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      • Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H<sub>2</sub>S Production

        Longchamp, Alban,Mirabella, Teodelinda,Arduini, Alessandro,MacArthur, Michael R.,Das, Abhirup,Treviñ,o-Villarreal, J. Humberto,Hine, Christopher,Ben-Sahra, Issam,Knudsen, Nelson H.,Brace, Lear E Elsevier 2018 Cell Vol.173 No.1

        <P><B>Summary</B></P> <P>Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1α. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in ECs <I>in vitro</I>, and increased capillary density in mouse skeletal muscle <I>in vivo</I> via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1α. We also identified a requirement for cystathionine-γ-lyase in VEGF-dependent angiogenesis via increased hydrogen sulfide (H<SUB>2</SUB>S) production. H<SUB>2</SUB>S mediated its proangiogenic effects in part by inhibiting mitochondrial electron transport and oxidative phosphorylation, resulting in increased glucose uptake and glycolytic ATP production.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sulfur amino acid (SAA) restriction triggers angiogenesis independent of hypoxia or HIF1α </LI> <LI> GCN2/ATF4 pathway regulates VEGF and CGL expression upon SAA restriction in ECs </LI> <LI> CGL is required for skeletal muscle angiogenesis activated by diet or exercise </LI> <LI> H<SUB>2</SUB>S triggers glucose uptake, glycolysis, and PPP concomitant with OXPHOS inhibition in ECs </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • A Transdisciplinary Approach to Exploring Body Image in School Projects

        Charlotte Graham,Philippe Longchamps,Michaela af Winklerfelt,Christian Berggren,Ola Forsmark,Marcus Rosenkvist,Ola Tindberg,Kristóf Fenyvesi 한국교원대학교 융합교육연구소 2024 융합교육연구 Vol.10 No.1

        This case study introduces the integration of Mathematics and Arts within a STEAM (Science, Technology, Engineering, Art, and Mathematics) project, focusing on the exploration of human body proportions and body-image perceptions. Through a project-based learning approach, a team of Swedish teachers collaboratively designed and implemented a curriculum that not only illustrates the Maths-Art relationship but also addresses the broader social and cultural implications of body image. This paper outlines the project's methodology, emphasising hands-on activities, critical thinking, and transformative learning experiences that connect real-life and artistic perspectives. By engaging students in a comprehensive exploration of body-image through historical, cultural, and mathematical lenses, the project aimed to foster a healthier understanding of body diversity. The transdisciplinary approach adopted by the teachers at Tångvalla School in Sweden serves as a model for integrating STEAM education in addressing contemporary educational and societal challenges.

      • Hypothalamic-Pituitary Axis Regulates Hydrogen Sulfide Production

        Hine, Christopher,Kim, Hyo-Jeong,Zhu, Yan,Harputlugil, Eylul,Longchamp, Alban,Matos, Marina Souza,Ramadoss, Preeti,Bauerle, Kevin,Brace, Lear,Asara, John M.,Ozaki, C. Keith,Cheng, Sheue-yann,Singha, S Cell Press 2017 Cell metabolism Vol.25 No.6

        <▼1><P><B>Summary</B></P><P>Decreased growth hormone (GH) and thyroid hormone (TH) signaling are associated with longevity and metabolic fitness. The mechanisms underlying these benefits are poorly understood, but may overlap with those of dietary restriction (DR), which imparts similar benefits. Recently we discovered that hydrogen sulfide (H<SUB>2</SUB>S) is increased upon DR and plays an essential role in mediating DR benefits across evolutionary boundaries. Here we found increased hepatic H<SUB>2</SUB>S production in long-lived mouse strains of reduced GH and/or TH action, and in a cell-autonomous manner upon serum withdrawal in vitro. Negative regulation of hepatic H<SUB>2</SUB>S production by GH and TH was additive and occurred via distinct mechanisms, namely direct transcriptional repression of the H<SUB>2</SUB>S-producing enzyme cystathionine γ-lyase (CGL) by TH, and substrate-level control of H<SUB>2</SUB>S production by GH. Mice lacking CGL failed to downregulate systemic T<SUB>4</SUB> metabolism and circulating IGF-1, revealing an essential role for H<SUB>2</SUB>S in the regulation of key longevity-associated hormones.</P></▼1><▼2><P><B>Highlights</B></P><P>•<P>Hepatic H<SUB>2</SUB>S production capacity is elevated in long-lived hypopituitary mouse models</P>•<P>Growth hormone (GH) represses hepatic H<SUB>2</SUB>S production post-transcriptionally</P>•<P>Thyroid hormone (TH) acts via TRβ to repress cystathionine γ-lyase and H<SUB>2</SUB>S levels</P>•<P>H<SUB>2</SUB>S negatively regulates circulating TH and IGF-1 levels</P></P></▼2><▼3><P>Reduced thyroid hormone (TH) and growth hormone (GH) activity are hallmarks of genetic models of longevity in mice. Here, Hine et al. find that TH and GH negatively regulate hepatic production of the longevity-associated gas hydrogen sulfide, which feeds back to negatively regulate circulating TH and IGF-1 levels.</P></▼3>

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