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        — Invited Review — Hydrogen production and hydrogen utilization in the rumen: key to mitigating enteric methane production

        Mackie Roderick I.,Kim Hyewon,Kim Na Kyung,Cann Isaac 아세아·태평양축산학회 2024 Animal Bioscience Vol.37 No.2

        Molecular hydrogen (H<sub>2</sub>) and formate (HCOO<sup>-</sup>) are metabolic end products of many primary fermenters in the rumen ecosystem. Both play a vital role in fermentation where they are electron sinks for individual microbes in an anaerobic environment that lacks external electron acceptors. If H<sub>2</sub> and/or formate accumulate within the rumen, the ability of primary fermenters to regenerate electron carriers may be inhibited and microbial metabolism and growth disrupted. Consequently, H<sub>2</sub>- and/or formate-consuming microbes such as methanogens and possibly homoacetogens play a key role in maintaining the metabolic efficiency of primary fermenters. There is increasing interest in identifying approaches to manipulate the rumen ecosystem for the benefit of the host and the environment. As H<sub>2</sub> and formate are important mediators of interspecies interactions, an understanding of their production and utilization could be a significant starting point for the development of successful interventions aimed at redirecting electron flow and reducing methane emissions. We conclude by discussing in brief ruminant methane mitigation approaches as a model to help understand the fate of H<sub>2</sub> and formate in the rumen ecosystem. Molecular hydrogen (H2) and formate (HCOO– ) are metabolic end products of many primary fermenters in the rumen ecosystem. Both play a vital role in fermentation where they are electron sinks for individual microbes in an anaerobic environment that lacks external electron acceptors. If H2 and/or formate accumulate within the rumen, the ability of primary fermenters to regenerate electron carriers may be inhibited and microbial metabolism and growth disrupted. Consequently, H2- and/or formate-consuming microbes such as methanogens and possibly homoacetogens play a key role in maintaining the metabolic efficiency of primary fermenters. There is increasing interest in identifying approaches to manipulate the rumen ecosystem for the benefit of the host and the environment. As H2 and formate are important mediators of interspecies interactions, an understanding of their production and utilization could be a significant starting point for the development of successful interventions aimed at redirecting electron flow and reducing methane emissions. We conclude by discussing in brief ruminant methane mitigation approaches as a model to help understand the fate of H2 and formate in the rumen ecosystem.

      • Fmr1 deletion enhances and ultimately desensitizes CB<sub>1</sub> signaling in autaptic hippocampal neurons

        Straiker, A.,Min, K.T.,Mackie, K. Blackwell Science ; Academic Press 2013 Neurobiology of disease Vol.56 No.-

        Fragile X Syndrome (FXS) is a heritable form of mental retardation caused by a non-coding trinucleotide expansion of the FMR1 gene leading to loss of expression of this RNA binding protein. Mutations in this gene are strongly linked to enhanced Group I metabotropic glutamate receptor (mGluR) signaling. A recent report found that mGluR5-dependent endogenous cannabinoid signaling is enhanced in hippocampal slices from fmr1 knockout mice, suggesting a link between FXS and cannabinoid signaling. Alterations in cannabinoid signaling have an impact on learning and memory and may therefore be linked to some aspects of the FXS phenotype. We have used autaptic hippocampal neurons cultured from fmr1 knockout mice to further explore the interaction between endocannabinoid signaling and FMRP. These neurons express several robust forms of retrograde endocannabinoid signaling including depolarization induced suppression of excitation (DSE) and a metabotropic form (MSE) that results from Group I mGluR activation. We now report that young fmr1 neurons exhibit considerably enhanced DSE, likely via increased production of 2-AG, rather than enhanced mGluR-MSE. We find that depolarizations as brief as 50ms, which do not ordinarily produce DSE, routinely inhibited glutamate release. Furthermore, as neuronal cultures mature, CB<SUB>1</SUB>-receptor signaling strongly desensitizes. Our results suggest that loss of FMRP broadly affects the endocannabinoid signaling system, possibly through local 2-AG over production. Furthermore, the net effect of the loss of FMRP may actually be diminished cannabinoid signaling due to receptor desensitization as an adaptation to 2-AG overproduction.

      • SCIESCOPUSKCI등재

        Molecular Analysis of Archaea, Bacteria and Eucarya Communities in the Rumen - Review-

        White, B.A.,Cann, I.K.O.,Kocherginskaya, S.A.,Aminov, R.I.,Thill, L.A.,Mackie, R.I.,Onodera, R. Asian Australasian Association of Animal Productio 1999 Animal Bioscience Vol.12 No.1

