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Showing papers by "Kagawa University published in 2015"


Journal ArticleDOI
TL;DR: Current knowledge of the possible mechanisms associated with H2O2-induced abiotic oxidative stress tolerance in plants is reviewed, with special reference to antioxidant metabolism.
Abstract: Plants are constantly challenged by various abiotic stresses that negatively affect growth and productivity worldwide. During the course of their evolution, plants have developed sophisticated mechanisms to recognize external signals allowing them to respond appropriately to environmental conditions, although the degree of adjustability or tolerance to specific stresses differs from species to species. Overproduction of reactive oxygen species (ROS) (hydrogen peroxide, H2O2; superoxide, O2ˉ˙; hydroxyl radical, OH. and singlet oxygen, 1O2) is enhanced under abiotic and/or biotic stresses, which can cause oxidative damage to plant macromolecules and cell structures, leading to inhibition of plant growth and development, or to death. Among the various ROS, freely diffusible and relatively long-lived H2O2 acts as a central player in stress signal transduction pathways. These pathways can then activate multiple acclamatory responses that reinforce resistance to various abiotic and biotic stressors. To utilize H2O2 as a signaling molecule, non-toxic levels must be maintained in a delicate balancing act between H2O2 production and scavenging. Several recent studies have demonstrated that the H2O2-priming can enhance abiotic stress tolerance by modulating ROS detoxification and by regulating multiple stress-responsive pathways and gene expression. Despite the importance of the H2O2-priming, little is known about how this process improves the tolerance of plants to stress. Understanding the mechanisms of H2O2-priming-induced abiotic stress tolerance will be valuable for identifying biotechnological strategies to improve abiotic stress tolerance in crop plants. This review is an overview of our current knowledge of the possible mechanisms associated with H2O2-induced abiotic oxidative stress tolerance in plants, with special reference to antioxidant metabolism.

553 citations


Journal ArticleDOI
TL;DR: An overview of abiotic stresses, ROS, and their metabolism is overviewed, and SODs and their types, significance, and appraises abiotic stress-mediated modulation in plants are introduced and major aspects so far least studied are highlighted.
Abstract: Abiotic stresses impact growth, development, and productivity, and significantly limit the global agricultural productivity mainly by impairing cellular physiology/biochemistry via elevating reactive oxygen species (ROS) generation. If not metabolized, ROS (such as O2 •−, OH•, H2O2, or 1O2) exceeds the status of antioxidants and cause damage to DNA, proteins, lipids, and other macromolecules, and finally cellular metabolism arrest. Plants are endowed with a family of enzymes called superoxide dismutases (SODs) that protects cells against potential consequences caused by cytotoxic O2 •− by catalyzing its conversion to O2 and H2O2. Hence, SODs constitute the first line of defense against abiotic stress-accrued enhanced ROS and its reaction products. In the light of recent reports, the present effort: (a) overviews abiotic stresses, ROS, and their metabolism; (b) introduces and discusses SODs and their types, significance, and appraises abiotic stress-mediated modulation in plants; (c) analyzes major reports available on genetic engineering of SODs in plants; and finally, (d) highlights major aspects so far least studied in the current context. Literature appraised herein reflects clear information paucity in context with the molecular/genetic insights into the major functions (and underlying mechanisms) performed by SODs, and also with the regulation of SODs by post-translational modifications. If the previous aspects are considered in the future works, the outcome can be significant in sustainably improving plant abiotic stress tolerance and efficiently managing agricultural challenges under changing climatic conditions.

224 citations


Journal ArticleDOI
TL;DR: H2S is proposed as a potential candidate for managing toxicity of cadmium, and perhaps other heavy metals, in rice and other crops by providing an insight into H2S-induced protective mechanisms of rice exposed to Cadmium stress.
Abstract: We investigated the physiological and biochemical mechanisms by which H2S mitigates the cadmium stress in rice. Results revealed that cadmium exposure resulted in growth inhibition and biomass reduction, which is correlated with the increased uptake of cadmium and depletion of the photosynthetic pigments, leaf water contents, essential minerals, water-soluble proteins, and enzymatic and non-enzymatic antioxidants. Excessive cadmium also potentiated its toxicity by inducing oxidative stress, as evidenced by increased levels of superoxide, hydrogen peroxide, methylglyoxal and malondialdehyde. However, elevating endogenous H2S level improved physiological and biochemical attributes, which was clearly observed in the growth and phenotypes of H2S-treated rice plants under cadmium stress. H2S reduced cadmium-induced oxidative stress, particularly by enhancing redox status and the activities of reactive oxygen species and methylglyoxal detoxifying enzymes. Notably, H2S maintained cadmium and mineral homeostases in roots and leaves of cadmium-stressed plants. By contrast, adding H2S-scavenger hypotaurine abolished the beneficial effect of H2S, further strengthening the clear role of H2S in alleviating cadmium toxicity in rice. Collectively, our findings provide an insight into H2S-induced protective mechanisms of rice exposed to cadmium stress, thus proposing H2S as a potential candidate for managing toxicity of cadmium, and perhaps other heavy metals, in rice and other crops.

