Analysis of the pharmacological properties of JWH-122 isomers and THJ-2201, RCS-4 and AB-CHMINACA in HEK293T cells and hippocampal neurons.

Synthetic cannabinoids are marketed as legal alternatives to Δ-THC, and are a growing worldwide concern as these drugs are associated with severe adverse effects. Unfortunately, insufficient information regarding the physiological and pharmacological effects of emerging synthetic cannabinoids (ESCs) makes their regulation by government authorities difficult. One strategy used to evade regulation is to distribute isomers of regulated synthetic cannabinoids.

Pharmacological characterization of emerging synthetic cannabinoids in HEK293T cells and hippocampal neurons.

There has been a worldwide proliferation of synthetic cannabinoids that have become marketed as legal alternatives to cannabis (marijuana). Unfortunately, there is a dearth of information about the pharmacological effects of many of these emerging synthetic cannabinoids (ESCs), which presents a challenge for regulatory authorities that need to take such scientific evidence into consideration in order to regulate ECSs as controlled substances. We aimed to characterize the pharmacological properties of ten ESCs using two cell based assays that enabled the determination of potency and efficacy relative to a panel of well-characterized cannabinoids.

Use of the zebrafish larvae as a model to study cigarette smoke condensate toxicity.

The smoking of tobacco continues to be the leading cause of premature death worldwide and is linked to the development of a number of serious illnesses including heart disease, respiratory diseases, stroke and cancer. Currently, cell line based toxicity assays are typically used to gain information on the general toxicity of cigarettes and other tobacco products. However, they provide little information regarding the complex disease-related changes that have been linked to smoking.

Mutagenicity of smoke condensates from Canadian cigarettes with different design features.

There is currently limited knowledge regarding the impact of different cigarette designs on the toxicological properties of cigarette smoke condensate (CSC). This study used the Salmonella Mutagenicity Assay to examine the mutagenic activity of mainstream CSCs from 11 commercial Canadian cigarette brands with different design features or tobacco blend. The brands were selected to include design features that are common for cigarettes sold in the Canadian market, as well as cigarettes with alternate filters (charcoal or MicroBlue™), the super slim design, and cigarettes containing mixed blends of different tobacco types.

Gene function hypotheses for the Campylobacter jejuni glycome generated by a logic-based approach.

Increasingly, experimental data on biological systems are obtained from several sources and computational approaches are required to integrate this information and derive models for the function of the system. Here, we demonstrate the power of a logic-based machine learning approach to propose hypotheses for gene function integrating information from two diverse experimental approaches. Specifically, we use inductive logic programming that automatically proposes hypotheses explaining the empirical data with respect to logically encoded background knowledge.

The analysis of mainstream smoke emissions of Canadian 'super slim' cigarettes.

Background: Super slim cigarettes are a relatively new type of cigarette in Canada, and an analysis of select toxicants in the mainstream smoke emissions of the super slim cigarette was conducted.

Method: The yields of selected toxicants in the mainstream smoke emissions of six brands of super slim cigarettes were compared with the Canadian Benchmark, which represents the cigarette designs most commonly found in Canada. A super slim cigarette was also compared with a 'Reference Cigarette' to study the impact of the significantly reduced circumference on mainstream smoke emissions.

Metabolomics in glycomics.

Metabolomics is essentially the study of all low molecular weight molecules in a biological system under defined conditions. In glycomics, there is much potential to gain insight into the biosynthesis of novel glycoconjugate structures by probing the metabolome for substrates that are suspected, or known, to be involved in the biosynthetic processes. Recently, we employed the use of hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) in a focused metabolomic study of sugar-nucleotides relevant to the biosynthesis of highly novel carbohydrate modifications on the flagellin of Campylobacter sp.

Campylobacter jejuni glycosylation island important in cell charge, legionaminic acid biosynthesis, and colonization of chickens.

Previously, we identified five genes (Cj1321 to Cj1326, of which Cj1325 and Cj1326 are a single gene) in the O-linked flagellin glycosylation island that are highly prevalent in Campylobacter jejuni isolates from chickens. We report mutagenesis, functional, and structural data to confirm that this locus, and Cj1324 in particular, has a significant contributory role in the colonization of chickens by C. jejuni.

Identification of novel carbohydrate modifications on Campylobacter jejuni 11168 flagellin using metabolomics-based approaches.

