Echovirus 30 Induced Neuronal Cell Death through TRIO-RhoA Signaling Activation

BACKGROUND: Echovirus 30 (Echo30) is one of the most frequently identified human enteroviruses (EVs) causing aseptic meningitis and encephalitis. However the mechanism underlying the pathogenesis of Echo30 infection with significant clinical outcomes is not completely understood. The aim of this investigation is to illustrate molecular pathologic alteration in neuronal cells induced by Echo30 infection using clinical isolate from young patient with neurologic involvement. METHODOLOGY/PRINCIPAL FINDINGS: To characterize the neuronal cellular response to Echo30 infection, we performed a proteomic analysis based on two-dimensional gel electrophoresis (2-DE) and MALDI-TOF/TOF Mass Spectrophotometric (MS) analysis. We identified significant alteration of several protein expression levels in Echo30-infected SK-N-SH cells. Among these proteins, we focused on an outstanding up-regulation of Triple functional domain (TRIO) in Echo30-infected SK-N-SH cells. Generally, TRIO acts as a key component in the regulation of axon guidance and cell migration. In this study, we determined that TRIO plays a role in the novel pathways in Echo30 induced neuronal cell death. CONCLUSIONS/SIGNIFICANCE: Our finding shows that TRIO plays a critical role in neuronal cell death by Echo30 infection. Echo30 infection activates TRIO-guanine nucleotide exchange factor (GEF) domains (GEFD2) and RhoA signaling in turn. These results suggest that Echo30 infection induced neuronal cell death by activation of the TRIO-RhoA signaling. We expect the regulation of TRIO-RhoA signaling may represent a new therapeutic approach in treating aseptic meningitis and encephalitis induced by Echo30

Aldosterone-Producing Adrenocortical Carcinoma without Hypertension

Although adrenocortical tumors are common, adrenocortical carcinomas are rare. Moreover, aldosterone-producing adrenocortical carcinomas without hypertension are exceedingly rare, with only two previously reported cases

IgA and Differentiation-associated Transcription Factors in Chronic Otitis Media with Effusion

ObjectivesInadequate antibody responses to pathogens may lead to the recurrence of otitis media with effusion (OME). Although B-cell production by antibodies is controlled by transcription factors, the status of these factors has not been assessed in patients with OME.MethodsExpression of immunoglobulin was measured by enzyme-linked immunosorbent assay. Expression of transcription factors Bcl-6, Blimp-1, Pax-5, and XBP-1 was assessed by RT-PCR in the middle-ear fluid of 29 children with >4 OME episodes in 12 months or >3 episodes in 6 months (the OME-prone group) and in 32 children with <3 OME episodes in 12 months (OME group). The relationship between recurrence of OME and expression levels of immunoglobulins and transcription factors in middle-ear fluid was determined.ResultsThe concentration of IgA in middle-ear fluid was significantly lower in the OME-prone than in the OME group, as was the expression of mRNA encoding the transcription factors Blimp-1 and XBP-1 (P<0.05 each). Expression of mRNA encoding the transcription factors Bcl-6 and Pax-5 was more intense in the OME-prone than in the OME group, but these differences were not significant (P>0.05).ConclusionLower concentrations of IgA, Blimp-1 and XBP-1 in middle ear fluid of patients with OME may be related to OME recurrence and chronicity

Earthquakes and very deep groundwater perturbation mutually induced

We report unique observations from drilling and hydraulic stimulation at a depth of approximately 4.3&nbsp;km in two Enhanced Geothermal System (EGS) wells at the Pohang EGS site, South Korea. We surveyed drilling logs and hydraulic stimulation data, simulated pore pressure diffusion around the fault delineated by seismic and drilling log analyses, conducted acoustic image logging through the EGS wells, observed significant water level drops (740&nbsp;m) in one of the two EGS wells, and obtained hydrochemical and isotopic variation data in conjunction with the microbial community characteristics of the two EGS wells. We discuss the hydraulic and hydrochemical responses of formation pore water to a few key seismic events near the hypocenter. We focused on how the geochemistry of water that flowed back from the geothermal wells changed in association with key seismic events. These were (1) a swarm of small earthquakes that occurred when a significant circulation mud loss occurred during well drilling, (2) the MW 3.2 earthquake during hydraulic stimulation, and (3) the MW 5.5 main shock two months after the end of hydraulic stimulation. This study highlights the value of real-time monitoring and water chemistry analysis, in addition to seismic monitoring during EGS operation. &nbsp;</p

Cortical activation change induced by neuromuscular electrical stimulation during hand movements: a functional NIRS study

