Pore-forming toxins (PFTs) are secreted proteins that contribute to the virulence of a great variety of bacterial pathogens. They inflict one of the more disastrous damages a target cell can be exposed to: disruption of plasma membrane integrity. Since this is an ancient form of attack, which bears similarities to mechanical membrane damage, cells have evolved response pathways to these perturbations. Here, it is reported that PFTs trigger very diverse yet specific response pathways. Many are triggered by the decrease in cytoplasmic potassium, which thus emerges as a central regulator. Upon plasma membrane damage, cells activate signalling pathways aimed at restoring plasma membrane integrity and ion homeostasis. Interestingly these pathways do not require protein synthesis. Cells also trigger signalling cascades that allow them to enter a quiescent-like state, where minimal energy is consumed while waiting for plasma membrane damage to be repaired. More specifically, protein synthesis is arrested, cytosolic constituents are recycled by autophagy and energy is stored in lipid droplets.
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http://dx.doi.org/10.1111/j.1462-5822.2011.01600.x | DOI Listing |
Sci Rep
December 2024
Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
Polymer electrolyte membrane water electrolyzers (PEMWEs) are a critical technology for efficient hydrogen production to decarbonize fuels and industrial feedstocks. To make hydrogen cost-effective, the overpotentials across the cell need to be decreased and platinum-group metal loading reduced. One overpotential that needs to be better understood is due to mass transport limitations from bubble formation within the porous transport layer (PTL) and anode catalyst layer (ACL), which can lead to a reduction in performance at typical operating current densities.
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December 2024
Nanobiology Institute, Yale University, West Haven, CT, USA.
Neurotransmitters are released from synaptic vesicles with remarkable precision in response to presynaptic calcium influx but exhibit significant heterogeneity in exocytosis timing and efficacy based on the recent history of activity. This heterogeneity is critical for information transfer in the brain, yet its molecular basis remains poorly understood. Here, we employ a biochemically-defined fusion assay under physiologically relevant conditions to delineate the minimal protein machinery sufficient to account for various modes of calcium-triggered vesicle fusion dynamics.
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December 2024
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Antibody-mediated protection against pathogens is crucial to a healthy life. However, the recent SARS-CoV-2 pandemic has shown that pre-existing comorbid conditions including kidney disease account for compromised humoral immunity to infections. Individuals with kidney disease are not only susceptible to infections but also exhibit poor vaccine-induced antibody response.
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December 2024
Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism Digestion and Reproduction, Imperial College London, London, UK.
Lactobacillus species dominance of the vaginal microbiome is a hallmark of vaginal health. Pathogen displacement of vaginal lactobacilli drives innate immune activation and mucosal barrier disruption, increasing the risks of STI acquisition and, in pregnancy, of preterm birth. We describe differential TLR mediated activation of the proinflammatory transcription factor NF-κB by vaginal pathogens and commensals.
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December 2024
Department of Chemical Engineering, Electrochemical Innovation Lab, University College London, London, UK.
High-temperature proton exchange membrane fuel cells (HT-PEMFCs) offer solutions to challenges intrinsic to low-temperature PEMFCs, such as complex water management, fuel inflexibility, and thermal integration. However, they are hindered by phosphoric acid (PA) leaching and catalyst migration, which destabilize the critical three-phase interface within the membrane electrode assembly (MEA). This study presents an innovative approach to enhance HT-PEMFC performance through membrane modification using picosecond laser scribing, which optimises the three-phase interface by forming a graphene-like structure that mitigates PA leaching.
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