Complexity and Diversity of the Mammalian Sialome Revealed by Nidovirus Virolectins.

Sialic acids (Sias), 9-carbon-backbone sugars, are among the most complex and versatile molecules of life. As terminal residues of glycans on proteins and lipids, Sias are key elements of glycotopes of both cellular and microbial lectins and thus act as important molecular tags in cell recognition and signaling events. Their functions in such interactions can be regulated by post-synthetic modifications, the most common of which is differential Sia-O-acetylation (O-Ac-Sias). The biology of O-Ac-Sias remains mostly unexplored, largely because of limitations associated with their specific in situ detection. Here, we show that dual-function hemagglutinin-esterase envelope proteins of nidoviruses distinguish between a variety of closely related O-Ac-Sias. By using soluble forms of hemagglutinin-esterases as lectins and sialate-O-acetylesterases, we demonstrate differential expression of distinct O-Ac-sialoglycan populations in an organ-, tissue- and cell-specific fashion. Our findings indicate that programmed Sia-O-acetylation/de-O-acetylation may be critical to key aspects of cell development, homeostasis, and/or function.

Cerebellar cortical degeneration in cattle caused by Solanum kwebense.

The pathology of maldronksiekte, a sporadic neurological disorder of cattle caused by the ingestion of the plant Solanum kwebense in certain parts of South Africa, was studied in three chronic field cases. There was loss of cerebellar Purkinje cells with the remaining neurons either swollen or shrunken and showing degeneration and necrosis. Ultrastructurally, neurons with a swollen perikaryon showed depletion and empty dilated cisternae of granular endoplasmic reticulum. In a few Purkinje cells, the cytoplasm contained small numbers of lamellar and membranous bodies. In the shrunken neurons, the highly condensed cytoplasm contained distended Golgi saccules, dense clusters of granular endoplasmic reticulum and swollen mitochondria. Lectin histochemistry revealed that the cytoplasmic vacuoles in some distended Purkinje cells stained strongly with Canavalia ensiformis (ConA) agglutinin and weakly with Triticum vulgaris (WGA) and succinyl-WGA (S-WGA) agglutinin. The pattern of lectin binding only partially agreed with that reported in calves poisoned with Solanum fastigiatum, causing a presumed glycolipid storage disease. Apoptosis was not detected in neurons using a commercial deoxyuridine triphosphate nick-end labelling (TUNEL) method. The pathogenesis of the cerebellar lesions is unknown but the intoxication may have resulted from the inability of neurons, in particular Purkinje cells, to metabolise a plant toxin or cellular substrate.

Histochemical accumulation of oxidative damage products is associated with Alzheimer-like pathology in the canine.

An important lesion in Alzheimer's disease (AD) patient brains is the neurofibrillary tangle (NFT). Hyperphosphorylated tau is its major component. In a former paper we described some NFT in the canine brain. During aging, moreover, advanced glycation end products (AGE) might accumulate. Glycated tau induces lipid peroxidation in vivo and tau and AGE antigens have been mentioned to co-localize in NFT. This indicates that AGE may play an important role in Alzheimer disease (AD) by oxidation of tau. The aim of the present study was to investigate amyloid, neurofibrillary tangles, Abeta precursor protein, Abeta, tau, ubiquitin, advanced glycation end products, 4-hyroxynonenal protein and lipofuscin in a series of dogs of varying ages. The results showed a significant positive correlation between age and amyloid quantity (Congo red staining), HNE staining and lipofuscin (LF), and between amyloid quantity and HNE staining and LF. Staining for AbetaPP seemed to have a tendency to increase with age, whereas staining for tau, ubiquitin and AGE each only gave limited positive results in a proportion of the older dogs. Preliminary studies including loss of cognitive capabilities in the older dogs and chemical measurement of lipofuscin-like pigment (LFP) accumulation in brain extracts revealed an increase with old age and dementia. The Congo red, HNE and LF results suggest that deposition of amyloid with aging might be associated with formation of end products of lipid peroxidation. The finding of the limited positive signals for tau, ubiquitin and AGE in some old cases might indicate that the spontaneous brain pathology of the aged dog reveals similarities to early stages observed in AD in humans especially those with Down syndrome.