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본 연구에서는 일본어 학습자의 가능표현의 사용이 모어, 레벨, 환경이라는 다 양한 요인과 어떻게 관계되어 있으며, 그 결과를 일본어 모어화자 데이터와 비교 검토함으로써 학습자의 가능표현 습득의 보편성과 특수성에 대해 밝히고자 하였 다. 이상의 분석을 통해 다음과 같은 사실을 알 수 있었다. (1) 학습자들의 일본어 가능표현의 사용은 ‘デキル형’이 중심이 되며, 이는 모 어･레벨･환경 요인에 관계없이 공통된다. 그리고 이는 모어화자의 사용과는 다른 학습자만의 특수성을 띠고 있다. (2) 학습자의 모어 요인은 가능형식의 사용 빈도, 접속 경향 등 가능표현의 사용 등에 특별한 상관관계를 나타내지 않는다. (3) 학습자의 레벨 요인은 3종류의 가능 형식 중에서 ‘デキル형’의 사용과 상관 관계를 지닌다. (4) 학습자의 환경 요인은 ‘デキル형’의 접속, 「ない」와의 사용 등과 상관관계를 지닌다. (5) 학습자와 모어화자의 가능표현 사용 양상을 비교 검토한 결과, 학습자의 중 간언어는 사용 형식의 측면에서 언어 외적 요인에 관계없이 보편성이 나타나며, 학습 레벨과 환경에 따른 특수성이 관찰된다.

This study attempted to clarify the universality and specificity of learners' acquisition of possible expressions by comparing and reviewing the results of the use of possible expressions of Japanese learners with various factors such as language, level, and environment. Through the above analysis, the following facts were found. (1) Learners' use of Japanese-speaking expressions is centered on the ‘Dekiru type’, which is common regardless of language, level, and environmental factors. And it has a unique characteristic of learners that is different from the use of more speakers. (2) The learner's more factors do not show any special correlation with the frequency of use of the possible form and the use of possible expressions such as access tendency. (3) The learner's level factor has a correlation with the use of the ‘Dekiru type’ among the three possible forms. (4) The learner's environmental factors have a correlation with the connection of the ‘Dekiru type’and the use with ‘Nai’. (5) As a result of comparing and reviewing the use of possible expressions by learners and native speakers, learners' intermediate languages show universality regardless of language-external factors in terms of usage type, and specificity according to learning level and environment is observed.

본 연구는 일본어 학습자들이 일본어 가능표현을 어떻게 습득해 가는지에 대해 밝히기 위하여 의미가 비슷한 유형의 문법항목 내에서 학습자들이 각각의 항목을 어떻게 구분하며 사용하고 있는지에 대해 운용분석의 관점에서 분석하는 것을 목적으로 한 것이다. 이를 위해 대규모 코퍼스 자료를 분석하여 JFL 환경의 학습자들이 가능표현을 습득함에 있어 3개의 가능형식을 레벨에 따라 어떻게 나누어 사용하는지, 그리고 그러한 사용 차이가 무엇을 의미하는지에 대해 살펴보았다. 분석 결과를 요약하면 다음과 같다. (1) 일본어 가능표현의 습득은 ‘デキル형’을 중심으로 이루어지며 중급 이후 ‘가능동사형’과 ‘(ラ)レル형’으로 확대되어 간다. (2) ‘가능동사형’은 레벨에 따른 사용 비율의 차이가 크지 않지만 ‘(ラ)レル형’은 레벨이 상승함에 따라 사용 비율이 증가한다. (3) ‘デキル형’의 경우, 학습 초기에는 「동사+こと(ガ)できる」의 형태로 주로 사용되지만 학습 중기 이후에는 「명사+(조사)+できる」의 형태로 분화된다. (4) 가능형식이 포함된 유닛은 특징적으로 나타나지 않지만 중위군의 학습자들에게서 「가능동사형+ない」, 「(ラ)レル+ない」라고 하는 정형적 사용 경향이 일부 관찰된다.

