Novel procedures for high-throughput analysis of a frequent insertion-deletion polymorphism in the human T-cell receptor beta locus

The human T-cell receptor beta locus (TRB) contains two frequent insertion-deletion polymorphisms. In one, the insertion comprises two functional variable beta genes, TRBV6-2/TRBV6-3 and TRBV4-3, and the pseudogene TRBV3-2. Deletion of these TRBV genes may confer resistance and/or susceptibility to autoimmunity, analogously to findings in rodent models. Curiously, the TRBV domains in the insertion react with the HERV-K18 superantigen associated with type1 diabetes. While this region has been extensively characterized before, typing methods compatible with high-throughput analysis are not yet available. Here, two novel procedures are reported that are suitable for large-scale association analysis of this polymorphism. One features a duplex TaqMan 5′-exonuclease assay that quantifies the gene dosage of TRBV3-2 present at 0, 1 or 2 copies, with its closely related diploid relative TRBV3-1 as an internal reference, using the 2-ΔΔC T method. The other technique consists of two complementary long PCRs with primers specific for unique regions in the locus. The first discriminates individuals heterozygous or homozygous for the deletion, and the second, individuals heterozygous or homozygous for the insertion from other genotypes. These simple, solid, and cross-validated procedures can now be used in conjunction with flanking single-nucleotide polymorphisms for large-scale linkage studie

Novel procedures for high-throughput analysis of a frequent insertion-deletion polymorphism in the human T-cell receptor beta locus

The human T-cell receptor beta locus ( TRB) contains two frequent insertion-deletion polymorphisms. In one, the insertion comprises two functional variable beta genes, TRBV6-2/TRBV6-3 and TRBV4-3, and the pseudogene TRBV3-2. Deletion of these TRBV genes may confer resistance and/or susceptibility to autoimmunity, analogously to findings in rodent models. Curiously, the TRBV domains in the insertion react with the HERV-K18 superantigen associated with type 1 diabetes. While this region has been extensively characterized before, typing methods compatible with high-throughput analysis are not yet available. Here, two novel procedures are reported that are suitable for large-scale association analysis of this polymorphism. One features a duplex TaqMan 5'-exonuclease assay that quantifies the gene dosage of TRBV3-2 present at 0, 1 or 2 copies, with its closely related diploid relative TRBV3-1 as an internal reference, using the 2(-DeltaDeltaC)(T) method. The other technique consists of two complementary long PCRs with primers specific for unique regions in the locus. The first discriminates individuals heterozygous or homozygous for the deletion, and the second, individuals heterozygous or homozygous for the insertion from other genotypes. These simple, solid, and cross-validated procedures can now be used in conjunction with flanking single-nucleotide polymorphisms for large-scale linkage studies

A Lithocodium and Bacinella signature of a late Hauterivian, local microbial event: the Urgonian limestone in South-East France

Sediment binding crusts of Lithocodium aggregatum and associated Bacinella irregularis abound in a shallow water limestone layer, in South–East France. The sudden appearance of these crusts denotes a local, conspicuous change in an otherwise balanced, open marine depositional environment. Based on regional correlation, the layer belongs to the Lower Hauterivian, Ligatus Zone, directly dated by an assemblage of orbitolinid foraminifera, and indirectly by a specimen of ammonite. It is older than the Faraoni oceanic anoxic event (OAE), (latest Hauterivian, Angulicostata auct. Zone), and presumably not linked with a global climate change. Two facies are recognized: (1) Lithocodium bindstone, with Bacinella, other microencrusters, and fluorescent automicrite of microbial origin; (2) fl oatstones containing numerous fragments of Lithocodium and accompanying biota. Coarse rhombohedral dolomite is locally present. Two modern analogues of microbial mediation are put forward to explain the Lithocodium event: (a) Lagoa Vermelha, in Brazil, along with anoxic, marginal marine conditions; (b) Highborne Cay, in the Bahamas, along with oxic, open marine conditions. A stack of four Upper Hauterivian parasequences is described: Parasequence 1 ends with oolitic deposits; the somewhat deeper water Parasequence 2 occurs only in the south-eastern part of the study area, towards the Subalpine depocenter; Parasequence 3 matches the layer with Lithocodium and Bacinella, of variable thickness (0.8 m – 11 m), resulting from syn-sedimentary tectonic activity in the area of the Vuache fault system which is a major feature; Parasequence 4 corresponds with the resumption of the normal, Urgonian carbonate factory

