Biomedical subjects

Jieun Kim

Publications and source records attributed to Jieun Kim.

16 recordsLinked to original sources

PubMed2025

Multiple effectors trigger non-host resistance in Solanum americanum against Pseudomonas syringae.

Wild plant species are threatened by diverse pathogens, but disease symptoms are rarely observed in nature. This suggests that wild plants harbor valuable sources of resistance. In this study, we show that the model bacterial pathogen Pseudomonas syringae pv. tomato (Pto) DC3000 triggered defense responses in all tested accessions of a wild Solanaceae species, Solanum americanum. Pto DC3000-triggered immunity in S. americanum required a type III secretion system. We show that seven Pto DC3000 effectors (AvrPto, HopAD1, HopAM1, HopC1, HopAA1-1, HopM1, and AvrE1) triggered hypersensitive responses (HR) in S. americanum accession SP2273. Significantly, sequential deletion of the HR-triggering effectors from Pto DC3000 resulted in enhanced virulence in S. americanum. However, the well-conserved effectors, HopM1 and AvrE1, were indispensable for virulence. We conclude that the immunity triggered by multiple effectors contributes to nonhost resistance in S. americanum against P. syringae. We propose that the identification of the corresponding disease resistance genes for HopM1 and AvrE1 in S. americanum would accelerate the development of durable immunity to P. syringae pathogens in Solanaceae crops.

Disease Resistance↗

PubMed2007

Unified structural equation modeling approach for the analysis of multisubject, multivariate functional MRI data.

The ultimate goal of brain connectivity studies is to propose, test, modify, and compare certain directional brain pathways. Path analysis or structural equation modeling (SEM) is an ideal statistical method for such studies. In this work, we propose a two-stage unified SEM plus GLM (General Linear Model) approach for the analysis of multisubject, multivariate functional magnetic resonance imaging (fMRI) time series data with subject-level covariates. In Stage 1, we analyze the fMRI multivariate time series for each subject individually via a unified SEM model by combining longitudinal pathways represented by a multivariate autoregressive (MAR) model, and contemporaneous pathways represented by a conventional SEM. In Stage 2, the resulting subject-level path coefficients are merged with subject-level covariates such as gender, age, IQ, etc., to examine the impact of these covariates on effective connectivity via a GLM. Our approach is exemplified via the analysis of an fMRI visual attention experiment. Furthermore, the significant path network from the unified SEM analysis is compared to that from a conventional SEM analysis without incorporating the longitudinal information as well as that from a Dynamic Causal Modeling (DCM) approach.

Attention↗

PubMed2006

Regulation of EphA8 gene expression by TALE homeobox transcription factors during development of the mesencephalon.

The mouse ephA8 gene is expressed in a rostral-to-caudal gradient in the developing superior colliculus, and these EphA gradients may contribute to the proper development of the retinocollicular projection. Thus, it is of considerable interest to elucidate how the ephA8 gene expression is controlled by upstream regulators during the development of the mesencephalon. In this study, we employed in vivo expression analysis in transgenic mouse embryos to dissect the cis-acting DNA regulatory region, leading to the identification of a CGGTCA sequence critical for the ephA8 enhancer activity. Using this element as the target in a yeast one-hybrid system, we identified a Meis homeobox transcription factor. Significantly, DNA binding sites for Pbx, another TALE homeobox transcription factor, were also identified in the ephA8 enhancer region. Meis2 and Pbx1/2 are specifically expressed in the entire region of the dorsal mesencephalon, where specific colocalization of EphA8 and Meis is restricted to a subset of cells. Meis2 and Pbx2 synergistically bind the ephA8 regulatory sequence in vitro, and this interaction is critical for the transcriptional activation of a reporter construct bearing the ephA8 regulatory region in the presence of histone deacetylase inhibitor. More importantly, when expressed in the embryonic midbrain, the dominant-negative form of Meis down-regulates endogenous ephA8. Interestingly, we found that both Meis2 and Pbx2 are constitutively bound in the ephA8 regulatory region in the dorsal mesencephalon. These studies strongly suggest that Meis and Pbx homeobox transcription factors tightly associate with the ephA8 regulatory sequence and require an additional unidentified regulator to ensure the specific activation of ephA8.

Animals↗

PubMed2006

Palatal fusion - where do the midline cells go? A review on cleft palate, a major human birth defect.

