SNX27 and SORLA interact to reduce amyloidogenic subcellular distribution and processing of amyloid precursor protein

Proteolytic generation of amyloidogenic amyloid {beta} (A{beta}) fragments from the amyloid precursor protein (APP) significantly contributes to Alzheimer's disease (AD). Although amyloidogenic APP proteolysis can be affected by trafficking through genetically associated AD components such as SORLA, how SORLA functionally interacts with other trafficking components is yet unclear. Here, we report that SNX27, an endosomal trafficking/recycling factor and a negative regulator of the {gamma}-secretase complex, binds to the SORLA cytosolic tail to form a ternary complex with APP. SNX27 enhances cell surface SORLA and APP levels in human cell lines and mouse primary neurons, and depletion of SNX27 or SORLA reduces APP endosome-to-cell surface recycling kinetics. SNX27 overexpression enhances the generation of cell surface APP cleavage products such as soluble alpha-APP C-terminal fragment (CTF{alpha}) in a SORLA-dependent manner. SORLA-mediated A{beta} reduction is attenuated by downregulation of SNX27. This indicates that an SNX27/SORLA complex functionally interacts to limit APP distribution to amyloidogenic compartments, forming a non-amyloidogenic shunt to promote APP recycling to the cell surface

Study on the Correlation between the Structure and Toxicity of Amines, Mercaptans and Halohydrocarbons

The aim of the present work was to understand the structure of amines, mercaptans and halohydrocarbons and their cell toxicity effect on rat liver BRL-3A cells. BRL-3A cells were seeded into each well of 96-well plates and treated with amines, mercaptans and halohydrocarbons (total 18 kinds) in DMEM culture medium containing 10% fetal calf serum. 24h later, the growth viability in vitro of BRL3A cells was measured using the MTT assay. The results show that the cytotoxic of propane diamine> ethidene diamine> n-butylamine> n-propylamine> ethylamine, butyl mercaptan> propanethiol> disulfide propane> dithioglycol, n-Butyl iodide> n-Propyl iodide> iodoethane, propylene bromide> 1, 2-dibromoethane> ethyl bromide, ethylene dichloride> butyl chloride> chloropropane. We can conclude that among amines, when the length of carbon chain is fixed, the more amidogen, the stronger the toxicity; when the number of hydroxyl group is fixed, the longer carbon chain, the stronger the toxicity. Among mercaptans, when the length of carbon chain is the same, the more hydrosulphonyl, the weaker the toxicity; when the number of hydrosulphonyl is the same, the longer carbon chain, the weaker the toxicity. Among halohydrocarbons, when the length of carbon chain is fixed, the more halogen, the stronger the toxicity; when the number of halogen is fixed, the longer carbon chain, the stronger the toxicity. Under the same conditions, the toxicity of mercaptans is greater than amines and halohydrocarbons

Isoquinoline Alkaloids Isolated from Corydalis yanhusuo and Their Binding Affinities at the Dopamine D1 Receptor

Bioactivity-guided fractionation of Corydalis yanhusuo has resulted in the isolation of eight known isoquinoline alkaloids - tetrahydropalmatine, isocorypalmine, stylopine, corydaline, columbamine, coptisin, 13-methylpalmatine, and dehydrocorybulbine. The tertiary alkaloids were further analyzed by chiral HPLC to determine the ratios of d-and l-isomers. The isolated compounds were screened for their binding affinities at the dopamine D(1) receptor. Isocorypalmine had the highest affinity (K(i) = 83 nM). The structure-affinity relationships of these alkaloids are discussed

Hawking Radiation of Black Holes in Infrared Modified Ho\v{r}ava-Lifshitz Gravity

We study the Hawking radiation of the spherically symmetric, asymptotically flat black holes in the infrared modified Horava-Lifshitz gravity by applying the methods of covariant anomaly cancellation and effective action, as well as the approach of Damour-Ruffini-Sannan's. These black holes behave as the usual Schwarzschild ones of the general relativity when the radial distance is very large. We also extend the method of covariant anomaly cancellation to derive the Hawking temperature of the spherically symmetric, asymptotically AdS black holes that represent the analogues of the Schwarzschild AdS ones.Comment: no figures, 16 pages,accepted by EPJ

