A gene expression atlas of the central nervous system based on bacterial artificial chromosomes

The mammalian central nervous system (CNS) contains a remarkable array of neural cells, each with a complex pattern of connections that together generate perceptions and higher brain functions. Here we describe a large-scale screen to create an atlas of CNS gene expression at the cellular level, and to provide a library of verified bacterial artificial chromosome (BAC) vectors and transgenic mouse lines that offer experimental access to CNS regions, cell classes and pathways. We illustrate the use of this atlas to derive novel insights into gene function in neural cells, and into principal steps of CNS development. The atlas, library of BAC vectors and BAC transgenic mice generated in this screen provide a rich resource that allows a broad array of investigations not previously available to the neuroscience community.     

Palaeolithic ivory sculptures from southwestern Germany and the origins of figurative art

Archaeologists have always viewed the origin of figurative art as a crucial threshold in human evolution. Here I report the discovery of three figurines carved from mammoth ivory at Hohle Fels Cave in the Swabian Jura of southwestern Germany, which provides new evidence for the appearance of figurative art more than 30,000 years ago. The finds include the oldest known representation of a bird, a therianthropic sculpture and an animal that most closely resembles a horse. The Aurignacian sculptures of the Swabian Jura belong to one of the oldest traditions of figurative art known worldwide and point to the Upper Danube as an important centre of cultural innovation during the early Upper Palaeolithic period.     

Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector

Pre-clinical studies in mice and haemophilic dogs have shown that introduction of an adeno-associated viral (AAV) vector encoding blood coagulation factor IX (FIX) into skeletal muscle results in sustained expression of F.IX at levels sufficient to correct the haemophilic phenotype. On the basis of these data and additional pre-clinical studies demonstrating an absence of vector-related toxicity, we initiated a clinical study of intramuscular injection of an AAV vector expressing human F.IX in adults with severe haemophilia B. The study has a dose-escalation design, and all patients have now been enrolled in the initial dose cohort (2 x 10(11) vg/kg). Assessment in the first three patients of safety and gene transfer and expression show no evidence of germline transmission of vector sequences or formation of inhibitory antibodies against F.IX. We found that the vector sequences are present in muscle by PCR and Southern-blot analyses of muscle biopsies and we demonstrated expression of F.IX by immunohistochemistry. We observed modest changes in clinical endpoints including circulating levels of F.IX and frequency of FIX protein infusion. The evidence of gene expression at low doses of vector suggests that dose calculations based on animal data may have overestimated the amount of vector required to achieve therapeutic levels in humans, and that the approach offers the possibility of converting severe haemophilia B to a milder form of the disease.     

Attention modulates synchronized neuronal firing in primate somatosensory cortex

A potentially powerful information processing strategy in the brain is to take advantage of the temporal structure of neuronal spike trains. An increase in synchrony within the neural representation of an object or location increases the efficacy of that neural representation at the next synaptic stage in the brain; thus, increasing synchrony is a candidate for the neural correlate of attentional selection. We investigated the synchronous firing of pairs of neurons in the secondary somatosensory cortex (SII) of three monkeys trained to switch attention between a visual task and a tactile discrimination task. We found that most neuron pairs in SII cortex fired synchronously and, furthermore, that the degree of synchrony was affected by the monkey's attentional state. In the monkey performing the most difficult task, 35% of neuron pairs that fired synchronously changed their degree of synchrony when the monkey switched attention between the tactile and visual tasks. Synchrony increased in 80% and decreased in 20% of neuron pairs affected by attention.     

Earthquake-induced changes in a hydrothermal system on the Juan de Fuca mid-ocean ridge

Hydrothermal vents on mid-ocean ridges of the northeast Pacific Ocean are known to respond to seismic disturbances, with observed changes in vent temperature. But these disturbances resulted from submarine volcanic activity; until now, there have been no observations of the response of a vent system to non-magmatic, tectonic events. Here we report measurements of hydrothermal vent temperature from several vents on the Juan de Fuca ridge in June 1999, before, during and after an earthquake swarm of apparent tectonic origin. Vent fluid temperatures began to rise 4-11 days after the first earthquake. Following this initial increase, the vent temperatures oscillated for about a month before settling down to higher values. We also observed a tenfold increase in fluid output from the hydrothermal system over a period of at least 80 days, extending along the entire ridge segment. Such a large, segment-wide thermal response to relatively modest tectonic activity is surprising, and raises questions about the sources of excess heat and fluid, and the possible effect on vent biological communities.     

Structure of a human common cold virus and functional relationship to other picornaviruses

We report the first atomic resolution structure of an animal virus, human rhinovirus 14. It is strikingly similar to known icosahedral plant RNA viruses. Four neutralizing immunogenic regions have been identified. These, and corresponding antigenic sequences of polio and foot-and-mouth disease viruses, reside on external protrusions. A large cleft on each icosahedral face is probably the host cell receptor binding site.