210 citations


Journal ArticleDOI
TL;DR: In this paper, the role of exogenous glutathione (GSH) in conferring high temperature stress (HT, 42°C) tolerance in mung bean (Vigna radiata L. cv. Binamoog-1) seedlings was investigated.

188 citations


Journal ArticleDOI
TL;DR: It is shown that modulation of the level of endogenous H2S genetically or exogenously could be employed to attain better growth and development of rice, and perhaps other crops, under salt stress, and reveals the importance of the implication of gasotransmitters like H1N2 for the management of salt stress.
Abstract: Being a salt sensitive crop, rice growth and development are frequently affected by soil salinity. Hydrogen sulfide (H2S) has been recently explored as an important priming agent regulating diverse physiological processes of plant growth and development. Despite its enormous prospects in plant systems, the role of H2S in plant stress tolerance is still elusive. Here, a combined pharmacological, physiological and biochemical approach was executed aiming to examine the possible mechanism of H2S in enhancement of salt stress tolerance in rice. We show that pretreating rice plants with H2S donor sodium bisulfide (NaHS) clearly improved, but application of H2S scavenger hypotaurine with NaHS decreased growth and biomass-related parameters under salt stress. NaHS-pretreated salt-stressed plants exhibited increased chlorophyll, carotenoid and soluble protein contents, as well as suppressed accumulation of reactive oxygen species (ROS), contributing to oxidative damage protection. The protective mechanism of H2S against oxidative stress was correlated with the elevated levels of ascorbic acid, glutathione, redox states, and the enhanced activities of ROS- and methylglyoxal-detoxifying enzymes. Notably, decreased uptake of Na+, decreased Na+/K+ ratio and balanced mineral contents indicated a role of H2S in ion homeostasis under salt stress. Altogether, our results highlight that modulation of the level of endogenous H2S genetically or exogenously could be employed to attain better growth and development of rice, and perhaps other crops, under salt stress. Furthermore, our study reveals the importance of the implication of gasotransmitter like H2S for the management of salt stress, thus assisting rice plants to adapt to adverse environmental changes.

171 citations


Journal ArticleDOI
TL;DR: Interactions between NPC-Exo and Treg represent a newly defined mechanism that may be involved in regulating peripheral tolerance by tumors and in supporting immune evasion in human NPC.
Abstract: BACKGROUND Regulatory T cells (Treg) and tumor-exosomes are thought to play a role in preventing the rejection of malignant cells in patients bearing nasopharyngeal carcinoma (NPC) METHODS Treg recruitment by exosomes derived from NPC cell lines (C15/C17-Exo), exosomes isolated from NPC patients' plasma (Patient-Exo), and CCL20 were tested in vitro using Boyden chamber assays and in vivo using a xenograft SCID mouse model (n = 5), both in the presence and absence of anti-CCL20 monoclonal antibodies (mAb) Impact of these NPC exosomes (NPC-Exo) on Treg phenotype and function was determined using adapted assays (FACS, Q-PCR, ELISA, and MLR) Experiments were performed in comparison with exosomes derived from plasma of healthy donors (HD-Exo) The Student's t test was used for group comparisons All statistical tests were two-sided RESULTS CCL20 allowed the intratumoral recruitment of human Treg NPC-Exo also facilitated Treg recruitment (330 ± 034 fold increase, P < 001), which was statistically significantly inhibited (P < 001) by an anti-CCL20 blocking mAb NPC-Exo also recruited conventional CD4(+)CD25(-) T cells and mediated their conversion into inhibitory CD4(+)CD25(high) cells Moreover, NPC-Exo enhanced (P = 0048) the expansion of human Treg, inducing the generation of Tim3(Low) Treg with increased expression of CD25 and FOXP3 Finally, NPC-Exo induced an overexpression of cell markers associated with Treg phenotype, properties and recruitment capacity For example, GZMB mean fold change was 2145 ± 175 (P < 001) These results were consistent with a stronger suppression of responder cells' proliferation and the secretion of immunosuppressive cytokines (IL10, TGFB1) CONCLUSION Interactions between NPC-Exo and Treg represent a newly defined mechanism that may be involved in regulating peripheral tolerance by tumors and in supporting immune evasion in human NPC