The purpose of this study is to analyze from the perspective of operational analysis how learners classify and use each item within grammar items of similar meaning in order to reveal how Japanese learners acquire Japanese expressions. To this end, large󰠏scale corpus data were analyzed to examine how learners in the JFL environment use the three possible forms divided by level in acquiring possible expressions, and what such differences in use mean. The analysis results are summarized as follows. (1) The acquisition of possible Japanese expressions is centered on the ‘Dekiru type’ and after the intermediate level, it expands to ‘Potential verbs type’ and ‘(Ra)Reru type’. (2) The ‘Potential verbs type’ does not have a large difference in the ratio of use according to the level, but the ‘(Ra)Reru type’ increases as the level increases. (3) In the case of the ‘Dekiru type’, it is mainly used in the form of ‘verb+koto(ga)dekiru’ in the early stages of learning, but after the middle of learning, it is divided into the form of ‘noun+(postposition)+dekiru’. (4) Units containing possible forms do not appear characteristically, but some formal use trends such as ‘Potential verbs type+nai’ and ‘(Ra)Reru type+nai’ are observed in the middle group of learners.

Oroxylin A is a flavone isolated from a medicinal herb reported to be effective in reducing the inflammatory and oxidative stresses. It also modulates the production of brain derived neurotrophic factor (BDNF) in cortical neurons by the transactivation of cAMP response element-binding protein (CREB). As a neurotrophin, BDNF plays roles in neuronal development, differentiation, synaptogenesis, and neural protection from the harmful stimuli. Adenosine $A2_A$ receptor colocalized with BDNF in brain and the functional interaction between $A2_A$ receptor stimulation and BDNF action has been suggested. In this study, we investigated the possibility that oroxylin A modulates BDNF production in cortical neuron through the regulation of $A2_A$ receptor system. As expected, CGS21680 ($A2_A$ receptor agonist) induced BDNF expression and release, however, an antagonist, ZM241385, prevented oroxylin A-induced increase in BDNF production. Oroxylin A activated the PI3K-Akt-GSK-$3{\beta}$ signaling pathway, which is inhibited by ZM241385 and the blockade of the signaling pathway abolished the increase in BDNF production. The physiological roles of oroxylin A-induced BDNF production were demonstrated by the increased neurite extension as well as synapse formation from neurons. Overall, oroxylin A might regulate BDNF production in cortical neuron through $A2_A$ receptor stimulation, which promotes cellular survival, synapse formation and neurite extension.

The purpose of this study is to analyze the discourse function and examine the distinctive characteristics of morpho-syntactic, semantic, and discourse of ‘-(으)ㄹ 수 있다/없다’ which is being taught as an important grammatical item and high in frequency of use by performing diverse discourse functions in various contexts in the four language register. For this purpose, the distribution and detailed characteristics are analyzed in 4 million word corpus consisting of academic prose, newspaper, fiction, and spoken. The main results are as follows. First, the morphological form, the sentence ending form, and the constituent elements in complex component are different from each other by language register when constructing a specific discourse function. Second, various interpretive meanings are derived from the meaning of ‘possibility’ and ‘impossibility’ which is combined with various contextual information related to the characteristics of language register. Third, it is found that the characteristics shared by the field, mode, style of discourse influence the use including preference style by language register.

Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C(PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and LĸB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction path-ways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins playa pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans.

Previously, we reported that DJ-1, encoded by a Parkinson’s disease (PD)-associated gene, inhibits expression of proinflammatorymediators in interferon-gamma (IFN-γ)-treated astrocytes and microglia through inhibition of STAT1 activation. Here, usingmicroglia and astrocytes cultured from wild-type (WT) and DJ-1-knockout (KO) mouse brains, we examined how DJ-1regulates suppressor of cytokine signaling 1 (SOCS1), a negative feedback regulator of STAT1 (signal transducer and activatorof transcription) that is also induced by STAT1. We found that IFN-γ significantly increased SOCS1 mRNA expression in WTmicroglia and astrocytes, but not in KO cells, although STAT1 was highly activated in these latter cells. We further found thatSOCS mRNA stability was decreased in DJ-1-KO cells, an effect that appeared to be mediated by the microRNA, miR-155. IFN-γincreased the levels of miR-155 in DJ-1-KO cells but not in WT cells. In addition, an miR-155 inhibitor rescued SOCS1 expressionand decreased STAT1 activation in DJ-1-KO cells. Taken together, these results suggest that DJ-1 efficiently regulates inflammationby maintaining SOCS1 expression through regulation of miR-155 levels, even under conditions in which STAT1 activation isdecreased.

