Cell death and inflammation are intimately linked during Yersinia infection. Pathogenic Yersinia inhibits the MAP kinase TGFβ-activated kinase 1 (TAK1) via the effector YopJ, thereby silencing cytokine expression while activating caspase-8–mediated cell death. Here, using Yersinia pseudotuberculosis in corroboration with costimulation of lipopolysaccharide and (5Z)-7-Oxozeaenol, a small-molecule inhibitor of TAK1, we show that caspase-8 activation during TAK1 inhibition results in cleavage of both gasdermin D (GSDMD) and gasdermin E (GSDME) in murine macrophages, resulting in pyroptosis. Loss of GsdmD delays membrane rupture, reverting the cell-death morphology to apoptosis. We found that the Yersinia-driven IL-1 response arises from asynchrony of macrophage death during bulk infections in which two cellular populations are required to provide signal 1 and signal 2 for IL-1α/β release. Furthermore, we found that human macrophages are resistant to YopJ-mediated pyroptosis, with dampened IL-1β production. Our results uncover a form of caspase-8–mediated pyroptosis and suggest a hypothesis for the increased sensitivity of humans to Yersinia infection compared with the rodent reservoir.
The tobacco cutworm, Spodoptera litura, is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione-S-transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect’s natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India–South China–Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S. litura.
Summary Cytokine-activated STAT proteins dimerize and bind to high-affinity motifs, and N-terminal domain-mediated oligomerization of dimers allows tetramer formation and binding to low-affinity tandem motifs, but the functions of dimers versus tetramers are unknown. We generated Stat5a-Stat5b double knock-in (DKI) N-domain mutant mice that form dimers but not tetramers, identified cytokine-regulated genes whose expression required STAT5 tetramers, and defined dimer versus tetramer consensus motifs. Whereas Stat5- deficient mice exhibited perinatal lethality, DKI mice were viable; thus, STAT5 dimers were sufficient for survival. Nevertheless, STAT5 DKI mice had fewer CD4+CD25+ T cells, NK cells, and CD8+ T cells, with impaired cytokine-induced and homeostatic proliferation of CD8+ T cells. DKI CD8+ T cell proliferation following viral infection was diminished and DKI Treg cells did not efficiently control colitis. Thus, tetramerization of STAT5 is dispensable for survival but is critical for cytokine responses and normal immune function, establishing a critical role for tetramerization in vivo.
Landsat-7 Enhanced Thematic Mapper Plus (ETM+) and Landsat-8 Operational Land Imager (OLI) and Thermal Infrared Sensor (TIRS) are currently operational for routine Earth observation. There are substantial differences between instruments onboard both satellites. The enhancements achieved with Landsat-8 refer to the scanning technology (replacing of whisk-broom scanners with two separate push-broom OLI and TIRS scanners), an extended number of spectral bands (two additional bands provided) and narrower bandwidths. Therefore, cross-comparative analysis is very necessary for the combined use of multi-decadal Landsat imagery. In this study, 3,311 independent sample points of four major land cover types (primary forest, unplanted cropland, swidden cultivation and water body) were used to compare the spectral bands of ETM+ and OLI. Eight sample plots with different land cover types were manually selected for comparison with the Normalized Difference Vegetation Index (NDVI), the Modified Normalized Difference Water Index (MNDWI), the Land Surface Water Index (LSWI) and the Normalized Burn Ratio (NBR). These indices were calculated with six pairs of ETM+ and OLI cloud-free images, which were acquired over the border area of Myanmar, Laos and Thailand just two days apart, when Landsat-8 achieved operational obit. Comparative results showed that: (1) the average surface reflectance of each band differed slightly, but with a high degree of similarities between both sensors. In comparison with ETM+, the OLI had higher values for the near-infrared band for vegetative land cover types, but lower values for non-vegetative types. The new sensor had lower values for the shortwave infrared (2.11-2.29 µm) band for
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