Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice.

Pigmentary glaucoma is a significant cause of human blindness. Abnormally liberated iris pigment and cell debris enter the ocular drainage structures, leading to increased intraocular pressure (IOP) and glaucoma. DBA/2J (D2) mice develop a form of pigmentary glaucoma involving iris pigment dispersion (IPD) and iris stromal atrophy (ISA). Using high-resolution mapping techniques, sequencing and functional genetic tests, we show that IPD and ISA result from mutations in related genes encoding melanosomal proteins. IPD is caused by a premature stop codon mutation in the Gpnmb (GpnmbR150X) gene, as proved by the occurrence of IPD only in D2 mice that are homozygous with respect to GpnmbR150X; otherwise, similar D2 mice that are not homozygous for GpnmbR150X do not develop IPD. ISA is caused by the recessive Tyrp1b mutant allele and rescued by the transgenic introduction of wildtype Tyrp1. We hypothesize that IPD and ISA alter melanosomes, allowing toxic intermediates of pigment production to leak from melanosomes, causing iris disease and subsequent pigmentary glaucoma. This is supported by the rescue of IPD and ISA in D2 eyes with substantially decreased pigment production. These data indicate that pigment production and mutant melanosomal protein genes may contribute to human pigmentary glaucoma. The fact that hypopigmentation profoundly alleviates the D2 disease indicates that therapeutic strategies designed to decrease pigment production may be beneficial in human pigmentary glaucoma.     

神经网络方法在胃收缩识别中的应用

胃收缩运动在消化过程中起着重要作用．传统的测量胃运动的方法是侵 袭性的．本文提出一种运用人工神经网络由体表胃电图（ｅｌｅｃｔｒｏｇａｓｔｒｏｇｒａｍ） 无损识别胃收缩运动的方法．以５个受试者的胃电图作为训练集，另５个受试 者的胃电图作为测试集．以同时检测的与每段胃电图对应的胃腔内压力记录 作为评价标准，运用经过优化的具有单个隐层的反向传播神经网络，以分段 后的每段胃电图的时－频表征作为网络的输入，实验结果表明：识别胃运动静 止期的准确度达９０呢，识别收缩运动期的准确度达９４％．     

The avian nature of the brain and inner ear of Archaeopteryx

Archaeopteryx, the earliest known flying bird (avialan) from the Late Jurassic period, exhibits many shared primitive characters with more basal coelurosaurian dinosaurs (the clade including all theropods more bird-like than Allosaurus), such as teeth, a long bony tail and pinnate feathers. However, Archaeopteryx possessed asymmetrical flight feathers on its wings and tail, together with a wing feather arrangement shared with modern birds. This suggests some degree of powered flight capability but, until now, little was understood about the extent to which its brain and special senses were adapted for flight. We investigated this problem by computed tomography scanning and three-dimensional reconstruction of the braincase of the London specimen of Archaeopteryx. Here we show the reconstruction of the braincase from which we derived endocasts of the brain and inner ear. These suggest that Archaeopteryx closely resembled modern birds in the dominance of the sense of vision and in the possession of expanded auditory and spatial sensory perception in the ear. We conclude that Archaeopteryx had acquired the derived neurological and structural adaptations necessary for flight. An enlarged forebrain suggests that it had also developed enhanced somatosensory integration with these special senses demanded by a lifestyle involving flying ability.     

Neurolinguistics: structural plasticity in the bilingual brain

Humans have a unique ability to learn more than one language--a skill that is thought to be mediated by functional (rather than structural) plastic changes in the brain. Here we show that learning a second language increases the density of grey matter in the left inferior parietal cortex and that the degree of structural reorganization in this region is modulated by the proficiency attained and the age at acquisition. This relation between grey-matter density and performance may represent a general principle of brain organization.     

A single population of olfactory sensory neurons mediates an innate avoidance behaviour in Drosophila

All animals exhibit innate behaviours in response to specific sensory stimuli that are likely to result from the activation of developmentally programmed neural circuits. Here we observe that Drosophila exhibit robust avoidance to odours released by stressed flies. Gas chromatography and mass spectrometry identifies one component of this 'Drosophila stress odorant (dSO)' as CO2. CO2 elicits avoidance behaviour, at levels as low as 0.1%. We used two-photon imaging with the Ca2+-sensitive fluorescent protein G-CaMP to map the primary sensory neurons governing avoidance to CO2. CO2 activates only a single glomerulus in the antennal lobe, the V glomerulus; moreover, this glomerulus is not activated by any of 26 other odorants tested. Inhibition of synaptic transmission in sensory neurons that innervate the V glomerulus, using a temperature-sensitive Shibire gene (Shi(ts)), blocks the avoidance response to CO2. Inhibition of synaptic release in the vast majority of other olfactory receptor neurons has no effect on this behaviour. These data demonstrate that the activation of a single population of sensory neurons innervating one glomerulus is responsible for an innate avoidance behaviour in Drosophila.     

