In vivo imaging of microenvironmental and anti-PD-L1-mediated dynamics in cancer using S100A8/S100A9 as an imaging biomarker

Purpose: As a promotor of tumor invasion and tumor microenvironment (TME) formation, the protein complex S100A8/S100A9 is associated with poor prognosis. Our aim was to further evaluate its origin and regulatory effects, and to establish an imaging biomarker for TME activity. Methods: S100A9−/−cells (ko) were created from syngeneic murine breast cancer 4T1 (high malignancy) and 67NR (low malignancy) wildtype (wt) cell lines and implanted into either female BALB/c wildtype or S100A9−/− mice (n = 10 each). Anti-S100A9-Cy5.5-targeted fluorescence reflectance imaging was performed at 0 h and 24 h after injection. Potential early changes of S100A9-presence under immune checkpoint inhibition (anti-PD-L1, n = 7 vs. rat IgG2b as isotype control, n = 3) were evaluated. Results: In S100A9−/−mice contrast-to-noise-ratios were significantly reduced for wt and S100A9−/−tumors. No significant differences were detected for 4T1 ko and 67NR ko cells as compared to wildtype cells. Under anti-PD-L1 treatment S100A9 presence significantly decreased compared with the control group. Conclusion: Our results confirm a secretion of S100A8/S100A9 by the TME, while tumor cells do not apparently release the protein. Under immune checkpoint inhibition S100A9-imaging reports an early decrease of TME activity. Therefore, S100A9-specific imaging may serve as an imaging biomarker for TME formation and activity

Tumor Suppressor Pdcd4 Attenuates Sin1 Translation to Inhibit Invasion in Colon Carcinoma

Programmed cell death 4 (Pdcd4), a tumor invasion suppressor, is frequently downregulated in colorectal cancer and other cancers. In this study, we find that loss of Pdcd4 increases the activity of mammalian target of rapamycin complex 2 (mTORC2) and thereby upregulates Snail expression. Examining the components of mTORC2 showed that Pdcd4 knockdown increased the protein but not mRNA level of stress-activated-protein kinase interacting protein 1 (Sin1), which resulted from enhanced Sin1 translation. To understand how Pdcd4 regulates Sin1 translation, the SIN1 5′ untranslated region (5′UTR) was fused with luciferase reporter and named as 5′Sin1-Luc. Pdcd4 knockdown/knockout significantly increased the translation of 5′Sin1-Luc but not the control luciferase without the SIN1 5′UTR, suggesting that Sin1 5′UTR is necessary for Pdcd4 to inhibit Sin1 translation. Ectopic expression of wild-type Pdcd4 and Pdcd4(157–469), a deletion mutant that binds to translation initiation factor 4A (eIF4A), sufficiently inhibited Sin1 translation, and thus suppressed mTORC2 kinase activity and invasion in colon tumor cells. By contrast, Pdcd4(157–469)(D253A,D418A), a mutant that does not bind to eIF4A, failed to inhibit Sin1 translation, and consequently failed to repress mTORC2 activity and invasion. In addition, directly inhibiting eIF4A with silvestrol significantly suppressed Sin1 translation and attenuated invasion. These results indicate that Pdcd4-inhibited Sin1 translation is through suppressing eIF4A, and functionally important for suppression of mTORC2 activity and invasion. Moreover, in colorectal cancer tissues, the Sin1 protein but not mRNA was significantly upregulated while Pdcd4 protein was downregulated, suggesting that loss of Pdcd4 might correlate with Sin1 protein level but not mRNA level in colorectal cancer patients. Taken together, our work reveals a novel mechanism by which Pdcd4 inhibits Sin1 translation to attenuatemTORC2 activity and thereby suppresses invasion

Catalog of locations of microseismic events accompanying the 2006-2007 fluid injection into the Basel Enhanced Geothermal System

Supplement data to Mukuhira et al. "Injection induced seismicity size distribution dependent on shear stress" published in Geophysical Research Letters (https://doi.org/10.1029/2020GL090934) This dataset contains the catalog of locations of microseismic events occurring in 2006-2007 that accompanied the fluid stimulation at the Basel Enhanced Geothermal System (EGS) site in Basel, Switzerland. The catalog includes event ID, occurrence date and time (trigger time), location, cluster ID and moment magnitude. The 1st row is a header line to explain data and units. The catalog was made using the multiplet analysis method by Asanuma et al., 2008 (Society of Exploration Geophysicists expanded abstract, 2008). For the detail, please see that paper, which is referenced below. Cluster ID 0 means non multiplet event (single event). The Catalog is the result of multiplet analysis performed using the 40-97 Hz frequency band of the waveforms. Hiroshi Asanuma, Yusuke Kumano, Hirokazu Moriya, Hiroaki Niitsuma, Ulrich Schanz, and Markus Häring, (2008), "Identification of microseismic multiplets in the frequency domain and interpretation of reservoir structure at Basel, Switzerland," SEG Technical Program Expanded Abstracts: 1451-1455.https://doi.org/10.1190/1.305918

Temperature data from satellite imagery and the distribution of schistosomiasis in Egypt

Polar orbiting environmental satellites operated by the National Oceanographic and Atmospheric Administration acquire daytime and nighttime thermal infrared measurements of the earth's surface around the world at a spatial resolution of 1.1 km. Day-night pairs of this imagery from the Advanced Very High Resolution Radiometer (AVHRR) were processed to produce temperature maximum, temperature minimum, and diurnal temperature difference (dT) maps of the lower Nile River valley. Nile delta subsets of the dT maps for August 16, 1990 and February 14, 1991 were analyzed in detail. Values of dT at specific locations were derived using the median of 5 x 5 pixels centered on the latitude and longitude of 41 survey sites listed in 1935, 1983, and 1990 schistosomiasis surveys of the Nile Delta. A Spearman correlation coefficient matrix revealed an inverse relationship between site dT values for August 16, 1990 and February 14, 1991 and prevalence of Schistosoma mansoni in the 1935 and 1983 surveys. For S. haematobium, a positive association of site dT values and prevalence was seen for 1935 only. A significant association was observed between 1935 S. mansoni prevalence and that observed in 1983 and 1990; S. haematobium prevalence in 1935 was not correlated with the later surveys. The results suggest that AVHRR thermal difference maps reflect regional hydrologic conditions that can be used as a predictor of environmental risk of schistosomiasis for control program managemen