        If rumen bacteria can be manipulated to utilize nutrients (i.e., ammonia and plant cell wall carbohydrates) more completely and efficiently, the need for protein supplementation can be reduced or eliminated and the digestion of fiber in forage or agricultural residue-based diets could be enhanced. However, these approaches require a complete and accurate description of the rumen community, as well as methods for the rapid and accurate detection of microbial density, diversity, phylogeny, and gene expression. Molecular ecology techniques based on small subunit (SSU) rRNA sequences, nucleic acid probes and the polymerase chain reaction (PCR) can potentially provide a complete description of the microbial ecology of the rumen of ruminant animals. The development of these molecular tools will result in greater insights into community structure and activity of gut microbial ecosystems in relation to functional interactions between different bacteria, spatial and temporal relationships between different microorganisms and between microorganisms and reed panicles. Molecular approaches based on SSU rRNA serve to evaluate the presence of specific sequences in the community and provide a link between knowledge obtained from pure cultures and the microbial populations they represent in the rumen. The successful development and application of these methods promises to provide opportunities to link distribution and identity of gastrointestinal microbes in their natural environment with their genetic potential and in situ activities. The use of approaches for assessing pupulation dynamics as well as for assessing community functionality will result in an increased understanding and a complete description of the gastrointestinal communities of production animals fed under different dietary regimes, and lead to new strategies for improving animal growth.

      • Use of Ledipasvir/Sofosbuvir (LDV/SOF) in Patients with Advanced Chronic Kidney Disease (eGFR ≤30ml/min): A Case Series

        ( Meghan E. Sise ),( Naim Alkhouri ),( Brian Borg ),( Sooji Lee ),( Thomas Mcquaid ),( Joseph Llewellyn ),( Macky Natha ),( Shampa De-oertel ),( Diana M. Brainard ),( Marc Carp ),( Michael Fuchs ),( H 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: Little is known about the safety and efficacy of LDV/SOF in patients with advanced chronic kidney disease (CKD) with eGFR ≤ 30 ml/min or on hemodialysis. Yet, off-label use of LDV/SOF in this population occurs. Methods: Providers proactively reporting such off-label use to Gilead Sciences were asked to submit de-identified case reports. Demographics, clinical characteristics at baseline, during, and after LDV/SOF treatment, and adverse events were collected. Summary statistics and paired sample t-tests are presented. Results: Twenty-one case summaries were submitted. Median Age was 59 (range 26-71). Eleven patients (52%) were black, 20 had genotype 1 (13-1a, 4-1b) and one patient had genotype 3. Median pretreatment viral load was 1,680,000 IU (range 133,000-37,200,000 IU). Twelve patients (56%) were on hemodialysis and 9 had CKD Stage 4 (eGFR 15-29 ml/min), 13 (62%) had cirrhosis, 11 (50%) had diabetes, 5 had history of organ transplantation (4 kidney, 1 liver). All patients received full dose LDV/SOF for 12 weeks with one patient also receiving 200 mg Ribavirin every other day in combination. Eight adverse events were reported; 2 patients (10%) with anemia, 1 case of insomnia, nausea/vomiting, headache, and chest pain (5%) each. Of the 9 patients with CKD stage 4, 2 experienced an increase in eGFR and 5 a decrease in eGFR post treatment. All 21 patients achieved SVR 12 (100%). No patient discontinued treatment due to an adverse event. Conclusions: In this small case series describing the use of ledipasvir/sofosbuvir in Patients with Advanced Chronic Kidney Disease: 62% had cirrhosis, 52% had diabetes mellitus, and 57% were on hemodialysis. All 21 patients achieved SVR12 including 12 patients on hemodialysis. LDV/SOF was relatively well tolerated and there were no treatment discontinuations. Most patients had stable renal function before and after treatment with LDV/SOF.

      • SCIEKCI등재

        Comparative Pathogenicity of Fusarium graminearum Isolates from Wheat Kernels in Korea

        Shin, Sanghyun,Son, Jae-Han,Park, Jong-Chul,Kim, Kyeong-Hoon,Yoon, Young-mi,Cheong, Young-Keun,Kim, Kyong-Ho,Hyun, Jong-Nae,Park, Chul Soo,Dill-Macky, Ruth,Kang, Chon-Sik The Korean Society of Plant Pathology 2018 Plant Pathology Journal Vol.34 No.5

        Fusarium head blight (FHB) caused by Fusarium species is a major disease of wheat and barley around the world. FHB causes yield reductions and contamination of grains with trichothecene mycotoxins including; nivalenol (NIV), deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), and 15-acetyldeoxynivalenol (15-ADON). The objectives of this study were to identify strains of F. graminearum isolated in Korea from 2012-harvested wheat grain and to test the pathogenicity of these NIV- and DON-producing isolates. Three hundred and four samples of wheat grain, harvested in 2012 in Chungnam, Chungbuk, Gyeongnam, Jeonbuk, Jeonnam, and Gangwon provinces were collected. We recovered 44 isolates from the 304 samples, based on the PCR amplification of internal transcribed spacer (ITS) rRNA region and sequencing. Our findings indicate that F. asiaticum was the predominant (95% of all isolates) species in Korea. We recovered both F. asiaticum and F. graminearum from samples collected in Chungnam province. Of the 44 isolates recovered, 36 isolates had a NIV genotype while 8 isolates belonged to the DON genotype (3-ADON and 15-ADON). In order to characterize the pathogenicity of the strains collected, disease severity was assessed visually on various greenhouse-grown wheat cultivars inoculated using both NIV- and DON-producing isolates. Our results suggest that Korean F. graminearum isolates from wheat belong to F. asiaticum producing NIV, and both F. graminearum and F. asiaticum are not significantly different on virulence in wheat cultivars.

