Introducing the Multivariate Dale Model in Population‐Based Genetic Association Studies

Until recently, the most common parametric approaches to study the combined effects of several genetic polymorphisms located within a gene or in a small genomic region are, at the genotype level, logistic regressions and at the haplotype level, haplotype analyses. An alternative modeling approach, based on the case/control principle, is to regard exposures (e.g., genetic data such as derived from Single Nucleotide Polymorphisms – SNPs) as random and disease status as fixed and to use a marginal multivariate model that accounts for inter‐relationships between exposures. One such model is the multivariate Dale model. This model is based on multiple logistic regressions. That is why the model, applied in a case/control setting, leads to straightforward interpretations that are similar to those drawn in a classical logistic modeling framework. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Nitrogen and Phosphorus in the Finnish Energy System, 1900–2003

In producing power, humans move the nutrients nitrogen (N) and phosphorus (P) from their long‐term geological and biological stocks and release or emit them in soil, water, and the atmosphere. In Finland, peat combustion is an important driver of N and P fluxes from the environment to human economy. The flows of N and P in the Finnish energy system were quantified with partial substance flow analysis, and the driving forces of emissions of nitrogen oxides (NOx) were analyzed using the ImPACT model. In the year 2000 in Finland, 140,000 tonnes of nitrogen entered the energy system, mainly in peat and hard coal. Combustion released an estimated 66,000 tonnes of N as nitrogen oxides (NOx) and nitrous oxides (N2O) and another 74,000 tonnes as elemental N2. Most of the emissions were borne in traffic. At the same time, 6,000 tonnes of P was estimated to enter the Finnish energy system, mostly in peat and wood. Ash was mainly used in earth construction and disposed in landfills; thus negligible levels of P were recycled back to nature. During the twentieth century, fuel‐borne input of N increased 20‐fold, and of P 8‐fold. In 1900–1950, the increasing use of hard coal slowly boosted N input, whereas wood fuels were the main carrier of P. Since 1970, the fluxes have been on the rise. NOx emissions leveled off in the 1980s, though, and then declined in conjunction with improvements in combustion technologies such as NOx removal (de‐NOx) technologies in energy production and catalytic converters in cars.     

Modelling intraspecific resting egg shape variation in a freshwater fairy shrimp Tanymastix stagnalis (L., 1758) (Crustacea, Branchiopoda)

The shape of the resting eggs of a large branchiopod crustacean, the Anostraca Tanymastix stagnalis , is represented very accurately by analytical expressions. The occurrence of atypical shape of some T. stagnalis eggs may be viewed as a simple change of the analytical expression describing the usual egg shape. Their unusual shape may be explained by a higher embryo volume within an envelope of a given size. Biological implications are briefly discussed and hypothesized in an evolutionary point of view.  © 2007 The Linnean Society of London, Biological Journal of the Linnean Society , 2007, 90 , 55–60.     

Bilayer stabilizing peptides and the inhibition of viral infection: antimeasles activity of carbobenzoxy-Ser-Leu-amide

A number of carbobenzoxy-dipeptide-amides raise the bilayer to hexagonal phase transition temperature of dielaidoylphosphatidylethanolamine (stabilizes the bilayer). The potency of the peptides in stabilizing the bilayer phase is Z-Tyr-Leu-NH₂= Z-Gly-Phe-NH₂>Z-Ser-Leu-NH₂>Z-Gly-Leu-NH₂>Z-Gly-Gly-NH₂. A linear correlation was found between the respective HPLC retention time parameterk for the peptide and the slope of the bilayer stabilization curve determined with model membranes by differential scanning calorimetry. One dipeptide, Z-Ser-Leu-NH₂, reduces measles virus cytopathic effect (CPE) in Vero cells. The mechanism by which this peptide reduces the CPE is not known, although some peptides which raise the bilayer to hexagonal phase transition temperature of phospholipids inhibit membrane fusion.Abbreviations Z carbobenzoxy - DEPE dielaidoylphosphatidylethanolamine - DSC differential scanning calorimetry - HPLC high pressure liquid chromatography - CPE cytopathic effect To whom correspondence should be addressed.     

