Induced pluripotent stem cells (iPSCs), which are used to produce transplantable tissues, may particularly benefit older patients, who are more likely to suffer from degenerative diseases. However, iPSCs generated from aged donors (A-iPSCs) exhibit higher genomic instability, defects in apoptosis and a blunted DNA damage response compared with iPSCs generated from younger donors. We demonstrated that A-iPSCs exhibit excessive glutathione-mediated reactive oxygen species (ROS) scavenging activity, which blocks the DNA damage response and apoptosis and permits survival of cells with genomic instability. We found that the pluripotency factor ZSCAN10 is poorly expressed in A-iPSCs and addition of ZSCAN10 to the four Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) during A-iPSC reprogramming normalizes ROS–glutathione homeostasis and the DNA damage response, and recovers genomic stability. Correcting the genomic instability of A-iPSCs will ultimately enhance our ability to produce histocompatible functional tissues from older patients’ own cells that are safe for transplantation.
Protein kinases play key roles in cellular functions. They are involved in many cellular functions including; signal transduction, cell cycle regulation, cell division, and cell differentiation. Alterations of protein kinase by gene amplification, mutation or viral factors often induce tumor formation and tumor progression toward malignancy. The identification and cloning of kinase genes can provide a better understanding of the mechanisms of tumorigenesis as well as diagnostic tools for tumor staging. In this study, we have used degenerated polymerase-chain-reaction primers according to the consensus catalytic domain motifs to amplify protein kinase genes (protein-tyrosine kinase, PTK, and protein-serine/threonine kinase, PSK) from human stomach cancer cells. Following amplification, the protein kinase molecules expressed in the gastric cancer cells were cloned into plasmid vectors for cloning and sequencing. Sequence analysis of polymerase-chain-reaction products resulted in the identification of 25 protein kinases, including two novel ones. Expression of several relevant PTK/PSK genes in gastric cancer cells and tissues was further substantiated by RT-PCR using gene-specific primers. The identification of protein kinases expressed or activated in the gastric cancer cells provide the framework to understand the oncogenic process of stomach cancer.
We demonstrate a swept-source optical coherence tomography system, including a broadband frequency sweeping light source with the central wavelength around 1250 nm, to achieve an axial resolution of 2.4 microns in tissue.
IntroductionThe spectral-domain optical coherence tomography (SDOCT) scheme using a fast frequency-sweeping light source (called a swept source) has the advantage of simple signal detection. However, the available swept source still sets constraint in SDOCT operation. So far, only the swept-source SDOCT operations of -1300 nm in central wavelength were reported. Although the fabrication of swept sources with the central wavelength shorter than one micron was reported, its further development for SDOCT operation is still unclear. Regarding the SDOCT operation in the 1300 nm wavelength range, so far the spectral full-widths at half-maximum (FWHMs) of the available swept (laser) sources are smaller than 120 nm, leading to the axial resolution limit of 6.2 microns in free space. Although the increase of the spectral width can be implemented, it may face certain technical difficulties, such as the slow-down of the frequency sweeping speed and the reduction of laser output power in increasing the laser tunable spectral width. Therefore, increasing the spectral width of a swept source for higher axial resolution in the 1300-nm spectral range without relying on the development of frequency-sweeping cw laser is important for SDOCT development. In this paper, we report the implementation of a swept-source SDOCT system based on a sweeping-frequency scheme of a spectrumexpanded Cr:forsterite laser. The output spectrum of a mode-locked Cr:forsterite laser is expanded from 35 nm to a FWHM of 150-220 nm through a high numerical-aperture (NA) fiber. The laser beam of expanded spectrum was swung through a setup of a resonance-scanning mirror. Then, the small aperture of a fiber collimator, connected to a fiber for delivering light to a free-space interferometer, receives the frequency-sweeping light for SDOCT operation. In the built SDOCT system, the largest sweeping spectral FWHM of 220 nm leads to the axial resolution of 3.3 microns in free space and hence 2.4 microns in tissue.
Autism spectrum disorder (ASD) imparts a tremendous health burden with psychological, social, and economic implications. The biology of ASD is complex involving genetic, molecular, hormonal and immunologic factors however the convergence point of these various factors has not been identified as of yet. Limited evidence exists to suggest that the placenta may play such a governing role in ASD manifestation. The placenta is a neuroendocrine modulator by participating in the fetal hypothalamic pituitary gonadal (HPG) axis and also regulates the intrauterine environment mitigating fetal exposure to damaging factors to modulate the fetal stress response. Placental dysfunction has been associated with developmental abnormality and neuropsychiatric pathology adding to the biologic plausibility of the governing role the placenta may play in ASD development. By using current technology like induced pluripotent stem cells (iPSCs), a practical model system can be created to study ASD providing an alternative method to further research the placenta in ASD development
First, we mistakenly incorporated two sentences in the first paragraph of the Introduction from an article by Venables et al. (2013). These two sentences have been deleted: "For example, different isoforms of Foxp1 produced from ESC-specific AS have differential effects on the induction of key pluripotency genes such as OCT4 and NANOG (Gabut et al. 2011). Similarly, alternative splice forms of DNMT3B are specific to stem cells, implying that layered and integrated regulation of gene expression occurs at the levels of transcription and splicing (Gopalakrishna-Pillai and Iverson 2011)." This text has been replaced as follows: "For example, different isoforms of Foxp1 and Oct4, which are important transcription factors that function in determining stem cell identities, are produced by ESC-specific AS, and this controls their transcriptional activities and targets (Atlasi et al. 2008; Gabut et al. 2011). Similarly, isoforms of DNMT3B produced by AS are also known to be specific for stem cells, suggesting that AS regulation contributes to maintaining a stem cell-specific epigenetic state in ESCs (Gopalakrishna-Pillai and Iverson 2011; Liao et al. 2015).
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