• Journal of Plant Biotechnology
• /
• v.48 no.3
• /
• pp.148-155
• /
• 2021

Gibberellins (GAs) are essential phytohormones for plant growth that influence developmental processes and crop yields. Recent functional genomic analyses of model plants have yielded good characterizations of the canonical GA signaling pathways and related genes. Although Panax ginseng has long been considered to have economic and medicinal importance, functional genomic studies of the GA signaling pathways in this crucial perennial herb plant have been rarely conducted. Here, we identified and performed functional analysis of the GA signaling-related genes, including PgGID1s, PgSLY1s, and PgRGAs. We confirmed that the physiological role of GA signaling components in P. ginseng was evolutionarily conserved. In addition, the important functional domains and amino acid residues for protein interactions among active GA, GID1, SCF^SLY1, and RGA were also functionally conserved. Prediction and comparison of crystallographic structural similarities between PgGID1s and AtGID1a supported their function as GA receptors. Moreover, the subcellular localization and GA-dependent promotion of DELLA degradation in P. ginseng was similar to the canonical GA signaling pathways in other plants. Finally, we found that overexpression of PgRGA2 and PgSLY1-1 was sufficient to complement the GA-related phenotypes of atgid1a/c double- and rga quintuple-mutants, respectively. This critical information for these GA signaling genes has the potential to facilitate future genetic engineering and breeding of P. ginseng for increased crop yield and production of useful substances.

• Molecules and Cells
• /
• v.42 no.4
• /
• pp.292-300
• /
• 2019

Immunometabolism, defined as the interaction of metabolic pathways with the immune system, influences the pathogenesis of metabolic diseases. Metformin and carbon monoxide (CO) are two pharmacological agents known to ameliorate metabolic disorders. There are notable similarities and differences in the reported effects of metformin and CO on immunometabolism. Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms. CO, an endogenous product of heme oxygenase-1 (HO-1), can exert anti-inflammatory and antioxidant effects at low concentration. CO can confer cytoprotection in metabolic disorders and cancer via selective activation of the protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) pathway. Both metformin and CO can induce mitochondrial stress to produce a mild elevation of mitochondrial ROS (mtROS) by distinct mechanisms. Metformin inhibits complex I of the mitochondrial electron transport chain (ETC), while CO inhibits ETC complex IV. Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect. However, metformin and CO regulate these effects via different pathways. Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway. Although further studies are needed to identify the mechanistic differences between metformin and CO, pharmacological application of these agents may represent useful strategies to ameliorate metabolic diseases associated with altered immunometabolism.

• Biomolecules & Therapeutics
• /
• v.32 no.1
• /
• pp.56-64
• /
• 2024

Biased signaling or functional selectivity refers to the ability of an agonist or receptor to selectively activate a subset of transducers such as G protein and arrestin in the case of G protein-coupled receptors (GPCRs). Although signaling through arrestin has been reported from various GPCRs, only a few studies have examined side-by-side how it differs from signaling via G protein. In this study, two signaling pathways were compared using dopamine D₂ receptor (D₂R) mutants engineered via the evolutionary tracer method to selectively transduce signals through G protein or arrestin (D₂G and D₂Arr, respectively). D₂G mediated the inhibition of cAMP production and ERK activation in the cytoplasm. D₂Arr, in contrast, mediated receptor endocytosis accompanied by arrestin ubiquitination and ERK activation in the nucleus as well as in the cytoplasm. D₂Arr-mediated ERK activation occurred in a manner dependent on arrestin3 but not arrestin2, accompanied by the nuclear translocation of arrestin3 via importin1. D₂R-mediated ERK activation, which occurred in both the cytosol and nucleus, was limited to the cytosol when cellular arrestin3 was depleted. This finding supports the results obtained with D₂Arr and D₂G. Taken together, these observations indicate that biased signal transduction pathways activate distinct downstream mechanisms and that the subcellular regions in which they occur could be different when the same effectors are involved. These findings broaden our understanding on the relation between biased receptors and the corresponding downstream signaling, which is critical for elucidating the functional roles of biased pathways.

