90-kDa ribosomal S6 kinase 1 is inhibited by S-glutathionylation of its active-site cysteine residue during oxidative stress

AbstractPreviously, we reported that p90-RSK1 phosphorylates neuronal nitric oxide synthase (nNOS) at Ser847 in cells treated with mitogens, leading to the inhibition of NOS activity. Here, we show RSK1 Cys223 glutathionylation limits the activity of the enzyme following an oxidative stimulus and attenuates the nNOS phosphorylation. Treatment of RSK1 with diamide/glutathione results in inactivation of the enzyme in vitro. Mutagenesis studies confirmed that S-glutathionylation of Cys223 is both necessary and sufficient for this inhibition of RSK1. In transfected cells expressing RSK1 and nNOS, treatment with diamide caused a decrease in EGF-induced phosphorylation of nNOS at Ser847. Cells expressing mutant RSK1 (C223S) proved resistant in this regard. Thus, RSK1 Cys223 glutathionylation may contribute to regulate the levels of NO in the brain

PLANEJAMENTO TURÍSTICO DO MONUMENTO NATURAL ESTADUAL MORRO DE SANTO ANTÔNIO, NO MUNICÍPIO DE SANTO ANTÔNIO DE LEVERGER-MT

TOURIST PLANNING OF THE STATE NATURAL MONUMENT MORRO DE SANTO ANTÔNIO, IN THE MUNICIPALITY OF SANTO ANTÔNIO DE LEVERGER-MTPLANIFICACIÓN TURÍSTICA DEL MONUMENTO NATURAL MORRO DE SANTO ANTÔNIO, EN EL MUNICIPIO DE SANTO ANTÔNIO DE LEVERGER-MTRESUMOO Monumento Natural Estadual Morro de Santo Antônio de Leverger (MNEMSAL), localizado no município de Santo Antônio de Leverger-MT, faz parte da história do estado e é visitado frequentemente pela população local. Sua história está diretamente ligada ao mito de origem do povo indígena Bororos. Entretanto, é impactado com as atividades realizadas na área, bem como com a falta de investimento e infraestrutura. O presente artigo tem como objetivo apontar as potencialidades e atrativos da área de estudo, com sugestões de diretrizes para o desenvolvimento do turismo local, por meio da análise do espaço geográfico. Assim, identificou-se a necessidade de realizar algumas obras de infraestrutura para que o turismo, que acontece neste patrimônio, não seja nocivo ao ambiente. Portanto, implantar fiscalização no ambiente, controlar o número de visitantes, executar obras de controle de processos erosivos, e de diminuição do impacto de visitação, são algumas das propostas apresentadas neste texto, contribuindo para o fortalecimento do desenvolvimento do turismo como componente e alternativa econômica.Palavras-chave: Turismo; Planejamento; Morro de Santo Antônio.ABSTRACTThe State Natural Monument Morro de Santo Antonio do Leverger (MNEMSAL), located in the municipality of Santo Antônio do Leverger-MT is part of the history of the state and is often visited by local people. Its history is directly linked to the origin myth of Bororos indigenous peoples, however it suffers from the activities in the area as well as the lack of investment and infrastructure. This article aims to evaluate the potential and attractiveness of the study area with guidelines suggestions for the development of local tourism, through the analysis of geographical space. Thus, it identified the need for some infrastructure projects for tourism, which takes place this heritage, is not harmful to the environment, therefore deploy monitoring the environment, control the number of visitors as well as perform erosion control works well as decreased visitation impact are some of the proposals presented in this text. Contributing to the strengthening of tourism development as a component and economical alternative.Keywords: Tourism; Planning; Morro Santo Antônio.RESUMENEl monumento natural estado Morro de Santo Antônio de Leverger (MNEMSAL), localizado en el municipio de Santo Antônio de Leverger – MT, es parte de la historia del estado y es visitado frecuentemente por la población local. Su historia está directamente vinculada al mito del origen del pueblo indígena Bororos. Sin embargo, sufre con las actividades realizadas en el área, con la falta de inversión e infraestructura. El presente artículo tiene como objetivo evaluar el potencial de los atractivos del área de estudio, con sugerencias de directrices para el desarrollo del turismo local, por medio del análisis del espacio geográfico. Así, se identificó la necesidad de realizar algunas obras de infraestructuras para que el turismo, que acontece en este sitio, no sea perjudicial al ambiente. Por lo tanto, desarrollar estudios de impacto ambiental, controlar el número de visitantes, bien como ejecutar obras de control de procesos erosivos, así como de disminución del impacto de visitas, son algunas de las propuestas presentadas en este texto, contribuyendo al fortalecimiento del desarrollo del turismo como alternativa económica.Palabras clave: Turismo; Planificación; Morro de Santo Antônio

