Mastophoropsis canaliculata (Harvey in Hooker) gen. et comb. nov. (Corallinaceae,Rhodophyta) in Southern Australia

Mastophoropsis canaliculata (Harvey in Hooker) gen. et comb. nov. (Corallinaceae, Rhodophyta) is restricted to south-eastern Australian waters. It is unique among Corallinaceae in possessing an erect, tenacular, branched, taeniform, non-geniculate thallus which produces multiporate tetrasporangial conceptacles. Based on a detailed morphological and anatomical study, including an examination of the designated lectotype, this taxon is referred to the tribe Phymatolitheae in the subfamily Melobesioideae and its relationships to other non-geniculate Corallinaceae are discussed. A simplified microtechnique procedure involving decalcification with nitric acid, resin embedding and staining serially mounted sections with KMnO₄ also is outlined. X-ray microanalysis of surface tissues indicates that calcification occurs largely as CaCO₃ and that various structures contain substantially differing amounts of Ca.     

The taxonomic identity and physiological ecology of Chlamydomonas hedleyi sp. nov. algal flagellate symbiont from the foraminifer Archaias angulatus

The fine structure of the symbiotic alga isolated from the formainiferan Archaias angulatus (Fichtel et Moll) DeMontfort is typical of the Chlorophyceae of the volvocalean and chlorococcalean lines. Spherical non-motile cells, 10–14 μm in diameter, characterise the dominant life cycle phase. Long oval motile forms with truncated apices are present 3–5 days after transfer to fresh medium. The pyrenoids are embedded anteriorly in the singly bilobed chloroplast and are surrounded by a sheath of starch platelets. In spite of the non-motile state of cells in older cultures (which is perhaps a reflection of its normally symbiotic condition), the alga is identified as a species of the volvocalean genus Chlamydomonas and is named C. hedleyi sp. nov.

The symbiont has no vitamin or organic requirements but growth is increased threefold in the presence of thiamine, and twofold in the presence of 1 μm glutamic acid, histidine and methionine. Urea was the best nitrogen source tested. Purines and pyrimidines did not serve as nitrogen sources. Chlamydomonas hedleyi grows well in a salinity range of 6->52‰. and a pH range of 6–8·5, 7·04 × 10^-7 m carbon h^-1 g^-1 was fixed by the symbiont, 57% being released into the medium as a chromatographically homogeneous organic molecule provisionally identified as mannitol.     

Subcellular localization of proflavine derivative and induction of oxidative stress—In vitro studies

Acridines have been studied for several decades because of their numerous biological effects, especially anticancer activity. Recently, cytotoxicity of novel acridine derivatives, 3,6-bis((1-alkyl-5-oxo-imidazolidin-2-yliden)imino)acridine hydrochlorides (AcrDIMs), was confirmed for leukemic cell lines [Bioorg. Med. Chem. 2011, 19, 1790]. The mechanism of action of the most cytotoxic hexyl-AcrDIM was studied in this paper focusing attention on a subcellular distribution of the drug. Accumulation of hexyl-AcrDIM in mitochondria was confirmed after labeling mitochondria with MitoRED using ImageStream Imaging Flow Cytometer. The derivative significantly decreased intracellular ATP level (reduction of ATP level was decreased by vitamin E), and induced oxidative stress (ROS production detected by DHE assay) as well as cell cycle arrest in the S-phase (flow cytometry analysis) already after short-time incubation and induction of apoptosis. Cytotoxicity of hexyl-AcrDIM is closely connected with induction of oxidative stress in cells.     

Macamides and their synthetic analogs: Evaluation of in vitro FAAH inhibition

Maca (Lepidium meyenii), a traditional food crop of the Peruvian Andes is now widely touted as a dietary supplement. Among the various chemical constituents isolated from the plant are a unique series of non-polar, long-chain fatty acid N-benzylamides known as macamides. We have synthesized 11 of the 19 reported macamides and have tested each as potential inhibitors of the human enzyme, fatty acid amide hydrolase (FAAH). The five most potent macamides were FAAH inhibitors (IC₅₀ = 10–17 μM). These amides were derivatives of oleic, linoleic and linolenic acids and benzylamine or 3-methoxybenzylamine. Of the three compounds evaluated in a pre-incubation time study, two macamides were not irreversible inhibitors of FAAH. The third, a carbamate structurally related to macamides, was shown to be an irreversible inhibitor of FAAH (IC₅₀ = 0.153 μM).     

Effect of ring-constrained phenylpropyloxyethylamines on sigma receptors

A series of ring-constrained phenylpropyloxyethylamines, partial opioid structure analogs and derivatives of a previously studied sigma (σ) receptor ligand, was synthesized and evaluated at σ and opioid receptors for receptor selectivity. The results of this study identified several compounds with nanomolar affinity at both σ receptor subtypes. Compounds 6 and 9 had the highest selectivity for both σ receptor subtypes, compared to μ opioid receptors. In addition, compounds 6 and 9 significantly reduced the convulsive effects of cocaine in mice, which would be consistent with antagonism of σ receptors.     

The kinetic deuterium isotope effect as applied to metabolic deactivation of imatinib to the des-methyl metabolite,CGP74588

There has recently been a burgeoning interest in impeding drug metabolism by replacing hydrogen atoms with deuterium to invoke a kinetic isotope effect. Imatinib, a front-line therapy for both chronic myeloid leukemia and of gastrointestinal stromal tumours, is often substantially metabolised via N-demethylation to the significantly less active CGP74588. Since deuterium–carbon bonds are stronger than hydrogen–carbon bonds, we hypothesised that the N-trideuteromethyl analogue of imatinib might be subject to a reduced metabolic turnover as compared to imatinib and lead to different pharmacokinetic properties, and hence improved efficacy, in vivo. Consequently, we investigated whether the N-trideuteromethyl analogue would maintain target inhibition and show a reduced propensity for N-demethylation in in vitro assays with liver microsomes and following oral administration to rats. The N-trideuteromethyl compound exhibited similar activity as a tyrosine kinase inhibitor as imatinib and similar efficacy as an antiproliferative in cellular assays. In comparison to imatinib, the trideuterated analogue also showed reduced N-demethylation upon incubation with both rat and human liver microsomes, consistent with a deuterium isotope effect. However, the reduced in vitro metabolism did not translate into increased exposure of the N-trideuteromethyl analogue following intravenous administration of the compound to rats and no significant difference was observed for the formation of the N-desmethyl metabolite from either parent drug.     

Intracellular signalling mechanisms regulating glucose transport in insulin-sensitive tissues

The rate of glucose transport into cells is of fundamental importance in whole body homeostasis and adaptation to metabolic stresses, and this review examines the signalling mechanisms controlling this process. The events that mediate the action of insulin on glucose transport, which is by far the best characterized paradigm for glucose transport regulation, are discussed. There are several excellent reviews on various aspects of this subject, which are referred to while highlighting very recent developments in the field, including the recently described CAP pathway, and emerging mechanisms for feedback regulation of insulin signalling. The manner in which hormonal signalling is modulated by stimuli such as oxidative and osmotic stress is then discussed. The second major physiological event where glucose transport regulation is critical is the contraction of skeletal muscle, due to the large metabolic demands of this activity. The mechanism of this regulation is distinct from that initiated by insulin, and recent developments will be examined that have begun to clarify how contraction stimulates glucose transport in skeletal muscle, including the roles performed by AMP-activated protein kinase and nitric oxide synthase.