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        Headache Relief Is Maintained 7 Years After Anterior Cervical Spine Surgery: Post Hoc Analysis From a Multicenter Randomized Clinical Trial and Cervicogenic Headache Hypothesis

        Harjot Thind,Dinesh Ramanathan,Julius Ebinu,David Copenhaver,Kee D. Kim 대한척추신경외과학회 2020 Neurospine Vol.17 No.2

        Objective: To evaluate whether anterior cervical spine surgery offers sustained (7 years) relief in patients with cervicogenic headaches (CGHs), and evaluate the difference between cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) for 1 and 2-level surgeries from a multicenter randomized clinical trial. Methods: A post hoc analysis was performed of 575 patients who underwent one or 2-level CDA or ACDF for symptomatic cervical spondylosis as part of a prospective randomized clinical trial. Assessment of pain and functional outcome was done with the Neck Disability Index (NDI) in the trial. We used the NDI headache component to assess headache outcome. Results: For both 1- and 2-level CDA and ACDF groups, there was significant headache improvement from preoperative baseline out to 7 years (p < 0.0001). For 1-level surgeries, headache improvement was similar for both groups at the 7-year point. For 2-level treatment, CDA patients had significantly improved headache scores versus ACDF patients at the 7-year point (p = 0.016). Conclusion: The headache improvement noted at early follow-up was sustained over the long-term period with ACDF and CDA populations. In the case of 2-level operations, CDA patients demonstrated significantly greater benefit compared to ACDF patients over the long-term. Sinuvertebral nerve irritation at the unco-vasculo-radicular junction and anterior dura may be the cause of CGH. Therefore, it is possible that improved cervical kinematics and preservation of range of motion at adjacent uncovertebral joints in CDA may contribute to the observed difference between the groups.

      • Homeobox Transcription Factors Are Required for Conidiation and Appressorium Development in the Rice Blast Fungus <i>Magnaporthe oryzae</i>

        Kim, Seryun,Park, Sook-Young,Kim, Kyoung Su,Rho, Hee-Sool,Chi, Myoung-Hwan,Choi, Jaehyuk,Park, Jongsun,Kong, Sunghyung,Park, Jaejin,Goh, Jaeduk,Lee, Yong-Hwan,Copenhaver, Gregory P. Public Library of Science 2009 PLoS genetics Vol.5 No.12

        <▼1><P>The appropriate development of conidia and appressoria is critical in the disease cycle of many fungal pathogens, including <I>Magnaporthe oryzae</I>. A total of eight genes (<I>MoHOX1</I> to <I>MoHOX8</I>) encoding putative homeobox transcription factors (TFs) were identified from the <I>M. oryzae</I> genome. Knockout mutants for each <I>MoHOX</I> gene were obtained via homology-dependent gene replacement. Two mutants, <I>ΔMohox3</I> and <I>ΔMohox5</I>, exhibited no difference to wild-type in growth, conidiation, conidium size, conidial germination, appressorium formation, and pathogenicity. However, the <I>ΔMohox1</I> showed a dramatic reduction in hyphal growth and increase in melanin pigmentation, compared to those in wild-type. <I>ΔMohox4</I> and <I>ΔMohox6</I> showed significantly reduced conidium size and hyphal growth, respectively. <I>ΔMohox8</I> formed normal appressoria, but failed in pathogenicity, probably due to defects in the development of penetration peg and invasive growth. It is most notable that asexual reproduction was completely abolished in <I>ΔMohox2</I>, in which no conidia formed. <I>ΔMohox2</I> was still pathogenic through hypha-driven appressoria in a manner similar to that of the wild-type. However, <I>ΔMohox7</I> was unable to form appressoria either on conidial germ tubes, or at hyphal tips, being non-pathogenic. These factors indicate that <I>M. oryzae</I> is able to cause foliar disease via hyphal appressorium-mediated penetration, and <I>MoHOX7</I> is mutually required to drive appressorium formation from hyphae and germ tubes. Transcriptional analyses suggest that the functioning of <I>M. oryzae</I> homeobox TFs is mediated through the regulation of gene expression and is affected by cAMP and Ca<SUP>2+</SUP> signaling and/or MAPK pathways. The divergent roles of this gene set may help reveal how the genome and regulatory pathways evolved within the rice blast pathogen and close relatives.</P></▼1><▼2><P><B>Author Summary</B></P><P>Pathogens have evolved diverse strategies to cause disease. <I>Magnaporthe oryzae</I> is the fungal phytopathogen that causes rice blast and is considered an important model for understanding mechanisms in fungal development and pathogenicity. Asexual reproduction and infection-related development play key roles in <I>M. oryzae</I> disease development. The conidium of <I>M. oryzae</I> differentiates a specialized structure, an appressorium. The appressorium generates turgor pressure that allows penetration through the mechanical rupture of host cuticle layers. After colonizing host cells, the fungus produces massive conidia via conidiogenesis, serving as secondary propagules for the polycyclic disease. To elucidate molecular mechanisms in asexual reproduction and appressorium-mediated disease development, we identified eight homeobox transcription factors through a genome-wide <I>in silico</I> analysis. Characterization using deletion mutants revealed that each homeobox TF functions as a stage-specific regulator for conidial shape, hyphal growth, conidiation, appressorium development, and invasive growth during <I>M. oryzae</I> development. Notably, conidiation and appressorium development were entirely abolished in <I>ΔMohox2</I> and <I>ΔMohox7</I>, respectively. This study also provides evidence that <I>M. oryzae</I> is able to cause rice blast by means of hypha-driven appressoria upon responses to host signaling factors. This study will aid in the understanding of regulatory networks associated with fungal development and pathogenicity.</P></▼2>

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