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1.
Proc Natl Acad Sci U S A ; 117(26): 14688-14693, 2020 06 30.
Article in English | MEDLINE | ID: mdl-32541039

ABSTRACT

Traces of lipids, absorbed and preserved for millennia within the inorganic matrix of ceramic vessels, act as molecular fossils and provide manifold information about past people's subsistence, diet, and rituals. It is widely assumed that lipids become preserved after adsorption into nano- to micrometer-sized pores, but to this day the distribution of these lipids in the ceramics was virtually unknown, which severely limits our understanding about the process of lipid preservation. Here we use secondary ion mass spectrometry (SIMS) imaging for direct in situ analysis of lipids absorbed in 700- to 2,000-y-old archaeological pottery. After sectioning from larger sherds, wall cross-sections of smaller fragments were used for SIMS analysis. Lipids were found in relatively large zones of 5- to 400-µm diameter, which does not support the notion of absorption only into individual nanometer-scale pores but indicates that more macroscopic structures in the ceramics are involved in lipid preservation as well. Furthermore, lipids were found concentrated on calcium carbonate inclusions in the ceramics, which suggests that precipitation of fatty acids as calcium salts is an important aspect of lipid preservation in archaeological samples. This has important implications for analytical methods based on extraction of lipids from archaeological ceramics and needs to be considered to maximize the yield and available information from each unique sample.


Subject(s)
Archaeology/methods , Ceramics/chemistry , Clay/chemistry , Lipids , Spectrometry, Mass, Secondary Ion/methods , Ceramics/history , Cooking/history , History, Ancient , Humans , Lipids/analysis , Lipids/chemistry , Molecular Imaging , United Kingdom
2.
Biomater Sci ; 7(10): 4099-4111, 2019 Sep 24.
Article in English | MEDLINE | ID: mdl-31355397

ABSTRACT

Many debilitating infections result from persistent microbial biofilms that do not respond to conventional antibiotic regimens. A potential method to treat such chronic infections is to combine agents which interfere with bacterial biofilm development together with an antibiotic in a single formulation. Here, we explore the use of a new bioresponsive polymer formulation derived from specifically modified alginate nanoparticles (NPs) in order to deliver ciprofloxacin (CIP) in combination with the quorum sensing inhibitor (QSI) 3-amino-7-chloro-2-nonylquinazolin-4(3H)-one (ACNQ) to mature Pseudomonas aeruginosa biofilms. The alginate NPs were engineered to incorporate a pH-responsive linker between the polysaccharide backbone and the QSI, and to encapsulate CIP via charge-charge interactions of the positively-charged drug with the carboxyl residues of the alginate matrix. In this way, a dual-action release of antibiotic and QSI was designed for the low-pH regions of a biofilm, involving cleavage of the QSI-linker to the alginate matrix and reduced charge-charge interactions between CIP and the polysaccharide as the alginate carboxyl side-chains protonated. When tested in a biofilm model the concomitant release of CIP + QSI from the pH-responsive nanoparticles significantly reduced the viability of the biofilm compared with CIP treatment alone. In addition, the alginate NPs were shown to penetrate deeply into P. aeruginosa biofilms, which we attribute in part to the charges of the NPs and the release of the QSI agent. Finally, we tested the formulation in both a 2D keratinocyte and a 3D ex vivo skin infection model. The dual-action bio-responsive QSI and CIP release nanoparticles effectively cleared the infection in the latter, suggesting considerable promise for combination therapeutics which prevent biofilm formation as well as effectively killing mature P. aeruginosa biofilms.


Subject(s)
Ciprofloxacin/therapeutic use , Nanoparticles/chemistry , Pseudomonas aeruginosa/drug effects , Quorum Sensing/drug effects , Animals , Biofilms/drug effects , Cell Line , Ciprofloxacin/chemistry , Humans , Hydrogen-Ion Concentration , Microbial Sensitivity Tests , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/pathogenicity , Swine
3.
Nat Mater ; 13(6): 570-9, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24845996

ABSTRACT

Polymeric substrates are being identified that could permit translation of human pluripotent stem cells from laboratory-based research to industrial-scale biomedicine. Well-defined materials are required to allow cell banking and to provide the raw material for reproducible differentiation into lineages for large-scale drug-screening programs and clinical use. Yet more than 1 billion cells for each patient are needed to replace losses during heart attack, multiple sclerosis and diabetes. Producing this number of cells is challenging, and a rethink of the current predominant cell-derived substrates is needed to provide technology that can be scaled to meet the needs of millions of patients a year. In this Review, we consider the role of materials discovery, an emerging area of materials chemistry that is in large part driven by the challenges posed by biologists to materials scientists.


Subject(s)
Biocompatible Materials/chemistry , Cell Culture Techniques/methods , Stem Cells/cytology , Animals , Cell Culture Techniques/instrumentation , Diabetes Mellitus/metabolism , Diabetes Mellitus/therapy , Drug Evaluation, Preclinical/methods , Humans , Multiple Sclerosis/metabolism , Multiple Sclerosis/therapy , Myocardial Infarction/metabolism , Myocardial Infarction/therapy , Stem Cell Transplantation , Stem Cells/metabolism
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