Formation of the palate, the organ that separates the oral cavity from the nasal cavity, is a developmental process characteristic to embryos of higher vertebrates. Failure in this process results in palatal cleft. During the final steps of palatogenesis, two palatal shelves outgrowing from the sides of the embryonic oronasal cavity elevate above the tongue, meet in the midline, and rapidly fuse together. Over the decades, multiple mechanisms have been proposed to explain how the superficial mucous membranes disappear from the contact line, thus allowing for normal midline mesenchymal confluence. A substantial body of experimental evidence exists for cell death, cell migration, epithelial-to-mesenchymal transdifferentiation (EMT), replacement through new tissue intercalation, and other mechanisms. However, the most recent use of gene recombination techniques in cell fate tracking disfavors the EMT concept, and suggests that apoptosis is the major fate of the midline cells during physiological palatal fusion. This article summarizes the benefits and drawbacks of histochemical and molecular tools used to determine the fates of cells within the palatal midline. Mechanisms of normal disintegration of the midline epithelial seam are reviewed together with pathologic processes that prevent this disintegration, thus causing cleft palate.

Animals↗

PubMed2006

Panax ginseng induces human Type I collagen synthesis through activation of Smad signaling.

Skin aging appears to be principally related to a decrease in levels of Type I collagen, the primary component of the dermal layer of skin. It is important to introduce an efficient agent for effective management of skin aging; this agent should have the fewest possible side effects and the greatest wrinkle-reducing effect. In the course of screening collagen production-promoting agents, we obtained Panax ginseng C.A. Meyer. This study was designed to investigate the possible collagen production-promoting activities of Panax ginseng C.A. Meyer root extract (PGRE) in human dermal fibroblast cells. As a first step to this end, human COL1A2 promoter luciferase assay was performed in human dermal fibroblast cells. In this assay, PGRE activated human COL1A2 promoter activity in a concentration-dependent manner. Human Type I procollagen synthesis was also induced by PGRE. These results suggest that PGRE promotes collagen production in human dermal fibroblast cells. Additionally, we have attempted to characterize the mechanism of action of PGRE in Type I procollagen synthesis. PGRE was found to induce the phosphorylation of Smad2, an important transcription factor in the production of Type I procollagen. When applied topically in a human skin primary irritation test, PGRE did not induce any adverse reactions. Therefore, based on these results, we suggest the possibility that PGRE may be considered as an attractive, wrinkle-reducing candidate for topical application.

Antioxidants↗

PubMed2006

Epithelial and ectomesenchymal role of the type I TGF-beta receptor ALK5 during facial morphogenesis and palatal fusion.

Transforming growth factor beta (TGF-beta) proteins play important roles in morphogenesis of many craniofacial tissues; however, detailed biological mechanisms of TGF-beta action, particularly in vivo, are still poorly understood. Here, we deleted the TGF-beta type I receptor gene Alk5 specifically in the embryonic ectodermal and neural crest cell lineages. Failure in signaling via this receptor, either in the epithelium or in the mesenchyme, caused severe craniofacial defects including cleft palate. Moreover, the facial phenotypes of neural crest-specific Alk5 mutants included devastating facial cleft and appeared significantly more severe than the defects seen in corresponding mutants lacking the TGF-beta type II receptor (TGFbetaRII), a prototypical binding partner of ALK5. Our data indicate that ALK5 plays unique, non-redundant cell-autonomous roles during facial development. Remarkable divergence between Tgfbr2 and Alk5 phenotypes, together with our biochemical in vitro data, imply that (1) ALK5 mediates signaling of a diverse set of ligands not limited to the three isoforms of TGF-beta, and (2) ALK5 acts also in conjunction with type II receptors other than TGFbetaRII.

Activin Receptors, Type I↗

PubMed2006

Asiaticoside induces human collagen I synthesis through TGFbeta receptor I kinase (TbetaRI kinase)-independent Smad signaling.

