Glasgow's Food Future(s) Local Neighbourhoods of Social Innovation in 2031

Collaborative Futures is an academic project which runs in partnership between the Innovation School at Glasgow School of Art (GSA) and the Centre for Civic Innovation (CCI) at Glasgow City Council over a four month period. This project forms a significant part of the Masters of European (MEDes) final year of study at GSA, and is the third iteration of Collaborative Futures with CCI as the project partner. This year’s brief Glasgow Food Future(s): Neighbourhoods of Innovation 2031 asked the project team to explore the Glasgow food system and the ways in which it impacts both people and place in order to help inform new social innovations for the city. The project findings incorporate tangible, future directions and opportunities communicated as compelling narratives to support and direct the ongoing work of the CCI team. The project builds on the successes of last year’s Collaborative Futures project, Glasgow’s Future(s) Stories; Social Innovation & Participatory Democracy in 2030, which explored how citizens can become more involved in decision-making processes that will determine the future of the city. Both projects have at their core an exploration of social innovation and speculative futures, storytelling as a means to communicate ideas and invite collaboration

AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology

Mitochondria are dynamic organelles that undergo membrane remodeling events in response to metabolic alterations to generate an adequate mitochondrial network. Here, we investigated the function of mitochondrial fission regulator 1-like protein (MTFR1L), an uncharacterized protein that has been identified in phosphoproteomic screens as a potential AMP-activated protein kinase (AMPK) substrate. We showed that MTFR1L is an outer mitochondrial membrane-localized protein modulating mitochondrial morphology. Loss of MTFR1L led to mitochondrial elongation associated with increased mitochondrial fusion events and levels of the mitochondrial fusion protein, optic atrophy 1. Mechanistically, we show that MTFR1L is phosphorylated by AMPK, which thereby controls the function of MTFR1L in regulating mitochondrial morphology both in mammalian cell lines and in murine cortical neurons in vivo. Furthermore, we demonstrate that MTFR1L is required for stress-induced AMPK-dependent mitochondrial fragmentation. Together, these findings identify MTFR1L as a critical mitochondrial protein transducing AMPK-dependent metabolic changes through regulation of mitochondrial dynamics.</p

Feasibility of image-guided radiotherapy based on helical tomotherapy to reduce contralateral parotid dose in head and neck cancer

Background To evaluate the feasibility of image-guided radiotherapy based on helical Tomotherapy to spare the contralateral parotid gland in head and neck cancer patients with unilateral or no neck node metastases. Methods A retrospective review of 52 patients undergoing radiotherapy for head and neck cancers with image guidance based on daily megavoltage CT imaging with helical tomotherapy was performed. Results Mean contralateral parotid dose and the volume of the contralateral parotid receiving 40 Gy or more were compared between radiotherapy plans with significant constraint (SC) of less than 20 Gy on parotid dose (23 patients) and the conventional constraint (CC) of 26 Gy (29 patients). All patients had PTV coverage of at least 95% to the contralateral elective neck nodes. Mean contralateral parotid dose was, respectively, 14.1 Gy and 24.7 Gy for the SC and CC plans (p < 0.0001). The volume of contralateral parotid receiving 40 Gy or more was respectively 5.3% and 18.2% (p < 0.0001) Conclusion Tomotherapy for head and neck cancer minimized radiotherapy dose to the contralateral parotid gland in patients undergoing elective node irradiation without sacrificing target coverage

Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo

Neuronal mitochondria play important roles beyond ATP generation, including Ca2+ uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly between the axon and dendrites of a given neuronal subtype, but in CA1 pyramidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer-specific compartmentalization. In the dendrites of these neurons, mitochondria morphology ranges from highly fused and elongated in the apical tuft, to more fragmented in the apical oblique and basal dendritic compartments, and thus occupy a smaller fraction of dendritic volume than in the apical tuft. However, the molecular mechanisms underlying this striking degree of subcellular compartmentalization of mitochondria morphology are unknown, precluding the assessment of its impact on neuronal function. Here, we demonstrate that this compartment-specific morphology of dendritic mitochondria requires activity-dependent, Ca2+ and Camkk2-dependent activation of AMPK and its ability to phosphorylate two direct effectors: the pro-fission Drp1 receptor Mff and the recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers a signaling pathway underlying the subcellular compartmentalization of mitochondrial morphology in dendrites of neurons in vivo through spatially precise and activity-dependent regulation of mitochondria fission/fusion balance.</p

