Conformational behavior of cyclic CCK-related peptides determined by 400-MHz 1H-NMR: relationships with affinity and selectivity for brain receptors

The conformational study of a homogenous series of cyclic analogues of CCK8, selective for central receptors, such as Boc-X-Tyr(SO3H)-Nle-D-Lys-Trp-Nle-Asp-Phe-NH2, where X = L-Glu, D-Glu, or gamma-D-Glu, was performed by 400-MHz 1H-nmr. The regular increase in affinity for central receptors when going from [L-Glu] to [gamma-D-Glu] is correlated to (a) an enhancement in internal flexibility of the cyclic moiety, (b) an external orientation of the tyrosine side chain, and (c) a restructuring of the C-terminal part of the peptide. All these results could permit a modeling of biologically active conformation of CCK8 for both receptors types to be performed.     

Protein kinase C: properties and possible role in cellular division and differentiation

Protein kinase C was first described some eight years ago. Recent results indicate that this kinase may have a crucial role in signal transduction for substances involved in cellular differentiation and division. Protein kinase C is activated by attachment to plasma membranes, in the presence of calcium and diacylglycerol. The activator is produced in the membrane following the signal-induced breakdown of phosphoinositides. Tumor promoters, such as phorbol ester, can substitute for diacylglycerol. The recent findings that: tyrosine kinases might be involved in the phosphoinositide turnover and, phosphorylation of growth factor receptors by protein kinase C regulates some of their functions, indicate more and more clearly that this kinase is involved in the control of cell growth division and differentiation. Purification procedures, properties and mechanisms of regulation will be summarized and discussed.     

Regulation of the BBB during viral encephalitis: roles of IL-12 and NOS.

Intranasal infection of mice by Vesicular Stomatitis Virus (VSV) often leads to breakdown of the blood-brain barrier (BBB). The role of Interleukin 12 (IL-12) and nitric oxide synthase (NOS) was examined here. Wild-type (WT), NOS-1 knockout (KO), and NOS-3 KO mice were infected with VSV and treated with either IL-12 or medium. IL-12 treatment of uninfected hosts did not result in pathology. In contrast with WT and NOS-1 KO mice, where extensive gross and ultrastructural correlation of BBB breakdown were evident following infection, in NOS-3 KO mice, integrity of the BBB was observed. Thus NOS-3 activity in astrocytes, endothelial cells, or ependymal cells may play an essential role in regulating the BBB.     

Protein Topology Prediction Algorithms Systematically Investigated in the Yeast Saccharomyces cerevisiae

Membrane proteins perform a variety of functions, all crucially dependent on their orientation in the membrane. However, neither the exact number of transmembrane domains (TMDs) nor the topology of most proteins have been experimentally determined. Due to this, most scientists rely primarily on prediction algorithms to determine topology and TMD assignments. Since these can give contradictory results, single‐algorithm‐based predictions are unreliable. To map the extent of potential misanalysis, the predictions of nine algorithms on the yeast proteome are compared and it is found that they have little agreement when predicting TMD number and termini orientation. To view all predictions in parallel, a webpage called TopologYeast: http://www.weizmann.ac.il/molgen/TopologYeast was created. Each algorithm is compared with experimental data and a poor agreement is found. The analysis suggests that more systematic data on protein topology are required to increase the training sets for prediction algorithms and to have accurate knowledge of membrane protein topology.     

Urban hypothermia: preferred temperature and thermal perception in old age.

A study of 17 elderly men and 13 young adults of similar body build and wearing equivalent clothing insulation (0.8 clo) showed that when given control over their environment the elderly preferred the same mean comfort temperature (22-23 degrees C) but manipulated ambient temperature much less precisely than the young. Slow adjustment of ambient temperature was related to some cases to a higher temperature-discrimination threshold. These findings suggest that both physiological and behavioural changes contribute to the increased vulnerability of old people in cold conditions.