Skin aging appears to be principally related to a decrease in the levels of type I collagen, the primary component of the skin dermis. Asiaticoside, a saponin component isolated from Centella asiatica, has been shown to induce type I collagen synthesis in human dermal fibroblast cells. However, the mechanism underlying asiaticoside-induced type I collagen synthesis, especially at a molecular level, remains only partially understood. In this study, we have attempted to characterize the action mechanism of asiaticoside in type I collagen synthesis. Asiaticoside was determined to induce the phosphorylation of both Smad 2 and Smad 3. In addition, we detected the asiaticoside-induced binding of Smad 3 and Smad 4. In a consistent result, the nuclear translocation of the Smad 3 and Smad 4 complex was induced via treatment with asiaticoside, pointing to the involvement of asiaticoside in Smad signaling. In addition, SB431542, an inhibitor of the TGFbeta receptor I (TbetaRI) kinase, which is known to be an activator of the Smad pathway, was not found to inhibit both Smad 2 phosphorylation and Type 1 collagen synthesis induced by asiaticoside. Therefore, our results show that asiaticoside can induce type I collagen synthesis via the activation of the TbetaRI kinase-independent Smad pathway.

Blotting, Western↗

PubMed2005

Modulation of effective connectivity by cognitive demand in phonological verbal fluency.

Verbal fluency is a classic neuropsychological measure of language production. Phonological verbal fluency involves the generation of words beginning with a specified letter, and its functional neuroanatomy is comprised of a distributed network of regions which is modulated by cognitive load. In order to investigate the functional relationship of these regions, the effective connectivity was analyzed with covariance structural equation modeling under conditions of varying cognitive load. Significant path coefficients were evident between the anterior cingulate, left middle frontal gyrus, and precuneus. The left middle frontal gyrus showed a facilitory projection to the precuneus which had a suppressive influence on anterior cingulate activation. With increasing cognitive demand, the left middle frontal projection to the precuneus became suppressive, and the path coefficient from the precuneus to the anterior cingulate showed a marked diminution in strength. The path analysis suggests that the lead-in process for letter verbal fluency may primarily involve an orthographic visual strategy. The marked changes in path coefficients with the increased cognitive load may reflect the greater demands placed on executive function. The significant changes in path coefficient values with increased cognitive demand indicate the importance of accounting for task difficulty not only in the interpretation of brain activation maps but also for effective connectivity measurements.

Adult↗

PubMed2005

The EphA8 receptor induces sustained MAP kinase activation to promote neurite outgrowth in neuronal cells.

Recent studies in our laboratory demonstrate that ligand-mediated activation of the EphA8 receptor critically regulates cell adhesion and migration. In this report, we show that the EphA8 receptor induces neurite outgrowth in NG108-15 cells in the absence of ligand stimulation. Using various deletion mutants lacking specific intracytoplasmic regions, we confirm that the tyrosine kinase domain of EphA8 is important for inducing neurite outgrowth. However, the tyrosine kinase activity of EphA8 is not crucial for neurite outgrowth induction. Treatment with various inhibitors further reveals that the mitogen-activated protein kinase (MAPK) signaling pathway is critical for neurite outgrowth induced by EphA8. Consistent with these results, EphA8 expression induced a sustained increase in the activity of MAPK, whereas ligand-mediated EphA8 activation had no further modulatory effects on MAP kinase activity. Additionally, activated MAPK relocalized from the cytoplasm to the nucleus in response to EphA8 transfection. These results collectively suggest that the EphA8 receptor is capable of inducing a sustained increase in MAPK activity, thereby promoting neurite outgrowth in neuronal cells.

Animals↗

PubMed2005

Anti-inflammatory effects of magnolol and honokiol are mediated through inhibition of the downstream pathway of MEKK-1 in NF-kappaB activation signaling.

