Optical pulsations from the anomalous X-ray pulsar 4U0142+61

Anomalous X-ray pulsars (AXPs) differ from ordinary radio pulsars in that their X-ray luminosity is orders of magnitude greater than their rate of rotational energy loss, and so they require an additional energy source. One possibility is that AXPs are highly magnetized neuron stars or 'magnetars' having surface magnetic fields greater than 10(14) G. This would make them similar to the soft gamma-ray repeaters (SGRs), but alternative models that do not require extreme magnetic fields also exist. An optical counterpart to the AXP 4U0142+61 was recently discovered, consistent with emission from a magnetar, but also from a magnetized hot white dwarf, or an accreting isolated neutron star. Here we report the detection of optical pulsations from 4U0142+61. The pulsed fraction of optical light (27 per cent) is five to ten times greater than that of soft X-rays, from which we conclude that 4U0142+61 is a magnetar. Although this establishes a direct relationship between AXPs and the soft gamma-ray repeaters, the evolutionary connection between AXPs, SGRs and radio pulsars remains controversial.     

A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome

Rett syndrome (RTT) is an inherited neurodevelopmental disorder of females that occurs once in 10,000-15,000 births. Affected females develop normally for 6-18 months, but then lose voluntary movements, including speech and hand skills. Most RTT patients are heterozygous for mutations in the X-linked gene MECP2 (refs. 3-12), encoding a protein that binds to methylated sites in genomic DNA and facilitates gene silencing. Previous work with Mecp2-null embryonic stem cells indicated that MeCP2 is essential for mouse embryogenesis. Here we generate mice lacking Mecp2 using Cre-loxP technology. Both Mecp2-null mice and mice in which Mecp2 was deleted in brain showed severe neurological symptoms at approximately six weeks of age. Compensation for absence of MeCP2 in other tissues by MeCP1 (refs. 19,20) was not apparent in genetic or biochemical tests. After several months, heterozygous female mice also showed behavioral symptoms. The overlapping delay before symptom onset in humans and mice, despite their profoundly different rates of development, raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2.     

Chromatic sensitivity of ganglion cells in the peripheral primate retina

Visual abilities change over the visual field. For example, our ability to detect movement is better in peripheral vision than in foveal vision, but colour discrimination is markedly worse. The deterioration of colour vision has been attributed to reduced colour specificity in cells of the midget, parvocellular (PC) visual pathway in the peripheral retina. We have measured the colour specificity (red-green chromatic modulation sensitivity) of PC cells at eccentricities between 20 and 50 degrees in the macaque retina. Here we show that most peripheral PC cells have red-green modulation sensitivity close to that of foveal PC cells. This result is incompatible with the view that PC pathway cells in peripheral retina make indiscriminate connections ('random wiring') with retinal circuits devoted to different spectral types of cone photoreceptors. We show that selective cone connections can be maintained by dendritic field anisotropy, consistent with the morphology of PC cell dendritic fields in peripheral retina. Our results also imply that postretinal mechanisms contribute to the psychophysically demonstrated deterioration of colour discrimination in the peripheral visual field.     

Antibody neutralization and escape by HIV-1

Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally, led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire.     

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.     

The evolution of reproductive isolation through sexual conflict

Classical population-genetics theory suggests that reproductive isolation will evolve fastest in small isolated populations. In contrast, recent theory suggests that divergence should occur fastest in larger allopatric populations. The rationale behind this is that sexual conflict, potentially the strongest driver of speciation, is greater in larger, higher-density populations. This idea is highly controversial and has little experimental support. Here we show, using replicate fly populations with varying levels of sexual conflict, that larger, more dense populations with more sexual conflict diverged to a greater degree than small populations with relaxed conflict. This result strongly suggests that speciation can occur rapidly in large populations through increased sexual conflict.