Evolutionary algorithms for the selection of single nucleotide polymorphisms

Background  

Large databases of single nucleotide polymorphisms (SNPs) are available for use in genomics studies. Typically, investigators must choose a subset of SNPs from these databases to employ in their studies. The choice of subset is influenced by many factors, including estimated or known reliability of the SNP, biochemical factors, intellectual property, cost, and effectiveness of the subset for mapping genes or identifying disease loci. We present an evolutionary algorithm for multiobjective SNP selection.     

PPAR activators inhibit endothelial cell migration by targeting Akt

Peroxisome proliferator-activated receptors (PPARs) regulate lipid and glucose metabolism and exert several vascular effects that may provide a dual benefit of these receptors on metabolic disorders and atherosclerotic vascular disease. Endothelial cell migration is a key event in the pathogenesis of atherosclerosis. We therefore investigated the effects of lipid-lowering PPARalpha-activators (fenofibrate, WY14643) and antidiabetic PPARgamma-activators (troglitazone, ciglitazone) on this endothelial cell function. Both PPARalpha- and PPARgamma-activators significantly inhibited VEGF-induced migration of human umbilical vein endothelial cells (EC) in a concentration-dependent manner. Chemotactic signaling in EC is known to require activation of two signaling pathways: the phosphatidylinositol-3-kinase (PI3K)-->Akt- and the ERK1/2 mitogen-activated protein kinase (ERK MAPK) pathway. Using the pharmacological PI3K-inhibitor wortmannin and the ERK MAPK-pathway inhibitor PD98059, we observed a complete inhibition of VEGF-induced EC migration. VEGF-induced Akt phosphorylation was significantly inhibited by both PPARalpha- and gamma-activators. In contrast, VEGF-stimulated ERK MAPK-activation was not affected by any of the PPAR-activators, indicating that they inhibit migration either downstream of ERK MAPK or independent from this pathway. These results provide first evidence for the antimigratory effects of PPAR-activators in EC. By inhibiting EC migration PPAR-activators may protect the vasculature from pathological alterations associated with metabolic disorders.     

Barremian Angiosperm Pollen and Associated Palynomorphs from the Dakhla Oasis Area, Egypt

Pollen grains characteristic of the local pre-tricolpate, pre-Aptian phase of angiosperm evolution have been recovered from the upper part of the Six Hills Formation in the Dakhla Oasis area, Egypt. Highest abundance (up to 16.5 per cent) and diversity of angiosperm pollen is attained in samples from the Tineida 2 borehole, which also display a remarkable variety of different aperture types for a palynoflora of late Barremian age. Monosulcate, columellate tectates such as Retimonocolpites are most important, but a single trichotomosulcate grain as well as monoporate and inaperturate types that have not been reported from many coeval palynofloras, are also present. The following new taxa are described using same-grain SEM/LM techniques: Tucanopollis annulatus Schrank, sp. nov., Retimonocolpites pennyi Schrank and Mahmoud, sp. nov. and Retiacolpites columellatus Schrank, gen. et sp. nov. Phytogeographic links are closest with palynofloras previously described from the late Barremian of West Africa (Gabon, Congo), that is within the Northern Gondwana or Dicheiropollis etruscus/Afropollis Province.     

Female Choice in Humans: A Conditional Mate Selection Strategy of the Krummhörn Women (Germany, 1720–1874)

The suitors' ownership of land influenced the marriage age of the women in the Krummhörn population (Germany, 1720–1874). This led to a characteristic distribution of the categories of land ownership of husbands by the wife's age at marriage: the younger the brides, the higher was the percentage of high-status males among their bridegrooms. But the natal status of brides did not exert any significant influence on their age at marriage. Moreover, socially hypergamous women married younger than those whose marriage meant a social drop. We have interpreted these findings as the expression of a conditional female choice strategy with age-dependent decrease in demands on a marriage partner: “If you are young, be very choosy and marry only a high-quality mate; the older you become, the more you must reduce your initial standards!” On the average this strategy was adaptive, because in this population land ownership correlated with the local reproductive success of a family.     

Coamplification on chromosomes 7p12-13 and 9q12-13 identified by reverse chromosome painting in a glioblastoma multiforme

DNA amplification is known to occur in approximately 50% of glioblastomas, with the epidermal growth factor receptor (EGFR) gene being the most frequently amplified. Whereas previous amplification studies have largely been limited to the analysis of known tumor-related genes, reverse chromosome painting allows us to search for as yet unidentified amplified domains. Here, we report the analysis of a glioblastoma multiforme by reverse chromosome painting. Hybridization signals were found on chromosome 7p12-13 and chromosome 9q12-13. Standard Southern blot analysis revealed amplification of the EGFR gene, which is localized on band 7p13. These findings corroborate previous reports on coamplification of sequences on different chromosomes in glioblastoma.     

