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Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in mice

null

《医学前沿（英文）》 2016年第10卷第4期页码 481-489 doi: 10.1007/s11684-016-0494-3

摘要：

The tumor suppressor gene liver kinase B1 (LKB1), also called STK11, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice (LKB1^Pax2 CKO mice) were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1^Pax2 CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1^Pax2 CKO mice were clustered and misoriented, respectively. Moreover, ectopic distribution of kinocilium bundles resulting from abnormal migration of kinocilium was observed in the mutant mice. The orientation of stereociliary bundles and the migration of kinocilia are critical indicators of planar cell polarity (PCP) of hair cells. LKB1 deficiency in LKB1^Pax2 CKO mice thus disrupted hair cell planar polarity during embryonic development. Our results suggest that LKB1 is required in PCP formation in cochlear hair cells in mice.

关键词： LKB1 stereociliary bundles kinocilium planar cell polarity hearing mice

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is essential for the integrity of stereociliary rootlet in cochlear hair cells in mice

Yuqin Men, Xiujuan Li, Hailong Tu, Aizhen Zhang, Xiaolong Fu, Zhishuo Wang, Yecheng Jin, Congzhe Hou, Tingting Zhang, Sen Zhang, Yichen Zhou, Boqin Li, Jianfeng Li, Xiaoyang Sun, Haibo Wang, Jiangang Gao

《医学前沿（英文）》 2019年第13卷第6期页码 690-704 doi: 10.1007/s11684-018-0638-8

摘要： encodes the taperin protein, which is concentrated in the tapered region of hair cell stereocilia in the inner ear. In humans, mutations cause autosomal recessive nonsyndromic deafness (DFNB79) by an unknown mechanism. To determine the role of in hearing, we generated -null mice by clustered regularly interspaced short palindromic repeat/Cas9 genome-editing technology from a CBA/CaJ background. We observed significant hearing loss and progressive degeneration of stereocilia in the outer hair cells of -null mice starting from postnatal day 30. Transmission electron microscopy images of stereociliary bundles in the mutant mice showed some stereociliary rootlets with curved shafts. The central cores of the stereociliary rootlets possessed hollow structures with surrounding loose peripheral dense rings. Radixin, a protein expressed at stereocilia tapering, was abnormally dispersed along the stereocilia shafts in null mice. The expression levels of radixin and -actin significantly decreased. We propose that is critical to the retention of the integrity of the stereociliary rootlet. Loss of in -null mice caused the disruption of the stereociliary rootlet, which resulted in damage to stereociliary bundles and hearing impairments. The generated -null mice are ideal models of human hereditary deafness DFNB79.

关键词： TPRN stereocilia stereociliary rootlet actin filament CRISPR/Cas9 hearing

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Study of two-phase flow regime identification in horizontal tube bundles under vertical upward cross-flow

HUANG Xinghua, WANG Li, JIA Feng

《能源前沿（英文）》 2008年第2卷第3期页码 333-338 doi: 10.1007/s11708-008-0043-0

摘要： A wavelet-transform based approach for flow regime identification in horizontal tube bundles under vertical upward cross-flow condition was presented. Tests on two-phase flow pattern of R134a were conducted under low mass velocity and flow boiling conditions over ranges of mass flux 4–25 kg/ms, vapor quality 0.02–0.90. Time series of differential pressure fluctuations were measured and analyzed with discrete wavelet transform. Different time-scale characteristics in bubbly flow, churn flow and annular flow were analyzed. The wavelet energy distributions over scales were found to be appropriate for flow regime identification. Based on the wavelet energy distribution over characteristic scales, a criterion of flow regime identification was proposed. The comparison with experiment results show that it is feasible to use the discrete wavelet transform as the tool of flow regime identification in horizontal tube bundles under vertical upward cross-flow condition.

关键词： two-phase discrete appropriate wavelet-transform criterion