2,077 research outputs found

    Matrix Metalloproteinase-3 Causes Dopaminergic Neuronal Death through Nox1-Regenerated Oxidative Stress

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    In the present study we investigated the interplay between matrix metalloproteinase 3 (MMP3) and NADPH oxidase 1 (Nox1) in the process of dopamine (DA) neuronal death. We found that MMP3 activation causes the induction of Nox1 via mitochondrial reactive oxygen species (ROS) production and subsequently Rac1 activation, eventually leading to Nox1-derived superoxide generation in a rat DA neuronal N27 cells exposed to 6-OHDA. While a MMP3 inhibitor, NNGH, largely attenuated mitochondrial ROS and subsequent Nox1 induction, both apocynin, a putative Nox inhibitor and GKT137831, a Nox1 selective inhibitor failed to reduce 6-OHDA-induced mitochondrial ROS. However, both inhibitors for MMP3 and Nox1 similarly attenuated 6-OHDA-induced N27 cell death. RNAi-mediated selective inhibition of MMP3 or Nox1 showed that knockdown of either MMP3 or Nox1 significantly reduced 6-OHDA-induced ROS generation in N27 cells. While 6-OHDA-induced Nox1 was abolished by MMP3 knockdown, Nox1 knockdown did not alter MMP3 expression. Direct overexpression of autoactivated MMP3 (actMMP3) in N27 cells or in rat substantia nigra (SN) increased expression of Nox1. Selective knockdown of Nox1 in the SN achieved by adeno-associated virus-mediated overexpression of Nox1-specific shRNA largely attenuated the actMMP3-mediated dopaminergic neuronal loss. Furthermore, Nox1 expression was significantly attenuated in Mmp3 null mice treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Together we established novel molecular mechanisms underlying oxidative stress-mediated dopaminergic neuronal death in which MMP3 activation is a key upstream event that leads to mitochondrial ROS, Nox1 induction and eventual dopaminergic neuronal death. Our findings may lead to the development of novel therapeutic approach

    Matrix Metalloproteinase-3 Causes Dopaminergic Neuronal Death through Nox1-Regenerated Oxidative Stress

    Get PDF
    In the present study we investigated the interplay between matrix metalloproteinase 3 (MMP3) and NADPH oxidase 1 (Nox1) in the process of dopamine (DA) neuronal death. We found that MMP3 activation causes the induction of Nox1 via mitochondrial reactive oxygen species (ROS) production and subsequently Rac1 activation, eventually leading to Nox1-derived superoxide generation in a rat DA neuronal N27 cells exposed to 6-OHDA. While a MMP3 inhibitor, NNGH, largely attenuated mitochondrial ROS and subsequent Nox1 induction, both apocynin, a putative Nox inhibitor and GKT137831, a Nox1 selective inhibitor failed to reduce 6-OHDA-induced mitochondrial ROS. However, both inhibitors for MMP3 and Nox1 similarly attenuated 6-OHDA-induced N27 cell death. RNAi-mediated selective inhibition of MMP3 or Nox1 showed that knockdown of either MMP3 or Nox1 significantly reduced 6-OHDA-induced ROS generation in N27 cells. While 6-OHDA-induced Nox1 was abolished by MMP3 knockdown, Nox1 knockdown did not alter MMP3 expression. Direct overexpression of autoactivated MMP3 (actMMP3) in N27 cells or in rat substantia nigra (SN) increased expression of Nox1. Selective knockdown of Nox1 in the SN achieved by adeno-associated virus-mediated overexpression of Nox1-specific shRNA largely attenuated the actMMP3-mediated dopaminergic neuronal loss. Furthermore, Nox1 expression was significantly attenuated in Mmp3 null mice treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Together we established novel molecular mechanisms underlying oxidative stress-mediated dopaminergic neuronal death in which MMP3 activation is a key upstream event that leads to mitochondrial ROS, Nox1 induction and eventual dopaminergic neuronal death. Our findings may lead to the development of novel therapeutic approach

    SPRINTING CHARACTERISTICS OF WOMEN’S 100 METER FINALS AT THE IAAF WORLD CHAMPIONSHOPS DAEGU 2011

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    This study analyzed the sprinting characteristics of the finalists during the women's 100 m event in the IAAF World Championships Daegu 2011 in order to provide important information to track and field coaches and athletes. Five high speed cameras (Casio, Japan) with a sampling frequency of 300 Hz were used to calculate the number of steps, step length, and stride frequency of the eight sprinters in the women’s final event. There was a tendency to show a better performance time with a high number of steps (p=0.13) and shorter stride length (p=0.14) among the eight sprinters. Furthermore, stride frequency and performance time were negatively correlated as a higher stride frequency had a positive impact on performance time (p=0.02). Based on the relationship between COM velocity and lower extremity joint angles, the 4 top ranked sprinters showed the different strategies to maintain a high COM velocity during the mid portion of the race

