Herpes simplex virus interferes with amyloid precursor protein processing

Background The early events underlying Alzheimer's disease (AD) remain uncertain, although environmental factors may be involved. Work in this laboratory has shown that the combination of herpes simplex virus type 1 (HSV1) in brain and carriage of the APOE-ε4 allele of the APOE gene strongly increases the risk of developing AD. The development of AD is thought to involve abnormal aggregation or deposition of a 39–43 amino acid protein – β amyloid (Aβ) – within the brain. This is cleaved from the much larger transmembranal protein 'amyloid precursor protein' (APP). Any agent able to interfere directly with Aβ or APP metabolism may therefore have the capacity to contribute towards AD. One recent report showed that certain HSV1 glycoprotein peptides may aggregate like Aβ; a second study described a role for APP in transport of virus in squid axons. However to date the effects of acute herpesvirus infection on metabolism of APP in human neuronal-type cells have not been investigated. In order to find if HSV1 directly affects APP and its degradation, we have examined this protein from human neuroblastoma cells (normal and transfected with APP 695) infected with the virus, using Western blotting. Results We have found that acute HSV1 (and also HSV2) infection rapidly reduces full length APP levels – as might be expected – yet surprisingly markedly increases levels of a novel C-terminal fragment of APP of about 55 kDa. This band was not increased in cells treated with the protein synthesis inhibitor cycloheximide Conclusion Herpes virus infection leads to rapid loss of full length APP from cells, yet also causes increased levels of a novel 55 kDa C-terminal APP fragment. These data suggest that infection can directly alter the processing of a transmembranal protein intimately linked to the aetiology of AD

The Chiral Soliton Model for Arbitrary Colors and Flavors

The quantum numbers of the chiral soliton are derived for an arbitrary number of colors and flavors

The theta^+ baryon in soliton models: large Nc QCD and the validity of rigid-rotor quantization

A light collective theta+ baryon state (with strangeness +1) was predicted via rigid-rotor collective quantization of SU(3) chiral soliton models. This paper explores the validity of this treatment. A number of rather general analyses suggest that predictions of exotic baryon properties based on this approximation do not follow from large Nc QCD. These include an analysis of the baryon's width, a comparison of the predictions with general large Nc consistency conditions of the Gervais-Sakita-Dashen-Manohar type; an application of the technique to QCD in the limit where the quarks are heavy; a comparison of this method with the vibration approach of Callan and Klebanov; and the 1/Nc scaling of the excitation energy. It is suggested that the origin of the problem lies in an implicit assumption in the that the collective motion is orthogonal to vibrational motion. While true for non-exotic motion, the Wess-Zumino term induces mixing at leading order between collective and vibrational motion with exotic quantum numbers. This suggests that successful phenomenological predictions of theta+ properties based on rigid-rotor quantization were accidental.Comment: 19 pages; A shorter more readable versio

Examination of the Nitric Oxide Production-Suppressing Component in Tinospora tuberculata

The component of aqueous Tinospora tuberculata extract that inhibits nitric oxide (NO) production was examined using macrophages activated by the addition of lipopolysaccharide. The aqueous extract was partitioned with ethyl acetate. The aqueous layer was fractionated with a Diaion column. The residue of the aqueous extract was extracted with methanol, and partitioned with ethyl acetate. The ethyl acetate layer was found to be associated with a distinct decrease in the NO level and inducible NO synthase. On further fractionation, the subfraction of E-3 showed high anti-NO activity. N-trans-Feruloyltyramine isolated from E-3 was identified as exhibiting strong anti-NO activity. This compound is the most active component of Tinospora tuberculata with respect to the suppression of NO production

Meeting report: 2012 Caenorhabditis elegans Neurobiology meeting, EMBL Advanced Training Centre, Germany

Some of the finest minds in the field of Caenorhabditis elegans neurobiology were brought together from 14 June to 17 June 2012 in the small, quaint and picturesque German city of Heidelberg for the biannual C. elegans neurobiology conference. Held at the EMBL Advanced Training Centre and wonderfully organised by Diah Yulianti, Jean-Louis Bessereau, Gert Jansen and William Schafer, the meeting contained 62 verbal presentations and hundreds of posters that were displayed around the double-helical walkways that looped throughout the conference centre. Presentations on recent advances in microfluidics, cell ablation and targeted gene expression exemplified the strengths of C. elegans as a model organism, with these advances allowing detailed high-throughput analysis and study. Interesting behaviours that were previously poorly characterised were widely discussed, as were the advantages of C. elegans as a model for neurodevelopment and neurodegeneration and the investigation of neuropeptide function. The examples discussed in this meeting report seek to illustrate the breadth and depth of presentations given on these recurring topics