Drought-induced tree mortality has recently received considerable attention. Questions have arisen over the necessary intensity and duration thresholds of droughts that are sufficient to trigger rapid forest declines. The values of such tipping points leading to forest declines due to drought are presently unknown. In this study, we have evaluated the potential relationship between the level of tree growth and concurrent drought conditions with data of the tree growth-related ring width index (RWI) of the two dominant conifer species (Pinus edulis and Pinus ponderosa) in the Southwestern United States (SWUS) and the meteorological drought-related standardized precipitation evapotranspiration index (SPEI). In this effort, we determined the binned averages of RWI and the 11 month SPEI within the month of July within each bin of 30 of RWI in the range of 0-3000. We found a significant correlation between the binned averages of RWI and SPEI at the regional-scale under dryer conditions. The tipping point of forest declines to drought is predicted by the regression model as SPEI tp = −1.64 and RWI tp = 0, that is, persistence of the water deficit (11 month) with intensity of −1.64 leading to negligible growth for the conifer species. When climate conditions are wetter, the correlation between the binned averages of RWI and SPEI is weaker which we believe is most likely due to soil water and atmospheric moisture levels no longer being the dominant factor limiting tree growth. We also illustrate a potential application of the derived tipping point (SPEI tp = −1.64) through an examination of the 2002 extreme drought event in the SWUS conifer forest regions. Distinguished differences in remote-sensing based NDVI anomalies were found between the two regions partitioned by the derived tipping point.
The advantage of oncolytic viruses (OV) in cancer therapy is their dual effect of directly killing tumours while prompting anti-tumour immune response. Oncolytic parapoxvirus ovis (ORFV) and other OVs are thought to induce apoptosis, but apoptosis, being the immunogenically inert compared to other types of cell death, does not explain the highly inflamed microenvironment in OV-challenged tumors. Here we show that ORFV and its recombinant therapeutic derivatives are able to trigger tumor cell pyroptosis via Gasdermin E (GSDME). This effect is especially prominent in GSDME-low tumor cells, in which ORFV-challenge pre-stabilizes GSDME by decreasing its ubiquitination and subsequently initiates pyroptosis. Consistently, GSDME depletion reduces the proportion of intratumoral cytotoxic T lymphocytes, pyroptotic cell death and the success of tumor ORFV virotherapy. In vivo, the OV preferentially accumulates in the tumour upon systemic delivery and elicits pyroptotic tumor killing. Consequentially, ORFV sensitizes immunologically ‘cold’ tumors to checkpoint blockade. This study thus highlights the critical role of GSDME-mediated pyroptosis in oncolytic ORFV-based antitumor immunity and identifies combinatorial cancer therapy strategies.
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