162 citations


Journal ArticleDOI
TL;DR: An appraisal of recent reports on both thiol and non-thiol compounds is presented in an effort to shed light on the significance of these compounds in plant-metal tolerance, as well as to provide scientific clues for the advancement of metal-phytoextraction strategies.
Abstract: Varied environmental compartments including soils are being contaminated by a myriad toxic metal(loid)s (hereafter termed as ‘metal/s’) mainly through anthropogenic activities. These metals may contaminate food chain and bring irreparable consequences in human. Plant-based approach (phytoremediation) stands second to none among bioremediation technologies meant for sustainable cleanup of soils/sites with metal-contamination. In turn, the capacity of plants to tolerate potential consequences caused by the extracted/accumulated metals decides the effectiveness and success of phytoremediation system. Chelation is among the potential mechanisms that largely govern metal-tolerance in plant cells by maintaining low concentrations of free metals in cytoplasm. Metal-chelation can be performed by compounds of glutathione (GSH) (reduced GSH; phytochelatins, PCs; metallothioneins, MTs) and non-GSH (histidine, nicotianamine, organic acids) origin. This paper presents an appraisal of recent reports on both GSH and non-GSH associated compounds in an effort to shed light on the significance of these compounds in metal-plant tolerance, as well as to provide scientific clues for the development of phytoextraction strategies.

153 citations


Journal ArticleDOI
TL;DR: The adoption of the space dimension is identified as a promising solution for the capacity expansion of future networks, while novel spatial-spectral switching solutions show that the flexible networking concept can be further expanded over both the spatial and spectral dimensions.
Abstract: The advent of spectrally flexible (a.k.a. elastic) optical networking is widely identified as the next generation optical network solution that permits varying bandwidth demands to be dynamically assigned over flexible spectral containers, targeting optimum use of the available network resources. Additionally, the adoption of the space dimension is identified as a promising solution for the capacity expansion of future networks, while novel spatial-spectral switching solutions show that the flexible networking concept can be further expanded over both the spatial and spectral dimensions. This article provides an overview of the latest developments and possible approaches with respect to flexible optical networking and the emerging benefits that spatially flexible networking approaches can offer. The focus is on the network planning and resource optimization functions, the main network operations related to fragmentation and IP/optical layer integration, and the control plane solutions.

149 citations


Journal ArticleDOI
TL;DR: Exogenous GSH enhanced components of the antioxidant system in drought-affected mung bean seedlings, which alleviated oxidative damage, up-regulated the glyoxalase system, reduced MG toxicity, and modulated the proline and water content, contributing to drought tolerance.
Abstract: Drought is considered one of the most acute environmental stresses presently affecting agriculture. We studied the role of exogenous glutathione (GSH) in conferring drought stress tolerance in mung bean (Vigna radiata L. cv. Binamoog-1) seedlings by examining the antioxidant defence and methylglyoxal (MG) detoxification systems and physiological features. Six-day-old seedlings were exposed to drought stress (-0.7 MPa), induced by polyethylene glycol alone and in combination with GSH (1 mM) for 24 and 48 h. Drought stress decreased seedling dry weight and leaf area; resulted in oxidative stress as evidenced by histochemical detection of hydrogen peroxide (H2O2) and [Formula: see text] in the leaves; increased lipid peroxidation (malondialdehyde), reactive oxygen species like H2O2 content and [Formula: see text] generation rate and lipoxygenase activity; and increased the MG level. Drought decreased leaf succulence, leaf chlorophyll and relative water content (RWC); increased proline (Pro); decreased ascorbate (AsA); increased endogenous GSH and glutathione disulfide (GSSG) content; decreased the GSH/GSSG ratio; increased ascorbate peroxidase and glutathione S-transferase activities; and decreased the activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and catalase. The activities of glyoxalase I (Gly I) and glyoxalase II (Gly II) increased due to drought stress. In contrast to drought stress alone, exogenous GSH enhanced most of the components of the antioxidant and glyoxalase systems in drought-affected mung bean seedlings at 24 h, but GSH did not significantly affect AsA, Pro, RWC, leaf succulence and the activities of Gly I and DHAR after 48 h of stress. Thus, exogenous GSH supplementation with drought significantly enhanced the antioxidant components and successively reduced oxidative damage, and GSH up-regulated the glyoxalase system and reduced MG toxicity, which played a significant role in improving the physiological features and drought tolerance.