Ruthenium ammine complexes as electron acceptors for growth stimulation by plasma membrane electron transport

Ammineruthenium(III) complexes have been found to act as electron acceptors for the transplasmalemma electron transport system of animal cells. The active complexes hexaammineruthenium(III), pyridine pentaammineruthenium(III), and chloropentaammineruthenium(III) range in redox potential (E ₀) from 305 to –42 mV. These compounds also act as electron acceptors for the NADH dehydrogenase of isolated plasma membranes. Stimulation of HeLa cell growth, in the absence of calf serum, by these compounds provides evidence that growth stimulation by the transplasma membrane electron transport system is not entirely based on reduction and uptake of iron.     

Up- and down-regulation of membrane receptors as possible mechanisms related to the antiulcer actions of milk in rat gastric mucosa

The effects of a cow's milk diet on receptor activity and histamine metabolism in gastric glands and mucosa isolated from adult rats were examined. The milk diet was associated with (1) a decreased mobilization of H₂ receptors by histamine and (2) an increased mobilization of PGE₂ (prostaglandin E₂) receptors in mucous cells (cytoprotective effect) and parietal cells (antiacid effect). These changes are not observed for the receptors reducing pentagastrin- and histamine-induced gastric acid secretion (pancreatic/enteroglucagons, somatostatin) and stimulating mucus, bicarbonate and pepsin secretions in the rat (secretin). Cimetidine produced a parallel displacement of the histamine dose-response curve, suggesting competitive inhibition between this classical H₂ receptor antagonist and histamine in the two experimental groups. Prostaglandins and other components in milk such as EGF (epidermal growth factor) and somatostatin might therefore protect gastric mucosa by a differential control of PGE₂ and histamine H₂ receptor activity eitherdirectly (PGE₂ in milk) orindirectly (inhibition of endogeneous histamine synthesis/release and stimulation of PGE-I synthesis/release).     

Gramicidin A-phospholipid model systems

Gramicidin A forms ion-conducting channels which can traverse the hydrocarbon core of lipid bilayer membranes. The structures formed by gramicidin A are among the best characterized of all membrane-bound polypeptides or proteins. In this review a brief summary is given of the occurrence, conformation, and synthesis of gramicidin A, and of its use as a model for ion transport and the interaction of proteins and lipids in biological membranes.     

Insertion of the precursor of the light-harvesting chlorophylla/b-protein into the thylakoids requires the presence of a developmentally regulated stromal factor

The precursor of the major light-harvesting chlorophylla/b-proteins of photosystem II was synthesizedin vitro from a gene fromLemna gibba. When the labelled precursor was incubated with developing barley plastids, the precursor and the processed polypeptide were incorporated in the thylakoids in proportions that varied depending on the developmental stage of plastids. At early stages of development most of the precursor associated with the thylakoids could be removed by washing with 0.1 M NaOH, while in more mature plastids most of its was resistant to a NaOH wash. Insertion of the precursor into thylakoids required the presence of a stromal factor and Mg-ATP. The stromal factor is probably a protein. The insertion reaction has an optimal temperature of 25°C and a pH of 8. The appearance of the stromal factor and the thylakoid membrane's receptivity for the insertion of the precursor depended on the stage of plastid development. These observations are consistent with the hypothesis that the insertion of the precursor into the thylakoid prior to its proteolytic processing, is one of the steps involved in the assembly of the light-harvesting complex of photosystem II.     

Three-dimensional structure of deoxycholate-treated purple membrane at 6 Å resolution and molecular averaging of three crystal forms of bacteriorhodopsin

The three-dimensional structure of the deoxycholate-treated form of purple membrane has been determined to a resolution of about 6 Å. Using low temperature electron diffraction data, room temperature electron microscope images and improved methods of data analysis, higher resolution has been reached than was obtained using native membranes of the same size. Statistical analysis of the data shows that the new map is considerably better than earlier maps. The map indicates the probable sites for the lipid molecules that remain in the deoxycholate-treated membranes; some of these sites differ from those suggested by the projection map of Glaeser et al. (1985). Comparison of the bacteriorhodopsin structures now determined independently from three crystal forms shows that the monomer structure is independent of the detailed contacts with lipid molecules. The average of the three structures gives a picture with very little noise showing seven similar rod-like features which are clearly best interpreted as -helices; there is no indication that part of the structure is -sheet as suggested by Jap et al. (1983). Phases from the averaged structure at 6 Å resolution will enable better refinement of the parameters that will be required in the analysis of higher resolution images from tilted specimens needed to extend the projection map at 3.5 Å resolution (Henderson et al. 1986) to produce a three-dimensional atomic resolution map.