Hox Genes are Differentially Expressed during Mouse Placentation

The placenta is an extraembryonic tissue that is formed between mother and fetus and mediates delivery of nutrients and oxygen from the mother to the fetus. Because of its essential role in sustaining the growth of the fetus during gestation, defects in its development and function frequently result in fetal growth retardation or intrauterine death, depending on its severity. Vertebrate Hox genes are well known transcription factors that are essential for the proper organization of the body plan during embryogenesis. However, certain Hox genes have been known to be expressed in placenta, implying that Hox genes not only play a crucial role during embryonic patterning but also play an important role in placental development. So far, there has been no report that shows the expression pattern of the whole Hox genes during placentation. In this study, therefore, we investigated the Hox gene expression pattern in mouse placenta, from day 10.5 to 18.5 of gestation using real-time RT-PCR method. In general, the 5" posterior Hox genes were expressed more in the developing placenta compared to the 3" Hox genes. Statistical analysis revealed that the expression of 15 Hox genes (Hoxa9, -a11, -a13/ -b8, -b9/ -c6, -c9, -c13/ -d1, -d3, -d8, -d9, -d10, -d11, -d12) were significantly changed in the course of gestation. The majority of these genes showed highest expression at gestational day 10.5, suggesting their possible role in the early stage during placental development.ope

Therapeutic effect of NLRP3 inhibition on hearing loss induced by systemic inflammation in a CAPS-associated mouse model

Background: Cryopyrin-associated periodic syndrome (CAPS) is an inherited autoinflammatory disease caused by a gain-of-function mutation in NLRP3. Although CAPS patients frequently suffer from sensorineural hearing loss, it remains unclear whether CAPS-associated mutation in NLRP3 is associated with the progression of hearing loss. Methods: We generated a mice with conditional expression of CAPS-associated NLRP3 mutant (D301N) in cochlea-resident CX3CR1 macrophages and examined the susceptibility of CAPS mice to inflammation-mediated hearing loss in a local and systemic inflammation context. Findings: Upon lipopolysaccharide (LPS) injection into middle ear cavity, NLRP3 mutant mice exhibited severe cochlear inflammation, inflammasome activation and hearing loss. However, this middle ear injection model induced a considerable hearing loss in control mice and inevitably caused an inflammation-independent hearing loss possibly due to ear tissue damages by injection procedure. Subsequently, we optimized a systemic LPS injection model, which induced a significant hearing loss in NLRP3 mutant mice but not in control mice. Peripheral inflammation induced by a repetitive low dose of LPS injection caused a blood-labyrinth barrier disruption, macrophage infiltration into cochlea and cochlear inflammasome activation in an NLRP3-dependent manner. Interestingly, both cochlea-infiltrating and -resident macrophages contribute to peripheral inflammation-mediated hearing loss of CAPS mice. Furthermore, NLRP3-specific inhibitor, MCC950, as well as an interleukin-1 receptor antagonist significantly alleviated systemic LPS-induced hearing loss and inflammatory phenotypes in NLRP3 mutant mice. Interpretation: Our findings reveal that CAPS-associated NLRP3 mutation is critical for peripheral inflammation-induced hearing loss in our CAPS mice model, and an NLRP3-specific inhibitor can be used to treat inflammation-mediated sensorineural hearing loss. Funding: National Research Foundation of Korea Grant funded by the Korean Government and the Team Science Award of Yonsei University College of Medicine.ope

Dysregulation of sonic hedgehog signaling causes hearing loss in ciliopathy mouse models