142 citations


Journal ArticleDOI
TL;DR: The 3rd English edition of the Japanese classification of biliary tract cancers was released approximately 10 years after the 5th Japanese edition and the 2nd English edition, and principally adopted the 7th edition of staging system developed by the International Union Against Cancer and the American Joint Committee on Cancer.
Abstract: The 3(rd) English edition of the Japanese classification of biliary tract cancers was released approximately 10 years after the 5(th) Japanese edition and the 2(nd) English edition. Since the first Japanese edition was published in 1981, the Japanese classification has been in extensive use, particularly among Japanese surgeons and pathologists, because the cancer status and clinical outcomes in surgically resected cases have been the main objects of interest. However, recent advances in the diagnosis, management and research of the disease prompted the revision of the classification that can be used by not only surgeons and pathologists but also by all clinicians and researchers, for the evaluation of current disease status, the determination of current appropriate treatment, and the future development of medical practice for biliary tract cancers. Furthermore, during the past 10 years, globalization has advanced rapidly, and therefore, internationalization of the classification was an important issue to revise the Japanese original staging system, which would facilitate to compare the disease information among institutions worldwide. In order to achieve these objectives, the new Japanese classification of the biliary tract cancers principally adopted the 7(th) edition of staging system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). However, because there are some points pending in these systems, several distinctive points were also included for the purpose of collection of information for the future optimization of the staging system. Free mobile application of the new Japanese classification of the biliary tract cancers is available via http://www.jshbps.jp/en/classification/cbt15.html.

142 citations


Journal ArticleDOI
TL;DR: Modifying the endogenous Tre content by Tre pretreatment improved Cu tolerance in rice plants by inhibiting Cu uptake and regulating the antioxidant and glyoxalase systems, and thereby demonstrated the important role of Tre in mitigating heavy metal toxicity.
Abstract: In this study, we examined the possible mechanisms of trehalose (Tre) in improving copper-stress (Cu-stress) tolerance in rice seedlings. Our findings indicated that pretreatment of rice seedlings with Tre enhanced the endogenous Tre level and significantly mitigated the toxic effects of excessive Cu on photosynthesis- and plant growth-related parameters. The improved tolerance induced by Tre could be attributed to its ability to reduce Cu uptake and decrease Cu-induced oxidative damage by lowering the accumulation of reactive oxygen species (ROS) and malondialdehyde in Cu-stressed plants. Tre counteracted the Cu-induced increase in proline and glutathione content, but significantly improved ascorbic acid content and redox status. The activities of major antioxidant enzymes were largely stimulated by Tre pretreatment in rice plants exposed to excessive Cu. Additionally, increased activities of glyoxalases I and II correlated with reduced levels of methylglyoxal in Tre-pretreated Cu-stressed rice plants. These results indicate that modifying the endogenous Tre content by Tre pretreatment improved Cu tolerance in rice plants by inhibiting Cu uptake and regulating the antioxidant and glyoxalase systems, and thereby demonstrated the important role of Tre in mitigating heavy metal toxicity. Our findings provide a solid foundation for developing metal toxicity-tolerant crops by genetic engineering of Tre biosynthesis.

Journal ArticleDOI
TL;DR: Results implicate that the etiologies of the two conditions must be different, and it will be necessary to distinguish these two conditions in future studies.
Abstract: Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV) As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD This is because its characteristics have yet to be well described To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD Pachychoroid neovasculopathy was observed in 39 individuals (195%), which corresponds to one fourth of neovascular AMD Patients with pachychoroid neovasculopathy were significantly younger (p = 51 × 10(-5)) and showed a greater subfoveal choroidal thickness (p = 34 × 10(-14)) Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0029), CFH rs800292 (p = 0013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 38 × 10(-3)) Current results implicate that the etiologies of the two conditions must be different Thus, it will be necessary to distinguish these two conditions in future studies

Journal ArticleDOI
TL;DR: Primary data on markers, genetic factors, and risk stratification for patient selection and predictors of progression during active surveillance are reviewed to review a growing body of literature on patient characteristics, biopsy features, and biomarkers with potential utility in AS.

Journal ArticleDOI
TL;DR: The anti-hyperlipidemic effect of D-allulose, combined with its anti-inflammatory actions on adipocytes, is beneficial for the prevention of both obesity and atherosclerosis and is accompanied by improvements in insulin resistance and impaired glucose tolerance.

Journal ArticleDOI
TL;DR: Compliance with an active surveillance protocol for low-risk prostate cancer in a large active surveillance study was looked at and reluctance to undergo yearly biopsies because of fast rising prostate-specific antigen was observed, despite a higher risk of disease progression.

