Genetic profiling of protein burden and nuclear export overload

Overproduction (op) of proteins triggers cellular defects. One of the consequences of overproduction is the protein burden/cost, which is produced by an overloading of the protein synthesis process. However, the physiology of cells under a protein burden is not well characterized. We performed genetic profiling of protein burden by systematic analysis of genetic interactions between GFP-op, surveying both deletion and temperature-sensitive mutants in budding yeast. We also performed genetic profiling in cells with overproduction of triple-GFP (tGFP), and the nuclear export signal-containing tGFP (NES-tGFP). The mutants specifically interacted with GFP-op were suggestive of unexpected connections between actin-related processes like polarization and the protein burden, which was supported by morphological analysis. The tGFP-op interactions suggested that this protein probe overloads the proteasome, whereas those that interacted with NES-tGFP involved genes encoding components of the nuclear export process, providing a resource for further analysis of the protein burden and nuclear export overload

Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors

Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts

Synthesis of Overall Dose Distribution for Multiple Radiation Therapy by Nonlinear Registration Method

In recent years, the precise irradiation methods, such as IMRT and heavyion radiotherapy, have developed and used widely for cancer treatment.They have made possible correct irradiation to complicated-shaped targetand greatly improved the effect of radiotherapy. Meanwhile, for thepatients who receive two or more radiotherapy because of a localrecurrence and/or a remote metastasis, for physicians it is necessary toplan the radiation treatment so that the dose distribution would notoverlap with previous radiation. Conventionally, a radiation oncologistdetermine a new plan by referring to a past radiation treatment planvisually. However, this work is very complex and difficult, and highskill is required of doctors. In this study, we tried to develop a nextgeneration system to support designing multiple treatments with reliableand effective radiation, and the nonlinear registration method foraligning the intra-subject X-ray CT images obtained on another day wasexamined.The goal of this study is to combine the dose distribution of therepeated radiation therapy on the nominal CT-image atlas and to evaluatethe tolerance dose of the each treated organs. This paper is the firststep of the study.CARS2011 ( 25rd International Congress and Exhibition