RUNX3 Has an Oncogenic Role in Head and Neck Cancer

Background: Runt-related transcription factor 3 (RUNX3) is a tumor suppressor of cancer and appears to be an important component of the transforming growth factor-beta (TGF-ß)-induced tumor suppression pathway. Surprisingly, we found that RUNX3 expression level in head and neck squamous cell carcinoma (HNSCC) tissues, which is one of the most common types of human cancer, was higher than that in normal tissues by a previously published microarray dataset in our preliminary study. Therefore, here we examined the oncogenic role of RUNX3 in HNSCC. Principal Findings: Frequent RUNX3 expression and its correlation with malignant behavior were observed in HNSCC. Ectopic RUNX3 overexpression promoted cell growth and inhibited serum starvation-induced apoptosis and chemotherapeutic drug induced apoptosis in HNSCC cells. These findings were confirmed by RUNX3 knockdown. Moreover, RUNX3 overexpression enhanced tumorsphere formation. RUNX3 expression level was well correlated with the methylation status in HNSCC cells. Moreover, RUNX3 expression was low due to the methylation of its promoter in normal oral epithelial cells. Conclusions/Significance: Our findings suggest that i) RUNX3 has an oncogenic role in HNSCC, ii) RUNX3 expression observed in HNSCC may be caused in part by demethylation during cancer development, and iii) RUNX3 expression can b

MRI of Early-Stage Lumbar Spondylolysis

Purpose : To analyze extraosseous signal changes (ESCs) on magnetic resonance imaging (MRI) in pediatric patients with stress fractures occurring in the lamina. Methods : This study was a retrospective review of 69 consecutive pediatric patients with stress fractures occurring in the lamina. We analyzed MRI scans obtained at the first presentation. Results : We used mainly axial short tau inversion recovery images acquired through the pedicle of these 84 fracture sites to identify the ESCs. These were then divided into three groups: “invisible” when no ESC was detected, “periosteal” for ESC seen on only the dorsal side of the lamina, and “perimuscular” for ESC distinctly spread around / in the paravertebral muscles. In total, 78 (92.9%) fracture sites showed ESCs on the dorsal side of the lamina among which 72 ESCs were located on only the “dorsal” side, while 6 ESCs were on the ventral side against the transverse process. Conclusion : ESCs on MRI were detected in more than 90% of patients before stress fracture became apparent in the lamina, which was considered similar to findings of periosteal thickening / edema detected at the onset of stress fracture in long bone

RUNX3 Has an Oncogenic Role

Background: Runt-related transcription factor 3 (RUNX3) is a tumor suppressor of cancer and appears to be an important component of the transforming growth factor-beta (TGF-ß)-induced tumor suppression pathway. Surprisingly, we found that RUNX3 expression level in head and neck squamous cell carcinoma (HNSCC) tissues, which is one of the most common types of human cancer, was higher than that in normal tissues by a previously published microarray dataset in our preliminary study. Therefore, here we examined the oncogenic role of RUNX3 in HNSCC. Principal Findings: Frequent RUNX3 expression and its correlation with malignant behavior were observed in HNSCC. Ectopic RUNX3 overexpression promoted cell growth and inhibited serum starvation-induced apoptosis and chemotherapeutic drug induced apoptosis in HNSCC cells. These findings were confirmed by RUNX3 knockdown. Moreover, RUNX3 overexpression enhanced tumorsphere formation. RUNX3 expression level was well correlated with the methylation status in HNSCC cells. Moreover, RUNX3 expression was low due to the methylation of its promoter in normal oral epithelial cells. Conclusions/Significance: Our findings suggest that i) RUNX3 has an oncogenic role in HNSCC, ii) RUNX3 expression observed in HNSCC may be caused in part by demethylation during cancer development, and iii) RUNX3 expression can be a useful marker for predicting malignant behavior and the effect of chemotherapeutic drugs in HNSCC

Effect of Cetuximab and EGFR Small Interfering RNA Combination Treatment in NSCLC Cell Lines with Wild Type EGFR and Use of KRAS as a Possible Biomarker for Treatment Responsiveness