Journal ArticleDOI
TL;DR: A role for Tre is suggested in protecting against salt-induced oxidative damage attributed to reduced ROS accumulation, elevation of non-enzymatic antioxidants, and co-activation of the antioxidative and glyoxalase systems.
Abstract: Salinity in the form of abiotic stress adversely effects plant growth, development, and productivity. Various osmoprotectants are involved in regulating plant responses to salinity; however, the precise role of trehalose (Tre) in this process remains to be further elucidated. The present study investigated the regulatory role of Tre in alleviating salt-induced oxidative stress in hydroponically grown rice seedlings. Salt stress (150 and 250 mM NaCl) for 72 h resulted in toxicity symptoms such as stunted growth, severe yellowing, and leaf rolling, particularly at 250 mM NaCl. Histochemical observation of reactive oxygen species (ROS; O2 (∙-) and H2O2) indicated evident oxidative stress in salt-stressed seedlings. In these seedlings, the levels of lipoxygenase (LOX) activity, malondialdehyde (MDA), H2O2, and proline (Pro) increased significantly whereas total chlorophyll (Chl) and relative water content (RWC) decreased. Salt stress caused an imbalance in non-enzymatic antioxidants, i.e., ascorbic acid (AsA) content, AsA/DHA ratio, and GSH/GSSG ratio decreased but glutathione (GSH) content increased significantly. In contrast, Tre pretreatment (10 mM, 48 h) significantly addressed salt-induced toxicity symptoms and dramatically depressed LOX activity, ROS, MDA, and Pro accumulation whereas AsA, GSH, RWC, Chl contents, and redox status improved considerably. Salt stress stimulated the activities of SOD, GPX, APX, MDHAR, DHAR, and GR but decreased the activities of CAT and GST. However, Tre-pretreated salt-stressed seedlings counteracted SOD and MDHAR activities, elevated CAT and GST activities, further enhanced APX and DHAR activities, and maintained GPX and GR activities similar to the seedlings stressed with salt alone. In addition, Tre pretreatment enhanced the activities of methylglyoxal detoxifying enzymes (Gly I and Gly II) more efficiently in salt-stressed seedlings. Our results suggest a role for Tre in protecting against salt-induced oxidative damage attributed to reduced ROS accumulation, elevation of non-enzymatic antioxidants, and co-activation of the antioxidative and glyoxalase systems.

Journal ArticleDOI
TL;DR: The Japanese Association for Thoracic Surgery has conducted annual surveys of thoracic surgery throughout Japan since 1986 to determine the statistics regarding the number of procedures according to operative category, and was able to gain a better understanding of present problems as well as future prospects.
Abstract: The Japanese Association for Thoracic Surgery has conducted annual surveys of thoracic surgery throughout Japan since 1986 to determine the statistics regarding the number of procedures according to operative category. Here, we have summarized the results from our annual survey of thoracic surgery performed during 2013. The incidence of hospital mortality was added to the survey to determine the nationwide status, which has contributed to the Japanese surgeons to understand the present status of thoracic surgery in Japan and to make progress to improve operative results by comparing their work with those of others. The Association was able to gain a better understanding of present problems as well as future prospects, which has been reflected to its activity including education of its members. Thirty-day mortality (so called “operative mortality”) is defined as death within 30 days of operation regardless of the patient’s geographic location and even though the patient had been discharged from the hospital. Hospital mortality is defined as death within any time interval after an operation if the patient had not been discharged from the hospital. Hospital-to-hospital transfer is not considered discharge: transfer to a nursing home or a rehabilitation unit is considered hospital discharge unless the patient subsequently dies of complications of the operation. (The definitions of the Ad Hoc Liaison Committee for Standardizing Definitions of Prosthetic Heart Valve Morbidity of the Society of Thoracic Surgeons and the American Association for Thoracic Surgery (Edmunds et al. Ann Thorac Surg 1996;62:932–5; J Thorac Cardiovasc Surg 1996;112:708–11). Thoracic surgery was classified into three categories—cardiovascular, general thoracic, and esophageal surgery—and the patient data were examined and analyzed for each group. Access to the computerized data is offered to all members of this Association. We honor and value all member’s continued kind support and contributions (Tables 1, ​,22). Table 1 Questionnaires sent out and received back by the end of December 2014 Table 2 Categories subclassified according to the number of operations performed

Journal ArticleDOI
TL;DR: New possibilities that may be useful as diagnostic and prognostic markers, as well as novel therapeutic targets in HCC are elucidated.

