Toxic tau oligomer formation blocked by capping of cysteine residues with 1,2-dihydroxybenzene groups

Neurofibrillary tangles, composed of hyperphosphorylated tau fibrils, are a pathological hallmark of Alzheimer's disease; the neurofibrillary tangle load correlates strongly with clinical progression of the disease. A growing body of evidence indicates that tau oligomer formation precedes the appearance of neurofibrillary tangles and contributes to neuronal loss. Here we show that tau oligomer formation can be inhibited by compounds whose chemical backbone includes 1,2-dihydroxybenzene. Specifically, we demonstrate that 1,2-dihydroxybenzene-containing compounds bind to and cap cysteine residues of tau and prevent its aggregation by hindering interactions between tau molecules. Further, we show that orally administered DL-isoproterenol, an adrenergic receptor agonist whose skeleton includes 1,2-dihydroxybenzene and which penetrates the brain, reduces the levels of detergent-insoluble tau, neuronal loss and reverses neurofibrillary tangle-associated brain dysfunction. Thus, compounds that target the cysteine residues of tau may prove useful in halting the progression of Alzheimer's disease and other tauopathies

The Large-scale Bipolar Wind in the Galactic Center

During a 9-month campaign (1996--1997), the Midcourse Space Experiment (MSX) satellite mapped the Galactic Plane at mid-infrared wavelengths (4.3--21.3um). Here we report evidence for a spectacular limb- brightened, bipolar structure at the Galactic Center extending more than a degree (170 pc at 8.0 kpc) on either side of the plane. The 8.3um emission shows a tight correlation with the 3, 6 and 11 cm continuum structure over the same scales. Dense gas and dust are being entrained in a large-scale bipolar wind powered by a central starburst. The inferred energy injection at the source is ~10^54/kappa erg for which \kappa is the covering fraction of the dusty shell (kappa <= 0.1). There is observational evidence for a galactic wind on much larger scales, presumably from the same central source which produced the bipolar shell seen by MSX. Sofue has argued that the North Polar Spur -- a thermal x-ray/radio loop which extends from the Galactic Plane to b = +80 deg -- was powered by a nuclear explosion (1-30 x 10^55 erg) roughly 15 Myr ago. We demonstrate that an open-ended bipolar wind (~10^55 erg), when viewed in near-field projection, provides the most natural explanation for the observed loop structure. The ROSAT 1.5 keV diffuse x-ray map over the inner 45 deg provides compelling evidence for this interpretation. Since the faint bipolar emission would be very difficult to detect beyond the Galaxy, the phenomenon of large-scale galactic winds may be far more common than has been observed to date.Comment: 24 pages, 6 figures, aastex. High resolution figures are available at ftp://www.aao.gov.au/pub/local/jbh/astro-ph/GC/. Astrophysical Journal, accepte

Microstructure and kinematics of H2O masers in the massive star forming region IRAS 06061+2151

We have made multi-epoch VLBI observations of H2O maser emission in the massive star forming region IRAS 06061+2151 with the Japanese VLBI network (JVN) from 2005 May to 2007 October. The detected maser features are distributed within an 1\arcsec$\times$1\arcsec (2000 au$\times$2000 au at the source position) around the ultra-compact H {\small\bf II} region seen in radio continuum emission. Their bipolar morphology and expanding motion traced through their relative proper motions indicate that they are excited by an energetic bipolar outflow. Our three-dimensional model fitting has shown that the maser kinematical structure in IRAS 06061+2151 is able to be explained by a biconical outflow with a large opening angle ($>$ 50\degr). The position angle of the flow major axis coincides very well with that of the large scale jet seen in 2.1\:\mu\rmn{m} hydrogen emission. This maser geometry indicates the existence of dual structures composed of a collimated jet and a less collimated massive molecular flow. We have also detected a large velocity gradient in the southern maser group. This can be explained by a very small (on a scale of several tens of au) and clumpy (the density contrast by an order of magnitude or more) structure of the parental cloud. Such a structure may be formed by strong instability of shock front or splitting of high density core.Comment: 14 pages, 6 figures accepted for publication in MNRA

The Cherenkov Telescope Array Large Size Telescope

The two arrays of the Very High Energy gamma-ray observatory Cherenkov Telescope Array (CTA) will include four Large Size Telescopes (LSTs) each with a 23 m diameter dish and 28 m focal distance. These telescopes will enable CTA to achieve a low-energy threshold of 20 GeV, which is critical for important studies in astrophysics, astroparticle physics and cosmology. This work presents the key specifications and performance of the current LST design in the light of the CTA scientific objectives.Comment: 4 pages, 5 figures, In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223

