48 research outputs found

    Component Interaction of ESCRT Complexes Is Essential for Endocytosis-Dependent Growth, Reproduction, DON Production and Full Virulence in Fusarium graminearum

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    Multivesicular bodies (MVBs) are critical intermediates in the trafficking of ubiquitinated endocytosed surface proteins to the lysosome/vacuole for destruction. Recognizing and packaging ubiquitin modified cargoes to the MVB pathway require ESCRT (Endosomal sorting complexes required for transport) machinery, which consists of four core subcomplexes, ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III. Fusarium graminearum is an important plant pathogen that causes head blight of major cereal crops. Our previous results showed that ESCRT-0 is essential for fungal development and pathogenicity in Fusarium graminearum. We then, in this study, systemically studied the protein-protein interactions within F. graminearum ESCRT-I, -II or -III complex, as well as between ESCRT-0 and ESCRT-I, ESCRT-I and ESCRT-II, and ESCRT-II and ESCRT-III complexes and found that loss of any ESCRT component resulted in abnormal function in endocytosis. In addition, ESCRT deletion mutants displayed severe defects in growth, deoxynivalenol (DON) production, virulence, sexual, and asexual reproduction. Importantly genetic complementation with corresponding ESCRT genes fully rescued all these defective phenotypes, indicating the essential role of ESCRT machinery in fungal development and plant infection in F. graminearum. Taken together, the protein-protein interactome and biological functions of the ESCRT machinery is first profoundly characterized in F. graminearum, providing a foundation for further exploration of ESCRT machinery in filamentous fungi

    Mechanism and Treatment Related to Oxidative Stress in Neonatal Hypoxic-Ischemic Encephalopathy

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    Hypoxic ischemic encephalopathy (HIE) is a type of neonatal brain injury, which occurs due to lack of supply and oxygen deprivation to the brain. It is associated with a high morbidity and mortality rate. There are several therapeutic strategies that can be used to improve outcomes in patients with HIE. These include cell therapies such as marrow mesenchymal stem cells (MSCs) and umbilical cord blood stem cells (UCBCs), which are being incorporated into the new protocols for the prevention of ischemic brain damage. The focus of this review is to discuss the mechanism of oxidative stress in HIE and summarize the current available treatments for HIE. We hope that a better understanding of the relationship between oxidative stress and HIE will provide new insights on the potential therapy of this devastating condition

    Retromer Is Essential for Autophagy-Dependent Plant Infection by the Rice Blast Fungus

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    We thank Dr. Yizhen Deng at the Temasek Life sciences Laboratory (TLL) for providing the RFP-MoAtg8 plasmid. We would like to thank Drs. Zhenbiao Yang (University of California, Riverside) and Xianying Dou (Fujian Agriculture and Forestry University) for helpful discussions.Author Summary The rice blast fungus Magnaporthe oryzae utilizes key infection structures, called appressoria, elaborated at the tips of the conidial germ tubes to gain entry into the host tissue. Development of the appressorium is accompanied with autophagy in the conidium leading to programmed cell death. This work highlights the significance of the Vps35/retromer membrane-trafficking machinery in the regulation of autophagy during appressorium-mediated host penetration, and thus sheds light on a novel molecular mechanism underlying autophagy-based membrane trafficking events during pathogen-host interaction in rice blast disease. Our findings provide the first genetic evidence that the retromer controls the initiation of autophagy in filamentous fungi.Yeshttp://www.plosgenetics.org/static/editorial#pee

    Clinical value of different anti-D immunoglobulin strategies for preventing Rh hemolytic disease of the fetus and newborn: A network meta-analysis.

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    BACKGROUND:Several anti-D immunoglobulin strategies exist for preventing Rh hemolytic disease of the fetus and newborn. This study systematically assessed the clinical value of those therapeutic strategies. METHODS:The Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for eligible studies that evaluated the value of different anti-D immunoglobulin strategies in preventing maternal anti-D antibody sensitization. Combined odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. The network meta-analysis was conducted using Stata 14.2 and WinBUGS 1.4.3 software. RESULTS:Twenty-four original studies involving 64860 patients were included. Among all therapeutic measures, injecting 300 μg anti-D immunoglobulin at 28 and 34 gestational weeks (antenatal 5/E) appeared to be the most effective measure for preventing maternal antibody sensitization (surface under the cumulative ranking curve [SUCRA] = 96.8%), while a single injection at 28 gestational weeks (SUCRA = 89.2%) was the second most effective. Administering no injection or a placebo (SUCRA = 0.0%) was the least effective intervention measure. CONCLUSION:Among the therapeutic measures, antenatal 5/E appeared to be the best method for reducing the positive incidence of anti-D antibodies in the maternal serum; thus, it may be the most effective treatment for preventing fetal hemolytic disease

