Regulation of male sex determination: genital ridge formation and Sry activation in mice

Sex determination is essential for the sexual reproduction to generate the next generation by the formation of functional male or female gametes. In mammals, primary sex determination is commenced by the presence or absence of the Y chromosome, which controls the fate of the gonadal primordium. The somatic precursor of gonads, the genital ridge is formed at the mid-gestation stage and gives rise to one of two organs, a testis or an ovary. The fate of the genital ridge, which is governed by the differentiation of somatic cells into Sertoli cells in the testes or granulosa cells in the ovaries, further determines the sex of an individual and their germ cells. Mutation studies in human patients with disorders of sex development and mouse models have revealed factors that are involved in mammalian sex determination. In most of mammals, a single genetic trigger, the Y-linked gene Sry (sex determination region on Y chromosome), regulates testicular differentiation. Despite identification of Sry in 1990, precise mechanisms underlying the sex determination of bipotential genital ridges are still largely unknown. Here, we review the recent progress that has provided new insights into the mechanisms underlying genital ridge formation as well as the regulation of Sry expression and its functions in male sex determination of mice.     

基于VLBI和GPS测量2009年7月22日日全食期间电离层TEC变化

2009年7月22日上午发生的日全食是21世纪全食持续时间最长的日全食,跨越了中国北纬约30°的广大地区,为研究太阳对地球电离层的影响提供了一次难得的机会.上海位于此次日全食带中心线附近.为此,上海佘山站、乌鲁木齐南山站和日本鹿岛站开展了VLBI联合观测实验.与此同时,TEC测量还配合使用了GPS观测站.本文介绍了此次日全食观测实验的背景、测量方案、观测实验详情和数据处理流程.根据相关处理结果,利用二维条纹搜索方法在上海一乌鲁木齐基线获得了优质干涉条纹,预示着VLBI测量取得成功.对单站GPS数据的初步分析表明.日全食食甚时刻TEC值存在快速下降.此次观测实验预期将首次获得电离层TEC变化的VLBI实测结果.并开展VLBI与GPS测量结果的比较研究.     

Spin crossover and iron-rich silicate melt in the Earth's deep mantle

A melt has greater volume than a silicate solid of the same composition. But this difference diminishes at high pressure, and the possibility that a melt sufficiently enriched in the heavy element iron might then become more dense than solids at the pressures in the interior of the Earth (and other terrestrial bodies) has long been a source of considerable speculation. The occurrence of such dense silicate melts in the Earth's lowermost mantle would carry important consequences for its physical and chemical evolution and could provide a unifying model for explaining a variety of observed features in the core-mantle boundary region. Recent theoretical calculations combined with estimates of iron partitioning between (Mg,Fe)SiO(3) perovskite and melt at shallower mantle conditions suggest that melt is more dense than solids at pressures in the Earth's deepest mantle, consistent with analysis of shockwave experiments. Here we extend measurements of iron partitioning over the entire mantle pressure range, and find a precipitous change at pressures greater than ～76?GPa, resulting in strong iron enrichment in melts. Additional X-ray emission spectroscopy measurements on (Mg(0.95)Fe(0.05))SiO(3) glass indicate a spin collapse around 70?GPa, suggesting that the observed change in iron partitioning could be explained by a spin crossover of iron (from high-spin to low-spin) in silicate melt. These results imply that (Mg,Fe)SiO(3) liquid becomes more dense than coexisting solid at ～1,800?km depth in the lower mantle. Soon after the Earth's formation, the heat dissipated by accretion and internal differentiation could have produced a dense melt layer up to ～1,000?km in thickness underneath the solid mantle. We also infer that (Mg,Fe)SiO(3) perovskite is on the liquidus at deep mantle conditions, and predict that fractional crystallization of dense magma would have evolved towards an iron-rich and silicon-poor composition, consistent with seismic inferences of structures in the core-mantle boundary region.     

Structural basis for recognition of acidic-cluster dileucine sequence by GGA1

GGAs (Golgi-localizing, gamma-adaptin ear homology domain, ARF-interacting proteins) are critical for the transport of soluble proteins from the trans-Golgi network (TGN) to endosomes/lysosomes by means of interactions with TGN-sorting receptors, ADP-ribosylation factor (ARF), and clathrin. The amino-terminal VHS domains of GGAs form complexes with the cytoplasmic domains of sorting receptors by recognizing acidic-cluster dileucine (ACLL) sequences. Here we report the X-ray structure of the GGA1 VHS domain alone, and in complex with the carboxy-terminal peptide of cation-independent mannose 6-phosphate receptor containing an ACLL sequence. The VHS domain forms a super helix with eight alpha-helices, similar to the VHS domains of TOM1 and Hrs. Unidirectional movements of helices alpha6 and alpha8, and some of their side chains, create a set of electrostatic and hydrophobic interactions for correct recognition of the ACLL peptide. This recognition mechanism provides the basis for regulation of protein transport from the TGN to endosomes/lysosomes, which is shared by sortilin and low-density lipoprotein receptor-related protein.     

