Biofluid Biomarkers in Huntington's Disease

Huntington's disease (HD) is a chronic progressive neurodegenerative condition where new markers of disease progression are needed. So far no disease-modifying interventions have been found, and few interventions have been proven to alleviate symptoms. This may be partially explained by the lack of reliable indicators of disease severity, progression, and phenotype.Biofluid biomarkers may bring advantages in addition to clinical measures, such as reliability, reproducibility, price, accuracy, and direct quantification of pathobiological processes at the molecular level; and in addition to empowering clinical trials, they have the potential to generate useful hypotheses for new drug development.In this chapter we review biofluid biomarker reports in HD, emphasizing those we feel are likely to be closest to clinical applicability

Differential splicing creates a diversity of transcripts from a neurospecific developmentally regulated gene encoding a protein with new zinc-finger motifs

We have cloned a novel neurospecific gene, named neuro-d4, by differential screening a rat cerebral cortex cDNA library. Northern blot hybridization showed that neuro-d4 expression is restricted to neuronal tissues both in newborn and adult animals. The level of neuro-d4 mRNA in the rat central nervous system is high during the later stages of embryonic development and gradually decreases during the postnatal period. In situ hybridization suggests that the gene transcripts are localized in neuronal cell bodies. Nucleotide sequences of overlapped cDNA clones and all 12 exons in genomic clone were determined. The deduced protein has consensus sequences for a nuclear localization signal, a Krüppel-type zinc-finger and a new type of cysteine/histidine-rich motif resembling zinc-fingers. Several differential splicing variants were found, each of which influences the structure of the encoded protein

Use of the big liquid argon spectrometer BARS for neutrino and cosmic ray studies

The design of the fine grained 300 t liquid argon calorimeter BARS is described. The BARS electronics include about 30 K channels of low noise amplifiers and ADCs. The DAQ system makes it possible to select channels with signals above the chosen threshold. 48 scintillation hodoscopes placed inside the liquid argon are used to form the first level trigger. The total number of scintillation counters in liquid argon is 384. Sums of ionization signals are used to produce the second level trigger. Results of the first use of liquid argon calorimetry for the measurements of tagged neutrino interactions, cosmic-ray muon spectra and composition of extensive atmospheric showers are discussed. (C) 1998 Elsevier Science B.V. All rights reserved