Hepatitis C Virus Genotype 1b Core Protein Does Not Exert Immunomodulatory Effects on Virus-Induced Cellular Immunity

The hepatitis C virus (HCV) core protein is among the most conserved proteins in HCV and is known to induce sensitization of cytotoxic T lymphocytes (CTL). Therefore, it is a prime candidate for a component of a potential HCV vaccine. The HCV core protein has, however, been reported to exert multiple effects on cell functions, raising questions as to its suitability for this purpose. This question was investigated here with mice into which replication-deficient adenoviruses expressing core protein of an HCV genotype 1b isolate were injected. We show that induction of cytokines in response to the infection, infiltration of lymphocytes into the infected liver, priming of virus-specific CTL, and liver injury are not modulated by expression of the core protein in the liver. Moreover, no changes in the sensitivity to tumor necrosis factor alpha- or Fas-mediated liver injury are demonstrable. A similar lack of demonstrable effects of the core protein on immune functions has also been obtained using transgenic mice expressing another HCV genotype 1b core protein. It is concluded that the HCV core protein of genotype 1b has no modulatory effects on induction of virus-specific immune responses and may therefore be a suitable component of an HCV vaccine.     

Respiratory Syncytial Virus Fusion Protein Mediates Inhibition of Mitogen-Induced T-Cell Proliferation by Contact

Human respiratory syncytial virus (HRSV) and bovine respiratory syncytial virus (BRSV) are major pathogens in infants and calves, respectively. Experimental BRSV infection of calves and lambs is associated with lymphopenia and a reduction in responsiveness of peripheral blood lymphocytes (PBLs) to mitogens ex vivo. In this report, we show that in vitro mitogen-induced proliferation of PBLs is inhibited after contact with RSV-infected and UV-inactivated cells or with cells expressing RSV envelope proteins on the cell surface. The protein responsible was identified as the RSV fusion protein (F), as cells infected with a recombinant RSV expressing F as the single envelope protein or cells transfected with a plasmid encoding F were able to induce this effect. Thus, direct contact with RSV F is necessary and sufficient to inhibit proliferation of PBLs. Interestingly, F derived from HRSV was more efficient in inhibiting human PBL proliferation, while F from BRSV was more efficient in inhibiting bovine PBLs. Since various T-cell activation markers were upregulated after presenter cell contact, T lymphocytes are viable and may still be activated by mitogen. However, a significant fraction of PBLs were delayed or defective in G0/G1 to S-phase transit.     

Butyrate reversibly arrests the proliferation of normal and Rous sarcoma virus-infected chicken heart mesenchymal cells

Sodium butyrate at 5 X 10(-3) M reversibly arrests the proliferation of both normal and RSV-infected chicken heart mesenchymal cells. This finding suggests that butyrate acts by causing non-specific inhibition of cell proliferation, rather then by specifically suppressing the neoplastic phenotype or by inducing recovery of cells from the neoplastic state.     

Phytochrome and UV signal transduction pathways

The phytochromes are the best studied plant photoreceptors, controlling a wide variety of responses at both whole plant and single cell levels. Three signal transduction pathways, dependent on cGMP and/or calcium, have been found to be utilized by phytochrome to control the expression of genes required for chloroplast development (e.g., CAB and FNR) and anthocyanin biosynthesis (e.g., CHS). In particular, cGMP is a second messenger positively regulating CHS gene expression whilst calcium and calmodulin act as negative regulators. In addition to phytochrome regulation of CHS we have begun to examine the signal transduction pathways utilized by UV photoreceptors. In contrast to phytochrome-mediated responses, results indicate a role for calcium and calmodulin as positive regulators of CHS gene expression in UV light.     

Occurrence of Urotensin II (Bladder-Contracting Activity) in the Caudal Spinal Cord of Anamniote Vertebrates

• 1 Urotensin II (bladder-contracting activity) is present in the caudal spinal cords of teleosts, elasmobranchs, holosteans, and chondrosteans, in order of decreasing activity. It is questionably present in holocephalans and probably absent from lungfishes.
• 2 Cyclostomes and tailed amphibians show no evidence for any specific caudal urotensin II.
• 3 The pharmacological evidence parallels the cytological evidence for the occurrence of a caudal neurosecretory system.

     

Characterisation of a novel gene family of putative cyclic nucleotide- and calmodulin-regulated ion channels in Arabidopsis thaliana

In plants, cyclic GMP is involved in signal transduction in response to light and gibberellic acid. For cyclic AMP, a potential role during the plant cell cycle was recently reported. However, cellular targets for cyclic nucleotides in plants are largely unknown. Here we report on the identification and characterisation of a new gene family in Arabidopsis, which share features with cyclic nucleotide-gated channels from animals and inward-rectifying K⁺ channels from plants. The identified gene family comprises six members (Arabidopsis thaliana cyclic nucleotide-gated channels, AtCNGC1–6) with significant homology among the deduced proteins. Hydrophobicity analysis predicted six membrane-spanning domains flanked by hydrophilic amino and carboxy termini. A putative cyclic nucleotide binding domain (CNBD) which contains several residues that are invariant in other CNBDs was located in the carboxy terminus. This domain overlaps with a predicted calmodulin (CaM) binding site, suggesting interaction between cyclic nucleotide and CaM regulation. We demonstrated interaction of the carboxy termini of AtCNGC1 and AtCNGC2 with CaM in yeast, indicating that the CaM binding sites are functional. Furthermore, it was shown that both AtCNGC1 and AtCNGC2 can partly complement the K⁺-uptake-deficient yeast mutant CY162. Therefore, we propose that the identified genes constitute a family of plant cyclic nucleotide- and CaM-regulated ion channels.     

Validating the prediction accuracies of marker-assisted and genomic selection of Fusarium head blight resistance in wheat using an independent sample

Key message

Compared with independent validation, cross-validation simultaneously sampling genotypes and environments provided similar estimates of accuracy for genomic selection, but inflated estimates for marker-assisted selection.

Abstract

Estimates of prediction accuracy of marker-assisted (MAS) and genomic selection (GS) require validations. The main goal of our study was to compare the prediction accuracies of MAS and GS validated in an independent sample with results obtained from fivefold cross-validation using genomic and phenotypic data for Fusarium head blight resistance in wheat. In addition, the applicability of the reliability criterion, a concept originally developed in the context of classic animal breeding and GS, was explored for MAS. We observed that prediction accuracies of MAS were overestimated by 127% using cross-validation sampling genotype and environments in contrast to independent validation. In contrast, prediction accuracies of GS determined in independent samples are similar to those estimated with cross-validation sampling genotype and environments. This can be explained by small population differentiation between the training and validation sets in our study. For European wheat breeding, which is so far characterized by a slow temporal dynamic in allele frequencies, this assumption seems to be realistic. Thus, GS models used to improve European wheat populations are expected to possess a long-lasting validity. Since quantitative trait loci information can be exploited more precisely if the predicted genotype is more related to the training population, the reliability criterion is also a valuable tool to judge the level of prediction accuracy of individual genotypes in MAS.