Intracellular Amyloid β Oligomers Impair Organelle Transport and Induce Dendritic Spine Loss in Primary Neurons

Introduction Synaptic dysfunction and intracellular transport defects are early events in Alzheimer’s disease (AD). Extracellular amyloid β (Aβ) oligomers cause spine alterations and impede the transport of proteins and organelles such as brain-derived neurotrophic factor (BDNF) and mitochondria that are required for synaptic function. Meanwhile, intraneuronal accumulation of Aβ precedes its extracellular deposition and is also associated with synaptic dysfunction in AD. However, the links between intracellular Aβ, spine alteration, and mechanisms that support synaptic maintenance such as organelle trafficking are poorly understood. Results We compared the effects of wild-type and Osaka (E693Δ)-mutant amyloid precursor proteins: the former secretes Aβ into extracellular space and the latter accumulates Aβ oligomers within cells. First we investigated the effects of intracellular Aβ oligomers on dendritic spines in primary neurons and their tau-dependency using tau knockout neurons. We found that intracellular Aβ oligomers caused a reduction in mushroom, or mature spines, independently of tau. We also found that intracellular Aβ oligomers significantly impaired the intracellular transport of BDNF, mitochondria, and recycling endosomes: cargoes essential for synaptic maintenance. A reduction in BDNF transport by intracellular Aβ oligomers was also observed in tau knockout neurons. Conclusions Our findings indicate that intracellular Aβ oligomers likely contribute to early synaptic pathology in AD and argue against the consensus that Aβ-induced spine loss and transport defects require tau

Current Performance and On-Going Improvements of the 8.2 m Subaru Telescope

An overview of the current status of the 8.2 m Subaru Telescope constructed and operated at Mauna Kea, Hawaii, by the National Astronomical Observatory of Japan is presented. The basic design concept and the verified performance of the telescope system are described. Also given are the status of the instrument package offered to the astronomical community, the status of operation, and some of the future plans. The status of the telescope reported in a number of SPIE papers as of the summer of 2002 are incorporated with some updates included as of 2004 February. However, readers are encouraged to check the most updated status of the telescope through the home page, http://subarutelescope.org/index.html, and/or the direct contact with the observatory staff.Comment: 18 pages (17 pages in published version), 29 figures (GIF format), This is the version before the galley proo

Augmentation of Neovascularizaiton in Hindlimb Ischemia by Combined Transplantation of Human Embryonic Stem Cells-Derived Endothelial and Mural Cells

BACKGROUND: We demonstrated that mouse embryonic stem (ES) cells-derived vascular endothelial growth factor receptor-2 (VEGF-R2) positive cells could differentiate into both endothelial cells (EC) and mural cells (MC), and termed them as vascular progenitor cells (VPC). Recently, we have established a method to expand monkey and human ES cells-derived VPC with the proper differentiation stage in a large quantity. Here we investigated the therapeutic potential of human VPC-derived EC and MC for vascular regeneration. METHODS AND RESULTS: After the expansion of human VPC-derived vascular cells, we transplanted these cells to nude mice with hindlimb ischemia. The blood flow recovery and capillary density in ischemic hindlimbs were significantly improved in human VPC-derived EC-transplanted mice, compared to human peripheral and umbilical cord blood-derived endothelial progenitor cells (pEPC and uEPC) transplanted mice. The combined transplantation of human VPC-derived EC and MC synergistically improved blood flow of ischemic hindlimbs remarkably, compared to the single cell transplantations. Transplanted VPC-derived vascular cells were effectively incorporated into host circulating vessels as EC and MC to maintain long-term vascular integrity. CONCLUSIONS: Our findings suggest that the combined transplantation of human ES cells-derived EC and MC can be used as a new promising strategy for therapeutic vascular regeneration in patients with tissue ischemia

The SPICA coronagraphic instrument (SCI) for the study of exoplanets

We present the SPICA Coronagraphic Instrument (SCI), which has been designed for a concentrated study of extra-solar planets (exoplanets). SPICA mission provides us with a unique opportunity to make high contrast observations because of its large telescope aperture, the simple pupil shape, and the capability for making infrared observations from space. The primary objectives for the SCI are the direct coronagraphic detection and spectroscopy of Jovian exoplanets in infrared, while the monitoring of transiting planets is another important target. The specification and an overview of the design of the instrument are shown. In the SCI, coronagraphic and non-coronagraphic modes are applicable for both an imaging and a spectroscopy. The core wavelength range and the goal contrast of the coronagraphic mode are 3.5--27$\mu$m, and 10$^{-6}$, respectively. Two complemental designs of binary shaped pupil mask coronagraph are presented. The SCI has capability of simultaneous observations of one target using two channels, a short channel with an InSb detector and a long wavelength channel with a Si:As detector. We also give a report on the current progress in the development of key technologies for the SCI.Comment: 22 pages, 10 figure