The Impact of Plant-Parasitic Nematodes on Agriculture and Methods of Control

Plant-parasitic nematodes are costly burdens of crop production. Ubiquitous in nature, phytoparasitic nematodes are associated with nearly every important agricultural crop and represent a significant constraint on global food security. Root-knot nematodes (Meloidogyne spp.) cyst nematodes (Heterodera and Globodera spp.) and lesion nematodes (Pratylenchus spp.) rank at the top of list of the most economically and scientifically important species due to their intricate relationship with the host plants, wide host range, and the level of damage ensued by infection. Limitations on the use of chemical pesticides have brought increasing interest in studies on alternative methods of nematode control. Among these strategies of nonchemical nematode management is the identification and implementation of host resistance. In addition, nematode genes involved in parasitism represent key targets for the development of control through gene silencing methods such as RNA interference. Recently, transcriptome profiling analyses has been used to distinguish nematode resistant and susceptible genotypes and identify the specific molecular components and pathways triggered during the plant immune response to nematode invasion. This summary highlights the importance of plant-parasitic nematodes in agriculture and the molecular events involved in plant-nematode interactions

Epstein-Barr Virus Transactivates the Human Endogenous Retrovirus HERV-K18 that Encodes a Superantigen

AbstractSuperantigens (SAgs) are proteins produced by pathogenic microbes to elicit potent, antigen-independent T cell responses that are believed to enhance the microbes' pathogenicity. Here we show that the human lymphotropic herpesvirus Epstein-Barr virus (EBV) transcriptionally activates the env gene of an endogenous retrovirus, HERV-K18, that possesses SAg activity. SAg activity was demonstrated by MHC class II dependent preferential activation of TCRVB13 T cells in response to murine B cells transfected with the HERV-K18 env gene. This is a unique demonstration of a pathogen inducing a host-encoded Sag and accounts for the previously described EBV associated Sag activity. The T cell activation elicited by the Sag could play a central role in EBV infection and associated diseases

How does law affect finance? An examination of equity tunneling in Bulgaria

Draft version dated May 2010 deposited in SSRN. Final version, published in Journal of Financial EconomicsWe model and test the mechanisms through which securities law affects tunneling and tunneling affects firm valuation. In 2002, Bulgaria adopted securities law changes which limit two forms of equity tunneling - dilutive equity offerings and freezeouts. We document that following the change, minority shareholders participate equally in secondary equity offers, where before they suffered severe dilution; freezeout offer prices quadruple; and Tobin's q values rise sharply for firms at high risk of tunneling. At the same time, return on assets declines for high-equity-tunneling-risk firms, suggesting that controlling shareholders partly substitute for reduced equity tunneling by engaging in more cash-flow tunneling. We thus present evidence on (i) the importance of legal rules in limiting equity tunneling, (ii) the role of equity tunneling risk as an important factor in determining equity prices; and (iii) substitution by controlling shareholders between different forms of tunneling

The Cretaceous of the Swiss Jura Mountains: an improved lithostratigraphic scheme

