TMEM97 and PGRMC1 do not mediate sigma-2 ligand-induced cell death

Abstract Sigma-2 receptors have been implicated in both tumor proliferation and neurodegenerative diseases. Recently the sigma-2 receptor was identified as transmembrane protein 97 (TMEM97). Progesterone receptor membrane component 1 (PGRMC1) was also recently reported to form a complex with TMEM97 and the low density lipoprotein (LDL) receptor, and this trimeric complex is responsible for the rapid internalization of LDL. Sigma-2 receptor ligands with various structures have been shown to induce cell death in cancer cells. In the current study, we examined the role of TMEM97 and PGRMC1 in mediating sigma-2 ligand-induced cell death. Cell viability and caspase-3 assays were performed in control, TMEM97 knockout (KO), PGRMC1 KO, and TMEM97/PGRMC1 double KO cell lines treated with several sigma-2 ligands. The data showed that knockout of TMEM97, PGRMC1, or both did not affect the concentrations of sigma-2 ligands that induced 50% of cell death (EC50), suggesting that cytotoxic effects of these compounds are not mediated by TMEM97 or PGRMC1. Sigma-1 receptor ligands, (+)-pentazocine and NE-100, did not block sigma-2 ligand cytotoxicity, suggesting that sigma-1 receptor was not responsible for sigma-2 ligand cytotoxicity. We also examined whether the alternative, residual binding site (RBS) of 1,3-Di-o-tolylguanidine (DTG) could be responsible for sigma-2 ligand cytotoxicity. Our data showed that the binding affinities (K i) of sigma-2 ligands on the DTG RBS did not correlate with the cytotoxicity potency (EC50) of these ligands, suggesting that the DTG RBS was not fully responsible for sigma-2 ligand cytotoxicity. In addition, we showed that knocking out TMEM97, PGRMC1, or both reduced the initial internalization rate of a sigma-2 fluorescent ligand, SW120. However, concentrations of internalized SW120 became identical later in the control and knockout cells. These data suggest that the initial internalization process of sigma-2 ligands does not appear to mediate the cell-killing effect of sigma-2 ligands. In summary, we have provided evidence that sigma-2 receptor/TMEM97 and PGRMC1 do not mediate sigma-2 ligand cytotoxicity. Our work will facilitate elucidating mechanisms of sigma-2 ligand cytotoxicity

Imaging of the gravitational lens system PG 1115+080 with the Hubble Space Telescope

This paper is the first of a series presenting observations of gravitational lenses and lens candidates, taken with the Wide Field/Planetary Camera (WFPC) of the Hubble Space Telescope (HST). We have resolved the gravitational lens system PG 1115 + 080 into four point sources and a red, extended object that is presumably the lens galaxy; we present accurate relative intensities, colors, and positions of the four images, and lower accuracy intensity and position of the lens galaxy, all at the epoch 1991.2. Comparison with earlier data shows no compelling evidence for relative intensity variations between the QSO components having so far been observed. The new data agree with earlier conclusions that the system is rather simple, and can be produced by the single observed galaxy. The absence of asymmetry in the HST images implies that the emitting region of the quasar itself has an angular radius smaller than about 10 milliarcsec (100 pc for H_0=50, q_0=0.5)

The Postcollapse core of M15 imaged with the HST planetary camera

We have obtained U-band images of the M15 core with the Planetary Camera of the Hubble Space Telescope. We are able to resolve stars down to the main-sequence turnoff (m_v≈ 19.4) into the cluster center. We use crowded field photometry techniques to decompose M15 into bright resolved stars and a residual component consisting of stars at turnoff brightness or fainter. The residual component comprises 59% of the cluster light and follows a y = -0.71 power-law distribution for r > 1". The residual component flattens off interior to this radius and has a large core with r_c = 2".2 = 0.13 pc. The core size may reflect postcollapse core expansion. The resolved stars have a slightly shallower distribution (y = - 0.53) but have an abrupt overdensity for r < 1".5, which accounts for the unresolved surface brightness cusp at ground resolution. The bright stars do not become more highly concentrated at still smaller radii, however; neither the bright stars nor the residual component form a cusp at subarcsecond resolution. The total central density of light in all components is 8 x 10^5 L_☉ pc^(-3) (U-band). The Peterson, Seitzer, and Cudworth central velocity dispersion implies a high core M/L ≈ 8 (U-band). The existence of a core rather than a cusp at the 0.1 pc scale may imply that the centrally deduced dark matter is in a diffuse form rather than a massive black hole

Limits to Rest-Frame Ultraviolet Emission From Far-Infrared-Luminous z~6 Quasar Hosts

