Isolation and characterisation of a heparosan capsular polysaccharide and a core oligosaccharide from Moraxella lincolnii strain CCUG 52988.

Moraxella lincolnii is a Gram-negative bacterium that resides in the upper respiratory tract (URT) of humans and may have a role as a member of a protective microbial community. Structural characterisation studies of its outer membrane glycan structures are very limited. We report here the isolation and structural characterisation (NMR, GLC-MS) of a capsular polysaccharide (CPS) and an oligosaccharide (OS) (lipooligosaccharide (LOS)-derived) isolated from strain CCUG 52988.

Characterisation of a capsular polysaccharide from Moraxella nonliquefaciens CCUG 348T.

Moraxella nonliquefaciens is a commensal of the human upper respiratory tract (URT) but on rare occasions is recovered in cases of ocular, septic and pulmonary infections. Hence there is interest in the pathogenic determinants of M. nonliquefaciens, of which outer membrane (OM) structures such as fimbriae and two capsular polysaccharide (CPS) structures, →3)-β-D-GalpNAc-(1→5)-β-Kdop-(2→ and →8)-α-NeuAc-(2→, have been reported in the literature.

Otitis media: recent advances in otitis media vaccine development and model systems.

Otitis media is an inflammatory disorder of the middle ear caused by airways-associated bacterial or viral infections. It is one of the most common childhood infections as globally more than 80% of children are diagnosed with acute otitis media by 3 years of age and it is a common reason for doctor's visits, antibiotics prescriptions, and surgery among children. Otitis media is a multifactorial disease with various genetic, immunologic, infectious, and environmental factors predisposing children to develop ear infections.

Moraxella ovis and Moraxella bovoculi lipooligosaccharide biosynthesis genes, and structural characterisation of oligosaccharide from M. ovis 354T.

Moraxella ovis is a Gram-negative bacterium isolated from sheep conjunctivitis cases and is a rare isolate of infectious bovine keratoconjunctivitis (IBK). This species is closely related to M. bovoculi, another species which can also be isolated from IBK, or cattle upper respiratory tract (URT).

Reassessing the putative molecular Target(s) of potent antitubercular 2-(Alkylsulfonyl)acetamides.

Simple alkyl-sulfonylacetamides have potent antitubercular activity and significantly decrease mycolic acid levels in mycobacteria. Although these compounds were originally designed to inhibit the ketoacyl synthase domain of fatty acid synthase, structure-activity relationships and biochemical evidence do not fully support fatty acid synthase as the target. In 2004, an enzyme family involved in the activation and transfer of fatty acids as acyl-adenylates was identified in mycobacteria, separate from the universal acetyl-CoA carrier mechanism.

Novel Selective Galectin-3 Antagonists Are Cytotoxic to Acute Lymphoblastic Leukemia.

Galectin-3 is a β-galactoside-specific, carbohydrate-recognizing protein (lectin) that is strongly implicated in cancer development, metastasis, and drug resistance. Galectin-3 promotes migration and ability to withstand drug treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Due to high amino acid conservation among galectins and the shallow nature of their glycan-binding site, the design of selective potent antagonists targeting galectin-3 is challenging.

Overcoming Microenvironment-Mediated Chemoprotection through Stromal Galectin-3 Inhibition in Acute Lymphoblastic Leukemia.

Environmentally-mediated drug resistance in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) significantly contributes to relapse. Stromal cells in the bone marrow environment protect leukemia cells by secretion of chemokines as cues for BCP-ALL migration towards, and adhesion to, stroma. Stromal cells and BCP-ALL cells communicate through stromal galectin-3.

Structural characterisation of the oligosaccharide from Moraxella bovoculi type strain 237 (ATCC BAA-1259) lipooligosaccharide.

The Gram-negative bacterium Moraxella bovoculi is associated with infectious bovine keratoconjunctivitis (IBK), colloquially known as 'pink-eye'. IBK is an extremely contagious ocular disease of cattle. We report here the structure of the oligosaccharide derived from the lipooligosaccharide from M.