In the course of the HARMOS project of the Swiss Geological Survey, the lithostratigraphic subdivisions of the Cretaceous sedimentary rocks outcropping in the Swiss Jura Mountains were revisited. New formation names are proposed where only inadequate facies terms existed so far. As in some cases outcrop conditions in the Swiss Jura do not allow for logging complete sections to characterise the formations, type localities in neighbouring France have been chosen. The following formations (Fm.) are defined to describe the Cretaceous lithological units (from bottom to top): Goldberg Fm., Pierre-Châtel Fm., Vions Fm., Chambotte Fm., Vuache Fm., Grand Essert Fm., Gorges de l’Orbe Fm., Vallorbe Fm., Perte du Rhône Fm., Narlay Fm. Dating of the formations is based on biostratigraphy (ammonites, echinids, dasycladalean algae, foraminifera, calpionellids, dinocysts, nannofossils). The fossils indicate Berriasian through to Coniacian ages. The lithostratigraphic units describe the general evolution from a shallow, peritidal platform to deeper-water shelf environments, then the installation of a carbonate platform, and finally the drowning of this platform followed by the predominance of pelagic conditions. The common lateral and vertical changes in facies and sedimentation rates as well as numerous hiatuses within the formations testify to a complex interplay of tectonics, climate, and sea level that controlled the Swiss Jura realm during the Cretaceous

Comparison of Serum Lipoprotein(a) Distribution and its Correlates among Black and White Populations

Bovet P (Clinical Epidemiology Unit, Institute of Social and Preventive Medicine, University of Lausanne, Bugnon 17, CH-1005 Lausanne, Switzerland), Rickenbach M, Wietlisbach V, Riesen W, Shamlaye C, Darioli R and Burnand B. Comparison of lipoprotein(a) distribution and its correlates among black and white populations. International Journal of Epidemiology 1994; 23: 20-27. Background Epidemiological data on serum lipoprotein(a) (Lp(a)), a presumably strong risk factor for coronary artery disease in White populations, has mostly been derived, in Black populations, from small samples. This study compares the distribution and the determinants of serum Lp(a) in Blacks and in Whites using large representative samples and the same methods in both populations. Methods The distribution and the correlates of serum Lp(a) were investigated in population-based samples of 701 Blacks in the Seychelles and 634 Whites in Switzerland, aged 25-64 years. Serum Lp(a) was quantified using a commercial immunoradiometric assay. Results The distribution of serum Lp(a) was similarly skewed in both ethnic groups, but median Lp(a) concentration was about two fold higher in Blacks (210 mg/l) compared to Whites (100 mg/l). The proportions of individuals with elevated serum Lp(a) >300 mg/l) was about 50% higher in Blacks (37.5%) than in Whites (25.2%). In both ethnic groups, serum Lp(a) was found to correlate with total cholesterol, LDL-cholesterol and apoprotein B but not with HDL-cholesterol, alcohol intake, smoking, and body mass index. The variance in serum Lp(a) concentration explained by any combination of these factors was smaller than 5.3% in the two populations. Conclusions The measured factors did not explain the higher levels of serum Lp(a) found in Blacks compared to Whites. These findings are consistent with the hypothesis that genetic factors account for much of the variation of serum Lp(a) in both population

An integrated approach to modelling the fluid-structure interaction of a collapsible tube

The well known collapsible tube experiment was conducted to obtain flow, pressure and materials property data for steady state conditions. These were then used as the boundary conditions for a fully coupled fluid-structure interaction (FSI) model using a propriety computer code, LS-DYNA. The shape profiles for the tube were also recorded. In order to obtain similar collapse modes to the experiment, it was necessary to model the tube flat, and then inflate it into a circular profile, leaving residual stresses in the walls. The profile shape then agreed well with the experimental ones. Two departures from the physical properties were required to reduce computer time to an acceptable level. One of these was the lowering of the speed of sound by two orders of magnitude which, due to the low velocities involved, still left the mach number below 0.2. The other was to increase the thickness of the tube to prevent the numerical collapse of elements. A compensation for this was made by lowering the Young's modulus for the tube material. Overall the results are qualitatively good. They give an indication of the power of the current FSI algorithms and the need to combine experiment and computer models in order to maximise the information that can be extracted both in terms of quantity and quality