Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement

Embryonic cell movement is essential for morphogenesis and the establishment of body shapes, but little is known about its mechanism. Here we report that pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc), functions in promoting cell migration during epiboly. Epiboly is a process in which embryonic cells spread from the animal pole to cover the underlying yolk. During epiboly, cyp11a1 is expressed in an extra-embryonic yolk syncytial layer. Reducing cyp11a1 expression in zebrafish using antisense morpholino oligonucleotides did not perturb cell fates, but caused epibolic delay. This epibolic defect was partially rescued by the injection of cyp11a1 RNA or the supplementation of pregnenolone. We show that the epibolic delay is accompanied by a decrease in the level of polymerized microtubules, and that pregnenolone can rescue this microtubule defect. Our results indicate that pregnenolone preserves microtubule abundance and promotes cell movement during epiboly.     

Altered proteostasis in aging and heat shock response in C. elegans revealed by analysis of the global and de novo synthesized proteome

Protein misfolding and aggregation as a consequence of impaired protein homeostasis (proteostasis) not only characterizes numerous age-related diseases but also the aging process itself. Functionally related to the aging process are, among others, ribosomal proteins, suggesting an intimate link between proteostasis and aging. We determined by iTRAQ quantitative proteomic analysis in C. elegans how the proteome changes with age and in response to heat shock. Levels of ribosomal proteins and mitochondrial chaperones were decreased in aged animals, supporting the notion that proteostasis is altered during aging. Mitochondrial enzymes of the tricarboxylic acid cycle and the electron transport chain were also reduced, consistent with an age-associated energy impairment. Moreover, we observed an age-associated decline in the heat shock response. In order to determine how protein synthesis is altered in aging and in response to heat shock, we complemented our global analysis by determining the de novo proteome. For that, we established a novel method that enables both the visualization and identification of de novo synthesized proteins, by incorporating the non-canonical methionine analogue, azidohomoalanine (AHA), into the nascent polypeptides, followed by reacting the azide group of AHA by ‘click chemistry’ with an alkyne-labeled tag. Our analysis of AHA-tagged peptides demonstrated that the decreased abundance of, for example, ribosomal proteins in aged animals is not solely due to degradation but also reflects a relative decrease in their synthesis. Interestingly, although the net rate of protein synthesis is reduced in aged animals, our analyses indicate that the synthesis of certain proteins such as the vitellogenins increases with age.     

Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis

Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil. Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region. We have identified a new gene (EVC), encoding a 992-amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic conditions.     

日本

现在来看看G7成员国之一、亚洲的传统科技领袖——日本的表现.二战后,日本的重建进展迅猛,人口激增,在整个国家工业化环境塑造下的婴儿潮一代成长为推动上世纪六七十年代日本经济快速发展的中坚力量.日本以生产高质量创意工业产品为基础建立起良好的声誉,并在80年代达到经济巅峰,然而随后便进入了被称之为“丢失的10年”的发展停滞期...     

Human embryonic stem cell lines derived from single blastomeres

The derivation of human embryonic stem (hES) cells currently requires the destruction of ex utero embryos. A previous study in mice indicates that it might be possible to generate embryonic stem (ES) cells using a single-cell biopsy similar to that used in preimplantation genetic diagnosis (PGD), which does not interfere with the embryo's developmental potential. By growing the single blastomere overnight, the resulting cells could be used for both genetic testing and stem cell derivation without affecting the clinical outcome of the procedure. Here we report a series of ten separate experiments demonstrating that hES cells can be derived from single blastomeres. In this proof-of-principle study, multiple biopsies were taken from each embryo using micromanipulation techniques and none of the biopsied embryos were allowed to develop in culture. Nineteen ES-cell-like outgrowths and two stable hES cell lines were obtained. The latter hES cell lines maintained undifferentiated proliferation for more than eight months, and showed normal karyotype and expression of markers of pluripotency, including Oct-4, SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, nanog and alkaline phosphatase. These cells retained the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. The ability to create new stem cell lines and therapies without destroying embryos would address the ethical concerns of many, and allow the generation of matched tissue for children and siblings born from transferred PGD embryos.     

Modeling an Elastic-Demand Bimodal Transport Network with Park-and-Ride Trips

This paper presents a network equilibrium formulation for modeling commuters＇ travel choices in a bimodal transport system with park-and-ride （P＆R） trips while the total demand is elastic to the congestion level of the network. A super-network approach is adopted in the proposed model. It is assumed that commuters＇ trips are categorized into two types, auto mode only and a combined mode with both auto and transit modes. The former is referred to as the pure mode trip and the latter as the P＆R mode trip. The proposed model simultaneously considers the commuter＇s choice of the pure mode versus the P＆R mode, the choice of parking location for the pure mode, the choice of transfer point for the P＆R mode, as well as the route choice for each mode. The demand elasticity of transport system, the capacity constraints of transport facilities, and the congestion interaction throughout the super-network are also explicitly incorporated into the proposed model. The results of the numerical experiment show the following key findings： （i） traditional parking/P＆R models may overestimate or underestimate travel demand distribution over network; （ii） parking/P＆R, transit scheduling, and carpooling schemes bring significant impacts on commuters＇ travel behavior and network performance; and （iii） different transport policies may be to some extent mutually substituted .     

Te对高温超导陶瓷YBa4Cu6Oy超导电性的影响

对YBa_4Cu_6Oy陶瓷的研究表明,它具有与YBa_2Cu_3O_(7-δ)凸相近的超导电性。以CuTeO_3方式加入适量的Te使它的临界电流密度Jc增加近一个量级而Tc仍保持在90k附近。