    The Fruit Hull of Gleditsia sinensis

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    Lung cancer has substantial mortality worldwide, and chemotherapy is a routine regimen for the treatment of patients with lung cancer, despite undesirable effects such as drug resistance and chemotoxicity. Here, given a possible antitumor effect of the fruit hull of Gleditsia sinensis (FGS), we tested whether FGS enhances the effectiveness of cis-diammine dichloridoplatinum (II) (CDDP), a chemotherapeutic drug. We found that CDDP, when administered with FGS, significantly decreased the viability and increased the apoptosis and cell cycle arrest of Lewis lung carcinoma (LLC) cells, which were associated with the increase of p21 and decreases of cyclin D1 and CDK4. Concordantly, when combined with FGS, CDDP significantly reduced the volume and weight of tumors derived from LLC subcutaneously injected into C57BL/6 mice, with concomitant increases of phosphor-p53 and p21 in tumor tissue. Together, these results show that FGS could enhance the antitumor activity of CDDP, suggesting that FGS can be used as a complementary measure to enhance the efficacy of a chemotherapeutic agent such as CDDP

    Avoid Contamination in Soybean (Glycine Max, L. [Merrill]) Microspores Culture

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    Microspore culture is done to obtain pure strains. The purpose of soybean microspore culture to obtainquality seeds. Two important step that must be done is isolation of microspores in starvation medium andsubculture into embryogenesis medium. Many factors contributing to the contamination of soybeanmicrospore culture. Contamination in the B medium temperature 34 0C is more common than 4 0C. Vulnerableto contamination because of embryogenesis medium rich in nutrients. Bacterial contaminationcan be caused by internal contaminants such as shape of the anther. Other internal contaminants thatcause diseases such as fungi Colletotrichum truncatum and Phakopsora pachyrhizi. Antagonistic fungiwhich contaminate cultures that Trichoderma spp., Alternaria spp., Fusarium spp. Handling of contaminationis done by selecting the appropriate methods in order to remain viable microspores. Sterilization soybeanflower buds with 20% Tween for 10 minutes and then rinsed with distilled water. Moreover sterilizationwith 4% Hg Cl2 and 10% NaOCl for 10 minutes, rinsed with distilled water times, followed by 96%alcohol for 1 minute, can press up to 70% contamination

    Development of a dual optical fiber probe for the hydrodynamic investigation of a horizontal annular drive gas/liquid ejector

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    A dual-channel optical fiber probe was developed to quantify the bubble characteristics (void fraction, velocity, and bubble size) in a gas–liquid annular ejector system. Water is pumped upstream of the ejector contraction. Since a low pressure region exists downstream in the ejector diffuser, this permits air to be sucked into the flowing liquid by jet pump action and the inlet air volumetric flow rate is measured by a flow meter. Verification of the void fraction (range 0.15–0.5) measured by the optical fiber probe was then possible and deviations were generally around ± 5%. Also, bubble velocity was measured using the optical probe by cross-correlating signals from the two fibers whose tips are separated by a known distance. Alternatively measuring bubble velocity using a particle image velocimetry method provided validation for the optical fiber probe system where a high speed camera was used to capture instantaneous bubble images at time intervals of 0.125 ms. Excellent agreement between the velocities using both methods is reported. For bubble size measurements, analyzing the temporal signals from a single probe enabled estimation of the size of a bubble. Bubble sizes measured ranged between 1.5 and 6.0 mm and size distributions were constructed for different ejector water volumetric flow rates ranging from 0.0022 to 0.0063 m3/s. LabVIEW provided a convenient platform for coding the algorithms for estimating the void fraction, bubble velocity and bubble size. For further comparison, a CFD study of the ejector system was done, and the vertical radial profiles of the void fraction were compared with those obtained by the optical fiber system and these showed good agreement

    Neural Dynamics of Olfactory Perception: Low- and High-Frequency Modulations of Local Field Potential Spectra in Mice Revealed by an Oddball Stimulus

