High-density SNP mapping of the HLA region identifies multiple independent susceptibility loci associated with selective IgA deficiency

Selective IgA deficiency (IgAD; serum IgA<0.07 g/l) is the most common form of human primary immune deficiency, affecting approximately 1∶600 individuals in populations of Northern European ancestry. The polygenic nature of IgAD is underscored by the recent identification of several new risk genes in a genome-wide association study. Among the characterized susceptibility loci, the association with specific HLA haplotypes represents the major genetic risk factor for IgAD. Despite the robust association, the nature and location of the causal variants in the HLA region remains unknown. To better characterize the association signal in this region, we performed a high-density SNP mapping of the HLA locus and imputed the genotypes of common HLA-B, -DRB1, and -DQB1 alleles in a combined sample of 772 IgAD patients and 1,976 matched controls from 3 independent European populations. We confirmed the complex nature of the association with the HLA locus, which is the result of multiple effects spanning the entire HLA region. The primary association signal mapped to the HLA-DQB1*02 allele in the HLA Class II region (combined P = 7.69×10⁻⁵⁷; OR = 2.80) resulting from the combined independent effects of the HLA-B*0801-DRB1*0301-DQB1*02 and -DRB1*0701-DQB1*02 haplotypes, while additional secondary signals were associated with the DRB1*0102 (combined P = 5.86×10⁻¹⁷; OR = 4.28) and the DRB1*1501 (combined P = 2.24×10⁻³⁵; OR = 0.13) alleles. Despite the strong population-specific frequencies of HLA alleles, we found a remarkable conservation of these effects regardless of the ethnic background, which supports the use of large multi-ethnic populations to characterize shared genetic association signals in the HLA region. We also provide evidence for the location of association signals within the specific extended haplotypes, which will guide future sequencing studies aimed at characterizing the precise functional variants contributing to disease pathogenesis.     

SEASONALLY VARYING DIET QUALITY AND THE QUANTITATIVE GENETICS OF DEVELOPMENT TIME AND BODY SIZE IN BIRCH FEEDING INSECTS

Abstract Genetic variance‐covariance structures (G), describing genetic constraints on microevolutionary changes of populations, have a central role in the current theories of life‐history evolution. However, the evolution of Gs in natural environments has been poorly documented. Resource quality and quantity for many animals and plants vary seasonally, which may shape genetic architectures of their life histories. In the mountain birch‐insect herbivore community, leaf quality of birch for insect herbivores declines profoundly during both leaf growth and senescence, but remains stable during midsummer. Using six sawfly species specialized on the mountain birch foliage, we tested the ways in which the seasonal variation in foliage quality of birch is related to the genetic architectures of larval development time and body size. In the species consuming mature birch leaves of stable quality, that is, without diet‐imposed time constraints for development time, long development led to high body mass. This was revealed by the strongly positive phenotypic and genetic correlations between the traits. In the species consuming growing or senescing leaves, on the other hand, the rapidly deteriorating leaf quality prevented the larvae from gaining high body mass after long development. In these species, the phenotypic and genetic correlations between development time and final mass were negative or zero. In the early‐summer species with strong selection for rapid development, genetic variation in development time was low. These results show that the intuitively obvious positive genetic relationship between development time and final body mass is a probable outcome only when the constraints for long development are relaxed. Our study provides the first example of a modification in guild‐wide patterns in the genetic architectures brought about by seasonal variation in resource quality.     

Color sensitive retina based on bacteriorhodopsin

Bacteriorhodopsin (BR), a membrane protein of a microorganism Halobacterium salinarium has been studied since the 80's as a potential material for information technology. The information processing applications of BR employ either photochromic or photoelectric properties of the protein. In this study we discuss about design principles and describe our study of the use of bacteriorhodopsin as a sensor material for a color sensitive artificial retina. This retina includes low-level processing of input information. The design of a color sensitive matrix element, the self-organizing color adaptation algorithm and a system model for the retina are presented.     

Transient absorption and photovoltage study of' self-assembled bacteriorhodopsin/polycation multilayer films

A series of organized (PDAC/PM)(n) (poly(diallyldimethylammonium chloride)/purple membrane) multilayer films were prepared by alternate adsorptions of positively charged PDAC polyelectrolyte and negatively charged purple membrane (PM). The kinetics of the photocycle of bacteriorhodopsin (bR) in PM was studied by flash photolysis and transient photovoltage methods. Although the orientation of the adsorbed bR depends on the pH of the PM suspension, the kinetics of the photo-induced reaction cycle in dehydrated films is independent of the deposition pH. In dry (PDAC/PM)(n) films the decay of the M intermediate to the initial bR state is multiexponential and delayed to several minutes for both orientations. A simultaneous two-exponential decay in millisecond time domain was observed at red wavelengths. The source of the red-shifted absorption is suggested to be the C(610) intermediate of the cis photocycle of bR.     

