Behavioral metabolomics: how behavioral data can guide metabolomics research on neuropsychiatric disorders.

Introduction: Metabolomics produces vast quantities of data but determining which metabolites are the most relevant to the disease or disorder of interest can be challenging.

Objectives: This study sought to demonstrate how behavioral models of psychiatric disorders can be combined with metabolomics research to overcome this limitation.

Methods: We designed a preclinical, untargeted metabolomics procedure, that focuses on the determination of central metabolites relevant to substance use disorders that are (a) associated with changes in behavior produced by acute drug exposure and (b) impacted by repeated drug exposure.

Conformational interdomain flexibility in a bacterial α-isopropylmalate synthase is necessary for leucine biosynthesis.

α-Isopropylmalate synthase (IPMS) catalyzes the first step in leucine (Leu) biosynthesis and is allosterically regulated by the pathway end product, Leu. IPMS is a dimeric enzyme with each chain consisting of catalytic, accessory, and regulatory domains, with the accessory and regulatory domains of each chain sitting adjacent to the catalytic domain of the other chain. The IPMS crystal structure shows significant asymmetry because of different relative domain conformations in each chain.

The role of extracellular serotonin and MDMA in the sensitizing effects of MDMA.

MDMA is a non-selective monoamine releasing stimulant with potent serotonergic effects - a pharmacological effect not typically associated with drugs of misuse or efficacious reinforcers. Nonetheless, MDMA is misused by humans and self-administered by laboratory animals. We have previously shown that repeated exposure to MDMA sensitized both the locomotor activating and reinforcing effects of MDMA in rats.

Unraveling the binding mode of a methamphetamine aptamer: A spectroscopic and calorimetric study.

Nucleic-acid aptamers are bio-molecular recognition agents that bind to their targets with high specificity and affinity and hold promise in a range of biosensor and therapeutic applications. In the case of small-molecule targets, their small size and limited number of functional groups constitute challenges for their detection by aptamer-based biosensors because bio-recognition events may both be weak and produce poorly transduced signals. The binding affinity is principally used to characterize aptamer-ligand interactions; however, a structural understanding of bio-recognition is arguably more valuable in order to design a strong response in biosensor applications.

Hydrated Rubrolides from the New Zealand Tunicate .

LCMS analysis of an extract of the New Zealand tunicate showed evidence for numerous new rubrolides. Following a mass spectrometry-guided isolation procedure, new hydrated rubrolides V and W ( and ), along with previously reported rubrolide G (), were isolated and characterized using MS and NMR. The anti-bacterial and cell cytotoxic activity of the compounds were compared to the potent anti-MRSA compound rubrolide A; hydration across the C-5/C-6 bond was shown to abrogate antibacterial activity.

Adenoviral hepatitis in two Nile crocodile (Crocodylus niloticus) hatchlings from South Africa.

Adenoviral infections may cause mild to severe morbidity or fatality in a large array of animal species. In crocodilians, hatchlings under 5 months of age are usually affected. However, there is a paucity of information on actual incidences in hatchlings originating from South Africa.

Nodulisporic acid E biosynthesis: characterisation of NodD1, an indole-diterpene prenyltransferase that acts on an emindole SB derived indole-diterpene scaffold.

Prenylation of aromatic compounds is a key tailoring reaction in biosynthesis of bioactive indole-diterpenes. Here, we identify NodD1 as the enzyme responsible for the bisprenylation of nodulisporic acid F. This prenyltransferase showed a preference for its natural indole-diterpene substrate whereas other related enzymes were not able to catalyse this conversion.