A Quantitative Model of Energy Release and Heating by Time-dependent, Localized Reconnection in a Flare with a Thermal Loop-top X-ray Source

We present a quantitative model of the magnetic energy stored and then released through magnetic reconnection for a flare on 26 Feb 2004. This flare, well observed by RHESSI and TRACE, shows evidence of non-thermal electrons only for a brief, early phase. Throughout the main period of energy release there is a super-hot (T>30 MK) plasma emitting thermal bremsstrahlung atop the flare loops. Our model describes the heating and compression of such a source by localized, transient magnetic reconnection. It is a three-dimensional generalization of the Petschek model whereby Alfven-speed retraction following reconnection drives supersonic inflows parallel to the field lines, which form shocks heating, compressing, and confining a loop-top plasma plug. The confining inflows provide longer life than a freely-expanding or conductively-cooling plasma of similar size and temperature. Superposition of successive transient episodes of localized reconnection across a current sheet produces an apparently persistent, localized source of high-temperature emission. The temperature of the source decreases smoothly on a time scale consistent with observations, far longer than the cooling time of a single plug. Built from a disordered collection of small plugs, the source need not have the coherent jet-like structure predicted by steady-state reconnection models. This new model predicts temperatures and emission measure consistent with the observations of 26 Feb 2004. Furthermore, the total energy released by the flare is found to be roughly consistent with that predicted by the model. Only a small fraction of the energy released appears in the super-hot source at any one time, but roughly a quarter of the flare energy is thermalized by the reconnection shocks over the course of the flare. All energy is presumed to ultimately appear in the lower-temperature T<20 MK, post-flare loops

Anomaly analysis of Hawking radiation from Kaluza-Klein black hole with squashed horizon

Considering gravitational and gauge anomalies at the horizon, a new method that to derive Hawking radiations from black holes has been developed by Wilczek et al. In this paper, we apply this method to non-rotating and rotating Kaluza-Klein black holes with squashed horizon, respectively. For the rotating case, we found that, after the dimensional reduction, an effective U(1) gauge field is generated by an angular isometry. The results show that the gauge current and energy-momentum tensor fluxes are exactly equivalent to Hawking radiation from the event horizon.Comment: 15 pages, no figures, the improved version, accepted by Eur. Phys. J.

Cosmological distance indicators

We review three distance measurement techniques beyond the local universe: (1) gravitational lens time delays, (2) baryon acoustic oscillation (BAO), and (3) HI intensity mapping. We describe the principles and theory behind each method, the ingredients needed for measuring such distances, the current observational results, and future prospects. Time delays from strongly lensed quasars currently provide constraints on $H_0$ with < 4% uncertainty, and with 1% within reach from ongoing surveys and efforts. Recent exciting discoveries of strongly lensed supernovae hold great promise for time-delay cosmography. BAO features have been detected in redshift surveys up to z <~ 0.8 with galaxies and z ~ 2 with Ly-$\alpha$ forest, providing precise distance measurements and $H_0$ with < 2% uncertainty in flat $\Lambda$CDM. Future BAO surveys will probe the distance scale with percent-level precision. HI intensity mapping has great potential to map BAO distances at z ~ 0.8 and beyond with precisions of a few percent. The next years ahead will be exciting as various cosmological probes reach 1% uncertainty in determining $H_0$, to assess the current tension in $H_0$ measurements that could indicate new physics.Comment: Review article accepted for publication in Space Science Reviews (Springer), 45 pages, 10 figures. Chapter of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Ag

Toward an internally consistent astronomical distance scale

Accurate astronomical distance determination is crucial for all fields in astrophysics, from Galactic to cosmological scales. Despite, or perhaps because of, significant efforts to determine accurate distances, using a wide range of methods, tracers, and techniques, an internally consistent astronomical distance framework has not yet been established. We review current efforts to homogenize the Local Group's distance framework, with particular emphasis on the potential of RR Lyrae stars as distance indicators, and attempt to extend this in an internally consistent manner to cosmological distances. Calibration based on Type Ia supernovae and distance determinations based on gravitational lensing represent particularly promising approaches. We provide a positive outlook to improvements to the status quo expected from future surveys, missions, and facilities. Astronomical distance determination has clearly reached maturity and near-consistency.Comment: Review article, 59 pages (4 figures); Space Science Reviews, in press (chapter 8 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age