The expression and promoter specificity of the birch homologs for PISTILLATA/GLOBOSA and APETALA3/DEFICIENS

B-function genes determine the identity of petals and stamens in the flowers of model plants such as Arabidopsis and Antirrhinum . Here, we show that a putative B-function gene BpMADS2 , a birch homolog for PISTILLATA , is expressed in stamens and carpels of birch inflorescences. We also present a novel birch gene BpMADS8 , a homolog for APETALA3 / DEFICIENS , which is expressed in stamens. Promoter-GUS analysis revealed that BpMADS2 promoter is active in the receptacle of Arabidopsis flower buds while BpMADS8 promoter is highly specific in mature stamens. BpMADS2 promoter:: BARNASE construct prevented floral organ development in Arabidopsis and tobacco. In birch, inflorescences with degenerated stamens and carpels were obtained. BpMADS8::BARNASE resulted in degeneration of stamens in Arabidopsis and birch causing male sterility. In tobacco, only sepals were developed instead of normal flowers. The results show that the BpMADS2::BARNASE construct can be used to specifically disrupt floral organ development in phylogenetically distant plant species. The stamen-specific promoter of BpMADS8 is a promising tool for biotechnological applications in inducing male sterility or targeting gene expression in the late stamen development.     

Rapid wound-induced resistance in white birch (Betula pubescens) foliage to the geometrid Epirrita autumnata: a comparison of trees and moths within and outside the outbreak range of the moth

Two strains of a geometrid defoliator, Epirrita autumnata, were used in bioassays to test existence and relative efficacy of rapid, wound-induced foliage resistance in two provenances of the white birch. One birch and one moth strain originated in the outbreak range of the moth and another outside it. Both birch provenances responded to manual leaf damage by changes in foliage quality which significantly retarded growth of the insects, reducing their pupal weights and protracting larval periods. Leaves which were previously damaged were lower quality as Epirrita food than adjacent intact leaves. Both of them were lower quality than intact leaves without damaged leaves nearby. Because of variance between years in the efficacy of the response, and because of different transfer distances of the provenances to the common garden where the experiments were performed, we could not ascertain whether there is any overall difference in the efficacy of rapid inducible responses between the provenances. Both moth strains were affected by wound-induced deterioration in foliage quality. There were no differences in how the moth strains experienced inducible resistance in the two birch provenances. Moths achieved relatively higher pupal weights on the birch provenance matching their origin. Moths from the outbreak range completed their larval period in a shorter time and pupated in a smaller size and, due to dependence of fecundity on size, had a lower potential rate of increase than insects outside the outbreak range.     

Chemical diversity of several Betulaceae species: comparison of phenolics and terpenoids in northern birch stems

 Phenolics and terpenoids characteristic for silver birch (Betula pendula Roth) were screened in current-growth twigs of seedlings (1-growing-season-old individuals) and current-growth twigs of saplings (3 to 5-year-old individuals) of several birch species. Seedlings were grown in a greenhouse for 1 growing season. Saplings were field cultivated or wild-stand individuals. Chemicals were methanol-extracted, purified and HPLC-diode array detector-, gas chromatograph-flame ionizaton detector- and gas chromatograph-mass selective-analyzed. Species-specific qualitative and quantitative variation of secondary chemicals in birch stems were considerable and dependent on the age of the individual. The chemical diversity and amount were lower in seedlings than in saplings. In saplings, (+)-catechin and its derivatives were found in nearly all species, while arylbutanoids (±rhododendrol glucosides), an arylheptanoid (platyphylloside) and dammaraneterpenoids (papyriferic acid, deacetylpapyriferic acid and pendulic acid) showed a more restricted distribution. The chemicals analyzed in birch stems are a useful tool for recognition of species. Received: 18 September 1995 / Accepted: 19 December 1995     

Interactions of plasminogen and tissue plasminogen activator (t-PA) with amphoterin. Enhancement of t-PA-catalyzed plasminogen activation by amphoterin

The heparin-binding p30 protein amphoterin is proposed to mediate adhesive interactions of the advancing plasma membrane in migrating and differentiating cells. Since the NH2-terminal part of amphoterin is exceptionally rich in lysine residues, we have studied its interactions with plasminogen and tissue plasminogen activator (t-PA). On immunostaining of N18 neuroblastoma cells, amphoterin and t-PA showed a close co-localization in the filopodia of the leading membrane and in the substrate-attached material. In purified systems, both t-PA and plasminogen bound to immobilized amphoterin, and their binding was inhibited by the lysine analogue epsilon-aminocaproic acid. Plasminogen bound to immobilized amphoterin was activated by t-PA, and this resulted in effective degradation of the immobilized amphoterin. Correspondingly, amphoterin-bound t-PA activated plasminogen. In solution amphoterin accelerated t-PA-catalyzed plasminogen activation maximally 46-fold. The results indicate that t-PA and plasminogen form through their lysine-binding sites a complex with amphoterin, which results in acceleration of plasminogen activation and effective degradation of amphoterin. We suggest that local acceleration of t-PA-catalyzed plasminogen activation by amphoterin at the leading membrane enhances the penetration of growing cytoplasmic processes through extracellular materials during cell migration, differentiation and regeneration. The amphoterin-mediated adhesion at the leading membrane may be transient in nature, because the protein also enhances its own breakdown by accelerating t-PA-catalyzed plasminogen activation.