• Korean Journal of Adult Nursing
• /
• v.12 no.4
• /
• pp.517-532
• /
• 2000

The purpose of this study was to develop a critical pathway for case management of patients who have received Lumbar Laminectomy because of low back pain, arm and leg numbness, and radiating pain in the leg. For this study, a preliminary critical pathway was developed through a review of the literature including five critical pathways which are currently being used in the USA. In order to identify the overall service contents required by these patients, 30 cases were analyzed. These cases were taken from medical records of those with Lumbar Laminectomy between January, 1998 and December, 1998 in the department of neurosurgery at the Pusan National University Hospital in Pusan. An expert validity test was done for the preliminary critical pathway, a clinical validity test was also done using 12 patients with Lumbar Laminectomy between October 1, 1999 and January 31, 2000. After these processes, the final critical pathway was developed. The results are summarized as follows. 1. The vertical axis of the critical pathway includes the following eight items: assessment, consultation, diet, test, medication, treatment, activity, education/ discharge planning. The horizontal axis includes the time from the start of hospitalization to discharge. Analysis of the 30 medical records was done. analysis of the service contents showed the horizontal axis of the preliminary critical pathway was set from hospitalization to the 12th post operation day and the vertical axis was set to include eight items, the contents which should have occurred, according to the time frames of the horizontal axis. 2. As a result of the expert validity test, it was found that among the 233 items, 203 showed over 88% agreement and 30 of them showed less than 88% agreement, which were then revised or deleted from the critical pathway. At the preliminary meeting for the clinical validity test, the time of hospitalization on the horizontal axis was shortened to the 10th post operation day. A clinical validity test was done with 12 patients with Lumbar Laminectomy. All the cases progressed according to the critical pathway although some variances were noted in assessment, consultation, test, medication, and treatment. 3. Based on these results, a final critical pathway was determined. In conclusion, this critical pathway is partially applicable to the care of patients with Lumbar Laminectomy and needs further investigation.

• Korean Journal of Adult Nursing
• /
• v.28 no.1
• /
• pp.43-52
• /
• 2016

Purpose: The aim of this study was to identify demographic, clinical, physical, and psychosocial factors affecting discharge delay in lumbar spinal surgery patients who were treated according to a critical pathway. Methods: A sample of 170 patients with lumbar spinal surgery agreed to participate in the study, between April 1, 2014 and August 30, 2015. Data were analyzed by mean, standard deviation, t-test, ${\chi}^2$-test, ANCOVA, and logistic regression analysis using SPSS 22.0 program. Results: Approximately fifty-nine percent of the participants was delayed discharge. On logistic regression analysis, female gender (OR=2.63, 95% CI=1.40~4.94), age (OR=1.03, 95% CI=1.01~1.05), spondylolisthesis (OR=4.49, 95% CI=1.90~10.61), and spinal fusion operation (OR=4.14, 95% CI=1.89~9.05) were significant factors predicting discharge delay of the participants. However, discharge delay was not related with pain, physical function, depression, or family support. Conclusion: An analysis of discharge delay may assist in evaluating and revising critical pathway for optimal care. In addition, nurses need to understand the factors affecting discharge delay of the given population who were treated according to a critical pathway.

• Molecules and Cells
• /
• v.41 no.8
• /
• pp.762-770
• /
• 2018

Adiponectin, a hormone produced by adipose tissue, is very abundant in plasma, and its anti- and pro-inflammatory effects are reported. However, the mechanisms of these pro- and anti-inflammatory effects are not fully defined. Herein, we evaluated the dual inflammatory response mechanism of adiponectin in macrophages. Short-term globular adiponectin (gAd) treatment induced $I{\kappa}B{\alpha}$ degradation, $NF-{\kappa}B$ nuclear translocation, and $TNF-{\alpha}$ production in RAW 264.7 cells. Polymyxin B pretreatment did not block gAd-induced $I{\kappa}B{\alpha}$ degradation, and heated gAd was unable to degrade $I{\kappa}B{\alpha}$, suggesting that the effects of gAd were not due to endotoxin contamination. gAd activated IKK and Akt, and inhibition of either IKK or Akt by dominant-negative $IKK{\beta}$ ($DN-IKK{\beta}$) or DN-Akt overexpression blocked gAd-induced $I{\kappa}B{\alpha}$ degradation, suggesting that short-term incubation with gAd mediates inflammatory responses by activating the $I{\kappa}B/NF-{\kappa}B$ and PI3K/Akt pathways. Contrastingly, long-term stimulation with gAd induced, upon subsequent stimulation, tolerance to gAd, lipopolysaccharide, and CpG-oligodeoxynucleotide, which is associated with gAd-induced downregulation of IL-receptor-associated kinase-1 (IRAK-1) due to IRAK-1 transcriptional repression. Conclusively, our findings demonstrate that the pro- and anti-inflammatory responses to gAd in innate immune cells are time-dependent, and mediated by the activation of the $I{\kappa}B/NF-{\kappa}B$ pathway, and IRAK-1 downregulation, respectively.

