Retrospective detection of a subclinical hepatitis A virus (HAV) epidemic affecting juvenile cohorts of the Hungarian population

Sero-epidemiological surveys of serum samples taken in 1982, 1987, 1994 and 1999 have been performed with hepatitis A virus-specific (HAV-specific) serological tests. Results obtained during these surveys show that the proportion of seropositive blood donors decreased from 69% to 18% within 17 years. The authors have recognised a (mainly subclinical) epidemic, affecting about 115000 teenagers in 1992-1994 in Hungary, is a threatening phenomenon. It was calculated that only about 3600 clinical diseases were associated with the epidemic, recognised retrospectively from the findings of the four sero-epidemiological surveys. Epidemiological data indicated that the excess clinical diseases caused by HAV concentrated in the southern counties of Hungary, which have been affected by the social and military activities between 1992 and 1994. Due to the decrease of subjects seropositive for HAV, sera from preselected or actively immunised donors will be required in the future and vaccination against HAV with killed virus is likely to be recommended for risk groups. Furthermore, health authorities might promote active immunisation of young children against HAV infection; for that, promotion of manufacturing combination vaccines of HAV/HBV/DPT or, for certain countries, HAV/DPT would be desirable.     

Combining a polar resin and a pseudo-proline to optimize the solid-phase synthesis of a 'difficult sequence'.

This paper describes the optimization of a synthesis of a difficult sequence related to a 12-mer sequence of a Pan DR epitope (PADRE). Elongation was followed by on-line monitoring of the N(alpha)-Fmoc removal adapted for the batch methodology. Studying the intrinsic factors related to the peptide-resin, such as substitution level, resin nature and backbone protecting group, has led to an increase in the elongation yield and purity of the crude peptide. Optimal elongation was obtained by combining a polar resin such as PEGA and a pseudo-proline as the backbone protecting group.     

Growth of Escherichia coli MG1655 on LB medium: monitoring utilization of amino acids, peptides, and nucleotides with transcriptional microarrays

Analysis of gene expression data related to assimilation and biosynthesis of nitrogen-containing compounds amino acids, peptides, and nucleotides was used to monitor availability of these nutrients to Escherichia coli MG1655 growing on Luria-Bertani medium. The data indicate that free amino acids and nucleotides only transiently support the nitrogen requirement for growth and are no longer available by 3.5 h of fermentation. The resulting shortage of available nitrogen sources induces the Ntr response, which involves induction of the glnALG, glnK-amtB, dppABCDF, and oppABCDF operons as well as the genes coding for outer membrane proteins, porins OmpA and OmpC, and proteases OmpP and OmpT. The increased uptake of peptides facilitated by the products of dppABCDF, oppABCDF, ompA, ompC, ompP, and ompT alleviates nitrogen limitation of the growth.     

Human apoB overexpression and a high-cholesterol diet differently modify the brain APP metabolism in the transgenic mouse model of atherosclerosis

Epidemiological and biochemical data suggest a link between the cholesterol metabolism, the amyloid precursor protein (APP) processing and the increased cerebral beta-amyloid (Abeta) deposition in Alzheimer's disease (AD). The individual and combined effects of a high-cholesterol (HC) diet and the overexpression of the human apoB-100 gene were therefore examined on the cerebral expression and processing of APP in homozygous apoB-100 transgenic mice [Tg (apoB(+/+))], a validated model of atherosclerosis. When fed with 2% cholesterol for 17 weeks, only the wild-type mice exhibited significantly increased APP695 (123%) and APP770 (138%) mRNA levels in the cortex. The HC diet-induced hypercholesterolemia significantly increased the APP isoform levels in the membrane-bound fraction, not only in the wild-type animals (114%), but also in the Tg apoB(+/+) group (171%). The overexpression of human apoB-100 gene by the liver alone reduced the brain APP isoform levels in the membrane-bound fraction (78%), whereas the levels were increased by the combined effect of HC and the overexpression of the human apoB-100 gene (134%). The protein kinase C and beta-secretase protein levels were not altered by the individual or combined effects of these two factors. Our data indicate that the two atherogenic factors, the HC diet and the overexpression of the human apoB-100 gene by the liver, could exert different effects on the processing and expression of APP in the mice brain.     

