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Fibroblast growth factor (FGF) signaling is required for numerous aspects of neural development, including neural induction, CNS patterning and neurogenesis. The ability of FGFs to activate Ras/MAPK signaling is thought to be critical for these functions. However, it is unlikely that MAPK signaling can fully explain the diversity of responses to FGFs. We have characterized a Cdc42-dependent signaling pathway operating downstream of the Fgf8a splice isoform. We show that a Cdc42 effector 4-like protein (Cdc42ep4-l or Cep4l) has robust neuronal-inducing activity in Xenopus embryos. Furthermore, we find that Cep4l and Cdc42 itself are necessary and sufficient for sensory neurogenesis in vivo. Furthermore, both proteins are involved in Fgf8a-induced neuronal induction, and Cdc42/Cep4l association is promoted specifically by the Fgf8a isoform of Fgf8, but not by Fgf8b, which lacks neuronal inducing activity. Overall, these data suggest a novel role for Cdc42 in an Fgf8a-specific signaling pathway essential for vertebrate neuronal development. 相似文献
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Lithium is a critical energy material in part due to an array of emerging technologies from electric vehicles to renewable energy systems that rely on large‐format lithium ion batteries. Recent growth in demand for lithium is primarily from increased use in batteries, which comprised 46% of total lithium by end use in 2017. These technologies are often deployed to improve environmental sustainability, yet the environmental effects and sustainability of the resources they rely on are often not well understood, especially as demand increases over time. This is the first in a two part article series that together quantify the lithium resource use and its environmental effects over time by coupling a resource production model and life cycle assessment model. In this first part, a novel resource production model is developed to create scenarios of future lithium demand and production characteristics (e.g., timing, location, and ore type). These scenarios are then used to create a life cycle assessment in part two that captures temporal and spatial changes in production systems over time. Results of the resource production model show global lithium resources range from 293 to 527 million metric tons (Mt) of lithium carbonate equivalent (LCE). Global production will likely increase from 237,000 metric tons LCE in 2018 to 4.4–7.5 Mt LCE/year by 2100. Even with rapidly increasing demand, production from high‐grade brines may satisfy most lithium demand through 2035. Though resources can meet demand through 2100, development of lower grade and unfavorable deposits is likely required after 2050. 相似文献
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Charis E. Teh Alissa K. Robbins Darren C. Henstridge Grant Dewson Sarah T. Diepstraten Gemma Kelly Mark A. Febbraio Sarah S. Gabriel Lorraine A. O&#x;Reilly Andreas Strasser Daniel H. D. Gray 《Cell death and differentiation》2020,27(12):3374
FOXP3+ regulatory T (Treg) cells are essential for maintaining immunological tolerance. Given their importance in immune-related diseases, cancer and obesity, there is increasing interest in targeting the Treg cell compartment therapeutically. New pharmacological inhibitors that specifically target the prosurvival protein MCL-1 may provide this opportunity, as Treg cells are particularly reliant upon this protein. However, there are two distinct isoforms of MCL-1; one located at the outer mitochondrial membrane (OMM) that is required to antagonize apoptosis, and another at the inner mitochondrial membrane (IMM) that is reported to maintain IMM structure and metabolism via ATP production during oxidative phosphorylation. We set out to elucidate the relative importance of these distinct biological functions of MCL-1 in Treg cells to assess whether MCL-1 inhibition might impact upon the metabolism of cells able to resist apoptosis. Conditional deletion of Mcl1 in FOXP3+ Treg cells resulted in a lethal multiorgan autoimmunity due to the depletion of the Treg cell compartment. This striking phenotype was completely rescued by concomitant deletion of the apoptotic effector proteins BAK and BAX, indicating that apoptosis plays a pivotal role in the homeostasis of Treg cells. Notably, MCL-1-deficient Treg cells rescued from apoptosis displayed normal metabolic capacity. Moreover, pharmacological inhibition of MCL-1 in Treg cells resistant to apoptosis did not perturb their metabolic function. We conclude that Treg cells require MCL-1 only to antagonize apoptosis and not for metabolism. Therefore, MCL-1 inhibition could be used to manipulate Treg cell survival for clinical benefit without affecting the metabolic fitness of cells resisting apoptosis.Subject terms: Disease genetics, Immune cell death 相似文献
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Coastal marine ecosystems are threatened by a range of anthropogenic stressors, operating at global, local, and temporal scales. We investigated the impact of marine heatwaves (MHWs) combined with decreased light availability over two seasons on the ecophysiological responses of three kelp species (Laminaria digitata, L. hyperborea, and L. ochroleuca). These species function as important habitat-forming foundation organisms in the northeast Atlantic and have distinct but overlapping latitudinal distributions and thermal niches. Under low-light conditions, summertime MHWs induced significant declines in biomass, blade surface area, and Fv/Fm values (a measure of photosynthetic efficiency) in the cool-water kelps L. digitata and L. hyperborea, albeit to varying degrees. Under high-light conditions, all species were largely resistant to simulated MHW activity. In springtime, MHWs had minimal impacts and in some cases promoted kelp performance, while reduced light availability resulted in lower growth rates. While some species were negatively affected by summer MHWs under low-light conditions (particularly L. digitata), they were generally resilient to MHWs under high-light conditions. As such, maintaining good environmental quality and water clarity may increase resilience of populations to summertime MHWs. Our study informs predictions of how habitat-forming foundation kelp species will be affected by interacting, concurrent stressors, typical of compound events that are intensifying under anthropogenic climate change. 相似文献
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In sexually cannibalistic animals, male fitness is influenced not only by successful mate acquisition and egg fertilization, but also by avoiding being eaten. In the cannibalistic nursery web spider, Pisaurina mira, the legs of mature males are longer in relation to their body size than those of females, and males use these legs to aid in wrapping a female''s legs with silk prior to and during copulation. We hypothesized that elongated male legs and silk wrapping provide benefits to males, in part through a reduced likelihood of sexual cannibalism. To test this, we paired females of random size with males from one of two treatment groups—those capable of silk wrapping versus those incapable of silk wrapping. We found that males with relatively longer legs and larger body size were more likely to mate and were less likely to be cannibalized prior to copulation. Regardless of relative size, males capable of silk wrapping were less likely to be cannibalized during or following copulation and had more opportunities for sperm transfer (i.e. pedipalpal insertions). Our results suggest that male size and copulatory silk wrapping are sexually selected traits benefiting male reproductive success. 相似文献
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