High resolution imaging polarimetry of HL Tau and magnetic field structure

We present high quality near infrared imaging polarimetry of HL Tau at 0.4 to 0.6 arcsec resolution, obtained with Subaru/CIAO and UKIRT/IRCAM. 3-D Monte Carlo modelling with aligned oblate grains is used to probe the structure of the circumstellar envelope and the magnetic field, as well as the dust properties. At J band the source shows a centrosymmetric pattern dominated by scattered light. In the H and K bands the central source becomes visible and its polarisation appears to be dominated by dichroic extinction, with a position angle inclined by ~40 degrees to the disc axis. The polarisation pattern of the environs on scales up to 200 AU is consistent with the same dichroic extinction signature superimposed on the centrosymmetric scattering pattern. These data can be modelled with a magnetic field which is twisted on scales from tens to hundreds of AU, or alternatively by a field which is globally misaligned with the disc axis. A unique solution to the field structure will require spatially resolved circular polarisation data. The best fit Monte Carlo model indicates a shallow near infrared extinction law. When combined with the observed high polarisation and non-negligible albedo these constraints can be fitted with a grain model involving dirty water ice mantles in which the largest particles have radii slightly in excess of 1 um. The best fit model has an envelope structure which is slightly flattened on scales up to several hundred AU. Both lobes of the bipolar outflow cavity contain a substantial optical depth of dust (not just within the cavity walls). Curved, approximately parabolic, cavity walls fit the data better than a conical cavity. The small inner accretion disc observed at millimetre wavelengths is not seen at this spatial resolution.Comment: Accepted by MNRAS, 21 pages, 10 figure

Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity

[EN] Cell transplantation therapies in the nervous system are frequently hampered by glial scarring and cell drain from the damaged site, among others. To improve this situation, new biomaterials may be of help. Here, novel single-channel tubular conduits based on hyaluronic acid (HA) with and without poly-l-lactide acid fibers in their lumen were fabricated. Rat Schwann cells were seeded within the conduits and cultured for 10days. The conduits possessed a three-layered porous structure that impeded the leakage of the cells seeded in their interior and made them impervious to cell invasion from the exterior, while allowing free transport of nutrients and other molecules needed for cell survival. The channel's surface acted as a template for the formation of a cylindrical sheath-like tapestry of Schwann cells continuously spanning the whole length of the lumen. Schwann-cell tubes having a diameter of around 0.5mm and variable lengths can thus be generated. This structure is not found in nature and represents a truly engineered tissue, the outcome of the specific cell-material interactions. The conduits might be useful to sustain and protect cells for transplantation, and the biohybrids here described, together with neuronal precursors, might be of help in building bridges across significant distances in the central and peripheral nervous system.The authors acknowledge financing through projects MAT2011-28791-C03-02 and 03, and ERA-NET NEURON project PRI-PIMNEU-2011-1372. We thank the Cytomics Core Facility at Principe Felipe Research Center (CIPF, Valencia, Spain) for their support and advice in flow cytometry experiments, and the Electron Microscopy Service at the UPV, where the SEM images were obtained. The authors thankfully acknowledge the reviewers' comments, which have helped to improve the clarity of the paper's presentation.Vilariño Feltrer, G.; Martínez Ramos, C.; Monleon De La Fuente, A.; Vallés Lluch, A.; Moratal Pérez, D.; Barcia Albacar, JA.; Monleón Pradas, M. (2016). Schwann-cell cylinders grown inside hyaluronic-acid tubular scaffolds with gradient porosity. Acta Biomaterialia. 30:199-211. https://doi.org/10.1016/j.actbio.2015.10.040S1992113

Trends in hepatocellular carcinoma incident cases in Japan between 1996 and 2019

We examined the epidemiological trends, including the distribution of sex, age, and disease etiology, in HCC incident cases, over 24 years. Data of 20,547 HCC patients (1996–2019) were analyzed in this prospective study. We divided the study period into four 6-yearly quarters. HCC etiology was categorized as hepatitis B virus (HBV) infection, HBV + hepatitis C virus (HCV) infection, HCV infection, and both negative (non-BC). The incident cases of HCC per quarter of the study period were 4311 (21.0%), 5505 (26.8%), 5776 (28.1%), and 4955 (24.1%), sequentially. Overall, 14,020 (68.2%) patients were male. The number of HCC cases in patients < 60 years, 60–69 years, 70–79 years, and ≥ 80 years were 3711 (18.1%), 6652 (32.4%), 7448 (36.2%), and 2736 (13.3%), respectively. The average age of newly-diagnosed patients increased in each quarter. HCC was associated with HBV, HBV + HCV, and HCV infections and non-BC in 2997 (14.6%), 187 (0.9%), and 12,019 (58.5%), and 5344 (26.0%) cases, respectively. The number of HCV-associated cases decreased in each quarter, while that of non-BC-associated cases increased. HCC incident cases tend to increase in the elderly and in non-BC patients; in contrast, HCC incident cases due to HCV tend to decrease

withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

n/

Receiver-Triggered Handshake Protocol for DTN in Disaster Area

When a disaster hits a wide area, communication services for public use will be rendered unavailable. This will make it difficult to confirm the safety of people in the disaster area. A solution to this problem is to form delay/disruption tolerant networks (DTN) using mobile terminals of victims, those of rescuers, who serve as information carriers, and terminals (servers) in shelters. In this paper, we propose using a receiver-triggered handshake protocol for communication between these terminals. We have developed the bundle layer protocol for this handshake method. The proposed method has been implemented on a network simulator to build an evaluation environment. The disaster area has been modeled on an area around Shinjuku Station in Tokyo. Victims are randomly distributed in the area. We have compared the proposed method with Epidemic Routing and Spray and Wait in terms of the delivery rate at which messages reach their destinations, and the length of time taken for messages to reach their destinations. We have found that the delivery rate of the three methods are, more or less, the same, but that the proposed method is superior to the other two methods in terms of storage usage and battery consumption of terminals, and the number of bundles generated in the network