Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy

X-linked spinal and bulbar muscular atrophy (Kennedy's disease) is an adult-onset form of motorneuron disease which may be associated with signs of androgen insensitivity. We have now investigated whether the androgen receptor gene on the proximal long arm of the X chromosome is a candidate gene for this disease. In patient samples we found androgen receptor gene mutations with increased size of a polymorphic tandem CAG repeat in the coding region. These amplified repeats were absolutely associated with the disease, being present in 35 unrelated patients and none of 75 controls. They segregated with the disease in 15 families, with no recombination in 61 meioses (the maximum log likelihood ratio (lod score) is 13.2 at a recombination rate of 0). The association is unlikely to be due to linkage disequilibrium, because 11 different disease alleles were observed. We conclude that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of this disorder.     

Wormy mice in a hybrid zone

As one approach to analysing the genetic barriers between species, we studied the numbers and types of parasitic worms in two species of house mice (Mus musculus and M. domesticus) and in their natural hybrids. Where the ranges of these two species meet in southern Germany, there is a zone of hybridization less than 20 kilometres across, in which about 98% of the mice have backcross genotypes. Fourteen of the 46 mice tested from within the zone have over 500 pinworms per gut, a number far exceeding the mean of 40 per gut for other mice inside and outside the zone. Other nematodes have a similar, non-random distribution. The number of mice bearing 9 or more tapeworms per gut is also excessive in the hybrid zone. These extraordinarily wormy mice may be unusually susceptible to parasitism; the different species may have different genes for resistance, and recombinant backcross animals may lose both. Our findings support the view that the hybrid populations may have reduced fitness and thereby act as a genetic sink, interfering with the flow of genes between the two species. The possibility that environmental or ecological peculiarites in the zone of hybridization make the mice more liable to infection is not supported.     

Spin-dependent exciton formation in pi-conjugated compounds.

The efficiency of light-emitting diodes (LEDs) made from organic semiconductors is determined by the fraction of injected electrons and holes that recombine to form emissive spin-singlet states rather than non-emissive spin-triplet states. If the process by which these states form is spin-independent, the maximum efficiency of organic LEDs will be limited to 25 per cent. But recent reports have indicated fractions of emissive singlet states ranging from 22 to 63 per cent, and the reason for this variation remains unclear. Here we determine the absolute fraction of singlet states generated in a platinum-containing conjugated polymer and its corresponding monomer. The spin-orbit coupling introduced by the platinum atom allows triplet-state emission, so optically and electrically generated luminescence from both singlet and triplet states can be compared directly. We find an average singlet generation fraction of 22 +/- 1 per cent for the monomer, but 57 +/- 4 per cent for the polymer. This suggests that recombination is spin-independent for the monomer, but that a spin-dependent process, favouring singlet formation, is effective in the polymer. We suggest that this process is a consequence of the exchange interaction, which will operate on overlapping electron and hole wavefunctions on the same polymer chain at their capture radius.     

Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.

Salmonella enterica subspecies I, serovar Typhimurium (S. typhimurium), is a leading cause of human gastroenteritis, and is used as a mouse model of human typhoid fever. The incidence of non-typhoid salmonellosis is increasing worldwide, causing millions of infections and many deaths in the human population each year. Here we sequenced the 4,857-kilobase (kb) chromosome and 94-kb virulence plasmid of S. typhimurium strain LT2. The distribution of close homologues of S. typhimurium LT2 genes in eight related enterobacteria was determined using previously completed genomes of three related bacteria, sample sequencing of both S. enterica serovar Paratyphi A (S. paratyphi A) and Klebsiella pneumoniae, and hybridization of three unsequenced genomes to a microarray of S. typhimurium LT2 genes. Lateral transfer of genes is frequent, with 11% of the S. typhimurium LT2 genes missing from S. enterica serovar Typhi (S. typhi), and 29% missing from Escherichia coli K12. The 352 gene homologues of S. typhimurium LT2 confined to subspecies I of S. enterica-containing most mammalian and bird pathogens-are useful for studies of epidemiology, host specificity and pathogenesis. Most of these homologues were previously unknown, and 50 may be exported to the periplasm or outer membrane, rendering them accessible as therapeutic or vaccine targets.     

What is a text?

This paper argues that textuality—the property of being a text—is assigned by the reader, rather than constituting an inherent property, and that the being of texts was both captured and mystified by the figure of ‘the text’ as this developed from the 1970s onwards. Textuality consists in the abstraction of verbal content from its origins, entailing the apprehension of that content as copresent with the reader; and it is given a material embodiment in the process of publication, especially in the production of canonical works, which together comprise the locus classicus of the textual apprehension. Whole disciplines—here termed the hermeneutico-canonical disciplines—are based upon that apprehension, and the discipline or approach known as hermeneutics consists of its theoretical elaboration. In contrast, the discipline of history rests upon the apprehension of the verbal under the sign of the document or its cognates, and this difference renders intelligible the longstanding relationship of mutual suspicion between hermeneutics and history. The historiography of science, remarkably enough, manages to combine these approaches; the paper concludes by suggesting that these can be brought into a more fruitful synthesis by investigating historically the construction of scientific canons.     

Ebola virus: the search for vaccines and treatments

Ebola viruses belong to the family Filoviridae, which are among the most virulent infectious agents known. These viruses cause acute, and frequently fatal, hemorrhagic fever in humans and nonhuman primates. Currently, no vaccines or treatments are available for human use. This review describes Ebola viruses, with a particular focus on the status of research efforts to develop vaccines and therapeutics and to identify the immune mechanisms of protection.     

Habitat characteristics of leatherside chub ( Gila copei ) at two spatial scales

Populations of leatherside chub ( Gila copei ), a little-known species native to the eastern Great Basin, have declined and their distribution has become fragmented. To determine habitat requirements and possible factors responsible for population decline, we quantified macrohabitats and microhabitats occupied by leatherside chub. Macrohabitat was surveyed at 59 sites in the Sevier River drainage of south central Utah, and microhabitats occupied by leatherside chub were measured at 3 locations spanning the species latitudinal range. Characteristics of points in the stream where leatherside chub occurred were compared to points where they did not occur. Abundance of brown trout ( Salmo trutta ) and elevation were weakly negatively correlated with leatherside chub distribution on a macrohabitat scale. Microhabitats occupied by leatherside chub were characterized by low water velocities (2.5-45 cm sec -1 ), intermediate water depths (25-65 cm), and low percent composition of sand-silt or gravel substrates. This study suggests that the presence of introduced brown trout may have led to the decline of leatherside chub.