Cortinarius speciosissimus toxins — a preliminary report

Summary Methanolic extracts ofCortinarius speciosissimus yielded a fluorescent compound which was crystallized and shown to be a cyclic polypeptide. The compound, or an analogue, has been found in most members of the genusCortinarius.The authors acknowledge the help of Dr M. Stewart, Department of Biochemistry, Royal Infirmary, Glasgow, for the amino acid analysis. This work was supported by the Scottish Home and Health Department, grant No. H/MRS/S)/C350.     

Widespread aneuploidy revealed by DNA microarray expression profiling

Expression profiling using DNA microarrays holds great promise for a variety of research applications, including the systematic characterization of genes discovered by sequencing projects. To demonstrate the general usefulness of this approach, we recently obtained expression profiles for nearly 300 Saccharomyces cerevisiae deletion mutants. Approximately 8% of the mutants profiled exhibited chromosome-wide expression biases, leading to spurious correlations among profiles. Competitive hybridization of genomic DNA from the mutant strains and their isogenic parental wild-type strains showed they were aneuploid for whole chromosomes or chromosomal segments. Expression profile data published by several other laboratories also suggest the use of aneuploid strains. In five separate cases, the extra chromosome harboured a close homologue of the deleted gene; in two cases, a clear growth advantage for cells acquiring the extra chromosome was demonstrated. Our results have implications for interpreting whole-genome expression data, particularly from cells known to suffer genomic instability, such as malignant or immortalized cells.     

Population structure of the human pseudoautosomal boundary

The mammalian sex chromosomes are composed of two genetically distinct segments: the pseudoautosomal region, where recombination occurs between the X and Y chromosomes, and the sex chromosome-specific parts. Between these two segments the human sex chromosomes differ by the insertion of an Alu element on the Y chromosome. We have surveyed the sequence variation in the boundary region using the polymerase chain reaction. Fifty seven Y and sixty X chromosomes from ten different human populations were analysed. The X chromosomes were found to be polymorphic at five positions in a 300-base-pair region. By contrast, all Y chromosomes were identical except for one distal polymorphism shared with the X chromosome.     

Introduction: Reappraising Paul Feyerabend

This volume is devoted to a reappraisal of the philosophy of Paul Feyerabend. It has four aims. The first is to reassess his already well-known work from the 1960s and 1970s in light of contemporary developments in the history and philosophy of science. The second is to explore themes in his neglected later work, including recently published and previously unavailable writings. The third is to assess the contributions that Feyerabend can make to contemporary debate, on topics such as perspectivism, realism, and political philosophy of science. The fourth and final aim is to reconsider Feyerabend's place within the history of philosophy of science in the light of new scholarship.     

Inevitability,contingency, and epistemic humility

This paper offers an epistemological framework for the debate about whether the results of scientific enquiry are inevitable or contingent. I argue in Sections 2 and 3 that inevitabilist stances are doubly guilty of epistemic hubris—a lack of epistemic humility—and that the real question concerns the scope and strength of our contingentism. The latter stages of the paper—Sections 4 and 5—address some epistemological and historiographical worries and sketch some examples of deep contingencies to guide further debate. I conclude by affirming that the concept of epistemic humility can usefully inform critical reflection on the contingency of the sciences and the practice of history of science.     

Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish

Reanalysis of an Old Order Amish pedigree, to include several new individuals and two changes in clinical status, markedly reduces the probability of linkage between bipolar affective disorder and the Harvey-ras-1 oncogene and insulin loci on chromosome 11. This linkage can be excluded using a large lateral extension of the original Amish pedigree.     

Feyerabend on politics,education, and scientific culture

The purpose of this paper is to offer a sympathetic reconstruction of the political thought of Paul Feyerabend. Using a critical discussion of the idea of the ‘free society’ it is suggested that his political thought is best understood in terms of three thematic concerns—liberation, hegemony, and the authority of science—and that the political significance of those claims become clear when they are considered in the context of his educational views. It emerges that Feyerabend is best understood as calling for the grounding of cognitive and cultural authorities—like the sciences—in informed deliberation, rather than the uncritical embrace of prevailing convictions. It therefore emerges that a free society is best understood as one of epistemically responsible citizenship rather than epistemically anarchistic relativism of the ‘anything goes’ sort—a striking anticipation of current debates about philosophy of science in society.     

Structural diversity and African origin of the 17q21.31 inversion polymorphism

The 17q21.31 inversion polymorphism exists either as direct (H1) or inverted (H2) haplotypes with differential predispositions to disease and selection. We investigated its genetic diversity in 2,700 individuals, with an emphasis on African populations. We characterize eight structural haplotypes due to complex rearrangements that vary in size from 1.08-1.49 Mb and provide evidence for a 30-kb H1-H2 double recombination event. We show that recurrent partial duplications of the KANSL1 gene have occurred on both the H1 and H2 haplotypes and have risen to high frequency in European populations. We identify a likely ancestral H2 haplotype (H2') lacking these duplications that is enriched among African hunter-gatherer groups yet essentially absent from West African populations. Whereas H1 and H2 segmental duplications arose independently and before human migration out of Africa, they have reached high frequencies recently among Europeans, either because of extraordinary genetic drift or selective sweeps.     

The excitation by suxamethonium of non-proprioceptive afferents from the caudal muscles in the rat

Résumé Des afférences myéliniques non-proprioceptives, à vitesse de conduction lente, en provenance des muscles de la queue du rat, sont excitées par le suxaméthonium d'une concentration de 1,0×10⁴. On considère les mécanismes possibles de cette excitation, dont la signification est discutée.     

Evidence against linkage of schizophrenia to markers on chromosome 5 in a northern Swedish pedigree

Schizophrenia is a severe mental illness with a typically chronic course affecting nearly 1% of the human population. It is generally accepted that genetic factors have an important pathogenic role in a substantial portion of schizophrenia cases; however, despite decades of family studies, there is no agreed-upon mode of inheritance. The discovery of genetic aetiologic factors and resolution of the inheritance pattern(s) will undoubtably emerge from genetic linkage studies. With these objectives in mind, we undertook a linkage project, starting in 1985, in a previously well-documented kindred from north Sweden. Multipoint linkage analyses were used to screen the proximal long arm of chromosome 5 using restriction fragment length polymorphism (RFLP) markers at five loci and the distal long arm using RFLPs at two loci, one of which was the locus for the glucocorticoid receptor. We found strong evidence against linkage between schizophrenia and the seven loci. These results, together with the positive evidence for linkage of schizophrenia with markers in the proximal long arm of chromosome 5 lead us to conclude that the genetic factors underlying schizophrenia are heterogeneous.