Hypoxia is a hallmark of solid cancers, supporting proliferation, angiogenesis and escape from apoptosis. There is still limited understanding of how cancer cells adapt to hypoxic conditions and survive. We analyzed transcriptome changes of human lung and breast cancer cells under chronic hypoxia. Hypoxia induced highly concordant changes in transcript abundance, but divergent splicing responses, underlining the cell type-specificity of alternative splicing programs. While RNA-binding proteins were predominantly reduced, hypoxia specifically induced muscleblind-like protein 2 (MBNL2). Strikingly, MBNL2 induction was critical for hypoxia adaptation by controlling the transcript abundance of hypoxia response genes, such as vascular endothelial growth factor A (VEGFA). MBNL2 depletion reduced the proliferation and migration of cancer cells, demonstrating an important role of MBNL2 as cancer driver. Hypoxia control is specific for MBNL2 and not shared by its paralog MBNL1. Thus, our study revealed MBNL2 as central mediator of cancer cell responses to hypoxia, regulating the expression and alternative splicing of hypoxia-induced genes. Published by Cold Spring Harbor Laboratory Press for the RNA Society.BACKGROUND Improving the quality of care for patients who return home after a hospital stay is an international priority; however, few jurisdictions have engaged broadly with patients and caregivers to understand what most affects their experience transitioning home. We performed Ontario-wide group concept mapping, beginning with a brainstorming phase, to understand patient and caregiver priorities in the transition. METHODS We used group concept mapping to engage patients and caregivers who had lived experience transitioning from hospital to home in Ontario in the previous 3 years. We report on the first phase, brainstorming, conducted over 10 weeks beginning Jan. 11, 2018 via an online survey or facilitated group discussion. Participants responded to a single focal prompt "When leaving the hospital for home, some thing(s) that affected the experience were ____." The study team identified recurrent concepts and overarching themes. Patients and caregivers informed the study design, recruitment and data interprs.Acute (4 kPa PCO2 (preferential pHi regulation) before pHe compensation was observed. Here we test the hypothesis that preferential pHi regulation is a wide spread strategy of acid-base regulation among fish by measuring pHi regulation in 10 different fish species that are broadly phylogenetically separated, spanning 6 orders, 8 families and 10 genera. Contrary to previous views, we show that preferential pHi regulation is the most common strategy for acid-base regulation within these fishes during exposure to severe acute hypercarbia and that this strategy is associated with increased hypercarbia tolerance. This suggests preferential pHi regulation may confer tolerance to the respiratory acidosis associated with hypercarbia and we propose that it is an exaptation that facilitated key evolutionary transitions in vertebrate evolution, such as the evolution of air breathing. © 2020. Published by The Company of Biologists Ltd.High temperatures resulting in physiological stress and the reduced ability to resist predation can have life-or-death consequences for an organism. We investigated the effects of temperature on the susceptibility to predation for an ectothermic intertidal mollusc (the owl limpet, Lottia gigantea Sowerby) and its predator, the black oystercatcher (Haematopus bachmani Audubon). The ability of L. gigantea to resist bird predation during low tide is determined by the tenacity of attachment to the rock. We developed a transducer to measure the force of predatory attacks on limpets by a captive black oystercatcher and tested the hypothesis that exposure to warm temperatures during low tide emersion would affect the limpet's ability to resist dislodgement in trials with a morphometrically accurate beak mimic and a live bird. In beak mimic trials, four times as many limpets exposed to warm low tides were removed, as compared to limpets exposed to cool low tides or in 'no low tide' submerged conditions. Minimum time before limpet removal in captive bird trials was more than six times longer for limpets in cool low tide or no low tide treatments compared to limpets in the warm low tide treatment. We measured shear forces up to 36.63 N during predatory strikes. These direct measurements of the forces exerted by a living oystercatcher provide context for interactions with multiple prey species. Our data suggest that naturally occurring variation in body temperatures among individual prey items in the field could be an important driver of predator-prey interactions and subsequently community patterns. © 2020. Published by The Company of Biologists Ltd.The non-synovial temporomandibular jaw joint of rorqual whales is presumed to withstand intense stresses when huge volumes of water are engulfed during lunge feeding. Examination and manipulation of TMJs in fresh carcasses, plus CT scans and field/lab mechanical testing of excised tissue blocks, reveals that the TMJ's fibrocartilage pad fully and quickly rebounds after shrinking up to 68-88% in compression (by axis) and stretching 176-230%.  https://www.selleckchem.com/products/gsk-j4-hcl.html  It is more extensible along the mediolateral axis and less extensible dorsoventrally, but mostly isotropic, with collagen and elastin fibers running in all directions. The rorqual TMJ pad compresses as gape increases. Its stiffness is hypothesized to damp acceleration, whereas its elasticity is hypothesized to absorb shock during engulfment; to allow for rotation or other jaw motion during gape opening/closure; and to aid in returning jaws to their closed position during filtration via elastic recoil with conversion of stored potential energy into kinetic energy. © 2020. Published by The Company of Biologists Ltd.Although there is considerable evidence that bone responds to the loading environment in which it develops, few analyses have examined phenotypic plasticity or bone functional adaptation in the masticatory apparatus. Though prior work suggests that masticatory morphology is sensitive to differences in food mechanical properties during development, the importance of the timing/ duration of loading and variation in naturalistic diets is less clear. Here we examine micro- and macrostructural differences in the mandibular condyle in four groups of white rabbits (Oryctolagus cuniculus) raised for a year on diets that varied in mechanical properties and timing of the introduction of mechanically challenging foods, simulating seasonal variation in diet. We employ sliding semilandmarks to locate multiple volumes of interest deep to the mandibular condyle articular surface, and we compare bone volume fraction, trabecular thickness and spacing, and condylar size/shape among experimental groups. Results reveal a shared pattern of bony architecture across the articular surface of all treatment groups, while also demonstrating significant among-group differences.