Propionibacterium acnes, an anaerobic pathogen, plays an important role in the pathogenesis of acne and seems to initiate the inflammatory process by producing proinflammatory cytokines. In order to demonstrate the anti-inflammatory effects and action mechanisms of magnolol and honokiol, several methods were employed. Through DPPH and SOD activity assays, we found that although both magnolol and honokiol have antioxidant activities, honokiol has relatively stronger antioxidant activities than magnolol {[for DPPH assay, % of DPPH bleaching of magnolol and honokiol (500 microM magnolol: 19.8%; 500 microM honokiol: 67.3%)]; [for SOD assay, SOD activity (200 microM magnolol: 53.4%; 200 microM honokiol: 64.3%)]}. Moreover, the production of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) induced by P. acnes in THP-1 cells, a human monocytic cell line, was reduced by magnolol and honokiol {[for IL-8 (10 microM magnolol: 42.7% inhibition; 10 microM honokiol: 51.4% inhibition)]; [for TNF-alpha (10 microM magnolol: 20.3% inhibition; 10 microM honokiol: 39.0% inhibition)]}. Cyclooxygenase-2 (Cox-2) activity was also suppressed by them [(15 microM magnolol: 45.8% inhibition), (15 microM honokiol: 66.3% inhibition)]. Using a nuclear factor-kappaB (NF-kappaB) luciferase reporter assay system and Western analysis, we identified that magnolol and honokiol exert their anti-inflammatory effects by inhibiting the NF-kappaB element, which exists in Cox-2, IL-8, and TNF-alpha promoters [(15 microM magnolol: 44.8% inhibition), (15 microM honokiol: 42.3% inhibition)]. Of particular note is that magnolol and honokiol operate downstream of the MEKK-1 molecule. Together with their previously known antibacterial activity against P. acnes and based on these results, we suggest that magnolol and honokiol may be introduced as possible acne-mitigating agents.

Anti-Bacterial Agents↗

PubMed2005

Glycyrrhizin induces melanogenesis by elevating a cAMP level in b16 melanoma cells.

In mammalian melanocytes, melanin synthesis is controlled by tyrosinase, the critical enzyme in the melanogenic pathway. A recent report showed that the stimulation of melanogenesis by glycyrrhizin (GR) is because of an increased tyrosinase expression at mRNA and protein levels. But, the molecular events of melanogenesis induced by GR remain to be elucidated. In this study, using B16 melanoma cells, we showed that GR activated activator protein-1 (AP-1) and cyclic response filament "CRE" promoters, but not the nuclear factor-kappaB promoter. In addition, although GR stimulated mitogen-activated protein (MAP) kinase, p42/44(mapk), consistent with GR-induced AP-1 promoter activation, GR-induced melanogenesis was not blocked by PD98059, an MEK1 inhibitor, suggesting that MAPkinase induced by GR does not have a direct effect on the level of melanin content. But, GR-induced melanogenesis was inhibited by an inhibitor of protein kinase A (H-89). This result was further confirmed by the fact that GR induced the phosphorylation of CRE binding protein (CREB) and inhibition of glycogen synthase kinase 3beta phosphorylation as well as the production of cAMP, indicating that GR induces melanogenesis through cAMP signaling. In addition, the fact that GR-induced CRE activation was blocked by H-89 but GR-induced increase of cAMP production was not suggests that GR operates upstream of protein kinase A.

Animals↗

PubMed2004

In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp.

Honokiol and magnolol, two major phenolic constituents of Magnolia sp., have been known to exhibit antibacterial activities. However, until now, their antibacterial activity against Propionibacterium sp. has not been reported. To this end, the antibacterial activities of honokiol and magnolol were detected using the disk diffusion method and a two-fold serial dilution assay. Honokiol and magnolol showed strong antibacterial activities against both Propionibacterium acnes and Propionibacterium granulosum, which are acne-causing bacteria. The minimum inhibitory concentrations (MIC) of honokiol and magnolol was 3-4 microg/ml (11.3-15 microM) and 9 microg/ml (33.8 microM), respectively. In addition, the killing curve analysis showed that magnolol and honokiol killed P. acnes rapidly, with 10(5) organisms/ml eliminated within 10 min of treatment with either 45 microg (169.2 microM) of magnolol or 20 microg (75.2 microM) of honokiol per ml. The cytotoxic effect of honokiol and magnolol was determined by a colorimetric (3-(4,5-dimetyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) (MTT) assay using two animal cell lines, human normal fibroblasts and HaCaT. In this experiment, magnolol exhibited lower cytotoxic effects than honokiol at the same concentration, but they showed similar cytotoxicity when triclosan was employed as an acne-mitigating agent. In addition, they reduced secretion of interleukin-8 and tumor necrosis factor alpha (TNF-alpha) induced by P. acnes in THP-1 cells indicating the anti-inflammatory effects of them. When applied topically, neither phenolic compound induced any adverse reactions in a human skin primary irritation test. Therefore, based on these results, we suggest the possibility that magnolol and honokiol may be considered as attractive acne-mitigating candidates for topical application.

Adult↗

PubMed2004

Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study.