• Tuberculosis and Respiratory Diseases
• /
• v.72 no.3
• /
• pp.275-283
• /
• 2012

Background: Healthy individuals who develop nontuberculous mycobacteria (NTM) lung disease are likely to have specific susceptibility factors which can lead to a NTM infection. The aim of the present study was to investigate the mechanism underlying innate immune responses, including the role of mitogen-activated protein kinase (MAPK), in Mycobacterium abscessus lung disease. Methods: Extracellular signal-regulated kinase (ERK1/2) and p38 MAPK expression in monocytes from peripheral blood mononuclear cells were measured by Western blot analysis after stimulation by Mycobacterium avium in five patients with M. abscessus lung disease and seven healthy controls. A M. avium-induced cytokine assay was performed after inhibition of ERK1/2 and p38 MAPK pathways. Results: Mycobacterium avium induced p38 and ERK1/2 expression in monocytes from healthy controls and subsequently upregulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 production. In monocytes from patients with M. abscessus lung disease, however, induction of p38 and ERK1/2 expression, and the production of TNF-${\alpha}$, IL-6, and IL-10 were significantly lower. Conclusion: Decreased activity of MAPK and cytokine secretion in monocytes from patients with M. abscessus lung disease may provide an explanation regarding host susceptibility to these uncommon infections.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.4 no.3
• /
• pp.223-229
• /
• 2003

Annual radiation dose of residential individuals near 4 nuclear power plants in Korea was calculated via K-DOSE 60 based on the updated ICRP-60. The critical exposure variables were chosen as radionuclides, exposed organs and intake pathways. From the calculation results, the critical nuclides were found to be $^3$H, $^{133}$ Xe, $^{60}$ Co for Kori plants and $^{14}$ C, $^{41}$ Ar for Wolsung plants. The most critical pathway was 'vegetable intake' for adults and 'milk intake' for infants. However, there was no preference in the effective organs. Sensitivity analyses showed that the chemical composition in a nuclide much more influenced upon the radiation dose than any other input parameters such as food intake, radiation discharge, and transfer/concentration coefficients by more than 10$^2$ factor. The effect of transfer/concentration coefficients on the radiation dose was negligible. All input parameters showed highly estimated correlation with the radiation dose, approxinated to 1.0.

• Journal of Korean Academy of Nursing Administration
• /
• v.17 no.1
• /
• pp.66-73
• /
• 2011

Purpose: The purpose of this study was to demonstrate effects of a critical pathway (CP) for stroke patients seen in emergency rooms (ER). Method: The CP developed by the CP committee consisted of 8 criteria: behavior of doctors and nurses, laboratory tests, Image testing, medication, treatment, activity, and nutrition. According to application of CP, a control group (n=17) and experimental group (n=17) were defined. Time was checked by the electronic medical records. Result: Use of CP for stroke patients in the ER, resulted in a decreased length of stay in ER (t=2.341, p=.026), and time required for image testing (t=2.623, p=.021), and an increased number of patients using rtPA ($x^2$=4.802, p=.049). Time required for neurology doctor contact, for neurology doctor to see patient in the ER, and for report of blood tests decreased, but there were no statistical significance. Conclusion: Quick responses are most important in the ER, so CP for these patients is a very effective patient management tool. To reduce delay in stroke diagnosis, continuous education programs for similar symptoms are necessary. CPs for other patients in the ER should be developed, and studies on cost and satisfaction, as well as length of stay, should be done.

• Proceedings of the Korean Society of Developmental Biology Conference
• /
• 2001.10a
• /
• pp.14-17
• /
• 2001

Positional clonging (map-based cloning) of mutations or genetic variations has been served as an invaluable tool to understand in-vivo functions of genes and to identify molecular components underlying phenotypes of interest. Mice homozygous for the cerebellar deficient folia (cdf) mutation are ataxic, with cerebellar hypoplasia and abnormal lobulation of the cerebellum. In the cdf mutant cerebellum approximately 40% of Purkinje cells are ectopically located within the white matter and the inner granule cell layer (IGL). To identify the cdf gene, a high-resolution genetic map for the cdf-gene-encompassing region was constructed using 1997 F2 mice generated from C3H/HeSnJ-cdf/cdf and CAST/Ei intercross. The cdf gene showed complete linkage disequilibrium with three tightly linked markers D6Mit208, D6Mit359, and D6Mit225. A contig using YAC, BAC, and P1 clones was constructed for the cdf critical region to identify the gene. A deletion in the cdf critical region on chromosome 6 that removes approximately 150 kb of DNA selection. cdf mutant mice with the transgenic copy of the identified gene restored the brain abnormalities of the mutant mice. The positional cloning of cdf gene provides a good example showing the identification of a gene could lead to finding a new component of important molecular pathways.