Novel regulation and functions of AMPK in developing and adult neurons

The AMP-activated protein kinase (AMPK) is a master metabolic regulator and energy sensor that has been extensively studied in the context of cancer and metabolic disorders. However, its role in neuronal function and morphology remains largely unexplored. This dissertation aims to bridge this gap by investigating the roles of AMPK in maintaining axon homeostasis and regulating mitochondrial morphology in neurons. By identifying novel regulators of AMPK across different cellular compartments, this thesis sheds light on the multifaceted functions of AMPK in shaping neuronal and mitochondrial architecture. The dissertation is organized into five chapters. Chapter 1 provides a brief background on AMPK, its activation mechanisms, and the downstream pathways it regulates. Chapter 2 introduces with-no-lysine kinase (WNK), a novel axon morphogenic kinase with dual roles in terminal axon branch development and maintenance in mature axons. Chapter 3 investigates the role of AMPK in mediating the loss-of-WNK axonal phenotypes, revealing a critical link between AMPK and axonal integrity. Chapter 4 shifts focus to the mitochondrial, characterizing mitochondrial fission regulator 1-like (MTFR1L) as a novel AMPK-activated protein that regulates mitochondrial morphology. Finally, Chapter 5 explores the role of AMPK in mediating activity-dependent mitochondrial morphology in hippocampal CA1 neurons, highlighting the dynamic interplay between neuronal activity and mitochondrial dynamics. Collectively, these findings provide novel insights into the multifaceted roles of AMPK in neuronal development, degeneration, and organelle regulation, underscoring the importance of this master kinase in maintaining neuronal health and homeostasis

UCIMCO Stock Selection Semi-Annual Presentation, Fall 2021

The Ursinus College Investment Management Company (UCIMCO) consists of groups of student analysts who manage endowment-style and stock selection funds on behalf of the college endowment. This presentation, by the stock selection team, examines quarterly performance and strategy while discussing the most recent selections in the portfolio: Agios Pharmaceuticals, CubeSmart, Splunk and Nexstar Media Group

Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo

Abstract Neuronal mitochondria play important roles beyond ATP generation, including Ca2+ uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly between the axon and dendrites of a given neuronal subtype, but in CA1 pyramidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer-specific compartmentalization. In the dendrites of these neurons, mitochondria morphology ranges from highly fused and elongated in the apical tuft, to more fragmented in the apical oblique and basal dendritic compartments, and thus occupy a smaller fraction of dendritic volume than in the apical tuft. However, the molecular mechanisms underlying this striking degree of subcellular compartmentalization of mitochondria morphology are unknown, precluding the assessment of its impact on neuronal function. Here, we demonstrate that this compartment-specific morphology of dendritic mitochondria requires activity-dependent, Ca2+ and Camkk2-dependent activation of AMPK and its ability to phosphorylate two direct effectors: the pro-fission Drp1 receptor Mff and the recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers a signaling pathway underlying the subcellular compartmentalization of mitochondrial morphology in dendrites of neurons in vivo through spatially precise and activity-dependent regulation of mitochondria fission/fusion balance

Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo.

Acknowledgements: We thank past and present members of the Polleux and Lewis labs for feedback and discussion along the way. We thank Nelson Spruston (HHMI-Janelia) for sharing the CA1 serial EM dataset generated while EB was in his laboratory. We thank the Zuckerman Institute’s Cellular Imaging platform for instrument use and technical advice. We thank Patrycja Szybowska, Joshua Weertman, Klaudia Strucinska, Qiaolian Liu and Rhythm Sharma for excellent technical help. This research was supported by grants NIGMS R35GM137921 (TL), NIGMS P20GM103636-06 sub-project 2 (TL), Presbyterian Health Foundation (TL), NINDS R35 NS127232 (FP) and NINDS NS107483 (FP), HHMI/Janelia (EB), NIMH R01MH124047, NIMH R01MH124867, NINDS R01NS121106, NINDS U01NS115530, NINDS R01NS133381, NINDS R01NS131728, NIA, RF1AG080818 (AL), Medical Research Council (MC_UU_00028/5) (JP) and an Investigator Award from the Wellcome Trust (204766/Z/16/Z) (FMR and DGH).Funder: U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)Funder: Presbyterian Health Foundation; doi: https://doi.org/10.13039/100001298Funder: U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)Funder: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)Neuronal mitochondria play important roles beyond ATP generation, including Ca2+ uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly between the axon and dendrites of a given neuronal subtype, but in CA1 pyramidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer-specific compartmentalization. In the dendrites of these neurons, mitochondria morphology ranges from highly fused and elongated in the apical tuft, to more fragmented in the apical oblique and basal dendritic compartments, and thus occupy a smaller fraction of dendritic volume than in the apical tuft. However, the molecular mechanisms underlying this striking degree of subcellular compartmentalization of mitochondria morphology are unknown, precluding the assessment of its impact on neuronal function. Here, we demonstrate that this compartment-specific morphology of dendritic mitochondria requires activity-dependent, Ca2+ and Camkk2-dependent activation of AMPK and its ability to phosphorylate two direct effectors: the pro-fission Drp1 receptor Mff and the recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers a signaling pathway underlying the subcellular compartmentalization of mitochondrial morphology in dendrites of neurons in vivo through spatially precise and activity-dependent regulation of mitochondria fission/fusion balance

Axon morphogenesis and maintenance require an evolutionary conserved safeguard function of Wnk kinases antagonizing Sarm and Axed

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