Vaccination of alpacas against Rift Valley fever virus: Safety, immunogenicity and pathogenicity of MP-12 vaccine.

Rift Valley fever (RVF) is an emerging zoonosis of major public health concern in Africa and Arabia. Previous outbreaks attributed camelids a significant role in the epidemiology of Rift Valley fever virus (RVFV), making them an important target species for vaccination. Using three alpacas as model-organisms for dromedary camels, the safety, immunogenicity and pathogenicity of the MP-12 vaccine were evaluated in this study. To compare both acute and subacute effects, animals were euthanized at 3 and 31days post infection (dpi). Clinical monitoring, analysis of liver enzymes and hematological parameters demonstrated the tolerability of the vaccine, as no significant adverse effects were observed. Comprehensive analysis of serological parameters illustrated the immunogenicity of the vaccine, eliciting high neutralizing antibody titers and antibodies targeting different viral antigens. RVFV was detected in serum and liver of the alpaca euthanized 3dpi, whereas no virus was detectable at 31dpi. Viral replication was confirmed by detection of various RVFV-antigens in hepatocytes by immunohistochemistry and the presence of mild multifocal necrotizing hepatitis. In conclusion, results indicate that MP-12 is a promising vaccine candidate but still has a residual pathogenicity, which requires further investigation.

Development of adult-type inhibitory glycine receptors in the central auditory system of rats.

Inhibitory synaptic activity is crucial for many aspects of acoustic information processing and mainly mediated by glycine and gamma-aminobutyric acid, the two principal inhibitory neurotransmitters in the auditory system. Glycine exerts its inhibitory action via binding to postsynaptic receptors existing in various isoforms. Here we have investigated the spatiotemporal distribution of adult-type, strychnine-sensitive glycine receptors (GlyRs) in the rat auditory system by using a specific antibody against the ligand-binding alpha1 GlyR subunit. In adults, alpha1 GlyRs were found at all relay stations of the auditory pathway except for the medial geniculate body and the auditory cortex. In most brainstem nuclei, labeling was characterized by dense clusters of heavily immunoreactive puncta outlining the somata and proximal dendrites, indicative of a powerful glycinergic inhibition. No alpha1 immunoreactivity was seen in the auditory system of fetal rats, consistent with results obtained by others in the spinal cord. At birth, labeling was weak and restricted to defined nuclei of the cochlear nuclear complex and the superior olivary complex. By postnatal day 8, labeling was seen in all brainstem nuclei. At the first appearance of immunoreactivity, alpha1 GlyRs were diffusely distributed on the neuronal surface, yet they became clustered with age, finally densely incrusting the somata and proximal dendrites between the 3rd and 4th postnatal week, when the mature pattern of immunoreactivity was established. We never observed an overexpression of alpha1 GlyRs or a transient appearance in areas that are devoid of the receptor in adults. The late formation of glycinergic synapses harboring the adult-type GlyRs in the auditory system, at a time when internuclear connections have already formed, indicates that alpha1 GlyRs do not participate in early synaptogenesis.

Insights into the evolution of nuclear dualism in the ciliates revealed by phylogenetic analysis of rRNA sequences.

The small subunit rRNA gene sequences of the karyorelictean ciliates, Loxodes striatus and Protocruzia sp., and the heterotrichian ciliates, Climacostomum virens and Eufolliculina uhligi, were used to test the evolution of nuclear dualism in the Phylum Ciliophora. Phylogenies derived using a least squares distance method, neighbour joining, and maximum parsimony demonstrate that the karyorelictean ciliates sensu Small and Lynn, 1985 do not form a monophyletic group. However, Loxodes and the heterotrich ciliates form the first branch in the ciliate lineage, and Protocruzia branches, in distance methods, basal to the spirotrich lineage. It is proposed that Protocruzia be removed from the Class Karyorelictea, and placed in closer taxonomic association with the spirotrich lineage. The distribution of nuclear division types along the phylogenetic tree is consistent with the notion that macronuclei incapable of division represent a derived rather than a primitive or "karyorelictid" character trait.