Mu-opiate binding and morphine antagonism by octapeptide analogs of somatostatin

A series of cyclic conformationally restrained octapeptide analogs of somatostatin were examined for their ability to inhibit the binding of tritiated mu, kappa, and delta opiate receptor ligands. Several of these substances were found to have high affinity for mu opiate receptors while having very low affinity for both kappa and delta receptors. Previous suggestions that somatostatin analogs exhibit opiate antagonist activity led to a study of the ability of the two most potent compounds to inhibit morphine analgesia in rats after intracerebroventricular injection. One of the compounds significantly antagonized morphine analgesia although the other displayed severe toxicity. These two compounds differed in that the very toxic compound had previously been found to possess significant somatostatin activity. It thus appears that the structural requirements for toxicity and somatostatin activity can be differentiated from those for opiate activity.     

The western jewel butterfly (Hypochrysops halyaetus: Lycaenidae) II: factors affecting oviposition within native Banksia bushland in an urban setting

Oviposition by western jewel butterflies (Hypochrysops halyaetus Hewitson) was studied in the urban Koondoola regional bushland reserve, Western Australia in 1999. Observations were made in a small (70 × 120 m) localised breeding area the ‘microdistribution study area’, and in 14 paired 20 × 20 m quadrats randomly placed along established tracks in the interior of the northern half of the reserve. The principal host plant was Jacksonia sternbergiana with the secondary host being Daviesia divaricata. More Jacksonia were used for oviposition and attended by ants (40 and 71%, respectively) in the microdistribution study than plants in the ‘quadrat’ study (8 and 25%, respectively). Jacksonia stems with basal diameters below 5 mm were less likely to have eggs. PCA showed Jacksonia to be associated with disturbed conditions with a high proportion of bare ground whereas Daviesia was associated with more mature vegetation. Jacksonia density was principally correlated with the proportion of bare ground and time since the last fire. Host ant (Crematogaster perthensis) presence and proportion of bare ground were the most important factors influencing oviposition. The presence of ants was closely associated with bare ground conditions and the presence of coccids. Conservation management for floristic diversity and maturity of vegetation in reserves is likely to be a widespread phenomenon, and may negatively affect the persistence of species requiring ephemeral patches of early successional vegetation. For H. halyaetus, a species dependent on disturbed/ephemeral habitat conditions, this conflict may threaten its survival, especially in small reserves, and as a result its conservation status may be underestimated. Management options are discussed.     

Centrosome defects cause microcephaly by activating the 53BP1‐USP28‐TP53 mitotic surveillance pathway

Mutations in centrosome genes deplete neural progenitor cells (NPCs) during brain development, causing microcephaly. While NPC attrition is linked to TP53‐mediated cell death in several microcephaly models, how TP53 is activated remains unclear. In cultured cells, mitotic delays resulting from centrosome loss prevent the growth of unfit daughter cells by activating a pathway involving 53BP1, USP28, and TP53, termed the mitotic surveillance pathway. Whether this pathway is active in the developing brain is unknown. Here, we show that the depletion of centrosome proteins in NPCs prolongs mitosis and increases TP53‐mediated apoptosis. Cell death after a delayed mitosis was rescued by inactivation of the mitotic surveillance pathway. Moreover, 53BP1 or USP28 deletion restored NPC proliferation and brain size without correcting the upstream centrosome defects or extended mitosis. By contrast, microcephaly caused by the loss of the non‐centrosomal protein SMC5 is also TP53‐dependent but is not rescued by loss of 53BP1 or USP28. Thus, we propose that mutations in centrosome genes cause microcephaly by delaying mitosis and pathologically activating the mitotic surveillance pathway in the developing brain.     

Survey: Banking on finance

As the banking industry introduces new services, such as internet or telephone banking, so customer authentication methods are changing. Biometric technologies still have some way to go, however, before they capture the hearts and minds of the banking industry, despite developments in legislation, installations and research.     

Assignment of the orphan nuclear receptor Nurr1 by NMR

The orphan nuclear receptor Nurr1 has been implicated in a number of conditions including Parkinson’s disease and Schizophrenia. As such, it is of interest to study its interactions with other proteins, possibly mediated by small molecules, considering possible use as a drug target. We produced ²H, ¹⁵N, ¹³C labelled-Nurr1 to generate the backbone amide NH, carbonyl C′, C_alpha and C_beta assignments. About 84.0% of residues could be assigned. Most of the 37 missing assignments fall in 3 regions of the protein. Two of these surround a putative ligand-binding region of Nurr1, suggesting that this region of the protein is flexible, despite the ligand-binding pocket being filled with hydrophobic side-chains from residues surrounding the ligand binding pocket.     

Effect of acyl chain length on the structure and motion of gramicidin A in lipid bilayers

The transmembrane ion transport properties of gramicidin A have previously been shown to dependent on the nature of its lipid environment. Solid-state NMR spectroscopic studies of 13C-labelled analogues of gramicidin in oriented multilayers of phosphatidylcholine have shown that variation of the lipid hydrocarbon chain length has no effect on the structure or orientation of the peptide backbone.