BACKGROUND: Depression is associated with interpersonal difficulties related to abnormalities in affective facial processing. OBJECTIVES: To map brain systems activated by sad facial affect processing in patients with depression and to identify brain functional correlates of antidepressant treatment and symptomatic response. DESIGN: Two groups underwent scanning twice using functional magnetic resonance imaging (fMRI) during an 8-week period. The event-related fMRI paradigm entailed incidental affect recognition of facial stimuli morphed to express discriminable intensities of sadness. SETTING: Participants were recruited by advertisement from the local population; depressed subjects were treated as outpatients. PATIENTS AND OTHER PARTICIPANTS: We matched 19 medication-free, acutely symptomatic patients satisfying DSM-IV criteria for unipolar major depressive disorder by age, sex, and IQ with 19 healthy volunteers. Intervention After the baseline assessment, patients received fluoxetine hydrochloride, 20 mg/d, for 8 weeks. MAIN OUTCOME MEASURES: Average activation (capacity) and differential response to variable affective intensity (dynamic range) were estimated in each fMRI time series. We used analysis of variance to identify brain regions that demonstrated a main effect of group (depressed vs healthy subjects) and a group x time interaction (attributable to antidepressant treatment). Change in brain activation associated with reduction of depressive symptoms in the patient group was identified by means of regression analysis. Permutation tests were used for inference. RESULTS: Over time, depressed subjects showed reduced capacity for activation in the left amygdala, ventral striatum, and frontoparietal cortex and a negatively correlated increase of dynamic range in the prefrontal cortex. Symptomatic improvement was associated with reduction of dynamic range in the pregenual cingulate cortex, ventral striatum, and cerebellum. CONCLUSIONS: Antidepressant treatment reduces left limbic, subcortical, and neocortical capacity for activation in depressed subjects and increases the dynamic range of the left prefrontal cortex. Changes in anterior cingulate function associated with symptomatic improvement indicate that fMRI may be a useful surrogate marker of antidepressant treatment response.

Affect↗

PubMed2004

Lateralization of epileptic foci by neuropsychological testing in mesial temporal lobe epilepsy.

This study investigated the lateralizing value of neuropsychological testing in presurgical evaluation of mesial temporal lobe epilepsy (MTLE). This study differed from previous ones in that the cutoff values were determined to yield high positive predictive values (PPVs), multiple neuropsychological predictors were considered in combination, and patients with atypical language dominance or low intelligence were not excluded from the sample. The participants were 92 patients with MTLE (left, n = 47; right, n = 45) who showed good postoperative seizure control. With a stringent cutoff criterion, the multiple neuropsychological predictors considered in combination yielded a sensitivity of 15% and a PPV of 93%, and with a less stringent cutoff criterion, a sensitivity of 37% and a PPV of 83%.

Adult↗

PubMed2003

Differential effects of left versus right mesial temporal lobe epilepsy on Wechsler intelligence factors.

This study investigates the effects of left versus right mesial temporal lobe epilepsy (MTLE) on Wechsler intelligence factors. In the left MTLE group, the Verbal Comprehension (VC) factor score was significantly lower than the Perceptual Organization (PO) factor score, whereas in the right MTLE group, the PO factor score was significantly lower than the VC factor score. The VC factor score was significantly lower for the left than the right MTLE group, whereas the PO factor score was significantly lower for the right than the left MTLE group. Thus, left versus right MTLE was associated with relative deficits in verbal versus nonverbal intelligence, respectively. These findings indicate that lateralized cognitive deficits in unilateral MTLE patients are not limited to the learning-memory domain but include more global intelligence functions.

Adult↗

PubMed2003

Material-specific memory in temporal lobe epilepsy: effects of seizure laterality and language dominance.

This study investigated the effects of seizure laterality and language dominance on material-specific memory in temporal lobe epilepsy (TLE). Left TLE (LTLE) patients with left-hemisphere language dominance (LHLD) showed significantly higher nonverbal than verbal memory capacity, whereas right TLE patients with LHLD showed significantly better verbal than nonverbal memory capacity. LTLE patients with non-left-hemisphere language dominance (NLHLD) showed significantly better verbal memory capacity compared with LTLE patients with LHLD. Thus, selective verbal or nonverbal memory deficits that are dependent on side of seizure onset were apparent in patients with LHLD but not in patients with NLHLD. Relative sparing of verbal memory capacity in LTLE patients with NLHLD may reflect interhemispheric reorganization of verbal memory function.

Adult↗