Discovery of a Natural Product That Binds to the Protein Rv1466 Using Native Mass Spectrometry.

Elucidation of the mechanism of action of compounds with cellular bioactivity is important for progressing compounds into future drug development. In recent years, phenotype-based drug discovery has become the dominant approach to drug discovery over target-based drug discovery, which relies on the knowledge of a specific drug target of a disease. Still, when targeting an infectious disease via a high throughput phenotypic assay it is highly advantageous to identifying the compound's cellular activity.

Immunological characterisation of truncated lipooligosaccharide-outer membrane protein based conjugate vaccine against Moraxella catarrhalis and nontypeable Haemophilus influenzae.

Moraxella catarrhalis and nontypeable Haemophilus influenzae are important bacterial causes of otitis media in children and respiratory diseases in adults. Lipooligosaccharide (LOS) from M. catarrhalis and outer membrane protein 26 (OMP26) from NTHi are major surface antigens identified as potential vaccine components against these organisms.

The role of lipooligosaccharide in the biological activity of Moraxella bovis strains Epp63, Mb25 and L183/2, and isolation of capsular polysaccharide from L183/2.

The Gram-negative bovine pathogen Moraxella bovis is a causative agent of Infectious bovine keratoconjunctivitis, 'pink-eye' that affects cattle. Here we report that strain L183/2 has the same capsular polysaccharide (CPS) of unsulfated chondroitin, as does strain Mb25, whereas strain Epp63 does not express CPS. NMR analysis of the oligosaccharides (OS) derived from the lipooligosaccharides (LOS) in these three strains by NMR has shown that strain Mb25 and Epp63 have the same OS structure with a terminal N-acetylgalactosamine ((1S)-GalaNAc) residue →4,6-linked.

Structure-Based Design of a Monosaccharide Ligand Targeting Galectin-8.

Galectin-8 is a β-galactoside-recognising protein that has a role in the regulation of bone remodelling and is an emerging new target for tackling diseases with associated bone loss. We have designed and synthesised methyl 3-O-[1-carboxyethyl]-β-d-galactopyranoside (compound 6) as a ligand to target the N-terminal domain of galectin-8 (galectin-8N). Our design involved molecular dynamics (MD) simulations that predicted 6 to mimic the interactions made by the galactose ring as well as the carboxylic acid group of 3'-O-sialylated lactose (3'-SiaLac), with galectin-8N.

Assessment of the laxative activity of an ethanolic extract of Bambusa arundinacea (Retz.) Willd. shoot.

Ethnobotanical Relevance: Bambusa arundinacea (Retz.) Willd., commonly known as Kanta Bans, plays an important ethnobotanical role, especially in Asia.

Multi-constituent identification in Australian cane toad skin extracts using high-performance liquid chromatography high-resolution tandem mass spectrometry.

Toad skins and venom glandular secretions have been widely used for centuries in traditional Chinese and Japanese medicine for the treatment of various ailments such as cancer, sores, toothache, local inflammation and pain. The active chemical constituents from traditional oriental medicines have demonstrated potential in the development of effective therapeutic pharmaceuticals. Our primary focus in this research was to identify and characterise 'active' compounds or groups of compounds for their potential as neuropsychiatric disorder therapeutics.

Cane Toad Skin Extract-Induced Upregulation and Increased Interaction of Serotonin 2A and D Receptors via G Signaling Pathway in CLU213 Cells.

Recent evidences show that activation of serotonin 2A receptors (5-HT R) by agonists is significant in improving therapeutic activity of disease conditions, such as obsessive-compulsive disorder (OCD). Though the exact molecular mechanism is still not well understood, it is thought to involve agonist-driven, enhanced expression of 5-HT R in certain areas of brain, such as the pre-frontal cortex (PFC). Several other reports have also demonstrated association of OCD with lower dopamine receptor (D R) availability, primarily in the striatum of the brain along with dysfunction of 5-HT R-D R heteromer regulation.

