DISC1-dependent switch from progenitor proliferation to migration in the developing cortex

Regulatory mechanisms governing the sequence from progenitor cell proliferation to neuronal migration during corticogenesis are poorly understood. Here we report that phosphorylation of DISC1, a major susceptibility factor for several mental disorders, acts as a molecular switch from maintaining proliferation of mitotic progenitor cells to activating migration of postmitotic neurons in mice. Unphosphorylated DISC1 regulates canonical Wnt signalling via an interaction with GSK3β, whereas specific phosphorylation at serine 710 (S710) triggers the recruitment of Bardet-Biedl syndrome (BBS) proteins to the centrosome. In support of this model, loss of BBS1 leads to defects in migration, but not proliferation, whereas DISC1 knockdown leads to deficits in both. A phospho-dead mutant can only rescue proliferation, whereas a phospho-mimic mutant rescues exclusively migration defects. These data highlight a dual role for DISC1 in corticogenesis and indicate that phosphorylation of this protein at S710 activates a key developmental switch.     

An armoured Cambrian lobopodian from China with arthropod-like appendages

Cambrian fossil Lagerst?tten preserving soft-bodied organisms have contributed much towards our understanding of metazoan origins. Lobopodians are a particularly interesting group that diversified and flourished in the Cambrian seas. Resembling 'worms with legs', they have long attracted much attention in that they may have given rise to both Onychophora (velvet worms) and Tardigrada (water bears), as well as to arthropods in general. Here we describe Diania cactiformis gen. et sp. nov. as an 'armoured' lobopodian from the Chengjiang fossil Lagerst?tte (Cambrian Stage 3), Yunnan, southwestern China. Although sharing features with other typical lobopodians, it is remarkable for possessing robust and probably sclerotized appendages, with what appear to be articulated elements. In terms of limb morphology it is therefore closer to the arthropod condition, to our knowledge, than any lobopodian recorded until now. Phylogenetic analysis recovers it in a derived position, close to Arthropoda; thus, it seems to belong to a grade of organization close to the point of becoming a true arthropod. Further, D. cactiformis could imply that arthropodization (sclerotization of the limbs) preceded arthrodization (sclerotization of the body). Comparing our fossils with other lobopodian appendage morphologies--see Kerygmachela, Jianshanopodia and Megadictyon--reinforces the hypothesis that the group as a whole is paraphyletic, with different taxa expressing different grades of arthropodization.     

孤岛油田馆(1+2)地层划分对比与沉积模式

孤岛油田馆(1 2)砂层组属于河流相沉积，其纵向、横向相变迅速，砂体难以大面积追踪，本利用河流结构单元分析法、标准层与辅助标志层控制下的“旋回-厚度”对比法，很好地解决了馆(1 2)地层的划分对比问题，其中馆(1 2)砂层组内辅助标志层的发现为地层的划分对比提供了重要的保证．根据结构单元分析、砂体的岩性特征、粒度特征、河流砂体的空间展布形态以及河流曲率的计算，对馆(1 2)河流沉积的垂向旋回性及沉积模式进行了研究。对比Miall的16种河流分类方案，孤岛油田馆(1 2)砂层组属于细粒曲流河沉积．     

Correlation between continuous lobe reconnection in the mid magnetotail and substorm expansion onset

Data on plasma sheet crossing measured by Cluster/HIA and Cluster/FGM during the period from July to October in 2001 -2003 are analyzed. Based on previous work on the characteristic features of continuous lobe reconnection (CLR) described in reference, two case studies and a statistical analysis were carried out on correlation between CLR in the mid magnetotail and substorm expansion onset for the events occurring during this period. It is found that almost all CLR events are in close connection with substorms. The beginning of CLR is almost always a few minutes ahead of substorm activities seen in the near Earth magnetotail and on the ground-based stations. This provides a clear indication that CLR is the virtual cause of substorm expansion onset during the period of continuous southward interplanetary magnetic field.     

均匀细圆环和均匀薄圆盘对任意轴线的转动惯量

分别运用一般方法和投影法计算了均匀细圆环和均匀薄圆盘对任意轴线的转动惯量,在验证投影法计算结果正确性的基础上,对计算结果进行了讨论,可以用于对实际问题的分析研究.     

A cytoplasmic region determines single-channel conductance in 5-HT3 receptors

5-hydroxytryptamine type 3 (5-HT3) receptors are cation-selective transmitter-gated ion channels of the Cys-loop superfamily. The single-channel conductance of human recombinant 5-HT3 receptors assembled as homomers of 5-HT3A subunits, or heteromers of 5-HT3A and 5-HT3B subunits, are markedly different, being 0.4 pS (refs 6, 9) and 16 pS (ref. 7), respectively. Paradoxically, the channel-lining M2 domain of the 5-HT3A subunit would be predicted to promote cation conduction, whereas that of the 5-HT3B subunit would not. Here we describe a determinant of single-channel conductance that can explain these observations. By constructing chimaeric 5-HT3A and 5-HT3B subunits we identified a region (the 'HA-stretch') within the large cytoplasmic loop of the receptor that markedly influences channel conductance. Replacement of three arginine residues unique to the HA-stretch of the 5-HT3A subunit by their 5-HT3B subunit counterparts increased single-channel conductance 28-fold. Significantly, ultrastructural studies of the Torpedo nicotinic acetylcholine receptor indicate that the key residues might frame narrow openings that contribute to the permeation pathway. Our findings solve the conundrum of the anomalously low conductance of homomeric 5-HT3A receptors and indicate an important function for the HA-stretch in Cys-loop transmitter-gated ion channels.     

Phospholipid metabolism in pancreatic islets

Conclusions The secretion of insulin can be elicited by a wide spectrum of stimuli including nutrients, hormones and neurotransmitters as well as a large number of pharmacological agents such as tumor-promoters and sulphonylureas. The diversity of these secretagogues suggests that islets may be activated through a number of distinct biochemical mechanisms. The work discussed in this review suggests that certain of the above-mentioned secretagogues, especially nutrient and neurotransmitter stimuli, may induce insulin secretion by a mechanism involving enhanced metabolism of inositol-containing lipids. The way in which this process is coupled to secretion is not known, although several possibilities exist. The hydrolysis of phosphoinositides and release of inositol phosphates may result, respectively in altered calcium permeability of the plasma membrane and mobilization of calcium from intracellular sources. The accompanying production of diacylglycerol might also influence membrane permeability and fluidity and also lead to activation of protein kinase C. Diacylglycerol can be phosphorylated to form phosphatidic acid which may play a role as an endogenous ionophore. Finally, inositol lipid breakdown could lead, through diacylglycerol and/or phosphatidic intermediates, to the liberation of arachidonic acid and subsequent conversion to active metabolites of the cyclo-oxygenase and lipoxygenase pathways. Thus, enhanced phospholipid metabolism in islets could, theoretically, result in the generation of a range of intracellular signals which mediate or modulate insulin secretion during stimulation by certain types of secretagogues. Continued investigation is clearly neccessary in order to elucidate the mechanisms by which such secretagogues provoke increased phospholipid metabolism and to understand the role(s) of this process in the regulation of islet function.     

Cluster observations of high-altitude cusp during multiple fast-turning IMF

Using coordinated observations from the Cluster,DMSP and ESR radar,high-altitude cusp was investigated for a time period characterized by four fast reversals of the IMF BZ.On February 12,2003,Cluster was flying sunward at duskside over the Northern Hemisphere,across the high-altitude northern cusp twice.Both the two crossings are during steady northward IMF interval,whereas ion fluxes detected during the time period are quite different.The cusp in the first crossing is a typical northward-IMF one,with short...