Targeted inversion and reversion of the blood coagulation factor 8 gene in human iPS cells using TALENs

Hemophilia A, one of the most common genetic bleeding disorders, is caused by various mutations in the blood coagulation factor VIII (F8) gene. Among the genotypes that result in hemophilia A, two different types of chromosomal inversions that involve a portion of the F8 gene are most frequent, accounting for almost half of all severe hemophilia A cases. In this study, we used a transcription activator-like effector nuclease (TALEN) pair to invert a 140-kbp chromosomal segment that spans the portion of the F8 gene in human induced pluripotent stem cells (iPSCs) to create a hemophilia A model cell line. In addition, we reverted the inverted segment back to its normal orientation in the hemophilia model iPSCs using the same TALEN pair. Importantly, we detected the F8 mRNA in cells derived from the reverted iPSCs lines, but not in those derived from the clones with the inverted segment. Thus, we showed that TALENs can be used both for creating disease models associated with chromosomal rearrangements in iPSCs and for correcting genetic defects caused by chromosomal inversions. This strategy provides an iPSC-based novel therapeutic option for the treatment of hemophilia A and other genetic diseases caused by chromosomal inversions.

Targeted inversion and reversion of the blood coagulation factor 8 gene in iPS cells using TALENs

Hemophilia A, one of the most common genetic bleeding disorders, is caused by various mutations in the blood coagulation factor VIII (F8) gene. Among the genotypes that result in hemophilia A, two different types of chromosomal inversions that involve a portion of the F8 gene are most frequent, accounting for almost half of all severe hemophilia A cases. In this study, we used a transcription activator-like effector nuclease (TALEN) pair to invert a 140-kbp chromosomal segment that spans the portion of the F8 gene in human induced pluripotent stem cells (iPSCs) to create a hemophilia A model cell line. In addition, we reverted the inverted segment back to its normal orientation in the hemophilia model iPSCs using the same TALEN pair. Importantly, we detected the F8 mRNA in cells derived from the reverted iPSCs lines, but not in those derived from the clones with the inverted segment. Thus, we showed that TALENs can be used both for creating disease models associated with chromosomal rearrangements in iPSCs and for correcting genetic defects caused by chromosomal inversions. This strategy provides an iPSC-based novel therapeutic option for the treatment of hemophilia A and other genetic diseases caused by chromosomal inversions.153591sciescopu

A Study of Skin Reflectance Using Kubelka-Munk Model

빛은 피부에서 개개인마다 상이한 반사, 흡수 및 산란 등의 광학적 거동을 보여준다. 특히, 피부에서 빛의반사는 분광반사율이라는 물리량 측정을 통해 개인의 피부 밝기지표로 널리 활용되어 왔다. 따라서 피부에서빛의 반사 거동 연구는 개인 맞춤형 화장품, 특히 메이크업 제품 개발에 있어 좀 더 효율적인 처방 개선에 기여하거나 새로운 평가법에 활용될 수 있다. 본 연구에서는 Kubelka-Munk 모델을 이용하여 개인의 피부 특성에 따른 빛의 분광반사율 거동에 대해 다각적인 분석을 수행하였다. 또한, 상기 모델과 기존에 알려진 문헌 정보를이용하여 개인의 피부 분광반사율에 영향을 줄 수 있는 피부 두께 및 헤모글로빈 등의 다양한 파라미터들에 대한기여도 분석을 수행하였다. 이를 통해, 일반적인 여성의 피부에서의 분광반사율 이론치를 계산하였고, 분광반사율 실측을 통해 이론치와 실측치 간의 유사성을 확인하였다. Kubelka-Munk 모델을 이용한 피부 분광반사율연구는 향후 새로운 개인 맞춤형 메이크업 화장품 개발에 유용하게 이용될 수 있을 것으로 사료된다. Light shows various optical behaviors such as reflection, absorption, and scattering on skin for individuals. In particular, reflection of light from the skin has been widely used as the brightness index of the skin of individuals through the measurement of the physical quantity of spectral reflectance. Therefore, the study of light behavior on skin would be useful for the preparation of new evaluation method in the development stage of make-up products. In this study, multi-dimensional analysis for spectral reflectance behavior of light on individual skin was performed using Kubelka-Munk model. Also, we analyzed the contribution of skin parameters such as skin thickness and hemoglobin, which could affect the spectral reflectance, using above model and literature information. Base on this, we calculated the theoretical reflectance of normal women for visual light, which showed good agreement with the measured reflectance. Our study of light propagation in skin based on Kubelka-Munk model provides useful insight for the development of personalized cosmetic in the near future.22Nkc

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present