The factors regulating cellular identity are critical for understanding the transition from health to disease and responses to therapies. Recent literature suggests that autophagy compromise may cause opposite effects in different contexts by either activating or inhibiting YAP/TAZ co-transcriptional regulators of the Hippo pathway via unrelated mechanisms. Here, we confirm that autophagy perturbation in different cell types can cause opposite responses in growth-promoting oncogenic YAP/TAZ transcriptional signalling. These apparently contradictory responses can be resolved by a feedback loop where autophagy negatively regulates the levels of α-catenins, LC3-interacting proteins that inhibit YAP/TAZ, which, in turn, positively regulate autophagy. High basal levels of α-catenins enable autophagy induction to positively regulate YAP/TAZ, while low α-catenins cause YAP/TAZ activation upon autophagy inhibition. These data reveal how feedback loops enable post-transcriptional determination of cell identity and how levels of a single intermediary protein can dictate the direction of response to external or internal perturbations.GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37-/- mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria.In Pseudomonas aeruginosa the alp system encodes a programmed cell death pathway that is switched on in a subset of cells in response to DNA damage and is linked to the virulence of the organism. Here we show that the central regulator of this pathway, AlpA, exerts its effects by acting as an antiterminator rather than a transcription activator. In particular, we present evidence that AlpA positively regulates the alpBCDE cell lysis genes, as well as genes in a second newly identified target locus, by recognizing specific DNA sites within the promoter, then binding RNA polymerase directly and allowing it to bypass intrinsic terminators positioned downstream. Paclitaxel mouse AlpA thus functions in a mechanistically unusual manner to control the expression of virulence genes in this opportunistic pathogen.Gluten, which makes up 85% of endosperm wheat protein, is considered a crucial quality determinant of wheat-based food products. During wheat dough manufacture, the molecular packing of gluten causes formation of large structures that exceed the millimetre scale. However, due to lack of imaging techniques for complex systems composed of giant macromolecules, the entire gluten structure remains unknown. Here, we develop an optical clearing reagent (termed SoROCS) that makes wheat-based products transparent. Combined with two-photon microscopy, we image the three-dimensional (3D) structure of gluten at the size in the millimetre scale and at submicron resolution. Further, we demonstrate how the 3D structure of gluten dramatically changes from a honeycomb-shaped network to sparse large clumps in wheat noodles, depending on the salt added during dough making, thereby reducing stress when compressing the noodle. Moreover, we show that SoROCS can be used for noodle imaging using confocal laser scanning microscopy.Ferrovolcanism, yet to be directly observed, is the most exotic and poorly understood predicted manifestation of planetary volcanism. Large-scale experiments carried out at the Syracuse Lava Project offer insight into the emplacement dynamics of metallic flows as well as coeval metallic and silicate flows. Here, we find that, under the same environmental conditions, higher-density/lower-viscosity metallic lava moves ten times faster than lower-density/higher-viscosity silicate lava. The overall morphology of the silicate flow is not significantly affected by the co-emplacement of a metallic flow. Rather, the metallic flow is largely decoupled from the silicate flow, occurring mainly in braided channels underneath the silicate flow and as low-relief breakouts from the silicate flow front. Turbulent interactions at the metallic-silicate flow interface result in mingling of the two liquids, preserved as erosional surfaces and sharp contacts. The results have important implications for the interpretation of possible ferrovolcanic landscapes across our solar system.Our incomplete understanding of osteoarthritis (OA) pathogenesis has significantly hindered the development of disease-modifying therapy. The functional relationship between subchondral bone (SB) and articular cartilage (AC) is unclear. Here, we found that the changes of SB architecture altered the distribution of mechanical stress on AC. Importantly, the latter is well aligned with the pattern of transforming growth factor beta (TGFβ) activity in AC, which is essential in the regulation of AC homeostasis. Specifically, TGFβ activity is concentrated in the areas of AC with high mechanical stress. A high level of TGFβ disrupts the cartilage homeostasis and impairs the metabolic activity of chondrocytes. Mechanical stress stimulates talin-centered cytoskeletal reorganization and the consequent increase of cell contractile forces and cell stiffness of chondrocytes, which triggers αV integrin-mediated TGFβ activation. Knockout of αV integrin in chondrocytes reversed the alteration of TGFβ activation and subsequent metabolic abnormalities in AC and attenuated cartilage degeneration in an OA mouse model. Thus, SB structure determines the patterns of mechanical stress and the configuration of TGFβ activation in AC, which subsequently regulates chondrocyte metabolism and AC homeostasis.