Journal ArticleDOI
TL;DR: In this paper, the protection role of glutathione (GSH) applied on salt stress-affected mung bean (Vigna radiata L.) seedlings was studied.
Abstract: The protective roles of glutathione (GSH) applied on salt stress-affected mung bean (Vigna radiata L.) seedlings were studied. The salt stress (200 mM NaCl) significantly increased the malondialdehyde (MDA), methylglyoxal (MG), H2O2, and proline (Pro) content, O2 ·− generation rate, and lipoxygenase (LOX) activity and reduced the leaf relative water content (RWC) and chlorophyll (Chl) content. The salt stress also significantly reduced the ascorbate (AsA) content, increased the endogenous GSH and glutathione disulfide (GSSG) content, and reduced the GSH/GSSG ratio. The activities of mono-dehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and catalase (CAT) decreased; and the activities of ascorbate peroxidase (APX), glutathione reductase (GR), superoxide dismutase (SOD), glutathione S-transferase (GST), and glutathione peroxidase (GPX) increased under the salt stress. The activities of glyoxalase I (Gly I) and glyoxalase II (Gly II) decreased under the salt stress (except the Gly II activity at 48 h). Mung bean seedlings which were treated with NaCl together with GSH showed an improved AsA and GSH content, GSH/GSSG ratio, higher activities of APX (only at 24 h), MDHAR, DHAR, GR, SOD (only at 24 h), CAT, GPX (only at 48 h), GST (only at 24 h), Gly I and Gly II under the salt stress compared with those treated with NaCl alone. The improved antioxidant and glyoxalase systems by GSH application decreased the MDA, H2O2, and MG content, O2 ·− generation rate, as well as increased the leaf RWC and Chl content. Thus, exogenous GSH improved the response of the mung bean seedlings to the salt stress.

Journal ArticleDOI
TL;DR: A new neurotoxic mechanism that involves the interaction between patient-derived Aβ assemblies, termed amylospheroids, and the neuron-specific Na+/K+-ATPase α3 subunit (NAKα3) is revealed, which causes neurodegeneration through pre-synaptic calcium overload, which explains earlier observations that such neuronal hyperactivation is an early indicator of AD-related neurodegenersation.
Abstract: Neurodegeneration correlates with Alzheimer’s disease (AD) symptoms, but the molecular identities of pathogenic amyloid β-protein (Aβ) oligomers and their targets, leading to neurodegeneration, remain unclear. Amylospheroids (ASPD) are AD patient-derived 10- to 15-nm spherical Aβ oligomers that cause selective degeneration of mature neurons. Here, we show that the ASPD target is neuron-specific Na+/K+-ATPase α3 subunit (NAKα3). ASPD-binding to NAKα3 impaired NAKα3-specific activity, activated N-type voltage-gated calcium channels, and caused mitochondrial calcium dyshomeostasis, tau abnormalities, and neurodegeneration. NMR and molecular modeling studies suggested that spherical ASPD contain N-terminal-Aβ–derived “thorns” responsible for target binding, which are distinct from low molecular-weight oligomers and dodecamers. The fourth extracellular loop (Ex4) region of NAKα3 encompassing Asn879 and Trp880 is essential for ASPD–NAKα3 interaction, because tetrapeptides mimicking this Ex4 region bound to the ASPD surface and blocked ASPD neurotoxicity. Our findings open up new possibilities for knowledge-based design of peptidomimetics that inhibit neurodegeneration in AD by blocking aberrant ASPD–NAKα3 interaction.

Journal ArticleDOI
TL;DR: Both initial and deferred PDT combined with IVR to treat polypoidal choroidal vasculopathy show the similar visual and anatomical improvements at 12 months.
Abstract: Purpose:To compare the 1-year results of initial or deferred photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) for eyes with polypoidal choroidal vasculopathy.Methods:Prospectively, 72 men with treatment-naive polypoidal choroidal vasculopathy were randomized to initial or late

Journal ArticleDOI
TL;DR: In this article, the authors investigated the regulatory role of NO in H2O2-and SA-induced reduction of oxidative damage in salt-exposed rice seedlings, and found that NO might be involved in reducing the oxidative damage through upregulation of the antioxidant defense and MG detoxification systems.
Abstract: Nitric oxide (NO), hydrogen peroxide (H2O2), and salicylic acid (SA) are well-known signaling molecules that play multifaceted roles in the stress tolerance of plants; however, their interactions during stress alleviation have not been well studied. We investigated the possible regulatory role of NO in H2O2- and SA-induced reduction of oxidative damage in salt-exposed rice seedlings. For this purpose, hydroponically grown 14-day-old seedlings were pretreated with 100 μM H2O2 or 100 μM SA in the presence or absence of 100 μM hemoglobin (Hb, a potent NO scavenger) for 24 h followed by salt stress (200 mM NaCl) for 72 h. Salt stress significantly increased the levels of H2O2, malondialdehyde, and proline whereas H2O2 and SA pretreatment reduced the values of these parameters. H2O2 and SA pretreatment also inhibited salt-induced loss of total chlorophyll and relative water content. Histochemical detection of reactive oxygen species [ROS: superoxide (O 2 ·− ) and H2O2] indicated evident oxidative burst in the seedlings stressed with salt alone. Salt stress modulated the non-enzymatic and enzymatic antioxidants differentially; however, H2O2 and SA treatment prior to salt stress enhanced these antioxidants compared with the salt-stressed seedlings alone. H2O2 and SA pretreated salt-stressed seedlings also showed higher induction of the methylglyoxal (MG) detoxification system. Endogenous NO content was elevated following H2O2 and SA pretreatment over the experimental period. Adding Hb reduced the level of NO and subsequently abolished the beneficial effects of H2O2 and SA. Our results, therefore, suggest that NO might be involved in H2O2- and SA-induced reduction of oxidative damage through the upregulation of the antioxidant defense and MG detoxification systems to confer salt tolerance in rice seedlings. The data are of considerable value in elucidating the biochemical mechanisms of salt-stress tolerance and will augment the goal of developing appropriate and efficient methods for crop protection in saline environment.

