Induced Pluripotent Stem Cells for Clinical Use

Induced pluripotent stem cells (iPSCs) are expected to be a novel cell source for regenerative medicine. Although iPSCs represented a significant breakthrough, there were many initial obstacles for their clinical use such as exogenous sequence insertions, inefficient cell reprogramming, tumorigenic properties, and animal-derived culture components. However, much progress has been made in iPSC generation since their development. The first human trial of iPSC-derived cell transplantation was conducted in September 2014, in which iPSC-derived retinal pigment epithelial cells were transplanted to a patient with macular degeneration. Because multiple clinical trials using iPSCs are expected in the near future, preparation of guidelines for generating and selecting iPSC lines suitable for clinical application is a pressing issue

Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

BACKGROUND: Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue. METHODS: Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects. RESULTS: We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects. CONCLUSION: These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue

Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient.

Alteration of the nuclear Ca2+ transient is an early event in cardiac remodeling. Regulation of the nuclear Ca2+ transient is partly independent of the cytosolic Ca2+ transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca2+ homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca2+ transient. The cardiac hypertrophic stimuli increased the nuclear area, decreased nuclear invagination, and increased the half-decay time of the nuclear Ca2+ transient in cardiomyocytes. Emd knockdown cardiomyocytes showed similar properties after hypertrophic stimuli. The EDMD-iPS cell-derived cardiomyocytes showed increased nuclear area, decreased nuclear invagination, and increased half-decay time of the nuclear Ca2+ transient. An autopsied heart from a patient with EDMD also showed increased nuclear area and decreased nuclear invagination. These data suggest that Emerin plays a crucial role in nuclear structure and in the nuclear Ca2+ transient. Thus, emerin and the nuclear Ca2+ transient are possible therapeutic targets in heart failure and EDMD. © The Author(s) 2017

Reduced responsiveness is an essential feature of chronic fatigue syndrome: A fMRI study

BACKGROUND: Although the neural mechanism of chronic fatigue syndrome has been investigated by a number of researchers, it remains poorly understood. METHODS: Using functional magnetic resonance imaging, we studied brain responsiveness in 6 male chronic fatigue syndrome patients and in 7 age-matched male healthy volunteers. Responsiveness of auditory cortices to transient, short-lived, noise reduction was measured while subjects performed a fatigue-inducing continual visual search task. RESULTS: Responsiveness of the task-dependent brain regions was decreased after the fatigue-inducing task in the normal and chronic fatigue syndrome subjects and the decrement of the responsiveness was equivalent between the 2 groups. In contrast, during the fatigue-inducing period, although responsiveness of auditory cortices remained constant in the normal subjects, it was attenuated in the chronic fatigue syndrome patients. In addition, the rate of this attenuation was positively correlated with the subjective sensation of fatigue as measured using a fatigue visual analogue scale, immediately before the magnetic resonance imaging session. CONCLUSION: Chronic fatigue syndrome may be characterised by attenuation of the responsiveness to stimuli not directly related to the fatigue-inducing task

Difference between far-infrared photoconductivity spectroscopy and absorption spectroscopy: theoretical evidence of the electron reservoir mechanism

The intriguing difference between far-infrared photoconductivity spectroscopy and absorption spectroscopy in the measurement of the magnetoplasmon frequency in GaAs quantum wells reported by Holland et al. [Phys. Rev. Lett. 93, 186804 (2004)] remains unexplained to date. This Letter provides a consistent mechanism to solve this puzzle. The mechanism is based on the electron reservoir model for the integer quantum Hall effect in graphene [Phys. Lett. A 376, 616 (2012)]. We predict sharp kinks to appear in the magnetic induction dependence of the magnetoplasmon frequency at very low temperatures such as 14 mK in the same GaAs quantum well sample used by Holland et al.