Uncoupling of hypomyelination and glial cell death by a mutation in the proteolipid protein gene.

Proteolipid protein (PLP; M(r) 30,000) is a highly conserved major polytopic membrane protein in myelin but its cellular function remains obscure. Neurological mutant mice can often provide model systems for human genetic disorders. Mutations of the X-chromosome-linked PLP gene are lethal, identified first in the jimpy mouse and subsequently in patients with Pelizaeus-Merzbacher disease. The unexplained phenotype of these mutations includes degeneration and premature cell death of oligodendrocytes with associated hypomyelination. Here we show that a new mouse mutant rumpshaker is defined by the amino-acid substitution Ile-to-Thr at residue 186 in a membrane-embedded domain of PLP. Surprisingly, rumpshaker mice, although myelin-deficient, have normal longevity and a full complement of morphologically normal oligodendrocytes. Hypomyelination can thus be genetically separated from the PLP-dependent oligodendrocyte degeneration. We suggest that PLP has a vital function in glial cell development, distinct from its later role in myelin assembly, and that this dichotomy of action may explain the clinical spectrum of Pelizaeus-Merzbacher disease.     

Computational roles for dopamine in behavioural control

Neuromodulators such as dopamine have a central role in cognitive disorders. In the past decade, biological findings on dopamine function have been infused with concepts taken from computational theories of reinforcement learning. These more abstract approaches have now been applied to describe the biological algorithms at play in our brains when we form value judgements and make choices. The application of such quantitative models has opened up new fields, ripe for attack by young synthesizers and theoreticians.     

Continuous Communication Control Disruptors During Systems Development

This paper presents an open-ended, exploratory study of formal and informal communication and control subprocesses during information systems development (ISD) over an extended period in a large bureaucracy. Using a participant action research strategy, the case study explores the continuous unintended disruptions and barriers to the effective implementation of the ISD project and suggests major variables associated with them. Based on an inductive analysis of the data, the authors suggest some tentatively hypothesized action stages for future research and a broad conceptual model incorporating the process variables. Implications for MIS research, management, and MIS professionals are discussed.     

Cellular catabolism in apoptosis: DNA degradation and endonuclease activation

Recent research has focused on identifying the biochemical events associated with the apoptotic process. These include specific degradation of the chromatin which was described by Wyllie in 1980 [1], with the report of the appearance of discretely sized DNA fragments from apoptotic rat thymocytes. The fragments corresponded in size to strands of DNA that were cleaved at internucleosomal regions and create a ‘ladder patterns’ when electrophoresed on an agarose gel. Because of its near universality, internucleosomal DNA degradation is considered a diagnostic hallmark of cells undergoing apoptosis. It is of great interest to identify the enzymes involved, and some of the candidates will be discussed.