Seasonal effects on reconciliation in Macaca Fuscata Yakui

Dietary composition may have profound effects on the activity budgets, levelof food competition, and social behavior of a species. Similarly, in seasonally breeding species, the mating season is a period in which competition for mating partners increases, affecting amicable social interactions among group members. We analyzed the importance of the mating season and of seasonal variations in dietary composition and food competition on econciliation in wild female Japanese macaques (Macaca fuscata yakui) on Yakushima Island, Japan. Yakushima macaques are appropriate subjects because they are seasonal breeders and their dietary composition significantly changes among the seasons. Though large differences occurred between the summer months and the winter and early spring months in activity budgets and the consumption of the main food sources, i.e., fruits, seeds, and leaves, the level of food competition and conciliatory tendency remained unaffected. Conversely,conciliatory tendency is significantly lower during the mating season than in the nonmating season. Moreover, conciliatory tendency is lower when 1 or both female opponents is in estrous than when they are not. Thus the mating season has profound effects on reconciliation, whereas seasonal changes in activity budgets and dietary composition do not. The detrimental effects of the mating season on female social relationships and reconciliation may be due to the importance of female competition for access to male partners in multimale, multifemale societies

Study of spin-isospin responses of radioactive nuclei with the background-reduced neutron spectrometer, PANDORA

The status of a project to measure spin-isospin responses of neutron drip-line nuclei using a new low-energy neutron detector, PANDORA (Particle Analyzer Neutron Detector Of Real-time Acquisition), is reported. The performance of PANDORA was characterized by the 6He(p,n)6Li reaction in inverse kinematics at the HIMAC facility in Chiba. Observation of the strong transition to the ground state in 6Li is discussed. Preliminary results of 11Li(p,n)11Be and 14Be(p,n)14B experiments in inverse kinematics at RI Beam Factory (RIBF) of RIKEN Nishina Center are also presented including the exotic decay channel of 11Be→9Li + d. Details of the experimental setup based on PANDORA and the SAMURAI large-acceptance magnetic spectrometer, as well as the combined data-acquisition system are described. The neutron-gamma discrimination capability of PANDORA was evaluated, Figure-of-Merit (FoM) values higher than those found in the literature for similar materials were derived from experimental data

Diacylglycerol oil for the metabolic syndrome

Excess adiposity has been shown to play a crucial role in the development of the metabolic syndrome. The elevated fasting and postprandial triglyceride-rich lipoprotein levels is the central lipid abnormality observed in the metabolic syndrome. Recent studies have indicated that diacylglycerol (DAG) is effective for fasting and postprandial hyperlipidemia and preventing excess adiposity by increasing postprandial energy expenditure. We will here discuss the mechanisms of DAG-mediated improvements in hyperlipidemia and in postprandial energy expenditure, and effects of DAG oil on lipid/glucose metabolism and on body fat. Further, the therapeutic application of DAG for the metabolic syndrome will be considered

Measurement and comparison of individual external doses of high-school students living in Japan, France, Poland and Belarus -- the "D-shuttle" project --

Twelve high schools in Japan (of which six are in Fukushima Prefecture), four in France, eight in Poland and two in Belarus cooperated in the measurement and comparison of individual external doses in 2014. In total 216 high-school students and teachers participated in the study. Each participant wore an electronic personal dosimeter "D-shuttle" for two weeks, and kept a journal of his/her whereabouts and activities. The distributions of annual external doses estimated for each region overlap with each other, demonstrating that the personal external individual doses in locations where residence is currently allowed in Fukushima Prefecture and in Belarus are well within the range of estimated annual doses due to the background radiation level of other regions/countries

Traces of past activity in the Galactic Centre

The Milky Way centre hosts a supermassive Black Hole (BH) with a mass of ~4*10^6 M_Sun. Sgr A*, its electromagnetic counterpart, currently appears as an extremely weak source with a luminosity L~10^-9 L_Edd. The lowest known Eddington ratio BH. However, it was not always so; traces of "glorious" active periods can be found in the surrounding medium. We review here our current view of the X-ray emission from the Galactic Center (GC) and its environment, and the expected signatures (e.g. X-ray reflection) of a past flare. We discuss the history of Sgr A*'s past activity and its impact on the surrounding medium. The structure of the Central Molecular Zone (CMZ) has not changed significantly since the last active phase of Sgr A*. This relic torus provides us with the opportunity to image the structure of an AGN torus in exquisite detail.Comment: Invited refereed review. Chapter of the book: "Cosmic ray induced phenomenology in star forming environments" (eds. Olaf Reimer and Diego F. Torres