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1.
J Mater Chem B ; 11(17): 3958-3968, 2023 05 03.
Article in English | MEDLINE | ID: mdl-37070387

ABSTRACT

Antimicrobial resistance is one of the greatest threats to human health. Gram-positive methicillin resistant Staphylococcus aureus (MRSA), in both its planktonic and biofilm form, is of particular concern. Herein we identify the hydrogelation properties for a series of intrinsically fluorescent, structurally related supramolecular self-associating amphiphiles and determine their efficacy against both planktonic and biofilm forms of MRSA. To further explore the potential translation of this hydrogel technology for real-world applications, the toxicity of the amphiphiles was determined against the eukaryotic multicellular model organism, Caenorhabditis elegans. Due to the intrinsic fluorescent nature of these supramolecular amphiphiles, material characterisation of their molecular self-associating properties included; comparative optical density plate reader assays, rheometry and widefield fluorescence microscopy. This enabled determination of amphiphile structure and hydrogel sol dependence on resultant fibre formation.


Subject(s)
Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Animals , Humans , Microbial Sensitivity Tests , Biofilms , Caenorhabditis elegans , Plankton , Benzothiazoles
2.
Elife ; 92020 05 05.
Article in English | MEDLINE | ID: mdl-32366357

ABSTRACT

Eukaryotic 5'-3' mRNA decay plays important roles during development and in response to stress, regulating gene expression post-transcriptionally. In Caenorhabditis elegans, deficiency of DCAP-1/DCP1, the essential co-factor of the major cytoplasmic mRNA decapping enzyme, impacts normal development, stress survival and ageing. Here, we show that overexpression of dcap-1 in neurons of worms is sufficient to increase lifespan through the function of the insulin/IGF-like signaling and its effector DAF-16/FOXO transcription factor. Neuronal DCAP-1 affects basal levels of INS-7, an ageing-related insulin-like peptide, which acts in the intestine to determine lifespan. Short-lived dcap-1 mutants exhibit a neurosecretion-dependent upregulation of intestinal ins-7 transcription, and diminished nuclear localization of DAF-16/FOXO. Moreover, neuronal overexpression of DCP1 in Drosophila melanogaster confers longevity in adults, while neuronal DCP1 deficiency shortens lifespan and affects wing morphogenesis, cell non-autonomously. Our genetic analysis in two model-organisms suggests a critical and conserved function of DCAP-1/DCP1 in developmental events and lifespan modulation.


Subject(s)
Aging/genetics , Neurosecretory Systems/physiology , RNA Stability/genetics , RNA, Messenger/genetics , Aging/physiology , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/growth & development , Caenorhabditis elegans/physiology , Caenorhabditis elegans Proteins/physiology , Drosophila Proteins/physiology , Drosophila melanogaster/genetics , Drosophila melanogaster/growth & development , Drosophila melanogaster/physiology , Endoribonucleases/physiology , Forkhead Transcription Factors/physiology , Gene Expression Regulation, Developmental/genetics , Neurons/physiology , Neurosecretory Systems/growth & development , RNA Stability/physiology , RNA, Messenger/physiology
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