Mapping multiple features in the population response of visual cortex

Stimulus features such as edge orientation, motion direction and spatial frequency are thought to be encoded in the primary visual cortex by overlapping feature maps arranged so that the location of neurons activated by a particular combination of stimulus features can be predicted from the intersections of these maps. This view is based on the use of grating stimuli, which limit the range of stimulus combinations that can be examined. We used optical imaging of intrinsic signals in ferrets to assess patterns of population activity evoked by the motion of a texture (a field of iso-oriented bars). Here we show that the same neural population can be activated by multiple combinations of orientation, length, motion axis and speed. Rather than reflecting the intersection of multiple maps, our results indicate that population activity in primary visual cortex is better described as a single map of spatiotemporal energy.     

Synthesis and structure of the platelet aggregation factor thromboxane A2

In 1975, Hamberg et al. reported evidence for the existence of an unstable platelet-aggregating factor which they named thromboxane A2 (TXA2) and for which they proposed a novel bicyclic oxetane structure (1, below) based on the short half-life of the factor (t1/2 (37 degrees C) = 32 s at pH 7.4) and the isolation of degradation products related to thromboxane (TXB2) (2, below). As natural TXA2 has not yet been isolated and characterized as a pure compound, we have synthesized the proposed structure (1) from TXB2 and compared its biological properties with those of authentic, biologically generated material. Here we present evidence that synthetic material having structure (1) is indistinguishable from platelet-derived TXA2 in various biological assays and that the proposed structure (1) for TXA2 is correct.     

The contribution of sensory experience to the maturation of orientation selectivity in ferret visual cortex.

Sensory experience begins when neural circuits in the cerebral cortex are still immature; however, the contribution of experience to cortical maturation remains unclear. In the visual cortex, the selectivity of neurons for oriented stimuli at the time of eye opening is poor and increases dramatically after the onset of visual experience. Here we investigate whether visual experience has a significant role in the maturation of orientation selectivity and underlying cortical circuits using two forms of deprivation: dark rearing, which completely eliminates experience, and binocular lid suture, which alters the pattern of sensory driven activity. Orientation maps were present in dark-reared ferrets, but fully mature levels of tuning were never attained. In contrast, only rudimentary levels of orientation selectivity were observed in lid-sutured ferrets. Despite these differences, horizontal connections in both groups were less extensive and less clustered than normal, suggesting that long-range cortical processing is not essential for the expression of orientation selectivity, but may be needed for the full maturation of tuning. Thus, experience is beneficial or highly detrimental to cortical maturation, depending on the pattern of sensory driven activity.     

Families, groups and clusters of local and health authorities: revised for authorities in 1999

This is the second of two articles describing the revision of The ONS classification of local and health authorities of Great Britain to take account of area changes in the 1990's. It presents local authorities in Great Britain as at April 1999 in terms of Families, Groups and Clusters, based on 37 socio-economic and demographic variables from the 1991 Census. Health authorities are presented in terms of Families and Groups only, based on the same variables. The previous article (in Population Trends 98) presented, for each local and health authority, up to four other authorities to which it is 'most similar'.     

Cadmium toxicity among wildlife in the Colorado Rocky Mountains

Cadmium is known to be both extremely toxic and ubiquitous in natural environments. It occurs in almost all soils, surface waters and plants, and it is readily mobilized by human activities such as mining. As a result, cadmium has been named as a potential health threat to wildlife species; however, because it exists most commonly in the environment as a trace constituent, reported incidences of cadmium toxicity are rare. Here we have measured trace metals in the food web and tissues of white-tailed ptarmigan (Lagopus leucurus) in Colorado. Our results suggest that cadmium toxicity may be more common among natural populations of vertebrates than has been appreciated to date and that cadmium toxicity may often go undetected or unrecognized. In addition, our research shows that ingestion of even trace quantities of cadmium can influence not only the physiology and health of individual organisms, but also the demographics and the distribution of species.     

Maintaining a behaviour polymorphism by frequency-dependent selection on a single gene

Accounting for the abundance of genetic variation in the face of natural selection remains a central problem of evolutionary biology. Genetic polymorphisms are constantly arising through mutation, and although most are promptly eliminated, polymorphisms in functionally important traits are common. One mechanism that can maintain polymorphisms is negative frequency-dependent selection on alternative alleles, whereby the fitness of each decreases as its frequency increases. Examples of frequency-dependent selection are rare, especially when attempting to describe the genetic basis of the phenotype under selection. Here we show frequency-dependent selection in a well-known natural genetic polymorphism affecting fruitfly foraging behaviour. When raised in low nutrient conditions, both of the naturally occurring alleles of the foraging gene (for(s) and for(R)) have their highest fitness when rare-the hallmark of negative frequency-dependent selection. This effect disappears at higher resources levels, demonstrating the role of larval competition. We are able to confirm the involvement of the foraging gene by showing that a sitter-like mutant allele on a rover background has similar frequency-dependent fitness as the natural sitter allele. Our study represents a clear demonstration of frequency-dependent selection, and we are able to attribute this effect to a single, naturally polymorphic gene known to affect behaviour.     

Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a storage pool deficiency due to an absence of platelet dense bodies. Lysosomal ceroid lipofuscinosis, pulmonary fibrosis and granulomatous colitis are occasional manifestations of the disease. HPS occurs with a frequency of one in 1800 in north-west Puerto Rico due to a founder effect. Several non-Puerto Rican patients also have mutations in HPS1, which produces a protein of unknown function. Another gene, ADTB3A, causes HPS in the pearl mouse and in two brothers with HPS-2 (refs. 11,12). ADTB3A encodes a coat protein involved in vesicle formation, implicating HPS as a disorder of membrane trafficking. We sought to identify other HPS-causing genes. Using homozygosity mapping on pooled DNA of 6 families from central Puerto Rico, we localized a new HPS susceptibility gene to a 1.6-cM interval on chromosome 3q24. The gene, HPS3, has 17 exons, and a putative 113.7-kD product expected to reveal how new vesicles form in specialized cells. The homozygous, disease-causing mutation is a large deletion and represents the second example of a founder mutation causing HPS on the small island of Puerto Rico. We also present an allele-specific assay for diagnosing individuals heterozygous or homozygous for this mutation.     

Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome

Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic disorders. We tested 290 individuals with mental retardation by BAC array comparative genomic hybridization and identified 16 pathogenic rearrangements, including de novo microdeletions of 17q21.31 found in four individuals. Using oligonucleotide arrays, we refined the breakpoints of this microdeletion, defining a 478-kb critical region containing six genes that were deleted in all four individuals. We mapped the breakpoints of this deletion and of four other pathogenic rearrangements in 1q21.1, 15q13, 15q24 and 17q12 to flanking segmental duplications, suggesting that these are also sites of recurrent rearrangement. In common with the 17q21.31 deletion, these breakpoint regions are sites of copy number polymorphism in controls, indicating that these may be inherently unstable genomic regions.