We report on a Hubble Space Telescope search for rest-frame ultraviolet emission from the host galaxies of five far-infrared-luminous $z\simeq{}6$ quasars and the $z=5.85$ hot-dust free quasar SDSS J0005-0006. We perform 2D surface brightness modeling for each quasar using a Markov-Chain Monte-Carlo estimator, to simultaneously fit and subtract the quasar point source in order to constrain the underlying host galaxy emission. We measure upper limits for the quasar host galaxies of $m_J>22.7$ mag and $m_H>22.4$ mag, corresponding to stellar masses of $M_\ast<2\times10^{11}M_\odot$. These stellar mass limits are consistent with the local $M_{\textrm{BH}}$-$M_\ast$ relation. Our flux limits are consistent with those predicted for the UV stellar populations of $z\simeq6$ host galaxies, but likely in the presence of significant dust ($\langle A_{\mathrm{UV}}\rangle\simeq 2.6$ mag). We also detect a total of up to 9 potential $z\simeq6$ quasar companion galaxies surrounding five of the six quasars, separated from the quasars by 1.4''-3.2'', or 8.4-19.4 kpc, which may be interacting with the quasar hosts. These nearby companion galaxies have UV absolute magnitudes of -22.1 to -19.9 mag, and UV spectral slopes $\beta$ of -2.0 to -0.2, consistent with luminous star-forming galaxies at $z\simeq6$. These results suggest that the quasars are in dense environments typical of luminous $z\simeq6$ galaxies. However, we cannot rule out the possibility that some of these companions are foreground interlopers. Infrared observations with the James Webb Space Telescope will be needed to detect the $z\simeq6$ quasar host galaxies and better constrain their stellar mass and dust content.Comment: 22 pages, 13 figures. Accepted for publication in Ap

Open Science principles for accelerating trait-based science across the Tree of Life.

Synthesizing trait observations and knowledge across the Tree of Life remains a grand challenge for biodiversity science. Species traits are widely used in ecological and evolutionary science, and new data and methods have proliferated rapidly. Yet accessing and integrating disparate data sources remains a considerable challenge, slowing progress toward a global synthesis to integrate trait data across organisms. Trait science needs a vision for achieving global integration across all organisms. Here, we outline how the adoption of key Open Science principles-open data, open source and open methods-is transforming trait science, increasing transparency, democratizing access and accelerating global synthesis. To enhance widespread adoption of these principles, we introduce the Open Traits Network (OTN), a global, decentralized community welcoming all researchers and institutions pursuing the collaborative goal of standardizing and integrating trait data across organisms. We demonstrate how adherence to Open Science principles is key to the OTN community and outline five activities that can accelerate the synthesis of trait data across the Tree of Life, thereby facilitating rapid advances to address scientific inquiries and environmental issues. Lessons learned along the path to a global synthesis of trait data will provide a framework for addressing similarly complex data science and informatics challenges

Stellar photometry with the Hubble Space Telescope Wide-field/Planetary camera - A progress report

We describe the prospects for the use of the Wide-Field/Planetary Camera (WFPC) for stellar photometry. The large halos of the point-spread function (PSF) resulting from spherical aberration and from spatial, temporal, and color variations of the PSF are the main limitations to accurate photometry. Degradations caused by crowding are exacerbated by the halos of the PSF. Here we attempt to quantify these effects and determine the current accuracy of stellar photometry with the WFPC. In realistic cases, the brighter stars in crowded fields have 0.09 mag errors; fainter stars have larger errors depending on the degree of crowding. We find that measuring Cepheids in Virgo Cluster galaxies is not currently possible without inordinate increases in exposure times

Pulse energy packing effects on material transport during laser processing of &lt; 1

The effects of energy pulse packing on material transport during single-pulse laser processing of silicon is studied using temporarily shaped pulses with durations from 50 to 150 ns. Six regimes of material transport were identified and disambiguated through energy packing considerations over a range of pulse durations. Energy packing has been shown to shift the interaction to energetically costlier regimes without appreciable benefit in either depth, material removal or crater morphology and quality.The authors would like to thank the UK Technology Strategy Board under project TP14/HVM/6/I/BD5665. The authors acknowledge the EPSRC Centre for Doctoral Training in Photonic Systems Development for their generous support

Reduction of PG:1115+080 Images

The data are three exposures in PC6 through F785LP obtained on March 3, 1991. The exposure times are 120, 400, and 400 seconds. The data are reduced with the "standard" WFPC reduction scheme: A-to-D correction, DC bias subtraction, AC bias subtraction, dark current subtraction, preflash subtraction, and flat field normalization, using the best available calibration data. The exposures are combined into a weighted average normalized to 400 seconds exposure time, so one DN (data number) is about 17.25 electrons. At this step, cosmic rays are removed by intercomparison of the three images

EC85-219 1985 Nebraska Swine Report

This 1985 Nebraska Swine Report was prepared by the staff in Animal Science and cooperating departments for use in the Extension and Teaching programs at the University of Nebraska-Lincoln. Authors from the following areas contributed to this publication: Swine Nutrition, swine diseases, pathology, economics, engineering, swine breeding, meats, agronomy, and diagnostic laboratory. It covers the following areas: breeding, disease control, feeding, nutrition, economics, housing and meats