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

International Students’ Transition Experiences in Rural Texas: A Phenomenological Study

Due to the growth in the number of international students attending universities in Texas and the need to provide appropriate counseling services to them, nine international students were interviewed about their experiences of transitioning from their home country to college in rural Texas. The authors employed the transcendental phenomenological approach to qualitative research (Moustakas, 1994) which allowed for the following seven emergent themes were identified that described the participants’ experiences: American TV; Knowing Someone; Like a Movie; Everybody Saying Hi; Transportation is Inconvenient; I Miss Noodles; and Being Optimistic. The emergent themes provided the basis for implications and recommendations for counseling services with the international student populations. Implications and recommendations for counselors on college campuses include, but are not limited to: actively collaborating with international student services, participating in new international student orientation services, and developing preemptive approaches to assisting international student during their transitions The authors make recommendations for further qualitative research and focus groups inquiries should be conducted by college counselors to better inform outreach services, for campus counseling and career service center, directed at assisting international students during their numerous transitions (Lértora et al., 2017)

Experiment K-6-21. Effect of microgravity on 1) metabolic enzymes of type 1 and type 2 muscle fibers and on 2) metabolic enzymes, neutransmitter amino acids, and neurotransmitter associated enzymes in motor and somatosensory cerebral cortex. Part 1: Metabolic enzymes of individual muscle fibers; part 2: metabolic enzymes of hippocampus and spinal cord

The individual fibers of any individual muscle vary greatly in enzyme composition, a fact which is obscured when enzyme levels of a whole muscle are measured. The purpose of this study was therefore to assess the changes due to weightless on the enzyme patterns composed by the individual fibers within the flight muscles. In spite of the limitation in numbers of muscles examined, it is apparent that: (1) that the size of individual fibers (i.e., their dry weight) was reduced about a third, (2) that this loss in dry mass was accompanied by changes in the eight enzymes studied, and (3) that these changes were different for the two muscles, and different for the two enzyme groups. In the soleus muscle the absolute amounts of the three enzymes of oxidative metabolism decreased about in proportion to the dry weight loss, so that their concentration in the atrophic fibers was almost unchanged. In contrast, there was little loss among the four enzymes of glycogenolysis - glycolysis so that their concentrations were substantially increased in the atrophic fibers. In the TA muscle, these seven enzymes were affected in just the opposite direction. There appeared to be no absolute loss among the oxidative enzymes, whereas the glycogenolytic enzymes were reduced by nearly half, so that the concentrations of the first metabolic group were increased within the atrophic fibers and the concentrations of the second group were only marginally decreased. The behavior of hexokinase was exceptional in that it did not decrease in absolute terms in either type of muscle and probably increased as much as 50 percent in soleus. Thus, their was a large increase in concentration of this enzyme in the atrophied fibers of both muscles. Another clear-cut finding was the large increase in the range of activities of the glycolytic enzymes among individual fibers of TA muscles. This was due to the emergence of TA fibers with activities for enzymes of this group extending down to levels as low as those found in control soleus muscles. It would be interesting to know if this represents a transition stage, and whether with prolonged weightlessness most of the fibers would be transformed into a low glycogenolytic type

A Statistical Decomposition Based Neural Network For Multivariate Time Series Forecasting

Machine learning based time series forecasting methods are popular and can match the performance of statistical models, in terms of accuracy, scalability, speed, etc. This disclosure presents techniques that incorporate statistical modeling into a neural network framework. The hybrid time series forecasting model described herein is named Seasonality Trend AutoRegressive Residual Yeo-Johnson power transformation Neural Network (STARRY-N). STARRY-N combines the advantages of residual neural network structure (such as N-BEATS) and explainable statistical forecasting models (such as TBATS). The model utilizes a neural network structure with separate stacks for trend, power transformed trend, seasonality, residual correction, and covariate adoption such as holiday effects. STARRY-N has good accuracy and is an explainable forecasting model

Phosphorous Diffuser Diverged Blue Laser Diode for Indoor Lighting and Communication.

An advanced light-fidelity (Li-Fi) system based on the blue Gallium nitride (GaN) laser diode (LD) with a compact white-light phosphorous diffuser is demonstrated for fusing the indoor white-lighting and visible light communication (VLC). The phosphorous diffuser adhered blue GaN LD broadens luminescent spectrum and diverges beam spot to provide ample functionality including the completeness of Li-Fi feature and the quality of white-lighting. The phosphorous diffuser diverged white-light spot covers a radiant angle up to 120(o) with CIE coordinates of (0.34, 0.37). On the other hand, the degradation on throughput frequency response of the blue LD is mainly attributed to the self-feedback caused by the reflection from the phosphor-air interface. It represents the current state-of-the-art performance on carrying 5.2-Gbit/s orthogonal frequency-division multiplexed 16-quadrature-amplitude modulation (16-QAM OFDM) data with a bit error rate (BER) of 3.1 × 10(-3) over a 60-cm free-space link. This work aims to explore the plausibility of the phosphorous diffuser diverged blue GaN LD for future hybrid white-lighting and VLC systems