Defective primary cilia cause a range of diseases known as ciliopathies, including hearing loss. The etiology of hearing loss in ciliopathies, however, remains unclear. We analyzed cochleae from three ciliopathy mouse models exhibiting different ciliogenesis defects: Intraflagellar transport 88 (Ift88), Tbc1d32 (a.k.a. bromi), and Cilk1 (a.k.a. Ick) mutants. These mutants showed multiple developmental defects including shortened cochlear duct and abnormal apical patterning of the organ of Corti. Although ciliogenic defects in cochlear hair cells such as misalignment of the kinocilium are often associated with the planar cell polarity pathway, our results showed that inner ear defects in these mutants are primarily due to loss of sonic hedgehog signaling. Furthermore, an inner ear-specific deletion of Cilk1 elicits low-frequency hearing loss attributable to cellular changes in apical cochlear identity that is dedicated to low-frequency sound detection. This type of hearing loss may account for hearing deficits in some patients with ciliopathies.ope

Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea

Sound frequency discrimination begins at the organ of Corti in mammals and the basilar papilla in birds. Both of these hearing organs are tonotopically organized such that sensory hair cells at the basal (proximal) end respond to high frequency sound, whereas their counterparts at the apex (distal) respond to low frequencies. Sonic hedgehog (Shh) secreted by the developing notochord and floor plate is required for cochlear formation in both species. In mice, the apical region of the developing cochlea, closer to the ventral midline source of Shh, requires higher levels of Shh signaling than the basal cochlea farther away from the midline. Here, gain-of-function experiments using Shh-soaked beads in ovo or a mouse model expressing constitutively activated Smoothened (transducer of Shh signaling) show up-regulation of apical genes in the basal cochlea, even though these regionally expressed genes are not necessarily conserved between the two species. In chicken, these altered gene expression patterns precede morphological and physiological changes in sensory hair cells that are typically associated with tonotopy such as the total number of stereocilia per hair cell and gene expression of an inward rectifier potassium channel, IRK1, which is a bona fide feature of apical hair cells in the basilar papilla. Furthermore, our results suggest that this conserved role of Shh in establishing cochlear tonotopy is initiated early in development by Shh emanating from the notochord and floor plate.ope

미국 양적완화정책이 한국 주식시장에 미치는 영향

This paper studies the effects of the United States (US) quantitative easing on Korea by examining Financial market. Korea is an intriguing case because of its borderline position between advanced and emerging market country groups. In particular, we investigate the causality relationships by applying vector autoregressive (VAR) analysis. Our basic approach is to take the period of December 2001 - May 2014, when quantitative easing (QE) took place. We used four variables which are US Money Supply (M2), Korea Money Supply (M2), S&P500, and KOSPI. And we do Granger causality test to determine the Grager-cause between variables. Then we explain the relationship among these four factors with impulse response function. Notably, we provide evidence that the US Money Supply positively affects KOSPI and S&P500 during QE policy. We also investigate the impacts of QE policy on the relationship between S&P500 and KOSPI, and find that KOSPI positively affected by S&P500.;본 논문은 미국의 양적완화정책이 우리나라의 주식시장에 미치는 영향을 살펴보기 위해서 2001년 12월부터 2014년 5월까지 월별 시계열 자료를 사용하여 벡터자귀회귀모형(VAR)을 사용하여 실증 분석하였다. 사용된 변수는 미국 통화공급(M2), 한국 통화공급(M2)과 KOSPI와 S&P 500 이다. 분석결과 첫째, 금융위기 이전에는 미국의 통화공급이 한국주식시장에 유의한 영향을 미치지 못하였다. 하지만 금융위기 이후에는 미국의 통화공급이 한국주식시장에 양(+)의 영향을 미쳤다. 또한 미국의 주식시장이 한국주식시장에도 양의(+)의 영향을 미쳤다. 둘째, 금융위기 이전 이후 모두 장기일치적 균형과계인 공적분이 존재하지 않았다. 셋째, 그랜져 인과관계 분석결과, 전체기간동안 미국 주식시장과 미국 통화공급만이 쌍방 인과관계가 있었으며, 금융위기 이전에는 인과관계가 없었다. 또한 금융위기 이전에는 오직 KOSPI가 한국 통화공급에 일방적 인과관계가 있었다. 금융위기 이후에는 미국 통화공급이 한국 통화공급, KOSPI와 S&P 500에 일방적 인과관계가 있었다.Ⅰ. Introduction 1 Ⅱ. Related literature 3 2.1 Quantitative Easing of the US 3 2.2 Theoretical related studies 6 Ⅲ. Data 9 3.1 The Source of data 9 3.2 Description of data 10 Ⅳ. Methodologies 12 4.1 Unit Root Test 12 4.2 Johansen Cointegration Test 14 4.3 Granger Causality 17 4.4 Vector Autoregression Model 19 4.5 Impulse response and Variance decomposition 21 Ⅴ. Application and Empirical results 23 5.1 Unit root test 23 5.2 Lag length selection in VAR models 26 5.3 Cointegration Test: The Johansen Test 27 5.4 Granger Causality Test 28 5.5 Vector Auto-regression (VAR) 31 5.6 Impulse responses analysis and variance decomposition33 Ⅵ. Conclusion 36 A. Bibliography 37 B. Appendix 39 국문초록 4