[Background] The epidermal growth factor receptor (EGFR) is a therapeutic target for patients with non-small cell lung cancer (NSCLC). Cetuximab is an anti-EGFR monoclonal antibody that inhibits EGFR signaling and proliferation of colorectal cancer and head and neck cancers. Since only few NSCLC patients benefit from cetuximab therapy, we evaluated a novel combination treatment using cetuximab and EGFR small interfering RNA (siRNA) to strongly suppress EGFR signaling and searched for a biomarker in NSCLC cell lines harboring wild-type EGFR. [Methods] Alterations in EGFR and its downstream genes in five NSCLC cell lines (A549, Lu99, 86-2, Sq19 and Ma10) were assessed through sequencing. The protein expression levels of these molecules were assessed through western blotting. The effect of combination treatment was determined through cell proliferation assay, caspase-3/7 assay, invasion assay, and migration assay. [Results] All cell lines were harboring wild-type EGFR, whereas KRAS, PTEN, TP53 and TP53 were mutated in A549 and Lu99; Lu99 and Sq19; Lu99, 86-2, Sq19 and Ma10; and A549, 86-2, and Sq19 cell lines, respectively. PTEN was not expressed in Sq19, and LKB1 was not expressed in both A549 and Sq19. TP53 was not expressed in both A549 and Lu99. The combination of cetuximab and EGFR siRNA significantly suppressed cell proliferation in 86-2, Sq19 and Ma10, which express wild-type KRAS. It induced apoptosis in A549, 86-2 and Ma10 cells, which express wild type PTEN. The combination treatment had no effect either on cell invasion nor migration in all cell lines. [Conclusion] EGFR targeted therapy using the combination of cetuximab and EGFR siRNA is effective in NSCLC cell lines harboring wild-type EGFR. Wild-type KRAS may act as a potential biomarker for response to combination treatment by the induction of apoptosis in cells with wild-type PTEN

Brain pericytes among cells constituting the blood-brain barrier are highly sensitive to tumor necrosis factor-α, releasing matrix metalloproteinase-9 and migrating in vitro

<p>Abstract</p> <p>Background</p> <p>Increased matrix metalloproteinase (MMP)-9 in the plasma and brain is associated with blood-brain barrier (BBB) disruption through proteolytic activity in neuroinflammatory diseases. MMP-9 is present in the brain microvasculature and its vicinity, where brain microvascular endothelial cells (BMECs), pericytes and astrocytes constitute the BBB. Little is known about the cellular source and role of MMP-9 at the BBB. Here, we examined the ability of pericytes to release MMP-9 and migrate in response to inflammatory mediators in comparison with BMECs and astrocytes, using primary cultures isolated from rat brains.</p> <p>Methods</p> <p>The culture supernatants were collected from primary cultures of rat brain endothelial cells, pericytes, or astrocytes. MMP-9 activities and levels in the supernatants were measured by gelatin zymography and western blot, respectively. The involvement of signaling molecules including mitogen-activated protein kinases (MAPKs) and phosphoinositide-3-kinase (PI3K)/Akt in the mediation of tumor necrosis factor (TNF)-α-induced MMP-9 release was examined using specific inhibitors. The functional activity of MMP-9 was evaluated by a cell migration assay.</p> <p>Results</p> <p>Zymographic and western blot analyses demonstrated that TNF-α stimulated pericytes to release MMP-9, and this release was much higher than from BMECs or astrocytes. Other inflammatory mediators [interleukin (IL)-1β, interferon-γ, IL-6 and lipopolysaccharide] failed to induce MMP-9 release from pericytes. TNF-α-induced MMP-9 release from pericytes was found to be mediated by MAPKs and PI3K. Scratch wound healing assay showed that in contrast to BMECs and astrocytes the extent of pericyte migration was significantly increased by TNF-α. This pericyte migration was inhibited by anti-MMP-9 antibody.</p> <p>Conclusion</p> <p>These findings suggest that pericytes are most sensitive to TNF-α in terms of MMP-9 release, and are the major source of MMP-9 at the BBB. This pericyte-derived MMP-9 initiated cellular migration of pericytes, which might be involved in pericyte loss in the damaged BBB.</p

An Al-doped SrTiO3 photocatalyst maintaining sunlight-driven overall water splitting activity for over 1000 h of constant illumination

