Abstract: BACKGROUND: Excessive light exposure is a detrimental environmental factor that plays a critical role in the pathogenesis of retinal degeneration. However, the mechanism of light-induced death of retina/photoreceptor cells remains unclear. The mammalian/mechanistic target of rapamycin (mTOR) and Poly (ADP-ribose) polymerase-1 (PARP-1) have become the primary targets for treating many neurodegenerative disorders. The aim of this study was to elucidate the mechanisms underlying light-induced photoreceptor cell death and whether the neuroprotective effects of mTOR and PARP-1 inhibition against death are mediated through apoptosis-inducing factor (AIF). METHODS: Propidium iodide (PI)/Hoechst staining, lentiviral-mediated short hairpin RNA (shRNA), Western blot analysis, cellular fraction separation, plasmid transient transfection, laser confocal microscopy, a mice model, electroretinography (ERG), and hematoxylin-eosin (H & E) staining were employed to explore the mechanisms by which rapamycin/3-Aminobenzamide (3AB) exert neuroprotective effects of mTOR/PARP-1 inhibition in light-injured retinas. RESULTS: A parthanatos-like death mechanism was evaluated in light-injured 661 W cells that are an immortalized photoreceptor-like cell line that exhibit cellular and biochemical feature characteristics of cone photoreceptor cells. The death process featured over-activation of PARP-1 and AIF nuclear translocation. Either PARP-1 or AIF knockdown played a significantly protective role for light-damaged photoreceptors. More importantly, crosstalk was observed between mTOR and PARP-1 signaling and mTOR could have regulated parthanatos via the intermediate factor sirtuin 1 (SIRT1). The parthanatos-like injury was also verified in vivo, wherein either PARP-1 or mTOR inhibition provided significant neuroprotection against light-induced injury, which is evinced by both structural and functional retinal analysis. Overall, these results elucidate the mTOR-regulated parthanatos death mechanism in light-injured photoreceptors/retinas and may facilitate the development of novel neuroprotective therapies for retinal degeneration diseases. CONCLUSIONS: Our results demonstrate that inhibition of the mTOR/PARP-1 axis exerts protective effects on photoreceptors against visible-light-induced parthanatos. These protective effects are conducted by regulating the downstream factors of AIF, while mTOR possibly interacts with PARP-1 via SIRT1 to regulate parthanatos. Video Abstract Schematic diagram of mTOR interacting with PARP-1 to regulate visible light-induced parthanatos. Increased ROS caused by light exposure penetrates the nuclear membrane and causes nuclear DNA strand breaks. PARP-1 detects DNA breaks and synthesizes PAR polymers to initiate the DNA repair system that consumes a large amount of cellular NAD+. Over-production of PAR polymers prompts the release of AIF from the mitochondria and translocation to the nucleus, which leads to parthanatos. Activated mTOR may interact with PARP-1 via SIRT1 to regulate visible light-induced parthanatos.

Abstract: Previous research has recognized the importance of edges to crime. Various scholars have explored how one specific type of edges such as physical edges or social edges affect crime, but rarely investigated the importance of the composite edge effect. To address this gap, this study introduces nightlight data from the Visible Infrared Imaging Radiometer Suite sensor on the Suomi National Polar-orbiting Partnership Satellite (NPP-VIIRS) to measure composite edges. This study defines edges as nightlight gradients—the maximum change of nightlight from a pixel to its neighbors. Using nightlight gradients and other control variables at the tract level, this study applies negative binomial regression models to investigate the effects of edges on the street robbery rate and the burglary rate in Cincinnati. The Akaike Information Criterion (AIC) of models show that nightlight gradients improve the fitness of models of street robbery and burglary. Also, nightlight gradients make a positive impact on the street robbery rate whilst a negative impact on the burglary rate, both of which are statistically significant under the alpha level of 0.05. The different impacts on these two types of crimes may be explained by the nature of crimes and the in-situ characteristics, including nightlight.

Abstract: Experimental and epidemiologic studies suggest that light at night (LAN) exposure disrupts circadian rhythm, and this disruption may increase breast cancer risk. We investigated the potential association between residential outdoor LAN and breast cancer risk. A population-based case-control study was conducted in Vancouver, British Columbia and Kingston, Ontario, Canada with incident breast cancer cases, and controls frequency matched by age in the same region. This analysis was restricted to 844 cases and 905 controls who provided lifetime residential histories. Using time-weighted average duration at each home 5-20 years prior to study entry, two measures of cumulative average outdoor LAN were calculated using two satellite data sources. Logistic regression was used to estimate the relationship between outdoor LAN and breast cancer risk, considering interactions for menopausal status and night shift work. We found no association between residential outdoor LAN and breast cancer for either measure of LAN [OR comparing highest vs. lowest tertile (DNB) = 0.95, 95% CI 0.70-1.27]. We also found no association when considering interactions for menopausal status and past/current night work status. These findings were robust to changes to years of residential data considered, residential mobility, and longer exposure windows. Our findings are consistent with studies reporting that outdoor LAN has a small effect or no effect on breast cancer risk.