Competitive blocking of apical sodium channels in epithelia

Apical sodium-selective channels in frog skin, when blocked by amiloride or triamterene, exhibit fluctuations in current, the spectra of which are Lorentzian. These effects have been modeled previously with two-state and three-state models by Lindemann and Van Driessche. A recent observation by Hoshiko and Van Driessche that corner frequencies are lowered by increasing the apical sodium concentration cannot be accounted for by these models. We explore the possibility that sodium (S) and amiloride (A) compete for a site at the mouth of the channel. A new three-state channel model (sodium-occupied, open/unoccupied, open/amiloride-blocked) is analyzed. Its corner frequency is of the form f_c = f_co[1 + (A/K_A)/(1 + S/K_S)], consistent with the observed sodium dependence of the corner frequency. The minimum frequency, f_co, and the inhibition constants, K_A and K_S, are expressed in terms of the rate constants of the model. To account for sodium self-inhibition, we postulate that two sodium ions in the channel may result in clogging — a fourth state. The two corner frequencies are calculated; so are the plateau values of the noise power. The noise power shows a maximum as a function of blocker concentration, as observed previously using triamterene. The four-state model predicts the observed suppression by small amounts of blocker of the low-frequency sodium (clogging) noise.     

Development of the olfactory organ in the rainbow fish Nematocentris maccullochi (Atheriniformes,Melanotaeniidae)

Summary The development of the olfactory organ in the rainbow fish, Nematocentris maccullochi, was studied using scanning and transmission electron microscopy; it was compared with the developmental process in other teleosts, especially in the closely related atherinids and cyprinodonts. The formation of the nares parallels that in atherinids, salmonids, cyprinids and heterosomats, but differs from that found in cyprinodonts. Another ontogenetic feature in which the olfactory organs of the rainbow fish and also of atherinids differ from those of cyprinodonts, is the occurrence of transitory kinociliary cells which disappear during the postlarval period. The divergent evolutionary pathways are discussed with reference to experimental investigations. During development, ciliated and microvillous receptor cell types occur. At the primary larval stage ciliated receptor neurons are exclusively present. At a later stage the microvillous type develops and becomes equal in frequency. Thus, the microvillous receptor represents a separate type of olfactory neuron and is not a progenitor of the ciliated receptor cell.This work was supported by the Deutsche ForschungsgemeinschaftThe authors would like to acknowledge Prof. G. Hartmann (Hamburg) and Prof. V. Storch (Kiel) for use of the SEM, Prof. K. Seifert (Neumünster) for valuable discussion. For skillful technical assistance we are indebted to Miss C. Heim, Mrs. K. Hoffmann, and Mr. H.P. Dreyer     

Ultrastructural studies on the epithelia of the olfactory organ of cyprinodonts (teleostei,cyprinodontoidea)

Summary The epithelia of the olfactory organ of two cyprinodontoid fish species were studied both by transmission and scanning electron microscopy. The relatively flat floor of the organ is covered by sensory and nonsensory epithelia. The latter is distributed in the form of bands or ridges separating distinct areas of sensory epithelium. Differences between the olfactory organs of the two species investigated related only to the topography and quantitative distribution of the epithelia. Their ultrastructural features are very similar. The nonsensory stratified squamous epithelium contains numerous goblet cells and surface cells provided with microridges. A hypothetical function of the microridges is discussed. The sensory epithelium consists mainly of basal, supporting, and two types of sensory cells, i.e., ciliated and microvillous receptor cells. The cilia exhibit a predominant 9+0 microtubule pattern. Both epithelia are covered by a mucus layer in which all surface structures seem to be embedded. The possible nature, origin, and movement mechanisms of the mucus are discussed.This work was supported by the Deutsche ForschungsgemeinschaftDedicated to Prof. Dr. med. W. Bargmann on the occasion of his 70th birthday     

Deletions in exon 5 of the human rhodopsin gene causing a shift in the reading frame and autosomal dominant retinitis pigmentosa

By screening patients with autosomal dominant retinitis pigmentosa for mutations in the rhodopsin gene, two deletions (8bp and 1bp) have been identified in exon 5; these deletions cause a shift in the reading frame. The predicted proteins should be radically altered with translation continuing past the normal stop signal and resulting in a rhodopsin molecule that is, respectively, 1 and 10 amino acids longer. The clinical phenotype of the patients is described and is compared with that associated with other mutations in the same region of the gene.