Genetic variation in CRTh2 influences development of allergic phenotypes.

Background: Allergic disorders are characterized by an increase in the Th2 cytokines IL-4, IL-5 and IL-13, produced primarily by Th2 cells. These cells are marked by the expression of CRTh2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), a receptor for prostaglandin D(2). As genetic variation plays a significant role in the predisposition for allergic disorders, we investigated the influence of single nucleotide polymorphisms (SNPs) in CRTh2.

Short communication direct effect of Cd on glutathione S-transferase and glutathione reductase from Calystegia sepium.

Interactions between heavy metals, glutathione, glutathione S-transferase (GST), and glutathione reductase (GR) are being investigated by many working groups, but evaluation of the direct effect of Cd+ on these enzymes in vitro is lacking. We report here the effect of cadmium (10, 50, 100, 250 microM CdSO4) on partially purified enzymes from Calystegia sepium. Plants were grown under normal field conditions without metals and the enzymes were extracted by Tris buffer and partially purified by ammonium sulphate fractionation and gel filtration.

Effect of selenium on thioredoxin reductase activity in Txnrd1 or Txnrd2 hemizygous mice.

Thioredoxin reductase 1 (Txnrd1) and thioredoxin reductase 2 (Txnrd2) are selenoproteins whose expression and function depends on adequate supply of the trace element selenium (Se). As homozygous (-/-) knockout of both Txnrd1 and Txnrd2 is embryonically lethal, we investigated the effect of their hemizygosity (+/-) alone and in combination with dietary Se on enzymatic activity in various tissues. To assess the overall health of the corresponding mice, the growth, viability and fertility of the different experimental groups were also compared.

B- and T-cell-specific inactivation of thioredoxin reductase 2 does not impair lymphocyte development and maintenance.

Thioredoxin reductases (Txnrds) are a group of selenoenzymes participating in cellular redox regulation. Three Txnrd isoforms are known, each of which exhibits distinct cellular localisation and tissue-specific expression pattern. Txnrd1 is found in the cytoplasm, expression of Txnrd2 is restricted to mitochondria and Txnrd3 shows testis-specific expression.

BioHealth--the need for security and identity management standards in eHealth.

The experience gained in these last years and the several lesson learned have clearly shown that eHealth is more than just a simple change from paper records to electronic records. It necessitates a change of paradigms, on the one hand and the use of new technologies and introduction of new procedures on the other. Interoperability becomes a crucial issue.

Significant sequence similarities in promoters and precursors of Arabidopsis thaliana non-conserved microRNAs.

Some plant microRNAs have been shown to be de novo generated by inverted duplication from their target genes. Subsequent duplication events potentially generate multigene microRNA families. Within this article we provide supportive evidence for the inverted duplication model of plant microRNA evolution.

Dominant-negative Pes1 mutants inhibit ribosomal RNA processing and cell proliferation via incorporation into the PeBoW-complex.

The nucleolar PeBoW-complex, consisting of Pes1, Bop1 and WDR12, is essential for cell proliferation and processing of ribosomal RNA in mammalian cells. Here we have analysed the physical and functional interactions of Pes1 deletion mutants with the PeBoW-complex. Pes1 mutants M1 and M5, with N- and C-terminal truncations, respectively, displayed a dominant-negative phenotype.

Embryonic expression profile of phospholipid hydroperoxide glutathione peroxidase.

The selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) is indispensable for murine embryonic development; yet, the cellular mechanisms leading to embryonic death around gastrulation are still unclear. To investigate PHGPx expression patterns during embryogenesis, we performed a detailed analysis that revealed a complex expression profile. Up to embryonic day 9.

CREDO: a web-based tool for computational detection of conserved sequence motifs in noncoding sequences.

Summary: CREDO is a user-friendly, web-based tool that integrates the analysis and results of different algorithms widely used for the computational detection of conserved sequence motifs in noncoding sequences. It enables easy comparison of the individual results. CREDO offers intuitive interfaces for easy and rapid configuration of the applied algorithms and convenient views on the results in graphical and tabular formats.

Role of the mammalian RNA polymerase II C-terminal domain (CTD) nonconsensus repeats in CTD stability and cell proliferation.

The C-terminal domain (CTD) of mammalian RNA polymerase II (Pol II) consists of 52 repeats of the consensus heptapeptide YSPTSPS and links transcription to the processing of pre-mRNA. The length of the CTD and the number of repeats diverging from the consensus sequence have increased through evolution, but their functional importance remains unknown. Here, we show that the deletion of repeats 1 to 3 or 52 leads to cleavage and degradation of the CTD from Pol II in vivo.

The nuclear form of phospholipid hydroperoxide glutathione peroxidase is a protein thiol peroxidase contributing to sperm chromatin stability.

The selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) is regarded as the major molecular target of selenodeficiency in rodents, accounting for most of the histopathological and structural abnormalities of testicular tissue and male germ cells. PHGPx exists as a cytosolic form, mitochondrial form, and nuclear form (nPHGPx) predominantly expressed in late spermatids and spermatozoa. Here, we demonstrate that mice with a targeted deletion of the nPHGPx gene were, unlike mice with the full knockout (KO) of PHGPx, not only viable but also, surprisingly, fully fertile.

