Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A

Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1.     

Electrochemical processing of spent nuclear fuels: An overview of oxide reduction in pyroprocessing technology

The electrochemical reduction process has been used to reduce spent oxide fuel to a metallic form using pyroprocessing technology for a closed fuel cycle in combination with a metal-fuel fast reactor.In the electrochemical reduction process,oxides fuels are loaded at the cathode basket in molten Li_2O–LiCl salt and electrochemically reduced to the metal form.Various approaches based on thermodynamic calculations and experimental studies have been used to understand the electrode reaction and efficiently treat spent fuels.The factors that affect the speed of the electrochemical reduction have been determined to optimize the process and scale-up the electrolysis cell.In addition,demonstrations of the integrated series of processes(electrorefining and salt distillation) with the electrochemical reduction have been conducted to realize the oxide fuel cycle.This overview provides insight into the current status of and issues related to the electrochemical processing of spent nuclear fuels.     

The joining of ribosomal subunits in eukaryotes requires eIF5B

Initiation of eukaryotic protein synthesis begins with the ribosome separated into its 40S and 60S subunits. The 40S subunit first binds eukaryotic initiation factor (eIF) 3 and an eIF2-GTP-initiator transfer RNA ternary complex. The resulting complex requires eIF1, eIF1A, eIF4A, eIF4B and eIF4F to bind to a messenger RNA and to scan to the initiation codon. eIF5 stimulates hydrolysis of eIF2-bound GTP and eIF2 is released from the 48S complex formed at the initiation codon before it is joined by a 60S subunit to form an active 80S ribosome. Here we show that hydrolysis of eIF2-bound GTP induced by eIF5 in 48S complexes is necessary but not sufficient for the subunits to join. A second factor termed eIF5B (relative molecular mass 175,000) is essential for this process. It is a homologue of the prokaryotic initiation factor IF2 (re and, like it, mediates joining of subunits and has a ribosome-dependent GTPase activity that is essential for its function.     

基于可靠性的工程设计

现代结构要求更危险和更复杂的设计，需要精确地了解结构的载荷、几何、材料性能、制造过程和运行环境等的不确定性。可靠性评估技术可用来发展安全设计，并确定在结构系统中的不确定性所产生影响，然而通过进一步的研究、试验和质量控制来提高结构的安全性和功效。     

A role for graphene in silicon-based semiconductor devices

As silicon-based electronics approach the limit of improvements to performance and capacity through dimensional scaling, attention in the semiconductor field has turned to graphene, a single layer of carbon atoms arranged in a honeycomb lattice. Its high mobility of charge carriers (electrons and holes) could lead to its use in the next generation of high-performance devices. Graphene is unlikely to replace silicon completely, however, because of the poor on/off current ratio resulting from its zero bandgap. But it could be used to improve silicon-based devices, in particular in high-speed electronics and optical modulators.     

Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities

Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.     

The DNA sequence of human chromosome 21

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.     

定向生长碳纳米管的研究进展

由于碳纳米管具有独特的结构和性能，因而自从被发现以来一直受到人们的关注，近年来，已利用各种方法成合成出碳纳米管，特别是利用化学气相沉积（CVD）方法制备了高度准直的碳纳米管，实现了碳纳米管的定向生长，使得碳纳米管具有更加广泛的应用价值和研究价值。本文综述了近几年CVD定向生长碳纳米管的方法和生长机制，分析和讨论了不同制备方法对碳纳米管生长过程的影响，同时还着重分析了催化剂颗粒在碳纳米管的生长过程中对定向生长碳纳米管的作用。