Pseudovitamin D-deficiency rickets (PDDR) is an autosomal recessive disorder resulting from a defect in renal 25-hydroxyvitamin D 1α-hydroxylase, the key enzyme in the pathway of vitamin D metabolism. We identified ten different mutations in the 1α-hydroxylase gene (CYP27B1) in eight Chinese families with PDDR by DNA-sequence analysis. Six of them are novel missense mutations: G57V, G73W, L333F, R432C, R459C, R492W; three are novel deletion mutations: c48-60del, c1310delG, c1446delA; and an insertion mutation c1325-1332insCCCACCC reported previously. Functional assay revealed that the missense mutants identified in this study retain 5.5%~12.1% 1α-hydroxylase activity of the wild type . The study describes nine novel mutations in addition to 37 known mutations of CYP27B1 gene and shows the correlation between these mutations and the clinical findings of 1α-hydroxylase deficiency.

The χ_{b}(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider at sqrt[s]=7  TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4  fb^{-1}, these states are reconstructed through their radiative decays to Υ(1S,2S) with Υ→μ^{+}μ^{-}. In addition to the mass peaks corresponding to the decay modes χ_{b}(1P,2P)→Υ(1S)γ, a new structure centered at a mass of 10.530±0.005(stat)±0.009(syst)  GeV is also observed, in both the Υ(1S)γ and Υ(2S)γ decay modes. This structure is interpreted as the χ_{b}(3P) system.

Under investigation in this paper are the coupled nonlinear Schrödinger (CNLS) equations, which can be used to govern the optical-soliton propagation and interaction in such optical media as the multimode fibers, fiber arrays, and birefringent fibers. By taking the 3-CNLS equations as an example for the N-CNLS ones (N⩾3), we derive the analytic mixed-type two- and three-soliton solutions in more general forms than those obtained in the previous studies with the Hirota method and symbolic computation. With the choice of parameters for those soliton solutions, soliton interactions and complexes are investigated through the asymptotic and graphic analysis. Soliton interactions and complexes with the bound dark solitons in a mode or two modes are observed, including that (i) the two bright solitons display the breatherlike structures while the two dark ones stay parallel,(ii) the two bright and dark solitons all stay parallel, and (iii) the states of the bound solitons change from the breatherlike structures to the parallel one even with the distance between those solitons smaller than that before the interaction with the regular one soliton. Asymptotic analysis is also used to investigate the elastic and inelastic interactions between the bound solitons and the regular one soliton. Furthermore, some discussions are extended to the N-CNLS equations (N>3). Our results might be helpful in such applications as the soliton switch, optical computing, and soliton amplification in the nonlinear optics.

STING is an essential signaling molecule for DNA and cyclic di-GMP (c-di-GMP)-mediated type I interferon (IFN) production via TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) pathway. It contains an N-terminal transmembrane region and a cytosolic C-terminal domain (CTD). Here, we describe crystal structures of STING CTD alone and complexed with c-di-GMP in a unique binding mode. The strictly conserved aa 153-173 region was shown to be cytosolic and participated in dimerization via hydrophobic interactions. The STING CTD functions as a dimer and the dimerization was independent of posttranslational modifications. Binding of c-di-GMP enhanced interaction of a shorter construct of STING CTD (residues 139-344) with TBK1. This suggests an extra TBK1 binding site, other than serine 358. This study provides a glimpse into the unique architecture of STING and sheds light on the mechanism of c-di-GMP-mediated TBK1 signaling.

RNA editing can alter individual nucleotides in primary transcripts, which can cause the amino acids encoded by edited RNA to deviate from the ones predicted from the DNA template. We investigated RNA editing sites of protein-coding genes from the chloroplast genome of cotton. Fifty-four editing sites were identified in 27 transcripts, which is the highest editing frequency found until now in angiosperms. All these editing sites were C-to-U conversion, biased toward ndh genes and U_A context. Examining published editotypes in various angiosperms, we found that RNA editing mostly converts amino acid from hydrophilic to hydrophobic and restores evolutionary conserved amino acids. Using bioinformatics to analyze the effect of editing events on protein secondary and three-dimensional structures, we found that 21 editing sites can affect protein secondary structures and seven editing sites can alter three-dimensional protein structures. These results imply that 24 editing sites in cotton chloroplast transcripts may play an important role in their protein structures and functions.

