Light is a dominant mouse mutation resulting in premature cell death.

Light is a dominant mutant allele of the mouse brown locus which results in hairs pigmented only at their tips. The phenotype is due to premature melanocyte death. We have sequenced the tyrosinase-related protein-1 cDNA encoded at this locus from Light mice and found that it contains a single base alteration from wild-type, causing an Arg to Cys change in the protein. To further elucidate the mutant phenotype, we studied the expression of melanocyte specific genes in the skin of Light mice. We have demonstrated premature melanocyte death, but only in pigmented mice, indicating that the cell death is mediated through the inherent cytotoxicity of pigment production.     

The synthesis of stereoselectively labelled porphobilinogen and its incorporation into protoporphyrin-IX

Summary 11-(R)-²H porphobilinogen, stereospecifically labelled with deuterium in the aminomethylene group has been incorporated into protoporphyrin-IX by haemolysates of chicken erythrocytes. High field NMR spectroscopy confirms that the overall biochemical process is stereospecific, deuterium being retained at the -, -and -meso positions and lost from the -meso position.27 August 1986     

Rapid physiological adjustment of roots to localized soil enrichment

SOIL microsites rich in available nutrients are an important source of mineral nutrients for plants in many environments(1-5). Patchiness in nutrient availability below ground is analogous to resource availability in canopy gaps above ground(6). Although the physiological changes occurring in leaves exposed to sun and shade in canopy gaps are well known(7-9), we do not know any studies that show similar physiological changes in roots in enriched soil patches. Here we present evidence of large and rapid increases in the uptake kinetics of plant roots after creating nutrient-rich soil patches in the field. The mean rate of phosphate uptake at a given external phosphate concentration increased by as much as 80% for roots from enriched soil patches compared with roots of control patches treated with distilled water. The changes took place within days of patch treatment. This degree of plasticity was particularly notable for plants growing in soils of very low available phosphorus. These results showing rapid physiological plasticity of roots in fertile soil microsites have important implications for the theory and modelling of nutrient uptake in all soils.     

Functions of poly(ADP-ribose) polymerase in controlling telomere length and chromosomal stability.

In most eukaryotes, poly(ADP-ribose) polymerase (PARP) recognizes DNA strand interruptions generated in vivo. DNA binding by PARP triggers primarily its own modification by the sequential addition of ADP-ribose units to form polymers; this modification, in turn, causes the release of PARP from DNA ends. Studies on the effects of the disruption of the gene encoding PARP (Adprt1, formerly Adprp) in mice have demonstrated roles for PARP in recovery from DNA damage and in suppressing recombination processes involving DNA ends. Telomeres are the natural termini of chromosomes and are, therefore, potential targets of PARP. Here, by the use of two different techniques, we show that mice lacking PARP display telomere shortening compared with wild-type mice. Telomere shortening is seen in different genetic backgrounds and in different tissues, both from embryos and adult mice. In vitro telomerase activity, however, is not altered in Adprt1-/- mouse fibroblasts. Furthermore, cytogenetic analysis of mouse embryonic fibroblasts reveals that lack of PARP is associated with severe chromosomal instability, characterized by increased frequencies of chromosome fusions and aneuploidy. The absence of PARP does not affect the presence of single-strand overhangs, naturally present at the ends of telomeres. This study therefore reveals an unanticipated role for PARP in telomere length regulation and provides insights into its functions in maintaining genomic integrity.     

Long-term motor cortex plasticity induced by an electronic neural implant

It has been proposed that the efficacy of neuronal connections is strengthened when there is a persistent causal relationship between presynaptic and postsynaptic activity. Such activity-dependent plasticity may underlie the reorganization of cortical representations during learning, although direct in vivo evidence is lacking. Here we show that stable reorganization of motor output can be induced by an artificial connection between two sites in the motor cortex of freely behaving primates. An autonomously operating electronic implant used action potentials recorded on one electrode to trigger electrical stimuli delivered at another location. Over one or more days of continuous operation, the output evoked from the recording site shifted to resemble the output from the corresponding stimulation site, in a manner consistent with the potentiation of synaptic connections between the artificially synchronized populations of neurons. Changes persisted in some cases for more than one week, whereas the output from sites not incorporated in the connection was unaffected. This method for inducing functional reorganization in vivo by using physiologically derived stimulus trains may have practical application in neurorehabilitation after injury.     

Assumptional analysis: An elucidation and appraisal for systems practitioners

The purpose of this paper is to review the ‘assumptional analysis’ methodology developed by R. O. Mason and I. I. Mitroff. The importance of this approach is that it was primarily constructed to deal with ill-structured problems at the strategic level in social systems. The 1980s has seen systems practitioners demonstrating an increased interest in exactly this type of problem. The principles and procedures of the approach are set out, its use in three organisations described, and an assessment of its potential contribution to systems practice provided.     

Ecosystem carbon loss with woody plant invasion of grasslands

The invasion of woody vegetation into deserts, grasslands and savannas is generally thought to lead to an increase in the amount of carbon stored in those ecosystems. For this reason, shrub and forest expansion (for example, into grasslands) is also suggested to be a substantial, if uncertain, component of the terrestrial carbon sink. Here we investigate woody plant invasion along a precipitation gradient (200 to 1,100 mm yr(-1)) by comparing carbon and nitrogen budgets and soil delta(13)C profiles between six pairs of adjacent grasslands, in which one of each pair was invaded by woody species 30 to 100 years ago. We found a clear negative relationship between precipitation and changes in soil organic carbon and nitrogen content when grasslands were invaded by woody vegetation, with drier sites gaining, and wetter sites losing, soil organic carbon. Losses of soil organic carbon at the wetter sites were substantial enough to offset increases in plant biomass carbon, suggesting that current land-based assessments may overestimate carbon sinks. Assessments relying on carbon stored from woody plant invasions to balance emissions may therefore be incorrect.     

The DNA sequence, annotation and analysis of human chromosome 3

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.