Perinatal lethal osteogenesis imperfecta in transgenic mice bearing an engineered mutant pro-alpha 1(I) collagen gene

Substitutions of single glycine residues of alpha 1(I) collagen have previously been associated with the inherited disease osteogenesis imperfecta type II. Transgenic mice bearing a mutant alpha 1(I) collagen gene into which specific glycine substitutions have been engineered show a dominant lethal phenotype characteristic of the human disease, and demonstrate that as little as 10% mutant gene expression can disrupt normal collagen function.     

Structure of Sindbis virus core protein reveals a chymotrypsin-like serine proteinase and the organization of the virion

Sindbis virus consists of a nucleocapsid core surrounded by a lipid membrane through which penetrate 80 glycoprotein trimers. The structure of the core protein comprising the coat surrounding the genomic RNA has been determined. The polypeptide fold from residue 114 to residue 264 is homologous to that of chymotrypsin-like serine proteinases with catalytic residues His 141, Asp 163 and Ser 215 of the core protein positioned as in other serine proteinases. The C-terminal tryptophan remains in the P1 substrate site subsequent to the autocatalytic cis cleavage of the capsid protein, thus rendering the proteinase inactive. Model building of the Sindbis core protein dimer shows that the nucleocapsid is likely to have T = 4 quasisymmetry.     

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.     

Effect of hypoxia on human adipose-derived mesenchymal stem cells and its potential clinical applications

Human adipose-derived mesenchymal stem cells (hASCs) are an ideal cell source for regenerative medicine due to their capabilities of multipotency and the readily accessibility of adipose tissue. They have been found residing in a relatively low oxygen tension microenvironment in the body, but the physiological condition has been overlooked in most studies. In light of the escalating need for culturing hASCs under their physiological condition, this review summarizes the most recent advances in the hypoxia effect on hASCs. We first highlight the advantages of using hASCs in regenerative medicine and discuss the influence of hypoxia on the phenotype and functionality of hASCs in terms of viability, stemness, proliferation, differentiation, soluble factor secretion, and biosafety. We provide a glimpse of the possible cellular mechanism that involved under hypoxia and discuss the potential clinical applications. We then highlight the existing challenges and discuss the future perspective on the use of hypoxic-treated hASCs.     

Swiprosin-1 modulates actin dynamics by regulating the F-actin accessibility to cofilin

Membrane protrusions, like lamellipodia, and cell movement are dependent on actin dynamics, which are regulated by a variety of actin-binding proteins acting cooperatively to reorganize actin filaments. Here, we provide evidence that Swiprosin-1, a newly identified actin-binding protein, modulates lamellipodial dynamics by regulating the accessibility of F-actin to cofilin. Overexpression of Swiprosin-1 increased lamellipodia formation in B16F10 melanoma cells, whereas knockdown of Swiprosin-1 inhibited EGF-induced lamellipodia formation, and led to a loss of actin stress fibers at the leading edges of cells but not in the cell cortex. Swiprosin-1 strongly facilitated the formation of entangled or clustered F-actin, which remodeled the structural organization of actin filaments making them inaccessible to cofilin. EGF-induced phosphorylation of Swiprosin-1 at Ser183, a phosphorylation site newly identified using mass spectrometry, effectively inhibited clustering of actin filaments and permitted cofilin access to F-actin, resulting in actin depolymerization. Cells overexpressing a Swiprosin-1 phosphorylation-mimicking mutant or a phosphorylation-deficient mutant exhibited irregular membrane dynamics during the protrusion and retraction cycles of lamellipodia. Taken together, these findings suggest that dynamic exchange of Swiprosin-1 phosphorylation and dephosphorylation is a novel mechanism that regulates actin dynamics by modulating the pattern of cofilin activity at the leading edges of cells.     

Isolation and characterization of biologically active lectin from Korean mistletoe, Viscum album var. Coloratum

A mistletoe lectin was isolated from water extracts of Korean mistletoe, a subspecies of Viscum album, grown on Quercus mongolica using CM-Sepharose chromatography followed by an affinity chromatography on a concanavalin A-Sepharose column. The compound proved to be a mistletoe lectin II with D-galactose and N-acetyl-D-galactosamine specificity. Matrix-assisted laser desorption time-of-flight mass spectroscopy showed it to have an average molecular mass of 62.7 kDa and to consist of two subunits of 30.6 kDa and 32.5 kDa. It was a basic protein with isoelectric points of 9.4 and 9.6 by capillary isoelectric focusing and was cytotoxic to Molt4 cell. Received 17 November 1998; received after revision 3 March 1999; accepted 3 March 1999     

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。     

Sediment provenance and evolution of the East Asian winter monsoon since 700 ka recorded by major elements in the West Philippine Sea

To synthetically realize the character of major-element compositions as well as its significance for provenance and paleoenvironment recorded in core sediments of the West Philippine Sea over the last 700 ka,grain size and major elements of 221 bulk sediments,together with major-element compositions in the detrital phase of 16 typical samples,in core MD06-3047 collected from the Benham Rise were analyzed.Both discrimination plot and R-mode factor analysis indicate that vertical changes of major elements are mainly controlled by the sedimentation of nearby volcanic matter and the eolian dust input,whereas influences from marine biologic deposition and hydrothermal activity are minor.In particular,Al2O3 and K2O are representative of an eolian dust factor.The variation in the eolian dust factor score is characterized by the obviously glacial-interglacial periodicity and can be well compared with the paleotemperature record of the Antarctic ice core and the evolution of the East Asian winter monsoon(EAWM) recorded in the Chinese loess sequence,and then offers a new proxy for the evolution history of eolian dust input into the study area that is controlled by the EAWM intensity and aridity in the continental source regions of atmospheric dust.     

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.