Transcriptional silencing of subtelomeric genes is associated with telomere length, which is correlated with age. Long and short telomeres in young and old people, respectively, coincide with gene repression and activation in each case. In addition, differential location of genes with respect to telomeres causes telomere position effect. There is very little evidence of the manner in which age-related telomere length affects the expression of specific human subtelomeric genes. We analyzed the relationship between telomere length and gene expression levels in fibroblasts derived from human donors at ages ranging from 0-70 years. We studied three groups of genes located between 100 and 150 kb, 200 and 250 kb, and >300 kb away from telomeres. We found that the chromatin modifier-encoding genes Eu-HMTase1, ZMYND11, and RASA3 were overexpressed in adults. Our results suggest that short telomere length-related overexpression of chromatin modifiers could underlie transcriptional changes contributing to cellular senescence.

Background: Thyroid cancer is the most common endocrine malignancy, and exact causes remain unknown. The role of CYP450 1A1 (CYP1A1) in cancer initiation and progression has been investigated. The aim of this work was to analyze, for the first time, CYP1A1 gene expression and its relationship with several clinicopathological factors in Mexican patients diagnosed with thyroid cancer. Materials and Methods: Real-time PCR analysis was conducted on 32 sets of thyroid tumors and benign pathologies. Expression levels were tested for correlations with clinical and pathological data. All statistical analysis were performed using GraphPad Prism version 3.0 software. Results: We found that female gender was associated with thyroid cancer risk (P<0.05). A positive relationship was identified between CYP1A1 mRNA levels and the presence of chronic disease, alcohol use, tumor size, metastasis and an advanced clinical stage (P<0.05). Conclusions: The results suggest that CYP1A1 gene expression could be used as a marker for thyroid cancer.

A novel gene Jpk, originally isolated as a trans-acting factor associating with the position-specific regulatory element of murine Hox gene has been reported to be expressed differentially in the liver of diabetic animals. Therefore, in an attempt to develop a possible diagnostic marker and/or new therapeutic agent for the Diabetes Mellitus, we analysed the expression pattern of Jpk among organs of normal and diabetic Sprague-Dawley (SD) rats. Total RNAs were isolated from each organs (brain, lung, heart, liver, spleen, kidney, muscle, blood, and testis) of diabetic and normal rats in both normal feeding and after fasting condition. And then RT (reverse transcription) PCR has been performed using Jpk­specific primers. The Jpk gene turned out to be expressed in all organs tested, with some different expression profiles among normal and diabetes, though. Upon fasting, Jpk expressions were reduced in all organs tested except kidney, muscle and brain of normal rat. Whereas in diabetes, Jpk expressions were increased in all organs except heart, muscle and testis when fasted. Compared to the normal rat, the Jpk expression level in blood was remarkably upregulated (about 15-30times) in diabetic rat whether in normal feeding or fasting conditon, suggesting that the Jpk could be a candidate gene for the possible blood diagnostic marker for the Diabetes Mellitus.

