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"Symons, Jessica"
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Structural and functional consequences of reversible lipid asymmetry in living membranes
Maintenance of lipid asymmetry across the two leaflets of the plasma membrane (PM) bilayer is a ubiquitous feature of eukaryotic cells. Loss of this asymmetry has been widely associated with cell death. However, increasing evidence points to the physiological importance of non-apoptotic, transient changes in PM asymmetry. Such transient scrambling events are associated with a range of biological functions, including intercellular communication and intracellular signaling. Thus, regulation of interleaflet lipid distribution in the PM is a broadly important but underappreciated cellular process with key physiological and structural consequences. Here, we compile the mounting evidence revealing multifaceted, functional roles of PM asymmetry and transient loss thereof. We discuss the consequences of reversible asymmetry on PM structure, biophysical properties and interleaflet coupling. We argue that despite widespread recognition of broad aspects of membrane asymmetry, its importance in cell biology demands more in-depth investigation of its features, regulation, and physiological and pathological implications.
The asymmetric distribution of lipids, including cholesterol, in biological membranes established actively by flippases and scramblases has structural, biophysical and functional consequences in cells and implications for communication across membranes.
Journal Article
Lipidomic and biophysical homeostasis of mammalian membranes counteracts dietary lipid perturbations to maintain cellular fitness
Proper membrane physiology requires maintenance of biophysical properties, which must be buffered from external perturbations. While homeostatic adaptation of membrane fluidity to temperature variation is a ubiquitous feature of ectothermic organisms, such responsive membrane adaptation to external inputs has not been directly observed in mammals. Here, we report that challenging mammalian membranes by dietary lipids leads to robust lipidomic remodeling to preserve membrane physical properties. Specifically, exogenous polyunsaturated fatty acids are rapidly incorporated into membrane lipids, inducing a reduction in membrane packing. These effects are rapidly compensated both in culture and in vivo by lipidome-wide remodeling, most notably upregulation of saturated lipids and cholesterol, resulting in recovery of membrane packing and permeability. Abrogation of this response results in cytotoxicity when membrane homeostasis is challenged by dietary lipids. These results reveal an essential mammalian mechanism for membrane homeostasis wherein lipidome remodeling in response to dietary lipid inputs preserves functional membrane phenotypes.
Proper membrane physiology requires maintenance of a narrow range of physicochemical properties, which must be buffered from external perturbations. Here, authors report lipidomic remodeling to preserve membrane physical properties upon exogenous polyunsaturated fatty acids exposure.
Journal Article
I see therefore we are: the potential for aggregating individual future visions into a collective imaginary through artificial intelligence (AI)
Purpose
This analysis draws on ethnographic research in a Northern UK city where a series of engagement activities produced hand-drawn sketches about the future. This paper shows how different groups revealed contradictory aspirations for the area with growth-focused politicians and planners projecting affluent prosperity rather than the modest, family-oriented social stability sought by local people.
Design/methodology/approach
Reconciling multiple perspectives is the greatest challenge of civic leadership. This paper considers how the emerging potential of artificial intelligence (AI) could support a structured imagining process for masterplanners to aggregate aspirational sketches at scale and so develop a closer relationship between citizen ideas for the future and civic decision makers’ own strategies and action plans.
Findings
This paper argues for a collective intelligence paradigm that aggregates individual futures thinking at city scale. Urban masterplanning strategies provide an organising structure to allow a city to emerge as a flourishing of multiple aspirations all at once.
Research limitations/implications
Rather than having individualism or collectivism as binary alternatives, generative AI offers an intriguing process for combining individual aspirations into a pluralist endeavour.
Practical implications
Engaging with citizens on the ground, in their homes and community spaces is the only way to uncover what is important to them. Ethnography provides that.
Social implications
Although AI’s use of aggregated data is collective, intelligence comes from nuanced and ethnographic engagement with the data.
Originality/value
The principle of the emergent city (Symons 2017) provides a conceptual approach to amalgamating the individual with the collective.
Journal Article
Ultra high dose rate (35 Gy/sec) radiation does not spare the normal tissue in cardiac and splenic models of lymphopenia and gastrointestinal syndrome
Recent reports have shown that very high dose rate radiation (35–100 Gy/second) referred to as FLASH tends to spare the normal tissues while retaining the therapeutic effect on tumor. We undertook a series of experiments to assess if ultra-high dose rate of 35 Gy/second can spare the immune system in models of radiation induced lymphopenia. We compared the tumoricidal potency of ultra-high dose rate and conventional dose rate radiation using a classical clonogenic assay in murine pancreatic cancer cell lines. We also assessed the lymphocyte sparing potential in cardiac and splenic irradiation models of lymphopenia and assessed the severity of radiation-induced gastrointestinal toxicity triggered by the two dose rate regimes
in vivo
. Ultra-high dose rate irradiation more potently induces clonogenic cell death than conventional dose rate irradiation with a dose enhancement factor at 10% survival (DEF
10
) of 1.310 and 1.365 for KPC and Panc02 cell lines, respectively. Ultra-high dose rate was equally potent in depleting CD3, CD4, CD8, and CD19 lymphocyte populations in both cardiac and splenic irradiation models of lymphopenia. Radiation-induced gastrointestinal toxicity was more pronounced and mouse survival (7 days
vs
. 15 days,
p
= 0.0001) was inferior in the ultra-high dose rate arm compared to conventional dose rate arm. These results suggest that, contrary to published data in other models of radiation-induced acute and chronic toxicity, dose rates of 35 Gy/s do not protect mice from the detrimental side effects of irradiation in our models of cardiac and splenic radiation-induced lymphopenia or gastrointestinal mucosal injury.
Journal Article
Cell membranes sustain phospholipid imbalance via cholesterol asymmetry
Membranes are molecular interfaces that compartmentalize cells to control the flow of nutrients and information. These functions are facilitated by diverse collections of lipids, nearly all of which are distributed asymmetrically between the two bilayer leaflets. Most models of biomembrane structure and function often include the implicit assumption that these leaflets have similar abundances of phospholipids. Here, we show that this assumption is generally invalid and investigate the consequences of lipid abundance imbalances in mammalian plasma membranes (PM). Using quantitative lipidomics, we discovered that cytoplasmic leaflets of human erythrocyte membranes have >50% overabundance of phospholipids compared to exoplasmic leaflets. This imbalance is enabled by an asymmetric interleaflet distribution of cholesterol, which regulates cellular cholesterol homeostasis. These features produce unique functional characteristics, including low PM permeability and resting tension in the cytoplasmic leaflet that regulates protein localization. These largely overlooked aspects of membrane asymmetry represent an evolution of classic paradigms of biomembrane structure and physiology.
Journal Article
'Based on a true story': Ethnography's impact as a narrative form
The development of our ideas around storytelling gathered pace at the Association of Social Anthropologists annual conference in Edinburgh in 2014 when we co-convened a panel encouraging people to play with ethnographic narrative. Fiction, biography, literary non-fiction, poetry, prose, jokes, metaphors, parables, adverts, painting, sculpture, dance, song and so on, are established mechanisms for storytelling.
Journal Article