Conditioned media of glial cell lines induce alkaline phosphatase activity in cultured artery endothelial cells Identification of interleukin-6 as an induction factor

AbstractConditioned media of human glial cell lines induced alkaline phosphatase activity in cultured calf artery endothelial cells. The maximal alkaline phosphatase activity in the culture was comparable to the level in isolated brain capillary endothelial cells. An induction factor in the conditioned media was purified and identified as interleukin-6 from its amino-terminal sequence, molecular weight, amino acid composition and immunoreactivity. Recombinant interleukin-6 had similar induction activity. Our findings raise the possibility that interleukin-6 induces and modulates alkaline phosphatase activity in endothelial cells during normal development of the blood—brain barrier and under certain pathological conditions

Non-genetic cell-surface modification with a self-assembling molecular glue

A versatile non-genetic cell-surface modification method, in which a self-assembling small molecule is combined with Halo-tag proteins, permitted the sell functionalization

Coincidence analysis to search for inspiraling compact binaries using TAMA300 and LISM data

Japanese laser interferometric gravitational wave detectors, TAMA300 and LISM, performed a coincident observation during 2001. We perform a coincidence analysis to search for inspiraling compact binaries. The length of data used for the coincidence analysis is 275 hours when both TAMA300 and LISM detectors are operated simultaneously. TAMA300 and LISM data are analyzed by matched filtering, and candidates for gravitational wave events are obtained. If there is a true gravitational wave signal, it should appear in both data of detectors with consistent waveforms characterized by masses of stars, amplitude of the signal, the coalescence time and so on. We introduce a set of coincidence conditions of the parameters, and search for coincident events. This procedure reduces the number of fake events considerably, by a factor $\sim 10^{-4}$ compared with the number of fake events in single detector analysis. We find that the number of events after imposing the coincidence conditions is consistent with the number of accidental coincidences produced purely by noise. We thus find no evidence of gravitational wave signals. We obtain an upper limit of 0.046 /hours (CL $= 90$) to the Galactic event rate within 1kpc from the Earth. The method used in this paper can be applied straightforwardly to the case of coincidence observations with more than two detectors with arbitrary arm directions.Comment: 28 pages, 17 figures, Replaced with the version to be published in Physical Review

Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004

We analyze the data of TAMA300 detector to search for gravitational waves from inspiraling compact star binaries with masses of the component stars in the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the years 2000-2004, are used for the event search. We combine the results of different observation runs, and obtained a single upper limit on the rate of the coalescence of compact binaries in our Galaxy of 20 per year at a 90% confidence level. In this upper limit, the effect of various systematic errors such like the uncertainty of the background estimation and the calibration of the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was correcte

Observation results by the TAMA300 detector on gravitational wave bursts from stellar-core collapses

We present data-analysis schemes and results of observations with the TAMA300 gravitational-wave detector, targeting burst signals from stellar-core collapse events. In analyses for burst gravitational waves, the detection and fake-reduction schemes are different from well-investigated ones for a chirp-wave analysis, because precise waveform templates are not available. We used an excess-power filter for the extraction of gravitational-wave candidates, and developed two methods for the reduction of fake events caused by non-stationary noises of the detector. These analysis schemes were applied to real data from the TAMA300 interferometric gravitational wave detector. As a result, fake events were reduced by a factor of about 1000 in the best cases. The resultant event candidates were interpreted from an astronomical viewpoint. We set an upper limit of 2.2x10^3 events/sec on the burst gravitational-wave event rate in our Galaxy with a confidence level of 90%. This work sets a milestone and prospects on the search for burst gravitational waves, by establishing an analysis scheme for the observation data from an interferometric gravitational wave detector

Identification of 1,2,5-Oxadiazoles as a New Class of SENP2 Inhibitors Using Structure Based Virtual Screening

Small ubiquitin like modifier (SUMO) specific proteases (SENPs) are cysteine proteases that carry out the proteolytic processing of SUMO from its pro form as well as the deconjugation of SUMO from substrate proteins. SENPs are attractive targets for drug discovery due to their crucial role in the development of various diseases. However, the SENPs inhibitor discovery efforts were limited, and only a few inhibitors or activity based probes have been identified until now. Here, we report a new class of SENP2 inhibitors identified by a combination of structure based virtual screening and quantitative FRET based assay. Our virtual screening protocol initially involves the identification of small molecules that have similar shape and electrostatic properties with the conjugate of SUMO1 C-terminal residues and substrate lysine. Molecular docking was then used to prioritize these small molecules for a FRET based assay that quantifies their SENP2 endopeptidase activity. The initial round of virtual screening followed by FRET based assay has enabled the identification of eight compounds with >40% SENP2 inhibition at 30 μM compound concentration. Five of these compounds belong to two scaffolds containing a 1,2,5-oxadiazole core that represent a novel class of SENP2 inhibitors. To improve the inhibitory potency and explore the structure–activity relationship of these two 1,2,5-oxadiazole scaffolds, structurally related compounds were identified in another round of virtual screening. The biological assay results confirmed SENP2 inhibitory activity of these two scaffolds. The most potent compound of each scaffold showed an IC₅₀ of 5.9 and 3.7 μM. Most of the compounds also inhibited closely related isoform SENP1, while no detectable inhibition on other proteases, such as papain and trypsin, was observed. Our study suggests that 1,2,5-oxadiazoles could be used as a starting point for the development of novel therapeutic agents against various diseases targeting SENPs