Photocatalytic water splitting is a viable approach to the large-scale production of renewable solar hydrogen. The apparent quantum yield for this reaction has been improved, but the lifespan of photocatalysts functioning under sunlight at ambient pressure have rarely been examined, despite the critical importance of this factor in practical applications. Herein, we show that Al-doped SrTiO3 (SrTiO3: Al) loaded with a RhCrOx (rhodium chromium oxide) cocatalyst splits water with an apparent quantum yield greater than 50% at 365 nm. Moreover, following the photodeposition of CoOOH and TiO2, this material maintains 80% of its initial activity and a solar-to-hydrogen energy conversion efficiency greater than or equal to 0.3% over a span of 1300 h under constant illumination by simulated sunlight at ambient pressure. This result is attributed to reduced dissolution of Cr in the cocatalyst following the oxidative photodeposition of CoOOH. The photodeposition of TiO2 further improves the durability of this photocatalyst. This work demonstrates a concept that could allow the design of longterm, large-scale photocatalyst systems for practical sunlight-driven water splitting.ArticleCHEMICAL SCIENCE.10(11):3196-3201(2019)journal articl

Orthosis stability and patient satisfaction

Purpose : To evaluate the stabilizing effects of a Fit Cure-Spine® semi-rigid thoracolumbar orthosis and wearer satisfaction after lumbar surgery. Methods : In study 1, the spinal angle, spinal motion angle, and distribution of load were measured in 8 adult male volunteers when the orthosis was worn (1) with no custom-made stay (CMS), (2) with a CMS in the prone position (P-CMS), and (3) with a CMS in the prone position and decreased lordosis (DP-CMS). In study 2, pain scale scores and responses to a questionnaire were recorded in 40 consecutive patients who underwent lumbar spinal surgery in our hospital. Results : In study 1, the mean lumbar lordosis when standing was similar to that in the prone position. When the trunk was bent forward, loads on the back support in P-CMS and DP-CMS were concentrated at the center of the CMS, unlike those for No-CMS. In study 2, there was a significant decrease in postoperative wound pain after wearing the Fit Cure-Spine orthosis for 2 weeks. Most patients who wore the orthosis were satisfied with their pain outcome. Conclusion : Adjustment to lumbar lordosis and the prone position was restricted in volunteers wearing the Fit Cure-Spine with a CMS

Hyper-luminous Dust Obscured Galaxies discovered by the Hyper Suprime-Cam on Subaru and WISE

We present the photometric properties of a sample of infrared (IR) bright dust obscured galaxies (DOGs). Combining wide and deep optical images obtained with the Hyper Suprime-Cam (HSC) on the Subaru Telescope and all-sky mid-IR (MIR) images taken with Wide-Field Infrared Survey Explorer (WISE), we discovered 48 DOGs with $i - K_\mathrm{s} > 1.2$ and $i - [22] > 7.0$, where $i$, $K_\mathrm{s}$, and [22] represent AB magnitude in the $i$-band, $K_\mathrm{s}$-band, and 22 $\mu$m, respectively, in the GAMA 14hr field ($\sim$ 9 deg$^2$). Among these objects, 31 ($\sim$ 65 %) show power-law spectral energy distributions (SEDs) in the near-IR (NIR) and MIR regime, while the remainder show a NIR bump in their SEDs. Assuming that the redshift distribution for our DOGs sample is Gaussian, with mean and sigma $z$ = 1.99 $\pm$ 0.45, we calculated their total IR luminosity using an empirical relation between 22 $\mu$m luminosity and total IR luminosity. The average value of the total IR luminosity is (3.5 $\pm$ 1.1) $\times$ $10^{13}$ L$_{\odot}$, which classifies them as hyper-luminous infrared galaxies (HyLIRGs). We also derived the total IR luminosity function (LF) and IR luminosity density (LD) for a flux-limited subsample of 18 DOGs with 22 $\mu$m flux greater than 3.0 mJy and with $i$-band magnitude brighter than 24 AB magnitude. The derived space density for this subsample is log $\phi$ = -6.59 $\pm$ 0.11 [Mpc$^{-3}$]. The IR LF for DOGs including data obtained from the literature is well fitted by a double-power law. The derived lower limit for the IR LD for our sample is $\rho_{\mathrm{IR}}$ $\sim$ 3.8 $\times$ 10$^7$ [L$_{\odot}$ Mpc$^{-3}$] and its contributions to the total IR LD, IR LD of all ultra-luminous infrared galaxies (ULIRGs), and that of all DOGs are $>$ 3 %, $>$ 9 %, and $>$ 15 %, respectively.Comment: 15 pages, 15 figures, and 3 tables, accepted for publication in PASJ (Subaru special issue