It is well known that the flagellin of Campylobacter jejuni is extensively glycosylated by pseudaminic acid and the related acetamindino derivative, in addition to flagellin glycosylation being essential for motility and colonization of host cells. Recently, the use of metabolomics permitted the unequivocal characterization of unique flagellin modifications in Campylobacter, including novel legionaminic acid sugars in Campylobacter coli, which had been impossible to ascertain in earlier studies using proteomics-based approaches. To date, the precise identities of the flagellin glycosylation modifications have only been elucidated for C.

Estrogenic compounds in seawater and sediment from Halifax Harbour, Nova Scotia, Canada.

Abstract-Samples of seawater and surface sediment were collected from seven locations around Halifax Harbour, Nova Scotia, Canada, and analyzed for the presence of the organic estrogenic contaminants, bisphenol A (BPA), 17beta-estradiol (E2), and 17alpha-ethinylestradiol (EE2). Samples were extracted using solid phase extraction (seawater) or sonication (sediments), followed by fractionation on a two-layer alumina/silica gel column prior to analysis by liquid chromatography-tandem mass spectrometry (LCMS/MS) with negative-ion electrospray ionization. Levels of the three compounds consistently ranked as BPA > E2 > EE2.

Lipophilic sugar nucleotide synthesis by structure-based design of nucleotidylyltransferase substrates.

Structure-based design of alkyl sugar-1-phosphates provides an efficient nucleotidylyltransferase-catalyzed synthesis of a series of new lipophilic sugar nucleotides possessing long or branched alkyl chains, thereby demonstrating the utility of nucleotidylyltransferases to catalyze the synthesis of sugar nucleotides with potential applications in lipopolysaccharide and lipoglycopeptide biosynthesis.

Enzyme-catalyzed synthesis of furanosyl nucleotides.

A bacterial alpha-d-glucopyranosyl-1-phosphate thymidylyltransferase was found to couple four hexofuranosyl-1-phosphates, as well as a pentofuranosyl-1-phosphate, with deoxythymidine 5'-triphosphate, providing access to furanosyl nucleotides. The enzymatic reaction mixtures were analyzed by electrospray ionization mass spectrometry and NMR spectroscopy to determine the anomeric stereochemistry of furanosyl nucleotide products. This is the first demonstration of a nucleotidylyltransferase discriminating between diastereomeric mixtures of sugar-1-phosphates to produce stereopure, biologically relevant furanosyl nucleotides.

Selective detection of sugar phosphates by capillary electrophoresis/mass spectrometry and its application to an engineered E. coli host.

A highly selective method employing capillary electrophoresis and electrospray mass spectrometry (CE-ESMS) with precursor ion scanning for fragment ions characteristic of phosphate-linked sugars was developed for the determination of "unnatural" sugar phosphates generated in vivo, as part of a natural product glycorandomization study. Cell lysates from an engineered E. coli host were probed for "natural" and "unnatural" sugar phosphates resulting from in vivo galactokinase (GalK) bioconversions, and tandem mass spectrometry experiments were performed to confirm the identities of the sugar phosphates.

Targeted metabolomics analysis of Campylobacter coli VC167 reveals legionaminic acid derivatives as novel flagellar glycans.

Glycosylation of Campylobacter flagellin is required for the biogenesis of a functional flagella filament. Recently, we used a targeted metabolomics approach using mass spectrometry and NMR to identify changes in the metabolic profile of wild type and mutants in the flagellar glycosylation locus, characterize novel metabolites, and assign function to genes to define the pseudaminic acid biosynthetic pathway in Campylobacter jejuni 81-176 (McNally, D. J.

Functional characterization of the flagellar glycosylation locus in Campylobacter jejuni 81-176 using a focused metabolomics approach.

Bacterial genome sequencing has provided a wealth of genetic data. However, the definitive functional characterization of hypothetical open reading frames and novel biosynthetic genes remains challenging. This is particularly true for genes involved in protein glycosylation because the isolation of their glycan moieties is often problematic.

Selective detection and identification of sugar nucleotides by CE-electrospray-MS and its application to bacterial metabolomics.

A novel method employing CE-ESMS and precursor ion scanning was developed for the selective detection of nucleotide-activated sugars. By using precursor ion scanning for fragment ions specific to the different nucleotide carriers, i.e.