(The)Role of prosody in second language sentence processing

Thesis (master`s)--서울대학교 대학원 :외국어교육과 영어전공,2003.Maste

척추동물 와우의 tonotopic organization의 형성 기전

The auditory organ is able to discriminate the sound frequencies. Sound frequency discrimination starts at the basilar papilla in birds and the organ of Corti in mammals. These auditory organs tonotopically organized with a basal end (proximal region) that detects high frequencies and an apical end (distal region) that senses low frequencies. Sonic Hedgehog (Shh) secreted from the notochord and floor plate is crucial for cochlear duct development in species. Early otocyst is required high level of Shh signaling secreted in ventral midline source at apex but not at base in chicken and mouse. In this study, gain-of-function experiment involving of Shh-soaked beads in chicken embryo in ovo and in a continuously activated Shh signaling pathway mouse model, demonstrated the specification of the positional identity of the cochlear duct in these animal species. However, region specified regulator genes are not conserved between the both species. In chicken, expression of these altered genes, led to morphological and physiological characteristic alterations in hair cells. These features included tonotopic properties, such as the total number of stereocilia per hair cell and gene expression of an inward rectifier potassium channel (IRK), Kcnj2, which is an inherent characteristics of apical hair cells in the basilar papilla. In addition, this study suggests that Shh from the ventral midline, is required for the tonotopic organization during the developing cochlear duct in avian and mammal species.open박

Magnetic Force Nanoprobe for Direct Observation of Audio Frequency Tonotopy of Hair Cells.

Sound perception via mechano-sensation is a remarkably sensitive and fast transmission process, converting sound as a mechanical input to neural signals in a living organism. Although knowledge of auditory hair cell functions has advanced over the past decades, challenges remain in understanding their biomechanics, partly because of their biophysical complexity and the lack of appropriate probing tools. Most current studies of hair cells have been conducted in a relatively low-frequency range (<1000 Hz); therefore, fast kinetic study of hair cells has been difficult, even though mammalians have sound perception of 20 kHz or higher. Here, we demonstrate that the magnetic force nanoprobe (MFN) has superb spatiotemporal capabilities to mechanically stimulate spatially-targeted individual hair cells with a temporal resolution of up to 9 μs, which is equivalent to approximately 50 kHz; therefore, it is possible to investigate avian hair cell biomechanics at different tonotopic regions of the cochlea covering a full hearing frequency range of 50 to 5000 Hz. We found that the variation of the stimulation frequency and amplitude of hair bundles creates distinct mechanical responsive features along the tonotopic axis, where the kinetics of the hair bundle recovery motion exhibits unique frequency-dependent characteristics: basal, middle, and apical hair bundles can effectively respond at their respective ranges of frequency. We revealed that such recovery kinetics possesses two different time constants that are closely related to the passive and active motilities of hair cells. The use of MFN is critical for the kinetics study of free-standing hair cells in a spatiotemporally distinct tonotopic organization.restrictio