Objectives. Neuromuscular electrical stimulation (NMES) has been used in the field of rehabilitation for a long time. Previous studies on NMES have focused on the peripheral effect, in contrast, relatively little is known about the effect on the cerebral cortex. In the current study, we attempted to investigate the change of cortical activation pattern induced by NMES during execution of hand movements in normal subjects, using functional near infrared spectroscopy (fNIRS). Methods. Twelve healthy normal subjects were randomly assigned to the NMES group (six subjects) and the sham group (six subjects). We measured oxy-hemoglobin (HbO) in six regions of interest (ROI) during pre-NMES and post-NMES motor phase; the left dorsolateral and ventrolateral prefrontal cortex, premotor cortex, primary sensory-motor cortex (SM1), hand somatotopic area of SM1, and posterior parietal cortex. Between the pre-NMES and the post-NMES motor phases, real or sham NMES was applied on finger and wrist extensors of all subjects during a period of 5 minutes. Results: In all groups, during the pre-NMES motor phase, the HbO value in the hand somatotopic area of the left SM1 was higher than those of other ROIs. In the NMES group, during the post-NMES motor phase, HbO value variation in the hand somatotopic area of the left SM1 showed a significant decrease, compared with that of sham group (p &lt; 0.05). However, in the sham group, similar aspect of results in HbO values of all ROIs was observed between pre-NMES and post-NMES motor phases (p &gt; 0.05). Conclusions: Results of this study showed that NMES induced a decrease of cortical activation during execution of hand movements. This finding appears to indicate that application of NMES can increase the efficiency of the cerebral cortex during execution of motor tasks. © 2014 Jang et al.; licensee BioMed Central Ltd.1

Pogostemon cablin as ROS Scavenger in Oxidant-induced Cell Death of Human Neuroglioma Cells

Reactive oxygen species (ROS) have been implicated in the pathogenesis of a wide range of acute and long-term neurodegenerative diseases. This study was undertaken to examine the efficacy of Pogostemon cablin, a well-known herb in Korean traditional medicine, on ROS-induced brain cell injury. Pogostemon cablin effectively protected human neuroglioma cell line A172 against both the necrotic and apoptotic cell death induced by hydrogen peroxide (H2O2). The effect of Pogostemon cablin was dose dependent at concentrations ranging from 0.2 to 5 mg ml−1. Pogostemon cablin significantly prevented depletion of cellular ATP and activation of poly ADP-ribose polymerase induced by H2O2. The preservation of functional integrity of mitochondria upon the treatment of Pogostemon cablin was also confirmed by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Furthermore, Pogostemon cablin significantly prevented H2O2-induced release of cytochrome c into cytosol. Determination of intracellular ROS showed that Pogostemon cablin might exert its role as a powerful scavenger of intracellular ROS. The present study suggests the beneficial effect of Pogostemon cablin on ROS-induced neuroglial cell injury. The action of Pogostemon cablin as a ROS-scavenger might underlie the mechanism

Structural insights into the novel ARM-repeat protein CTNNBL1 and its association with the hPrp19-CDC5L complex

The hPrp19-CDC5L complex plays a crucial role during human pre-mRNA splicing by catalytic activation of the spliceosome. In order to elucidate the molecular architecture of the hPrp19-CDC5L complex, the crystal structure of CTNNBL1, one of the major components of this complex, was determined. Unlike canonical ARM-repeat proteins such as beta-catenin and importin-alpha, CTNNBL1 was found to contain a twisted and extended ARM-repeat structure at the C-terminal domain and, more importantly, the protein formed a stable dimer. A highly negatively charged patch formed in the N-terminal ARM-repeat domain of CTNNBL1 provides a binding site for CDC5L, a binding partner of the protein in the hPrp19-CDC5L complex, and these two proteins form a complex with a stoichiometry of 2:2. These findings not only present the crystal structure of a novel ARM-repeat protein, CTNNBL1, but also provide insights into the detailed molecular architecture of the hPrp19-CDC5L complex.open0

Metal-free, polyether-mediated H_2-release from ammonia borane: roles of hydrogen bonding interactions in promoting dehydrogenation

Polyetheral additives were found to be efficient promoters to enhance the rate of H2-release from ammonia borane (AB) at various temperatures. In particular, tetraethylene glycol dimethyl ether (T4EGDE, 29 wt% relative to AB + T4EGDE) exhibited significantly improved activities for AB dehydrogenation, with the material-based hydrogen storage capacity of 10.3 wt% at 125 °C within 40 min. In situ FT-IR spectroscopy indicated the formation of B-(cyclodiborazanyl)amino-borohydride (BCDB), borazine, and μ-aminodiborane as gaseous byproducts. In addition, 11B nuclear magnetic resonance (NMR) spectroscopy further revealed that diammoniate of diborane (DADB) was initially formed to give polyaminoborane as liquid and/or solid spent-fuel, consistent with previous reports. Density Functional Theory (DFT) calculations suggested that hydrogen bonding interactions between AB and a polyetheral promoter initially played an important role in increasing the reactivity of B–H bonds of AB by transferring electron density from oxygen atoms of the promoter into B–H bonds of AB. These partially activated, hydridic B–H bonds were proposed to help promote the formation of diammoniate of diborane (DADB), which is considered as a reactive intermediate, eventually enhancing the rate of H2-release from AB. In addition, our in situ solid state 11B magic angle spinning (MAS) NMR measurements further confirmed that the rate of DADB formation from AB with a small quantity of T4EGDE was found to be much faster than that of pristine AB even at 50 °C. This metal-free method for H2-release from AB with an added, small quantity of polyethers would be helpful to develop feasible hydrogen storage systems for long-term fuel cell applications