      • Ledipasvir/Sofosbuvir for 8 Weeks in Genotype 1 Treatment- naive Non-cirrhotic Patients with HCV RNA < 6 Million IU/mL: Phase-3 and Real World

        ( Peter Buggisch ),( Jorg Peterson ),( Stefan Mauss ),( Kris Kowdley ),( Micheal Curry ),( Peter Ruane ),( Dani Ain ),( Naoky Tsai ),( Yoori Lee ),( Edward Eggleton ),( Macky Natha ),( Bruce Kreter ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

        Aims: The optimal duration of therapy to achieve SVR depends on multiple factors. In a post-hoc analysis of the Phase 3 ION-3 (treatment-naive (TN), non-cirrhotic (NC) patients) 8 week of LDV/SOF data, a viral load (VL) <6M was shown to be the best predictor of SVR. Real world effectiveness (RWE) is often different from Phase III trials and there is a need to understand real-world 8 week regimens in a broader spectrum of patients. Methods: RWE 8 week LDV/SOF data is emerging from multiple single- center and multicenter retrospective and prospective cohorts. In this analysis, the phase-3 ION-3 data is compared with data from several diverse real world populations and one post-marketing investigator sponsored HIV/HCV trial. Patient demographics, characteristics, SVR12 and discontinuation data has been compared. Results: The ION-3 post-hoc analysis reported 123 patients who were TN, NC and VL<6M and treated with 8 weeks of LDV/SOF. Mean age was 52, 22% black, 72% GT1a; the SVR12 was 97% (119/123). The overall SVR12 rate from six diverse real world and post marketing cohorts was also 97% (638/658). There was no significant impact of HCV genotypes or subtypes (GT1a, 1b versus GT4), prior treatment history, presence or absence of cirrhosis, high viral load (HCV VL>6M), or HIV/HCV co-infection. All response rates are detailed in Figure1. Conclusions: LDV/SOF for 8 weeks yielded high SVR rates in ION-3. Analysis of RWE data from several diverse and heterogeneous cohorts from the US & EU show SVR outcomes that were consistent with the ION-3 results and supports the use of 8 weeks LDV/SOF in treatment- naive, non-cirrhotic GT1 patients with a baseline HCV VL <6M and possibly in other populations including HIV/HCV co-infected patients. Discontinuation rates were low despite diverse patients and clinical settings. Data from the TARGET and TRIO cohorts also suggests that the 8-week regimen is underutilized.

      • KCI등재

        Comparative Pathogenicity of Fusarium graminearum Isolates from Wheat Kernels in Korea

        Sanghyun Shin,Jae-Han Son,Jong-Chul Park,Kyeong-Hoon Kim,Young-mi Yoon,Young-Keun Cheong,Kyong-Ho Kim,Jong-Nae Hyun,Chul Soo Park,Ruth Dill-Macky,Chon-Sik Kang 한국식물병리학회 2018 Plant Pathology Journal Vol.34 No.5

        Fusarium head blight (FHB) caused by Fusarium species is a major disease of wheat and barley around the world. FHB causes yield reductions and contamination of grains with trichothecene mycotoxins including; nivalenol (NIV), deoxynivalenol (DON), 3-cetyldeoxynivalenol (3-ADON), and 15-acetyldeoxynivalenol (15-ADON). The objectives of this study were to identify strains of F. graminearum isolated in Korea from 2012-harvested wheat grain and to test the pathogenicity of these NIV- and DON-producing isolates. Three hundred and four samples of wheat grain, harvested in 2012 in Chungnam, Chungbuk, Gyeongnam, Jeonbuk, Jeonnam, and Gangwon provinces were collected. We recovered 44 isolates from the 304 samples, based on the PCR amplification of internal transcribed spacer (ITS) rRNA region and sequencing. Our findings indicate that F. asiaticum was the predominant (95% of all isolates) species in Korea. We recovered both F. asiaticum and F. graminearum from samples collected in Chungnam province. Of the 44 isolates recovered, 36 isolates had a NIV genotype while 8 isolates belonged to the DON genotype (3-ADON and 15-ADON). In order to characterize the pathogenicity of the strains collected, disease severity was assessed visually on various greenhouse-grown wheat cultivars inoculated using both NIV- and DON-producing isolates. Our results suggest that Korean F. graminearum isolates from wheat belong to F. asiaticum producing NIV, and both F. graminearum and F. asiaticum are not significantly different on virulence in wheat cultivars.

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