The synaptic contacts of cochlear afferent fibers (CAFs) with inner hair cells (IHCs) are spatially segregated according to their firing properties. CAFs also exhibit spatially segregated vulnerabilities to noise. The CAF fibers contacting the modiolar side of IHCs tend to be more vulnerable. Noise vulnerability is thought to be due to the absence of neuroprotective mechanisms in the modiolar side contacting CAFs. In this study, we investigated whether the expression of neuroprotective Ca2+-buffering proteins is spatially segregated in CAFs. The expression patterns of calretinin, parvalbumin, and calbindin were examined in rat CAFs using immunolabeling. Calretinin-rich fibers, which made up ~50% of the neurofilament (NF)-positive fibers, took the pillar side course and contacted all IHC sides. NF-positive and calretinin-poor fibers took the modiolar side pathway and contacted the modiolar side of IHCs. Both fiber categories juxtaposed the C-terminal binding protein 2 (CtBP2) puncta and were contacted by synaptophysin puncta. These results indicated that the calretinin-poor fibers, like the calretinin-rich ones, were afferent fibers and probably formed functional efferent synapses. However, the other Ca2+-buffering proteins did not exhibit CAF subgroup specificity. Most CAFs near IHCs were parvalbumin-positive. Only the pillar-side half of parvalbumin-positive fibers coexpressed calretinin. Calbindin was not detected in any nerve fibers near IHCs. Taken together, of the Ca2+-buffering proteins examined, only calretinin exhibited spatial segregation at IHC-CAF synapses. The absence of calretinin in modiolar-side CAFs might be related to the noise vulnerability of the fibers.

Purpose: Recent findings of increased cathelicidin protein and its proteolytic fragmentsin rosacea suggest a pathogenic role for cathelicidin in this disease. The relationshipbetween cathelicidin and protease-activated receptor 2 (PAR-2) is thereforeof interest, as PAR-2, expressed principally in keratinocytes, regulates pro-inflammatory cytokine expression in the skin. The purpose of this study was to determine the relationship between expression of PAR-2 and cathelicidin in rosaceaand to test the effect of direct PAR-2 activation on cathelicidin expression in keratinocytes. Materials and Methods: Samples from 40 patients with clinicopathologicdiagnosis of rosacea and facial skin tissue samples from 20 patients with no specific findings or milium without inflammation were retrieved. Intensitiesof immunohistochemical staining for PAR-2 and cathelicidin were compared between normal and rosacea-affected skin tissues. Additionally, correlations betweenPAR-2 and cathelicidin staining intensities within rosacea patients were analyzed. In cultured keratinocytes, changes in PAR-2, cathelicidin, and vascular endothelialgrowth factor (VEGF) mRNA and protein were analyzed after treatment with PAR-2 activating peptide (AP). Results: Cathelicidin expression was significantlyhigher in rosacea skin tissues than in normal tissues (p<0.001), while PAR-2 expression was not significantly higher in rosacea tissues than in normal skin tissues. A positive correlation between PAR-2 and cathelicidin within rosacea samples was observed (R=0.330, p=0.037). After treatment of PAR-2 AP, both mRNA and protein levels for PAR-2, cathelicidin, and VEGF significantly increased in culturedkeratinocytes, compared with PAR-2 control peptide treatment. Conclusion: PAR-2 may participate in the pathogenesis of rosacea through activation of cathelicidinLL-37, a mediator of innate immune responses in the skin.

ObjectiveThis study aimed to analyze the expression pattern of glycogen synthase kinase 3β (GSK3β) and its phosphorylatedforms, GSK3β phosphorylated at Ser9 (pS9GSK3β), and GSK3β phosphorylated at Tyr216 (pY216GSK3β), in cervicalsquamous cell carcinoma (SCC) and adenocarcinoma (AC). MethodsWe performed immunohistochemical staining for GSK3β, pS9GSK3β, and pY216GSK3β in 64 SCC and 20 AC cases andcompared their expression patterns between the 2 tumor types. ResultsIncreased GSK3β and pS9GSK3β expression but decreased pY216GSK3β expression compared with that in the normalcervix were observed in both SCC and AC specimens. Specifically, the levels of GSK3β and pS9GSK3β were significantlyincreased in SCC and AC, respectively. GSK3β was localized in the nucleus and/or cytoplasm of SCC and AC cells. However, pS9GSK3β was predominantly localized in the membrane of AC cells, whereas it was present in the nucleusand/or cytoplasm of SCC cells. ConclusionThe results suggest that the phosphorylation status of GSK3β changes during cervical cancer development and thedifferent expression levels and patterns of GSK3β and pS9GSK3β are associated with the specific histologic phenotypeof cervical cancer.