Journal ArticleDOI
TL;DR: Older age and male sex may predict recurrence after 3 monthly ranibizumab injections, and PCV may be associated with shorter interval to recurrence, which was shorter in eyes with polypoidal choroidal vasculopathy (PCV) than in Eyes with typical AMD.

Journal ArticleDOI
TL;DR: Results suggest that Ca supplementation improves rice seedlings tolerance to As-induced oxidative stress by reducing As uptake, enhancing their antioxidant defense and glyoxalase systems, and also improving growth and physiological condition.
Abstract: The effect of exogenous calcium (Ca) on hydroponically grown rice seedlings was studied under arsenic (As) stress by investigating the antioxidant and glyoxalase systems. Fourteen-day-old rice (Oryza sativa L. cv. BRRI dhan29) seedlings were exposed to 0.5 and 1 mM Na2HAsO4 alone and in combination with 10 mM CaCl2 (Ca) for 5 days. Both levels of As caused growth inhibition, chlorosis, reduced leaf RWC, and increased As accumulation in the rice seedlings. Both doses of As in growth medium induced oxidative stress through overproduction of reactive oxygen species (ROS) by disrupting the antioxidant defense and glyoxalase systems. Exogenous application of Ca along with both levels of As significantly decreased As accumulation and restored plant growth and water loss. Calcium supplementation in the As-exposed rice seedlings reduced ROS production, increased ascorbate (AsA) content, and increased the activities of monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), catalase (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD), and the glyoxalase I (Gly I) and glyoxalase II (Gly II) enzymes compared with seedlings exposed to As only. These results suggest that Ca supplementation improves rice seedlings tolerance to As-induced oxidative stress by reducing As uptake, enhancing their antioxidant defense and glyoxalase systems, and also improving growth and physiological condition.

Journal ArticleDOI
TL;DR: The first three-dimensional structure of fungus-derived glucose dehydrogenase using flavin adenine dinucleotide (FAD) as the cofactor is reported, similar to that of fungal glucose oxidases (GOxs) reported till date.
Abstract: We report the first three-dimensional structure of fungus-derived glucose dehydrogenase using flavin adenine dinucleotide (FAD) as the cofactor. This is currently the most advanced and popular enzyme used in glucose sensor strips manufactured for glycemic control by diabetic patients. We prepared recombinant nonglycosylated FAD-dependent glucose dehydrogenase (FADGDH) derived from Aspergillus flavus (AfGDH) and obtained the X-ray structures of the binary complex of enzyme and reduced FAD at a resolution of 1.78 A and the ternary complex with reduced FAD and D-glucono-1,5-lactone (LGC) at a resolution of 1.57 A. The overall structure is similar to that of fungal glucose oxidases (GOxs) reported till date. The ternary complex with reduced FAD and LGC revealed the residues recognizing the substrate. His505 and His548 were subjected for site-directed mutagenesis studies, and these two residues were revealed to form the catalytic pair, as those conserved in GOxs. The absence of residues that recognize the sixth hydroxyl group of the glucose of AfGDH, and the presence of significant cavity around the active site may account for this enzyme activity toward xylose. The structural information will contribute to the further engineering of FADGDH for use in more reliable and economical biosensing technology for diabetes management.