Hereditary prostate cancer in Finland: fine-mapping validates 3p26 as a major predisposition locus

In a recent genome-wide linkage (GWL) analysis of Finnish families at high risk for prostate cancer, we found two novel putative susceptibility loci at 3p25-p26 and 11q14. Here, we report the fine-mapping of these two critical regions at high resolution with 39 microsatellite markers in 16 families, including multiplex families that were not used in the GWL scan. The maximum multipoint HLOD was 3.39 at 3p26 and 1.42 at 11q14. The highest LOD scores were seen around markers D3S1270 and D3S4559 (=0.89), covering approximately two megabases. The two known genes in this region CHL1 (cell adhesion molecule with homology to L1CAM) and CNTN6 (contactin 6) were screened for exonic mutations in the families showing the strongest linkage, but no disease-segregating sequence variants were observed. The recombination map pointed to a region proximal to the area of best linkage, suggesting that more genes may need to be investigated as candidates. These results provide strong evidence for the existence of a prostate cancer susceptibility gene at 3p26 in Finnish prostate cancer families. This locus has not been strongly linked with hereditary prostate cancer in other populations. However, the mildly positive 3p LOD scores in a recent GWL analysis of patients from the United States suggest that the locus may also be important in other populations.     

Nuclear and mitochondrial sequence data reveal the major lineages of starlings, mynas and related taxa

We investigated the phylogenetic relationships among the major lineages of the avian family Sturnidae and their placement within the Muscicapoidea clade using two nuclear (RAG-1 and myoglobin) and one mitochondrial gene (ND2). Among Muscicapoidea, we recovered three clades corresponding to the families Cinclidae, Muscicapidae and Sturnidae (sensu [Sibley, C.G., Monroe Jr., B.L., 1990. Distribution and Taxonomy of Birds of the World. Yale University Press, New Haven, CT]). Within the sturnoid lineage Mimini and Sturnini are sister groups, with Buphagus basal to them. We identified three major lineages of starlings: the Philippine endemic genus Rhabdornis, an Oriental-Australasian clade (genera Scissirostrum, Gracula, Mino, Ampeliceps, Sarcops, Aplonis), and an Afrotropical-Palaearctic clade (all African taxa, Sturnus and Acridotheres). We discuss the biogeographic implications of our findings and suggest an Asiatic origin for this family. The congruence between the age of major clades, estimated by NPRS, and palaeoclimatic data present evidence for the role of climatic changes in shaping present day distribution of the group.     

Structure and expression of a cDNA encoding a histone H2A from Euglena gracilis

Screening of a gt11 cDNA expression library of Euglena gracilis with antibodies directed against histones H2 from maize resulted in the isolation of a full-length cDNA for a histone H2A. The open-reading frame of 408 bp corresponded to a protein of 136 amino acid residues (14 kDa). Despite the presence of a poly(A) tail, which is typical of plant histone mRNA but not of animal histone mRNA, the size of the deduced protein and its percentage of homology were closer to animal histone H2As than to plant or lower eukaryotic histone H2A.Sequence alignment revealed that the Euglena H2A protein was characterized by a shorter C-terminus and a N-terminus which extended 10 residues past the animal H2A.     