Purpose: This study aimed to analyze G3BP1 and VEZT expression profiles in patients with gastric cancer, and examine the possible relationship between the expressions of each gene and clinicopathological factors. Materials and Methods: Expression of these genes in formalin-fixed paraffin embedded (FFPE) tissues, collected from 40 patients with gastric cancer and 40 healthy controls, was analyzed. Differences in gene expression among patient and normal samples were identified using the GraphPad Prism 5 software. For the analysis of real-time polymerase chain reaction products, GelQuantNET software was used. Results: Our findings demonstrated that both VEZT and G3BP1 mRNA expression levels were downregulated in gastric cancer samples compared with those in the normal controls. No significant relationship was found between the expression of these genes and gender (P-value, 0.4835 vs. 0.6350), but there were significant changes associated with age (P-value, 0.0004 vs. 0.0001) and stage of disease (P-value, 0.0019 vs. 0.0001). In addition, there was a direct relationship between VEZT gene expression and metastasis (P-value, 0.0462), in contrast to G3BP1 that did not demonstrate any significant correlation (P-value, 0.1833). Conclusions: The results suggest that expression profiling of VEZT and G3BP1 can be used for diagnosis of gastric cancer, and specifically, VEZT gene could be considered as a biomarker for the detection of gastric cancer progression.

A cDNA encoding a cysteine protease inhibitor (CPI) was isolated from the cDNA library of clamworm Perinereis aibuhitensis Grube. The deduced amino acid sequence analysis showed that the protein had 51%, 48%, and 48% identity with Zgc:153129 from Danio rerio, cystatin B from Theromyzon tessulatum, and the ChainA, stefin B tetramer from Homo sapiens, respectively. The gene was cloned into the intracellular expression vector pET-15b and expressed in Escherichia coli. The recombinant CPI (PA-CPI) was purified by affinity chromatography on Ni-charged resin and ion-exchange chromatography on DEAE-Sepharose FF. The relative molecular mass of PA-CPI was 16 kDa as deduced by SDS-PAGE. Activity analysis showed that the recombinant protein could inhibit the proteolytic activity of papain. A constitutive and secretive expression vector was also constructed, and the cDNA encoding CPI was subcloned into the vector for extracellular expression. Western blotting analysis results showed that the PA-CPI was secreted into the medium. Bioassay demonstrated that E. coli DH5${\alpha}$ harboring pUC18ompAcat-CPI showed a significant difference in mortality to the Asian longhorned beetle Anoplophora glabripennis compared with untransformed E. coli DH5${\alpha}$ and control.

Purpose: Substantive evidence supports a role of chronic stress in the development, maintenance, and even enhancement of functional bladder disorders such as interstitial cystitis/bladder pain syndrome (IC/BPS). Increased urinary frequency and bladder hyperalgesia have been reported in rodents exposed to a chronic stress paradigm. Here, we utilized a water avoidance stress (WAS) model in rodents to investigate the effect of chronic stress on vascular perfusion and angiogenesis. Methods: Female Wistar-Kyoto rats were exposed to WAS for 10 consecutive days. Bladder neck tissues were analyzed by western immunoblot for vascular endothelial growth factor (VEGF) and nerve growth factor precursor (proNGF). Vascular perfusion was assessed by fluorescent microangiography followed by Hypoxyprobe testing to identify regions of tissue hypoxia. Results: The expression of VEGF and proNGF in the bladder neck mucosa was significantly higher in the WAS rats than in the controls. There was a trend toward increased vascular perfusion, but without a statistically significant difference from the control group. The WAS rats displayed a 1.6-fold increase in perfusion. Additionally, a greater abundance of vessels was observed in the WAS rats, most notably in the microvasculature. Conclusions: These findings show that chronic psychological stress induces factors that can lead to increased microvasculature formation, especially around the bladder neck, the region that contains most nociceptive bladder afferents. These findings may indicate a link between angiogenesis and other inflammatory factors that contribute to structural changes and pain in IC/ BPS.