Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo

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Genome-wide analysis of the Chinese sturgeon sox gene family: identification,characterisation and expression profiles of different tissues

The sox family is assumed to be responsible for a number of developmental systems. Genome sequencing technology makes it possible to scan sox genes and conduct characteristic analyses of different species. In fish, full characterisation of sox genes at the genome-wide level has been reported for pufferfish Takifugu rubripes, medaka Oryzias latipes, tilapia Oreochromis niloticus and channel catfish Ictalurus punctatus. However, no systematic investigation of the sox family in sturgeons (Acipenseridae) has been reported to date. This study conducted genome-wide identification of the sox genes in the Chinese sturgeon Acipenser sinensis and profiled their tissue distribution between male and female individuals. In total, 19 sox genes were identified, including soxb1, b2, c, d, e, f and h, in the Chinese sturgeon. Genomic structure analysis indicated relatively conserved exon–intron structures in each sox group and phylogenetic analysis supported the previous classification of the sox family. Most of the sox genes showed a tissue-specific expression pattern, indicating the possible involvement of Chinese sturgeon sox genes at different developmental processes such as cardiac and gonadal development. This study provides a comprehensive resource of Chinese sturgeon sox genes and enables a better understanding of the evolution and function of the sox family.     

Recent progress in artificial receptors for phosphate anions in aqueous solution

Phosphate esters exist ubiquitously in nature in the form of nucleoside phosphates (nucleotides) as components of RNA (or DNA), sugar nucleotides for glycosylation of oligosaccharides or proteins, activated form of proteins responding to extracellular signals, and chemical mediators playing central roles in intracellular signaling signals. Phosphorylation of anti-viral nucleoside analogues by intracellular kinases yields nucleoside phosphates (nucleotide) as biologically active forms as anti-viral agents. Development of artificial phosphate receptors would afford new methodologies for detection, separation, or transport of biologically important phosphates. Herein, a recent progress of artificial phosphate receptors is reviewed with special focus on macrocyclic polyamines and their metal complexes as a new prototype. In comparison to most of the previous artificial receptors (most of them are organic molecules), our system characteristically works in aqueous solution at neutral pH with extremely strong affinities with phosphate anions. Moreover, zinc(II)-macrocyclic tetraamine (cyclen) complexes were discovered to selectively bind thymine and uracil, so that nucleotides of these bases are specifically recognized by the bis(Zn2+-cyclen) complexes.     

Modeling Calcium Wave Based on Anomalous Subdiffusion of Calcium Sparks in Cardiac Myocytes

sparks and waves play important roles in calcium release and calcium propagation during the excitation-contraction (EC) coupling process in cardiac myocytes. Although the classical Fick’s law is widely used to model sparks and waves in cardiac myocytes, it fails to reasonably explain the full-width at half maximum(FWHM) paradox. However, the anomalous subdiffusion model successfully reproduces sparks of experimental results. In this paper, in the light of anomalous subdiffusion of sparks, we develop a mathematical model of calcium wave in cardiac myocytes by using stochastic release of release units (CRUs). Our model successfully reproduces calcium waves with physiological parameters. The results reveal how concentration waves propagate from an initial firing of one CRU at a corner or in the middle of considered region, answer how large in magnitude of an anomalous spark can induce a wave. With physiological currents (2pA) through CRUs, it is shown that an initial firing of four adjacent CRUs can form a wave. Furthermore, the phenomenon of calcium waves collision is also investigated.     

Screening of promoters from metagenomic DNA and their use for the construction of expression vectors

This study was focused on the screening of valuable genetic resources, such as promoters from metagenome, and describes a promoter trapping system with a bidirectional probe concept, which can select promoters or operons from various biological resources including metagenomic DNA. A pair of reporters, GFP and DsRed, facing the opposite direction without promoters, is an effective system that can function regardless of the direction of inserted promoters. The feasibility of this system was tested for the isolation of constitutively expressed promoters in E. coli from a soil metagenome, resulting in a potential pool of various promoters for practical application. The analyses of structural organization of the trapped genes demonstrated that constitutively expressible promoters in E. coli were broadly distributed within the metagenome, and suggested that some promoters were useful for the construction of expression vectors. Based on these observations, three constitutive promoters were employed in the expression vector system and their potentials for practical application were evaluated in terms of expression level, protein solubility, and effects on host growth.     

Syntheses of sphingosine-1-phosphate stereoisomers and analogues and their interaction with EDG receptors

Sphingosine-1-phosphate (S1P) is considered to be an important regulator of diverse biological processes acting as a natural ligand to EDG receptors. As a preliminary study to develop potent and selective agonist and antagonist for EDG receptors, we report synthesis of S1P stereoisomers and analogues and their binding affinities to EDG-1, -3, and -5.     

Simvastatin potentiates TNF-alpha-induced apoptosis through the down-regulation of NF-kappaB-dependent antiapoptotic gene products: role of IkappaBalpha kinase and TGF-beta-activated kinase-1

Numerous recent reports suggest that statins (hydroxy-3-methylglutaryl-CoA reductase inhibitors) exhibit potential to suppress tumorigenesis through a mechanism that is not fully understood. Therefore, in this article, we investigated the effects of simvastatin on TNF-alpha-induced cell signaling. We found that simvastatin potentiated the apoptosis induced by TNF-alpha as indicated by intracellular esterase activity, caspase activation, TUNEL, and annexin V staining. This effect of simvastatin correlated with down-regulation of various gene products that mediate cell proliferation (cyclin D1 and cyclooxygenase-2), cell survival (Bcl-2, Bcl-x(L), cellular FLIP, inhibitor of apoptosis protein 1, inhibitor of apoptosis protein 2, and survivin), invasion (matrix mellatoproteinase-9 and ICAM-1), and angiogenesis (vascular endothelial growth factor); all known to be regulated by the NF-kappaB. We found that simvastatin inhibited TNF-alpha-induced NF-kappaB activation, and l-mevalonate reversed the suppressive effect, indicating the role of hydroxy-3-methylglutaryl-CoA reductase. Simvastatin suppressed not only the inducible but also the constitutive NF-kappaB activation. Simvastatin inhibited TNF-alpha-induced IkappaBalpha kinase activation, which led to inhibition of IkappaBalpha phosphorylation and degradation, suppression of p65 phosphorylation, and translocation to the nucleus. NF-kappaB-dependent reporter gene expression induced by TNF-alpha, TNFR1, TNFR-associated death domain protein, TNFR-associated factor 2, TGF-beta-activated kinase 1, receptor-interacting protein, NF-kappaB-inducing kinase, and IkappaB kinase beta was abolished by simvastatin. Overall, our results provide novel insight into the role of simvastatin in potentially preventing and treating cancer through modulation of IkappaB kinase and NF-kappaB-regulated gene products.