A5042300878- Lipid Membrane Structure and Behavior
- Streptococcal Infections and Treatments
- Antimicrobial Resistance in Staphylococcus
- Antimicrobial Peptides and Activities
- Vibrio bacteria research studies
- Chemical Synthesis and Analysis
- Biochemical and Structural Characterization
- Bacterial Genetics and Biotechnology
- Atmospheric and Environmental Gas Dynamics
- Clostridium difficile and Clostridium perfringens research
- Nanopore and Nanochannel Transport Studies
- Microbial Natural Products and Biosynthesis
- Neonatal and Maternal Infections
- Atmospheric Ozone and Climate
- Climate variability and models
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- Toxin Mechanisms and Immunotoxins
- Erythrocyte Function and Pathophysiology
- Aquaculture disease management and microbiota
- Microbial Metabolites in Food Biotechnology
- Microbial infections and disease research
- Bacterial biofilms and quorum sensing
- Ion channel regulation and function
- Click Chemistry and Applications
Marine Biological Laboratory
2023
University of Waterloo
2012-2022
University of Saskatchewan
2021
University of Arizona
2012-2019
University of St Andrews
2019
University of Edinburgh
2019
University of Delaware
2016
University of Oxford
2004-2007
Rutherford Appleton Laboratory
2004-2005
Bristol Royal Infirmary
2001-2002
We describe a new method for evaluating the radiative forcing, climate feedback parameter (W m −2 K −1 ) and hence effective sensitivity from any GCM experiment in which is responding to constant forcing. The simply regress top of atmosphere flux against global average surface air temperature change. This does not require special integrations or off‐line estimates, such as stratospheric adjustment, obtain eliminates need double radiation calculations tropopause fluxes. show that CO 2 solar...
Daptomycin is an acidic lipopeptide antibiotic that, in the presence of calcium, forms oligomeric pores on membranes containing phosphatidylglycerol. It clinically used against various Gram-positive bacteria such as Staphylococcus aureus and Enterococcus species. Genetic studies have indicated that increased content cardiolipin bacterial membrane may contribute to resistance drug. Here, we a liposome model demonstrate directly inhibits permeabilization by daptomycin. When added at molar...
Abstract The interaction of the 11-yr solar cycle (SC) and quasi-biennial oscillation (QBO) their influence on Northern Hemisphere (NH) polar vortex are studied using idealized model experiments ECMWF Re-Analysis (ERA-40). In experiments, sensitivity NH to imposed easterlies at equatorial/subtropical latitudes over various height ranges is tested explore possible from zonal wind anomalies associated with QBO SC in those regions. show that timing modeled stratospheric sudden warmings (SSWs)...
A recombinant form of CAMP factor Streptococcus agalactiae has been expressed as glutathione S-transferase-CAMP fusion protein in Escherichia coli. After thrombin cleavage the protein, exhibited hemolytic activity comparable with that native form. Osmotic protection experiments polyethylene glycols show forms discrete transmembrane pores a diameter upward 1.6 nm on susceptible membranes; electron microscopy reveals circular membrane lesions heterogeneous size, up to 12-15 diameter. Liposome...
Staphylococcal α-toxin is a 293-residue, single-chain polypeptide that spontaneously assembles into heptameric pore in target cell membranes. To identify the pore-forming domain, substitution mutants have been produced which single cysteine residues were introduced throughout toxin molecule. By attaching environmentally sensitive dye acrylodan to sulfhydryl groups, environment of individual amino acid side chains could be probed. In liposomes, 23-amino sequence (residues 118–140) was found...
Observed globally‐averaged land precipitation changes over the 20th century are compared with simulations of HadCM3 climate model using an “optimal fingerprinting” method. We find that observed in too large to be consistent model‐generated internal variability and (attributable to) combination natural anthropogenic forcings applied model. By comparing observations shortwave longwave forcing timeseries, we most forced variation appears driven by forcings. unable detect a response isolation....
Vibrio cholerae cytolysin permeabilizes animal cell membranes. Upon binding to the target lipid bilayer, protein assembles into homo-oligomeric pores of an as yet unknown stoichiometry. Pore formation has been observed with model liposomes consisting phosphatidylcholine and cholesterol, but latter were much less susceptible than erythrocytes or intestinal epithelial cells. We here show that liposome permeabilization is strongly promoted if cholesterol combined sphingolipids, whereby most...
An entirely solid-phase synthesis of daptomycin, a cyclic lipodepsipeptide antibiotic currently in clinical use, was achieved using combination α-azido and Fmoc amino acids. This methodology applied to the several daptomycin analogs, one which did not contain kynurenine or synthetically challenging acid (2S,3R)-methylglutamate yet exhibited an MIC approaching that daptomycin.
Staphylococcal α-toxin is a 293 residue polypeptide that assembles into pore-forming heptamers, residues 118−140, thereby inserting to form an amphipathic β-barrel in the lipid bilayer. Fluorometric analyses were here conducted using cysteine-substitution mutants site-specifically-labeled at positions 35 or 130 with environmentally-sensitive fluorophore acrylodan. In conjunction functional assays, three conformational states of heptamer defined, which may represent transitional...
Cholesterol may affect the activity of microbial toxins in a direct, specific way, or it exert indirect effects because its role membrane fluidity, line tension, and stabilization rafts cytoplasmic membrane. The thiol-activated gram-positive bacteria, cytolysin Vibrio cholerae are presented as examples toxin-cholesterol interaction. Several mechanisms cholesterol discussed using such Staphylococcus aureusα-hemolysin, aerolysin, diphtheria toxin.
Vibrio cholerae cytolysin (VCC) forms oligomeric pores in lipid bilayers containing cholesterol. Membrane permeabilization is inefficient if the sterol embedded within prepared from phosphatidylcholine only but greatly enhanced target membrane also contains ceramide. Although enhancement of VCC action stereospecific with respect to cholesterol, we show here that no such specificity applies two stereocenters ceramide; all four stereoisomers ceramide activity cholesterol-containing bilayers. A...
Calmodulin (CaM) is a Ca2+ signal transducing protein that binds and activates many cellular enzymes with physiological relevance, including the mammalian nitric oxide synthase (NOS) isozymes: endothelial NOS (eNOS), neuronal (nNOS), inducible (iNOS). The mechanism of CaM binding activation to iNOS enzyme poorly understood in part due strength bound complex difficulty assessing role played by regions outside CaM-binding domain. To further elucidate these processes, we have developed...