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TL;DR: Planting sweet potato is a promising technique for reducing infestations of mile-a-minute, providing weed management benefits and economic returns from harvest of sweet potatoes, and the potential value of replacement control methods which may apply to other crop-weed systems or invaded natural ecosystems are shown.
Abstract: There are a variety of ways of increasing crop diversity to increase agricultural sustainability and in turn having a positive influence on nearby natural ecosystems. Competitive crops may provide potent management tools against invasive plants. To elucidate the competitive mechanisms between a sweet potato crop (Ipomoea batatas) and an invasive plant, mile-a-minute (Mikania micrantha), field experiments were carried out in Longchuan County of Yunnan Province, Southwest China, utilizing a de Wit replacement series. The trial incorporated seven ratios of sweet potato and mile-a-minute plants in 25 m2 plots. In monoculture, the total biomass, biomass of adventitious root, leafstalk length, and leaf area of sweet potato were all higher than those of mile-a-minute, and in mixed culture the plant height, branch, leaf, stem node, adventitious root, flowering and biomass of mile-a-minute were suppressed significantly (P < 0.05). The relative yield (RY) of mile-a-minute and sweet potato was less than 1.0 in mixed culture, indicating that intraspecific competition was less than interspecific competition. The competitive balance index of sweet potato demonstrated a higher competitive ability than mile-a-minute. Except pH, other soil nutrient contents of initial soil (CK) were significantly higher than those of seven treatments. The concentrations of soil organic matter, total N, total K, available N, available P, available K, exchange Ca, exchange Mg, available Mn, and available B were significantly greater (P < 0.05) in mile-a-minute monoculture soil than in sweet potato monoculture soil, and were reduced by the competition of sweet potato in the mixture. Evidently sweet potato has a competitive advantage in terms of plant growth characteristics and greater absorption of soil nutrients. Thus, planting sweet potato is a promising technique for reducing infestations of mile-a-minute, providing weed management benefits and economic returns from harvest of sweet potatoes. This study also shows the potential value of replacement control methods which may apply to other crop-weed systems or invaded natural ecosystems.

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TL;DR: This study aimed to identify the prevalence of, and risk factors for, infectious complications after pancreatic surgery, and the risks and benefits of routine and laparoscopic surgery.
Abstract: Background Although mortality associated with pancreatic surgery has decreased dramatically, high morbidity rates are still of major concern. This study aimed to identify the prevalence of, and risk factors for, infectious complications after pancreatic surgery. Methods The Japanese Society of Pancreatic Surgery conducted a multi-institutional analysis of complications in patients who underwent pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) between January 2010 and December 2012. Risk factors that were significantly associated with infectious complications in univariable models were included in a multivariable logistic regression model, and a nomogram was created to predict the risk of infectious complications after pancreatectomy. Results Infectious complications occurred in 1459 (35·2 per cent) of 4147 patients in the PD group and 426 (25·2 per cent) of 1692 patients in the DP group (P < 0·001). Nine risk factors for infectious complications after PD were identified: male sex, age 70 years or more, body mass index at least 25 kg/m2, other previous malignancy, liver disease, bile contamination, duration of surgery 7 h or longer, intraoperative blood transfusion and soft pancreas. Five risk factors for infectious complications after DP were identified: chronic steroid use, smoking, duration of surgery 5 h or more, intraoperative blood transfusion and non-laparoscopic surgery. Occurrence of a postoperative infectious complication was significantly associated with mortality and reoperation after PD (odds ratio (OR) 4·33, 95 per cent c.i. 2·01 to 9·92 and OR 3·26, 1·86 to 5·82, respectively) and DP (OR 6·32, 1·99 to 22·55; OR 3·74, 1·61 to 9·04). Conclusion Prolonged operating time, intraoperative blood transfusion, bile contamination (PD) and non-laparoscopic surgery (DP) are risk factors for postoperative infectious complications that could be targeted to improve outcome after pancreatectomy.

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TL;DR: This paper presents an amphibious spherical robot that consists of a sealed upper hemispheroid, two quarter spherical shells, and a plastic circular plate that has a plastic shelf for carrying the micro-robots, and four actuating units for movement.

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TL;DR: Key areas identified where improvements in color would provide immediate tangible benefits were those of digital microscopy, telemedicine, medical photography (particularly ophthalmic and dental photography), and display calibration.
Abstract: This article summarizes the consensus reached at the Summit on Color in Medical Imaging held at the Food and Drug Administration (FDA) on May 8–9, 2013, co-sponsored by the FDA and ICC (International Color Consortium). The purpose of the meeting was to gather information on how color is currently handled by medical imaging systems to identify areas where there is a need for improvement, to define objective requirements, and to facilitate consensus development of best practices. Participants were asked to identify areas of concern and unmet needs. This summary documents the topics that were discussed at the meeting and recommendations that were made by the participants. Key areas identified where improvements in color would provide immediate tangible benefits were those of digital microscopy, telemedicine, medical photography (particularly ophthalmic and dental photography), and display calibration. Work in these and other related areas has been started within several professional groups, including the creation of the ICC Medical Imaging Working Group.

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TL;DR: In this article, the effect of incorporating xanthan gum (XG) or guar gum (GG) in soy soluble polysaccharide (SSPS) stabilized oil-in-water (O/W) emulsions was studied.