Direct integration of Hox and segmentation gene inputs during Drosophila development

During Drosophila embryogenesis, segments, each with an anterior and posterior compartment, are generated by the segmentation genes while the Hox genes provide each segment with a unique identity. These two processes have been thought to occur independently. Here we show that abdominal Hox proteins work directly with two different segmentation proteins, Sloppy paired and Engrailed, to repress the Hox target gene Distalless in anterior and posterior compartments, respectively. These results suggest that segmentation proteins can function as Hox cofactors and reveal a previously unanticipated use of compartments for gene regulation by Hox proteins. Our results suggest that these two classes of proteins may collaborate to directly control gene expression at many downstream target genes.     

Surface mechanics mediate pattern formation in the developing retina

Pattern formation of biological structures involves organizing different types of cells into a spatial configuration. In this study, we investigate the physical basis of biological patterning of the Drosophila retina in vivo. We demonstrate that E- and N-cadherins mediate apical adhesion between retina epithelial cells. Differential expression of N-cadherin within a sub-group of retinal cells (cone cells) causes them to form an overall shape that minimizes their surface contact with surrounding cells. The cells within this group, in both normal and experimentally manipulated conditions, pack together in the same way as soap bubbles do. The shaping of the cone cell group and packing of its components precisely imitate the physical tendency for surfaces to be minimized. Thus, simple patterned expression of N-cadherin results in a complex spatial pattern of cells owing to cellular surface mechanics.     

Temporal difference models describe higher-order learning in humans

The ability to use environmental stimuli to predict impending harm is critical for survival. Such predictions should be available as early as they are reliable. In pavlovian conditioning, chains of successively earlier predictors are studied in terms of higher-order relationships, and have inspired computational theories such as temporal difference learning. However, there is at present no adequate neurobiological account of how this learning occurs. Here, in a functional magnetic resonance imaging (fMRI) study of higher-order aversive conditioning, we describe a key computational strategy that humans use to learn predictions about pain. We show that neural activity in the ventral striatum and the anterior insula displays a marked correspondence to the signals for sequential learning predicted by temporal difference models. This result reveals a flexible aversive learning process ideally suited to the changing and uncertain nature of real-world environments. Taken with existing data on reward learning, our results suggest a critical role for the ventral striatum in integrating complex appetitive and aversive predictions to coordinate behaviour.     

Prediction of Emperor-Hawaii seamount locations from a revised model of global plate motion and mantle flow

The bend in the Hawaiian-Emperor seamount chain is a prominent feature usually attributed to a change in Pacific plate motion approximately 47 Myr ago. However, global plate motion reconstructions fail to predict the bend. Here we show how the geometry of the Hawaiian-Emperor chain and other hotspot tracks can be explained when we combine global plate motions with intraplate deformation and movement of hotspot plumes through distortion by global mantle flow. Global mantle flow models predict a southward motion of the Hawaiian hotspot. This, in combination with a plate motion reconstruction connecting Pacific and African plates through Antarctica, predicts the Hawaiian track correctly since the date of the bend, but predicts the chain to be too far west before it. But if a reconstruction through Australia and Lord Howe rise is used instead, the track is predicted correctly back to 65 Myr ago, including the bend. The difference between the two predictions indicates the effect of intraplate deformation not yet recognized or else not recorded on the ocean floor. The remaining misfit before 65 Myr ago can be attributed to additional intraplate deformation of similar magnitude.     

Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo

Patterning of the mouse embryo along the anteroposterior axis during body plan development requires migration of the distal visceral endoderm (DVE) towards the future anterior side by a mechanism that has remained unknown. Here we show that Nodal signalling and the regionalization of its antagonists are required for normal migration of the DVE. Whereas Nodal signalling provides the driving force for DVE migration by stimulating the proliferation of visceral endoderm cells, the antagonists Lefty1 and Cerl determine the direction of migration by asymmetrically inhibiting Nodal activity on the future anterior side.