Reduced display of tumor necrosis factor receptor I at the host cell surface supports infection with Chlamydia trachomatis

The obligate intracellular human pathogenic bacterium Chlamydia trachomatis has evolved multiple mechanisms to circumvent the host immune system. Infected cells exhibit a profound resistance to the induction of apoptosis and down-regulate the expression of major histocompatibility complex class I and class II molecules to evade the cytotoxic effect of effector immune cells. Here we demonstrate the down-regulation of tumor necrosis factor receptor 1 (TNFR1) on the surface of infected cells. Interestingly, other members of the TNFR family such as TNFR2 and CD95 (Fas/Apo-1) were not modulated during infection, suggesting a selective mechanism underlying surface reduction of TNFR1. The observed effect was not due to reduced expression since the overall amount of TNFR1 protein was increased in infected cells. TNFR1 accumulated at the chlamydial inclusion and was shed by the infected cell into the culture supernatant. Receptor shedding depended on the infection-induced activation of the MEK-ERK pathway and the metalloproteinase TACE (TNFalpha converting enzyme). Our results point to a new function of TNFR1 modulation by C. trachomatis in controlling inflammatory signals during infection.     

The genetic structure of the European breeding populations of a declining farmland bird,the ortolan bunting (<Emphasis Type="Italic">Emberiza hortulana</Emphasis>), reveals conservation priorities

Anthropogenic activities, such as agricultural intensification, caused large declines in biodiversity, including farmland birds. In addition to demographic consequences, anthropogenic activities can result in loss of genetic diversity, reduction of gene flow and altered genetic structure. We investigated the distribution of the genetic variation of a declining farmland and long-distance migratory bird, the ortolan bunting Emberiza hortulana, across its European breeding range to assess the impact of human-driven population declines on genetic diversity and structure in order to advise conservation priorities. The large population declines observed have not resulted in dramatic loss of genetic diversity, which is moderate to high and constant across all sampled breeding sites. Extensive gene flow occurs across the breeding range, even across a migratory divide, which contributes little to genetic structuring. However, gene flow is asymmetric, with the large eastern populations acting as source populations for the smaller western ones. Furthermore, breeding populations that underwent the largest declines, in Fennoscandia and Baltic countries, appear to be recently isolated, with no gene exchange occurring with the eastern or the western populations. These are signs for concern as declines in the eastern populations could affect the strength of gene flow and in turn affect the western populations. The genetic, and demographic, isolation of the northern populations make them particularly sensitive to loss of genetic diversity and to extinction as no immigration is occurring to counter-act the drastic declines. In such a situation, conservation efforts are needed across the whole breeding range: in particular, protecting the eastern populations due to their key role in maintaining gene flow across the range, and focussing on the northern populations due to their recent isolation and endangered status.     

Human recombinant erythropoietin-alpha increases the efficacy of irradiation in preclinical model

According to recent data erythropoietin receptor (EPOR) is expressed not only by bone marrow erythroid progenitors but by endothelial- and cancer cells and it was suggested that erythropoietin (EPO) may affect their functions as well. We have analyzed the effects of recombinant human erythropoietin-alpha (rHuEPOalpha) on radiation sensitivity of EPOR+ human epidermoid carcinoma (A431) xenograft model. In vivo rHuEPOalpha treatment was started after tumor cell inoculation into SCID mice. 5 Gy irradiation was performed on day 14, the effect of which was measured on day 22. Hemoglobin level, tumor-associated microvessels and HIF-1alpha expression of the xenograft were monitored during the experiment. rHuEPOalpha administration prevented the development of tumor-induced anemia of SCID mice and reduced the level of HIF-1alpha expression of the xenograft tumor without affecting tumor growth. We have found that rHuEPOalpha treatment significantly increased the efficacy of antitumor effect of irradiation which was partly mediated by complex effects on tumor-associated microvessels. In vitro rHuEPOalpha did not affect proliferation of A431 cells but enhanced the antiproliferative and proapoptotic effects of irradiation. We concluded that rHuEPOalpha administration positively modulated the antitumoral effects of irradiation at least by two pathways, decreasing systemic hypoxia resulting in decreased tumoral HIF-1alpha expression and enhancing direct effects on tumor-associated microvessels.