Pantothenate kinase associated neurodegeneration (Hallervorden - Spatz syndrome).

Hallervorden-Spatz syndrome is a rare autosomal recessive hereditary condition characterized by early onset of progressive movement alteration that include dystonia, rigidity and choreoathetosis usually associated with pyramidal signs and mental deterioration. We report two sisters where diagnosis was missed till MRI showed classic imaging findings. Mutation analysis in one, revealed homozygous mutations in the PANK 2 gene.

Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function.

Oxygen radicals regulate many physiological processes, such as signaling, proliferation, and apoptosis, and thus play a pivotal role in pathophysiology and disease development. There are at least two thioredoxin reductase/thioredoxin/peroxiredoxin systems participating in the cellular defense against oxygen radicals. At present, relatively little is known about the contribution of individual enzymes to the redox metabolism in different cell types.

Improved proteome analysis of Saccharomyces cerevisiae mitochondria by free-flow electrophoresis.

The analysis of complex cellular proteomes by means of two-dimensional gel electrophoresis (2-DE) is significantly limited by the power of resolution of this technique. Although subcellular fractionation can be a fundamental first step to increase resolution, it frequently leads to preparations contaminated with other cellular structures. Here, we chose mitochondria of Saccharomyces cerevisiae to demonstrate that an integrated zone-electrophoretic purification step (ZE), with a free-flow electrophoresis device (FFE), can assist in overcoming this problem, while significantly improving their degree of purity.

Testis-specific expression of the nuclear form of phospholipid hydroperoxide glutathione peroxidase (PHGPx).

The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) is present in at least three different isoforms in testis: as a cytosolic, as a mitochondrial, and as a nuclear protein. We have recently shown that a sperm nucleus-specific glutathione peroxidase (snGPx) is identical to the mitochondrial and cytosolic forms of PHGPx apart from its N-terminus. This arginine-rich N-terminus of snGPx, reminiscent of protamines, is encoded by an alternative exon located in the first intron of the PHGPx gene and is responsible for nuclear localisation and chromatin binding of snGPx [Pfeifer et al.

An isoform of hPANK2, deficient in pantothenate kinase-associated neurodegeneration, localizes to mitochondria.

Mutations in the human PANK2 gene have been shown to occur in autosomal-recessive pantothenate kinase-associated neurodegeneration, a syndrome originally described by Hallervorden and Spatz. The kinase catalyses the first and rate-limiting step in the biosynthesis of coenzyme A, a key molecule in energy metabolism. We have determined the exon-intron structure of the hPANK2 gene and identified two alternatively used first exons.

Determination of 235U and 238U in urine samples using sector field inductively coupled plasma mass spectrometry.

The high sensitivity of SF-ICP-MS (sector field inductively coupled plasma mass spectrometry) using a torch with the "guard-electrode" (capacitive decoupled plasma) allows the determination of 238U (isotope abundance 99.2%) and 235U (0.8%) and their isotope ratio in human urine samples down to the physiological level of <10 ng/l total uranium.

Genetics of asthma and related phenotypes.

Asthma is the most common chronic childhood disease in developed nations. It has been clearly shown that several environmental, as well as genetic, factors play an important role in the development of this complex disease. In the last decade many genome-wide screens have been performed to specify the chromosomal localisation of the genes of interest.

Plant aquaporins.

Aquaporins are ubiquitous membrane channel proteins that facilitate and regulate the permeation of water across biological membranes. Aquaporins are members of the MIP family and some of them seem to be also able to transport other molecules such as urea or glycerol. In the plant kingdom, a single plant expresses a considerably large number of MIP homologues.

Encapsulated cells producing retroviral vectors for in vivo gene transfer.

Background: Because gene therapy of the future will primarily take an in vivo approach, a number of problems associated with its current implementation exist. Currently, repeated delivery of a vector in vivo is necessary to ensure adequate transfer of the therapeutic gene. This may lead to the development of an immune response against the vector, thus interfering with gene delivery.

Cloning and developmental expression of zebrafish GTP cyclohydrolase I.

GTP cyclohydrolase I (GCH) catalyses the conversion of GTP to dihydroneopterin triphosphate, initiating the pteridine pathway. The final product tetrahydrobiopterin (H4biopterin) is the cofactor for neurotransmitter synthesis and for tyrosine supply during melanogenesis. Sepiapterin accumulates as a pigment.

Large-scale production of mouse phenotypes: the search for animal models for inherited diseases in humans.

This paper is aimed principally at bioinformaticians and biologists as an introduction to recent advances in mouse mutagenesis, concentrating on genome-wide screens utilising the powerful mutagen N-ethyl-N-nitroso-urea (ENU). It contains a brief background to the underlying genetics as well as details of the practical aspects of organisation and data capture for such projects.