Aqueous and Ethanol Extracts of Australian Cane Toad Skins Suppress Pro-Inflammatory Cytokine Secretion in U937 Cells via NF-κB Signaling Pathway.

Toad skin extracts, such as aqueous extracts (AE) of Chinese toad skins, have demonstrated therapeutic benefits for a range of diseases including pain, inflammation, swelling, heart failure, and various types of cancers. In this study, we investigated the anti-inflammatory potential of an AE (0.1-10 μg/mL) and a 60% ethanol extract (EE; 0.

A new cytotoxic diterpenoid glycoside from the leaves of Blumea lacera and its effects on apoptosis and cell cycle.

A new diterpenoid glycoside, 6E,10E,14Z-(3S)-17-hydroxygeranyllinalool-17-O-β-d-glucopyranosyl-(1 → 2)-[α-l-rhamnopyranosyl-(1 → 6)]-β-d-glucopyranoside (1) together with the known diterpenoid glycoside (2) and two known flavonoid glycosides (3, 4) were isolated from the methanol extract of Blumea lacera leaves. The structures were determined by the interpretation of their spectroscopic data and comparison with the literature. All compounds were isolated for the first time from B.

Identification and characterisation of a biosynthetic locus for Moraxella bovis lipo-oligosaccharide.

Moraxella bovis is a Gram-negative gammaproteobacterium and is one of the causative agents of infectious bovine keratoconjunctivitis. The structure of lipooligosaccharide (LOS) from strain Epp63 was recently elucidated. In the present study a genetic locus of seven encoding genes with high similarity to glycosyltransferases has been identified.

A New Cytotoxic Steroidal Glycoalkaloid from the Methanol Extract of Blumea lacera Leaves.

Purpose: Blumea lacera (B. lacera) (Asteraceae) is a well-known Bangladeshi medicinal plant. This study aimed to identify and characterize constituents associated with the significant cytotoxic activity of this plant that we reported previously.

An Unusual Carbohydrate Conformation is Evident in Moraxella catarrhalis Oligosaccharides.

Oligosaccharide structures derived from the lipooligosaccharide of M. catarrhalis show that the highly branched glucose-rich inner core of the oligosaccharide has an altered conformation compared to the most truncated tetra-glucose-Kdo lgt1/4Δ oligosaccharide structure. Addition of one residue each to the (1-4) and (1-6) chains to give the lgt2Δ oligosaccharide is the minimum requirement for this conformational change to occur.

Precursor discrimination of designer drug benzylpiperazine using δ13C and δ15N stable isotopes.

Advances in analytical technology and emerging techniques have resulted in the increased exploitation of chemical and isotopic profiling for source linkage/discrimination of illicit drugs for forensic purposes. Although not routinely used for illicit drug investigations, such information has been obtained and its application demonstrated through the use of isotope ratio mass spectrometry (IRMS). There is a solid platform of research available relating to the isotopic analysis of methylenedioxymethamphetamine (MDMA) and methamphetamine (MA), however with the recently flourishing designer drug market it was of interest to examine the isotopic profiles of the popular 'party drug' benzylpiperazine hydrochloride (BZP·HCl).

Isotopic profiling of seized benzylpiperazine and trifluoromethylphenylpiperazine tablets using δ13C and δ15N stable isotopes.

This paper demonstrates the use of isotopic analysis of 23 benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) containing tablets seized on two independent occasions by the Northern Territory (NT) Police, Australia. Isolation (High Performance Liquid Chromatography (HPLC)) of BZP and TFMPP followed by Isotope Ratio Mass Spectrometry (IRMS) (carbon and nitrogen stable isotopes) analysis was performed. Results are presented for δ13C and δ15N values of the respective piperazine analogues.