Deletion of Peg10, an imprinted gene acquired from a retrotransposon, causes early embryonic lethality

By comparing mammalian genomes, we and others have identified actively transcribed Ty3/gypsy retrotransposon-derived genes with highly conserved DNA sequences and insertion sites. To elucidate the functions of evolutionarily conserved retrotransposon-derived genes in mammalian development, we produced mice that lack one of these genes, Peg10 (paternally expressed 10), which is a paternally expressed imprinted gene on mouse proximal chromosome 6. The Peg10 knockout mice showed early embryonic lethality owing to defects in the placenta. This indicates that Peg10 is critical for mouse parthenogenetic development and provides the first direct evidence of an essential role of an evolutionarily conserved retrotransposon-derived gene in mammalian development.     

Role of retrotransposon-derived imprinted gene, Rtl1, in the feto-maternal interface of mouse placenta

Eutherian placenta, an organ that emerged in the course of mammalian evolution, provides essential architecture, the so-called feto-maternal interface, for fetal development by exchanging nutrition, gas and waste between fetal and maternal blood. Functional defects of the placenta cause several developmental disorders, such as intrauterine growth retardation in humans and mice. A series of new inventions and/or adaptations must have been necessary to form and maintain eutherian chorioallantoic placenta, which consists of capillary endothelial cells and a surrounding trophoblast cell layer(s). Although many placental genes have been identified, it remains unknown how the feto-maternal interface is formed and maintained during development, and how this novel design evolved. Here we demonstrate that retrotransposon-derived Rtl1 (retrotransposon-like 1), also known as Peg11 (paternally expressed 11), is essential for maintenance of the fetal capillaries, and that both its loss and its overproduction cause late-fetal and/or neonatal lethality in mice.     

SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations

We conducted a genome-wide association study using 207,097 SNP markers in Japanese individuals with type 2 diabetes and unrelated controls, and identified KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) to be a strong candidate for conferring susceptibility to type 2 diabetes. We detected consistent association of a SNP in KCNQ1 (rs2283228) with the disease in several independent case-control studies (additive model P = 3.1 x 10(-12); OR = 1.26, 95% CI = 1.18-1.34). Several other SNPs in the same linkage disequilibrium (LD) block were strongly associated with type 2 diabetes (additive model: rs2237895, P = 7.3 x 10(-9); OR = 1.32, 95% CI = 1.20-1.45, rs2237897, P = 6.8 x 10(-13); OR = 1.41, 95% CI = 1.29-1.55). The association of these SNPs with type 2 diabetes was replicated in samples from Singaporean (additive model: rs2237895, P = 8.5 x 10(-3); OR = 1.14, rs2237897, P = 2.4 x 10(-4); OR = 1.22) and Danish populations (additive model: rs2237895, P = 3.7 x 10(-11); OR = 1.24, rs2237897, P = 1.2 x 10(-4); OR = 1.36).     

预蠕变损伤对高温疲劳宏观裂纹扩展的影响

针对ＳＵＳ３０４不锈钢光滑试棒预先导入１０７３ Ｋ·ｃｐ－ｔｙｐｅ条件下的预蠕变疲劳损伤，然后开小切口进行时间依存性 ９２３ Ｋ·ｃｐ－ｔｙｐｅ，１０７３ Ｋ·ｃｐ－ｔｙｐｅ及循环数依存性９２３ Ｋ·ｐｐ－ｔｙｐｅ的宏观裂纹扩展试验，考察了试棒内部因预蠕变疲劳而产生的大量的粒界微小裂纹对高温疲劳宏观裂纹扩展的影响．结果如下： １．预损伤加速了９２３ Ｋ·ｃｐ－ｔｙｐｅ下的蠕变裂纹扩展，对于同一蠕变Ｊ积分范围△Ｊｃ，损伤值越大，裂纹扩展速度ｄｌ／ｄＮ也越大．这种加速起因于主裂纹与微小裂纹的合体． ２．１０７３ Ｋ·ｃｐ－ｔｙｐｅ下的预损伤材料和处女材料的ｄｌ／ｄＮ在同一△Ｊｃ。下相等．即，损伤材料的裂纹扩展速度的上限值由１０７３ Ｋ·ｃｐ－ｔｙｐｅ下的处女材料的ｄｌ／ｄＮ－△Ｊｃ关系给出． ３．在９２３ Ｋ·ｐｐ－ｔｙｐｅ条件下，对于同一疲劳Ｊ积分范围△Ｊｆ，预损伤材料的ｄｌ／ｄＮ要比处女材料快１０倍左右．一般ｐｐ－ｔｙｐｅ的破坏形式为粒内破坏．预损伤材料的场合，因为试棒内部分布有大量的微小粒界裂纹，主裂纹便沿这些破坏阻抗最小的微小裂纹边合体边扩展，主要在粒界上扩展．即微小粒界裂纹是裂纹扩展阻抗减小的主因．     

Alpha-synuclein elicits glucose uptake and utilization in adipocytes through the Gab1/PI3K/Akt transduction pathway

Insulin is the main glucoregulator that promotes the uptake of glucose by tissues and the subsequent utilization of glucose as an energy source. In this paper, we describe a novel glucoregulator, the alpha-synuclein (SNCA) protein, that has previously been linked to Parkinson’s disease. Treatment with recombinant SNCA promotes glucose uptake in vitro in preadipocytes and in vivo in the adipose tissues and skeletal muscles of mice through the LPAR2/Gab1/PI3K/Akt pathway; these effects occur independently of the insulin receptor. This function of SNCA represents a new mechanistic insight that creates novel avenues of research with respect to the process of glucose regulation.