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The interferon-inducible human MxA protein plays an important role in innate defense against an array of viruses. One might expect allelic diversity at the MxA locus to influence the timing and magnitude of its expression or even the range of viruses whose biological cycle is inhibited by the encoded product. Here we have collected 267 samples of genomic DNA from three distinct populations (European, Asian, and African) and have systematically sequenced the promoter of the MxA gene and its 17 exons in order to inventory its allelic variants. Eighteen single-nucleotide polymorphisms were detected, four of which had never been identified before. Two of these, located in the promoter (at positions −309 and −101 respectively), might affect the MxA expression pattern. The other two result in substitutions (Gly255Glu and Val268Met) in the protein’s N-terminal region that might directly affect its antiviral function. Electronic supplementary material The online version of this article (doi:10.1007/s11033-012-1708-7) contains supplementary material, which is available to authorized users.

In the version of this article initially published, the accession code for the RNA-seq data set deposited in the NCBI public repository Sequence Read Archive was missing from the ‘Data availability’ subsection of the Methods section. The accession code is SRP125477.

The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings.

The in vivo ability of the specific PAF-antagonist WEB 2086, a thienotriazolodiazepine, to inhibit platelet-activating factor (PAF) in cattle was investigated by in vitro determination of platelet aggregation curves. WEB 2086 was infused intravenously into a group of 5 healthy male Friesian calves in a dose of 3 mg/kg over 1 min. The resultant inhibition peaked between 30 min and 1 h after administration of WEB 2086. The inhibition was significantly reduced after 3 h and became non-significant after 6 h, but maximal pre-treatment aggregation had not been restored by 24 h after the injection of WEB 2086. These results confirm previous results obtained in vitro and suggest that WEB 2086 is a potent antagonist of PAF activity in calves. They also suggest that further clinical studies with WEB 2086 in cattle are desirable.

N-acetylcysteine (NAC) has been recently proposed as an adjuvant therapeutic drug for influenza pneumonia in humans. This proposal is based on its ability to restrict influenza virus replication in vitro and to attenuate the severity of the disease in mouse models. Although available studies were made with different viruses (human and avian), published information related to the anti-influenza spectrum of NAC is scarce. In this study, we show that NAC is unable to alter the course of a fatal influenza pneumonia caused by inoculation of a murinized swine H1N1 influenza virus. NAC was indeed able to inhibit the swine virus in vitro but far less than reported for other strains. Therefore, susceptibility of influenza viruses to NAC appears to be strain-dependent, suggesting that it cannot be considered as a universal treatment for influenza pneumonia.

The purpose of this study was to investigate the variability of the peak systolic (PAPs) and the end diastolic (PAPd) pulmonary arterial pressures induced by intrapleural pressure changes in cattle. The pleural pressure (Ppl), the electrocardiogram and the pulmonary arterial pressure (PAP) were simultaneously recorded in five healthy calves under three different conditions, i.e. normoxia (N), normoxia with an added airflow resistance (R) and hypoxia (H). PAPs, PAPd and their corresponding transmural pressures were measured and averaged over 10 successive regular cardiac cycles. The maximum Ppl changes (max delta Ppl) were measured on the same tracings. The variance and coefficients of variation were calculated for each set of vascular measurements. Max delta Ppl was significantly increased with regard to N values during R and H conditions. This increase in max delta Ppl induced a simultaneous rise in the variability of PAP measurements, while in each condition, this variability was greatly lowered by use of the corresponding transmural pressure. It was concluded that, in calves with high max delta Ppl, the influence of respiration on PAP becomes considerable. In such cases, the use of transmural pressures rather than luminal pressures can greatly reduce the variability of these pulmonary pressure measurements and therefore increase their sensitivity.

BackgroundThe most predominantbeta2-integrin lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18,alphaLbeta2), expressed on all leukocytes, is essential for many adhesive functions of the immune system. Interestingly, RTX toxin-producing bacteria specifically target this leukocytebeta2-integrin which exacerbates lesions and disease development.ResultsThis study reports the sequencing of the wild boarbeta2-integrin CD11a and CD18 cDNAs. Predicted CD11a and CD18 subunits share all the main structural characteristics of their mammalian homologues, with a larger interspecies conservation for the CD18 than the CD11a. Besides these strong overall similarities, wild boar and domestic pig LFA-1 differ by 2 (CD18) and 1 or 3 (CD11a) substitutions, of which one is located in the crucial I-domain (CD11a, E168D).ConclusionAs most wild boars are seropositive to the RTX toxin-producing bacteriumActinobacillus pleuropneumoniaeand because they have sustained continuous natural selection, future studies addressing the functional impact of these polymorphisms could bring interesting new information on the physiopathology ofActinobacillus pleuropneumoniae-associated pneumonia in domestic pigs.

BackgroundLymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, alpha L beta 2) is required for many cellular adhesive interactions during the immune response.ResultsTheCapra hircusCD11a-encoding cDNA was sequenced and compared with its human, murine, rat, bovine and ovine counterparts. Despite some focal differences, it shares all the main characteristics of its known mammalian homologues.ConclusionTherefore, along with the caprine CD18-encoding cDNA, which has been available for a few months, the sequence data revealed here will allow theCapra hircusLFA-1 expressionin vitroas a tool to explore the specificities of inflammation in the caprine species.

Background The effects of proanthocyanidins (PACs), isolated from blackcurrant (Ribes nigrum L.) leaves, on neutrophil accumulation during inflammatory processes were investigated in vivo and in vitro. Methods In vivo studies were performed using carrageenin-induced pleurisy in rats pre-treated with PACs. Exudate volume and PMNs accumulation were measured. Leukocyte cell adhesion molecules (LFA-1, Mac-1 and VLA-4) mobilization in circulating granulocytes were analysed by flow cytometry and endothelial cell adhesion molecules (ICAM-1 and VCAM-1) were detected by immunohistochemistry on lung sections. In vitro studies were conducted on endothelial LT2 cells, stimulated with TNF-α, to evaluate ICAM-1, IL-8 and VEGF mRNA expression upon PACs treatment. Data sets were examined by one-way analysis of variance (ANOVA) followed by a Scheffe post-hoc test. Results Pretreatment of the animals with PACs (10, 30 and 60 mg/kg) inhibited dose-dependently carrageenin-induced pleurisy in rats by reducing pleural exudate formation and PMNs infliltration. Leukocyte cell adhesion molecules mobilization was not down-regulated on granulocytes by PACs. Immunohistochemistry on lung sections showed a decreased production of endothelial cell adhesion molecules. In vitro experiments demonstrated that PACs were able to significantly inhibit ICAM-1 but not IL-8 and VEGF165 mRNA expression. Moreover, VEGF121 mRNA expression was dose-dependently enhanced. Conclusion This study provides evidence to support the anti-inflammatory activity of proanthocyanidins is related to an inhibition of leukocyte infiltration which can be explained at least in part by a down-regulation of endothelial adhesion molecules, ICAM-1 and VCAM-1 and that these compounds are capable of modulating TNF-α-induced VEGF transcription.