Near-Infrared Imaging Survey of Faint Companions around Young Dwarfs in the Pleiades Cluster

We conducted a near-infrared imaging survey of 11 young dwarfs in the Pleiades cluster using the Subaru Telescope and the near-infrared coronagraph imager. We found 10 faint point sources, with magnitudes as faint as 20 mag in the K-band, around 7 dwarfs. Comparison with Spitzer archive images revealed that a pair of the faint sources around V 1171 Tau are very red in the infrared wavelengths, indicative of very low-mass young stellar objects. However, the results of our follow-up proper motion measurements implied that the central star and the faint sources do not share common proper motions, suggesting that they are not physically associated.Comment: 13 pages. Accepted for publication in Research in Astronomy and Astrophysic

Near-Infrared Coronagraphic Observations of the T Tauri Binary System UY Aur

We present a near-infrared image of UY Aur, a 0.9" separated binary system, using the Coronagraphic Imager with Adaptive Optics on the Subaru Telescope. Thanks to adaptive optics, the spatial resolution of our image was ~0.1" in the full width at half maximum of the point spread function, the highest achieved. By comparison with previous measurements, we estimated that the orbital period is ~1640 yrs and the total mass of the binary is ~1.73 solar mass. The observed H-band magnitude of the secondary varies by as much as 1.3 mag within a decade, while that of the primary is rather stable. This inconstancy may arise from photospheric variability caused by an uneven accretion rate or from the rotation of the secondary. We detected a half-ring shaped circumbinary disk around the binary with a bright southwest part but a barely detectable northeast portion. The brightness ratio is ~57. Its inner radius and inclination are about 520 AU and 42, respectively. The disk is not uniform but has remarkable features, including a clumpy structure along the disk, circumstellar material inside the inner cavity, and an extended armlike structure. The circumstellar material inside the cavity probably corresponds to a clump or material accreting from the disk onto the binary. The armlike structure is a part of the disk, created by the accretion from the outer region of the disk or encounters with other stellar systems.Comment: 16 pages, 6 figures; accepted for publication in A

iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD). Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ), a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development

Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

ヒトiPS細胞由来のグリア系神経前駆細胞移植でALSモデルマウスの生存期間を延長. 京都大学プレスリリース. 2014-06-27.Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1)-mediated amyotrophic lateral sclerosis (ALS). However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source

Induced pluripotent stem cells derived from a patient with familial idiopathic basal ganglia calcification (IBGC) caused by a mutation in SLC20A2 gene

Idiopathic basal ganglia calcification (IBGC), also known as Fahr disease or primary familial brain calcifications (PFBC), is a rare neurodegenerative disorder characterized by calcium deposits in basal ganglia and other brain regions, causing neuropsychiatric and motor symptoms. We established human induced pluripotent stem cells (iPSCs) from an IBGC patient. The established IBGC-iPSCs carried SLC20A2 c.1848G > A mutation (p.W616* of translated protein PiT2), and also showed typical iPSC morphology, pluripotency markers, normal karyotype, and the ability of in vitro differentiation into three-germ layers. The iPSC line will be useful for further elucidating the pathomechanism and/or drug development for IBGC

Establishment of DYT5 patient-specific induced pluripotent stem cells with a GCH1 mutation

Peripheral blood mononuclear cells (PBMCs) were collected from a clinically diagnosed 20-year-old dystonia patient with a GCH1 mutation (DYT5). Episomal vectors were used to introduce reprogramming factors (OCT3/4, SOX2, KLF4, L-MYC, LIN28, and p53 carboxy-terminal dominant-negative fragment) to the PBMCs. The generated iPSCs expressed pluripotency markers, and were capable of differentiating into derivates of all three germ layers in vitro. The iPSC line also showed a normal karyotype and preserved the GCH1 mutation. This cellular model can provide opportunities to perform pathophysiological studies for aberrant dopamine metabolism-related disorders

Modeling Alexander disease with patient iPSCs reveals cellular and molecular pathology of astrocytes

Alexander disease is a fatal neurological illness characterized by white-matter degeneration and formation of Rosenthal fibers, which contain glial fibrillary acidic protein as astrocytic inclusion. Alexander disease is mainly caused by a gene mutation encoding glial fibrillary acidic protein, although the underlying pathomechanism remains unclear. We established induced pluripotent stem cells from Alexander disease patients, and differentiated induced pluripotent stem cells into astrocytes. Alexander disease patient astrocytes exhibited Rosenthal fiber-like structures, a key Alexander disease pathology, and increased inflammatory cytokine release compared to healthy control. These results suggested that Alexander disease astrocytes contribute to leukodystrophy and a variety of symptoms as an inflammatory source in the Alexander disease patient brain. Astrocytes, differentiated from induced pluripotent stem cells of Alexander disease, could be a cellular model for future translational medicine

Induced pluripotent stem cells derived from an autosomal dominant lateral temporal epilepsy (ADLTE) patient carrying S473L mutation in leucine-rich glioma inactivated 1 (LGI1)

Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited epileptic syndrome, and it is associated with mutations of leucine-rich glioma inactivated 1 (LGI1) gene. The underlying mechanisms of ADLTE are still unknown, as human neurons are difficult to obtain as a research tool. Human induced pluripotent stem cells (iPSCs) allow the generation of patient-derived neuronal cells in a dish, and can be a promising tool to model ADLTE. Here, we report the establishment of human iPSCs from an ADLTE patient carrying LGI1 mutation (c.1418C>T, p.Ser473Leu)