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    Recent brain connectome studies have evidenced distinct and overlapping brain regions involved in processing olfactory perception. However, neural correlates of hypo- or anosmia in olfactory disorder patients are poorly known. Furthermore, the bottom-up and top-down processing of olfactory perception have not been well-documented, resulting in difficulty in locating the disease foci of olfactory disorder patients. The primary aim of this study is to characterize the bottom-up process of the neural dynamics across peripheral and central brain regions in anesthetized mice. We particularly focused on the neural oscillations of local field potential (LFP) in olfactory epithelium (OE), olfactory blub (OB), prefrontal cortex (PFC), and hippocampus (HC) during an olfactory oddball paradigm in urethane anesthetized mice. Odorant presentations evoked neural oscillations across slow and fast frequency bands including delta (1–4 Hz), theta (6–10 Hz), beta (15–30 Hz), low gamma (30–50 Hz), and high gamma (70–100 Hz) in both peripheral and central nervous systems, and the increases were more prominent in the infrequently presented odorant. During 5 s odorant exposures, the oscillatory responses in power were persistent in OE, OB, and PFC, whereas neural oscillations of HC increased only for short time at stimulus onset. These oscillatory responses in power were insignificant in both peripheral and central regions of the ZnSO4-treated anosmia model. These results suggest that olfactory stimulation induce LFP oscillations both in the peripheral and central nervous systems and suggest the possibility of linkage of LFP oscillations in the brain to the oscillations in the peripheral olfactory system

    KMT-2016-BLG-1107: A New Hollywood-Planet Close/Wide Degeneracy

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    We show that microlensing event KMT-2016-BLG-1107 displays a new type of degeneracy between wide-binary and close-binary Hollywood events in which a giant-star source envelops the planetary caustic. The planetary anomaly takes the form of a smooth, two-day "bump" far out on the falling wing of the light curve, which can be interpreted either as the source completely enveloping a minor-image caustic due to a close companion with mass ratio q=0.036q=0.036, or partially enveloping a major-image caustic due to a wide companion with q=0.004q=0.004. The best estimates of the companion masses are both in the planetary regime (3.31.8+3.5Mjup3.3^{+3.5}_{-1.8}\,M_{\rm jup} and 0.0900.037+0.096Mjup0.090^{+0.096}_{-0.037}\,M_{\rm jup}) but differ by an even larger factor than the mass ratios due to different inferred host masses. We show that the two solutions can be distinguished by high-resolution imaging at first light on next-generation ("30m") telescopes. We provide analytic guidance to understand the conditions under which this new type of degeneracy can appear.Comment: 23 pages, 7 figures, accepted for publication in A

    KMT-2018-BLG-1990Lb: A Nearby Jovian Planet From A Low-Cadence Microlensing Field

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    We report the discovery and characterization of KMT-2018-BLG-1990Lb, a Jovian planet (mp=0.570.25+0.79MJ)(m_p=0.57_{-0.25}^{+0.79}\,M_J) orbiting a late M dwarf (M=0.140.06+0.20M)(M=0.14_{-0.06}^{+0.20}\,M_\odot), at a distance (D_L=1.23_{-0.43}^{+1.06}\,\kpc), and projected at 2.6±0.62.6\pm 0.6 times the snow line distance, i.e., a_{\rm snow}\equiv 2.7\,\au (M/M_\odot), This is the second Jovian planet discovered by KMTNet in its low cadence (0.4hr10.4\,{\rm hr}^{-1}) fields, demonstrating that this population will be well characterized based on survey-only microlensing data.Comment: 24 pages, 7 figures, 4 table

    Left atrial wall thickness and its relationship with reconnection after pulmonary vein isolation in patients with atrial fibrillation evaluated using a three-dimensional wall thickness map

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    Background The major cause of recurrence after pulmonary vein (PV) isolation for atrial fibrillation (AF) is PV reconnection, and thicker wall could be associated with reconnection. Objectives This study aimed to evaluate the wall thickness of the PV antrum in reconnection sites using a three-dimensional (3D) wall thickness map. Methods A total of 91 patients who underwent a second ablation procedure due to AF recurrence were evaluated. The locations of the PV reconnection sites were confirmed in electroanatomical maps. A 3D atrial wall thickness (AWT) map was created using computed tomography scan data. The AWT values of the ablation lines of the index procedure were graded in each segment of the PV antrum: grade 1, 0.5  2.5 mm. Results A total of 281 PV reconnection sites among 1256 segments of the PV antrum in 79 patients were detected. The average AWT grades were 2.7 ± 1.0 and 2.2 ± 1.0 in the reconnected and non-reconnected segments, respectively (P < 0.01). Higher AWT grades were observed in the reconnected superior segments of the left superior PV, carina and inferior segments of the left inferior PV, superior and posterior segments of the right superior PV, and posterior and inferior segments of the right inferior PV. Conclusion The reconnected segments of the PV antrum showed thicker myocardium than the non-reconnected ones in patients with recurrent AF after catheter ablation. A wall thickness map for PV isolation could be considered for customized ablation in order to reduce PV reconnection.The three-dimensional left atrial wall thickness map developed in this research was supported by the Bio & Medical Technology Development Program of the National Research Foundation, which was funded by the Ministry of Science & ICT, Republic of Korea (Grant No. 2015M3A9B6029139)
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