    Neurobiomechanical mechanism of Tai Chi to improve upper limb coordination function in post-stroke patients: a study protocol for a randomized controlled trial

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    Abstract Background Upper limb dysfunction seriously affects the ability of stroke patients to perform activities of daily living. As a popular exercise therapy, Tai Chi may become an alternative intervention. However, the neurophysiological mechanism by which Tai Chi improves upper limb dysfunction in stroke patients is still unclear, which limits its further promotion and application. Therefore, conducting a strict randomized clinical trial is necessary to observe how Tai Chi affects upper limb dysfunction in stroke patients and to explore its neurophysiological mechanism. Methods/design This report describes a randomized, parallel-controlled trial with distributive concealment and evaluator blinding. A total of 84 eligible participants will be randomly assigned to the Tai Chi group or the control group in a 1:1 ratio. The participants in the Tai Chi group will receive 4 weeks of Tai Chi training: five 60-min sessions a week for a total of 20 sessions. The participants in the control group will not receive Tai Chi training. Both groups will receive medical treatment and routine rehabilitation training. The primary outcome measure is the mean change in the Fugl-Meyer Assessment Upper Extremity (FMA-UE) scale score between baseline and 4 weeks; the secondary outcomes are the mean changes in kinematic characteristics and the Wolf Motor Function Test (WMFT) and Stroke Impact Scale (SIS) scores. In addition, the corticomuscular coupling level and near-infrared brain functional imaging will be monitored to explore the mechanism by which Tai Chi improves upper limb function of stroke patients. Discussion This randomized controlled trial will examine the effectiveness of Tai Chi in stroke patients with upper limb dysfunction and explore the neurophysiological mechanism. Positive results will verify that Tai Chi can improve upper limb function of stroke patients. Trial registration Chinese Clinical Trial Registration Center, ChiCTR2200061376 (retrospectively registered). Registered June 22, 2022. http://www.chictr.org.cn/listbycreater.aspx . Manuscript Version: 3.0 Manuscript Date: October 10, 2023

    Research status of correlation between myopia and accommodative function

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    Ocular accommodation refers to the process by which the ciliary muscle creates a clear image of the object in the retina by changing the refractive power of the lens. When the accommodation ability of the eye is insufficient, the imaging focus falls on the region behind the retina and hyperopic defocus is easily formed, resulting in axial growth and leading to the development of myopia, and it is found that most myopic patients usually have some accommodation dysfunction. Myopia has become a public health problem in China, and the prevalence of adolescents has increased dramatically. How to prevent and stop the occurrence and development of myopia is a major challenge. Previous studies have found that ocular accommodation dysfunction is associated with the occurrence and development of myopia, and the measurement of parameters related to accommodation function has certain guiding significance for the prevention and control of myopia. The purpose of this paper is to review the correlation between myopia and ocular accommodation function, with a view to providing new ideas for the prevention, control and treatment of myopia

    Spatial regulation of Raf kinase signaling by RKTG

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    Subcellular compartmentalization has become an important theme in cell signaling such as spatial regulation of Ras by RasGRP1 and MEK/ERK by Sef. Here, we report spatial regulation of Raf kinase by RKTG (Raf kinase trapping to Golgi). RKTG is a seven-transmembrane protein localized at the Golgi apparatus. RKTG expression inhibits EGF-stimulated ERK and RSK phosphorylation, blocks NGF-mediated PC12 cell differentiation, and antagonizes Ras- and Raf-1-stimulated Elk-1 transactivation. Through interaction with Raf-1, RKTG changes the localization of Raf-1 from cytoplasm to the Golgi apparatus, blocks EGF-stimulated Raf-1 membrane translocation, and reduces the interaction of Raf-1 with Ras and MEK1. In RKTG-null mice, the basal ERK phosphorylation level is increased in the brain and liver. In RKTG-deleted mouse embryonic fibroblasts, EGF-induced ERK phosphorylation is enhanced. Collectively, our results reveal a paradigm of spatial regulation of Raf kinase by RKTG via sequestrating Raf-1 to the Golgi apparatus and thereby inhibiting the ERK signaling pathway
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