ABSTRACT
Bioluminescence has been drawing broad attention due to its high signal-to-noise ratio and high bioluminescence quantum yields, which has been widely applied in the fields of biomedicine, bioanalysis, and so on. Among numerous bioluminescent substrates, coelenterazine is famous for its wide distribution. However, the oxygenation reaction mechanism of coelenterazine is far from being completely understood. In this paper, the formation and decomposition mechanisms of coelenterazine dioxetanone were investigated via density functional theory (DFT) and time-dependent (TD) DFT approaches. The results showed that the oxygenation reaction first occurred along the triplet-state potential energy surface (PES), after the intersystem crossing (ISC), second jumped to the diradical-state PES, and ultimately formed coelenterazine dioxetanone. For the decomposition mechanism of dioxetanone, the computational results showed that the chemiexcitation of neutral dioxetanone was more efficient than that of other dioxetanone species. Moreover, the diradical properties and the degree of ionic character are modified by the counter ions.
ABSTRACT
AIM: To investigate the polymorphism of KIR genes in systemic lupus erythematosus (SLE) patients, and to study the correlation between KIR genes and susceptibility of SLE. METHODS: The polymorphism of KIR genes were detected by PCR-SSP technique in 62 patients with SLE and 61 healthy persons as controls from North of China. RESULTS: The differences of KIR frequency between the SLE group and the control were tested by statistical analysis. The most frequent genotype was KIR 3DP1, 2DL1, 2DP1, 3DL1, 2DL3, 1D, followed by 2DS4, 2DL5, 3DS1, 2DS2, 2DS5 and 2DL2. KIR 2DS1, 2DS3 and 3DP1v were lower in frequency compared with others. The frequency of KIR 3DS1, 2DL2, 2DL5 and 2DL3 were significantly lower in SLE group than that in the control èP<0.01é. CONCLUSION: There may be a association between the polymorphism of KIR genes with SLE in North of China should be investigated further.
Subject(s)
Lupus Erythematosus, Systemic/genetics , Polymorphism, Genetic/genetics , Receptors, KIR/genetics , Adult , China , Female , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Humans , Male , Middle Aged , Polymerase Chain ReactionABSTRACT
The structures and stabilities of square-hexagon alternant boron nitrides (Bx Nx , x=12-36) vs their tube isomers containing octagons, decagons and dodecagons have been computed at the B3LYP density functional level of theory with the correlation-consistent cc-pVDZ basis set of Dunning. It is found that octagonal B20N20 and B24N24 tube structures are more stable than their square-hexagon alternants by 18.6 and 2.4 kcal mol(-1), respectively, while the square-hexagon alternants of other cages are more stable. Trends in stability as a function of cluster size are discussed.
Subject(s)
Boron Compounds/chemistry , Imaging, Three-Dimensional , Models, Molecular , Molecular ConformationABSTRACT
Neurons and glia in the vertebrate central nervous system arise in temporally distinct, albeit overlapping, phases. Neurons are generated first followed by astrocytes and oligodendrocytes from common progenitor cells. Increasing evidence indicates that axon-derived signals spatiotemporally modulate oligodendrocyte maturation and myelin formation. Our previous observations demonstrate that F3/contactin is a functional ligand of Notch during oligodendrocyte maturation, revealing the existence of another group of Notch ligands. Here, we establish that NB-3, a member of the F3/contactin family, acts as a novel Notch ligand to participate in oligodendrocyte generation. NB-3 triggers nuclear translocation of the Notch intracellular domain and promotes oligodendrogliogenesis from progenitor cells and differentiation of oligodendrocyte precursor cells via Deltex1. In primary oligodendrocytes, NB-3 increases myelin-associated glycoprotein transcripts. Thus, the NB-3/Notch signaling pathway may prove to be a molecular handle to treat demyelinating diseases.
Subject(s)
Carrier Proteins/physiology , Cell Adhesion Molecules, Neuronal/physiology , Neurons/cytology , Oligodendroglia/cytology , Receptors, Cell Surface/physiology , Stem Cells/cytology , Transcription Factors , Active Transport, Cell Nucleus , Animals , Cell Differentiation , Cells, Cultured , Contactins , Mice , Mice, Inbred BALB C , Rats , Rats, Wistar , Receptor, Notch1 , Signal TransductionABSTRACT
Axon-derived molecules are temporally and spatially required as positive or negative signals to coordinate oligodendrocyte differentiation. Increasing evidence suggests that, in addition to the inhibitory Jagged1/Notch1 signaling cascade, other pathways act via Notch to mediate oligodendrocyte differentiation. The GPI-linked neural cell recognition molecule F3/contactin is clustered during development at the paranodal region, a vital site for axoglial interaction. Here, we show that F3/contactin acts as a functional ligand of Notch. This trans-extracellular interaction triggers gamma-secretase-dependent nuclear translocation of the Notch intracellular domain. F3/Notch signaling promotes oligodendrocyte precursor cell differentiation and upregulates the myelin-related protein MAG in OLN-93 cells. This can be blocked by dominant negative Notch1, Notch2, and two Deltex1 mutants lacking the RING-H2 finger motif, but not by dominant-negative RBP-J or Hes1 antisense oligonucleotides. Expression of constitutively active Notch1 or Notch2 does not upregulate MAG. Thus, F3/contactin specifically initiates a Notch/Deltex1 signaling pathway that promotes oligodendrocyte maturation and myelination.
