mononuclear cells of acute IM (AIM) patients were analyzed by flow cytometry, a continuous spectrum of CD28 intensity ranging from negative to high, which could be separated into CD28 negative, intermediate (int), and positive, was seen for CD8 T cells. We studied 26 IM patients who were diagnosed on the basis of standard methods and found that all patients had the continuous CD28 spectrum. CD28 is a costimulatory molecule on T cells, and its expression is associated with the subdivision of CD8 cells into cytotoxic (CD28-positive) and suppressor (CD28-negative) T cells. After 24 h of ex vivo culturing, however, the continuous spectrum was found to consist of only CD28-positive and CD28-negative CD8 T cells, because the CD28-int cells had disappeared due to apoptosis. The CD28-int T cells have several cytotoxic functions, suggesting that CD28-int T cells are effectors. Examination of other costimulatory markers in AIM patients showed that CD80 and CD152 were not affected. In patients with other viral infections, such as measles or rubella, however, the continuous spectrum was not detected. These results suggest that there is an unusual CD28 expression pattern in patients with AIM, namely, the presence of a functional CD28-int subset among CD8 T cells. These findings are of special importance for clarifying the defense mechanism against Epstein-Barr virus infection, and the role of CD28 molecules in humans and should also be helpful for the diagnosis of AIM

Transient Modulation of Working Memory Performance and Event-Related Potentials by Transcranial Static Magnetic Field Stimulation over the Dorsolateral Prefrontal Cortex

Transcranial static magnetic field stimulation (tSMS) can modulate human cortical excitability and behavior. To better understand the neuromodulatory effect of tSMS, this study investigates whether tSMS applied over the left dorsolateral prefrontal cortex (DLPFC) modulates working memory (WM) performance and its associated event-related potentials (ERPs). Thirteen healthy participants received tSMS or sham stimulation over the left DLPFC for 26 min on different days. The participants performed a 2-back version of the n-back task before, during (20 min after the start of stimulation), immediately after, and 15 min after the stimulation. We examine reaction time for correct responses, d-prime reflecting WM performance, and the N2 and P3 components of ERPs. Our results show that there was no effect of tSMS on reaction time. The d-prime was reduced, and the N2 latency was prolonged immediately after tSMS. These findings indicate that tSMS over the left DLPFC affects WM performance and its associated electrophysiological signals, which can be considered an important step toward a greater understanding of tSMS and its use in studies of higher-order cognitive processes