STUDY OBJECTIVES: 1) To develop an in vitro system to simulate the kinetics of ionized calcium in mixed venous blood during rapid transfusion of fresh frozen plasma (FFP) and 2) to use the in vitro data to estimate the effect of the transfusion rate relative to cardiac output (CO) on ionized calcium. DESIGN: Experimental study. SETTING: Research laboratory of an academic hospital. MEASUREMENTS: Citrated FFP was mixed with compatible heparinized whole blood at various volume ratios in vitro to simulate the mixed venous blood obtained at various flow ratios of FFP transfusion to the recipient's venous system in vivo. Ionized calcium was measured after each mixture. MAIN RESULTS: Mixing FFP and whole blood at volume ratios of 0:100, 5:95, 10:90, and 15:85 yielded ionized calcium levels (mean ± SD, mmol/L) of 1.23, 0.81 ± 0.02, 0.54 ± 0.08, and 0.34 ± 0.02, respectively. The 50% reduction in ionized calcium occurred at a volume ratio of 7:93. CONCLUSIONS: An instantaneous 50% reduction in ionized calcium occurs in vitro at a proportion equivalent to a transfusion rate of FFP representing 7% of CO.

ABSTRACT: One-dimensional silicon nanowires (SiNWs) were prepared by electron beam evaporation inultrahigh vacuum (UHV). The SiNWs can be grown through either vapor-liquid-solid (VLS)or oxide-assisted growth (OAG) mechanism. In VLS growth, SiNWs can be formed on Sisurface, not on SiO2 surfaces. Moreover, low deposition rate is helpful for producing lateralSiNWs by VLS. But in OAG process, SiNWs can be grown on SiO2 surfaces, not on Sisurfaces. This work reveals the methods of producing large-scale SiNWs in UHV.

The activation of the NF-κB signaling pathway plays a critical role in carcinogenesis. The role of the NF-κB pathway in esophageal squamous cell carcinoma (ESCC) remains ill-defined. The objective was to detect whether p65siRNA and curcumin could promote ESCC cell apoptosis and increase the sensitivity of ESCC cells to chemotherapeutic drugs by inhibiting the NF-κB signaling pathway, and to compared these two treatments. In the present study, the status of the NF-κB pathway, in the two ESCC cell lines Eca109 and EC9706, was analyzed and the ability of p65 siRNA and curcumin alone or in combination with 5-FU to modulate this pathway in vitro and in vivo was investigated. The results showed that the NF-κB signaling pathway in the ESCC cell lines was constitutively activated. Both p65 siRNA and curcumin mediated suppression of activation of the NF-κB signaling pathway via inhibition of the expression of p65 or IκBα phosphorylation in ESCC cell lines. The cells treated with combination of p65 siRNA or curcumin and 5-FU revealed a lower cell viability and higher apoptosis compared to those treated with 5-FU alone. In a human ESCC xenograft model, p65 siRNA or curcumin and 5-FU alone reduced the tumor volume, respectively, but their combination had the strongest anticancer effects. Curcumin was more effective than p65 siRNA in vitro and in vivo. Overall, our results indicate that the constitutively activated NF-κB signaling pathway plays a crucial role in these two ESCC cell lines and both p65siRNA and curcumin can promote ESCC cell apoptosis and enhance the sensitivity to 5-FU through suppression of the NF-κB signaling pathway. It is still a long time before RNA interference will be used in the clinic. Therefore, curcumin is proved to be useful in the treatment of ESCC as it is a pharmacologically safe compound without side effects.

Chronic low-grade inflammation is crucial for the development of insulin resistance and type 2 diabetes mellitus (T2DM), and immunocompetent cells, such as T-cells, B-cells, mast cells and macrophages, regulate the pathogenesis of T2DM. However, little is known about the role of natural killer (NK) and natural killer T (NKT) cells in the pathogenic process of T2DM. A total of 16 patients with new onset T2DM and nine healthy subjects were recruited, and the frequency of peripheral blood activated and inhibitory NK and NKT cells in individual subjects was determined by flow cytometry. The frequency of spontaneous and inducible interferon gamma (IFN-γ) and CD107a(+) NK cells was further examined, and the potential association of the frequency of NK cells with clinical measures was analyzed. While there was no significant difference in the frequency of peripheral blood NK and NKT cells between patients and controls, the frequency of NKG2D(+) NK and NKT cells in patients was significantly higher than those in the controls (P = 0.011). In contrast, the frequency of NKG2A(+) and KIR2DL3(+) inhibitory NK and NKT cells in patients was significantly lower than those in the controls (P = 0.002, P < 0.0001, respectively). Furthermore, the frequencies of NKG2D(+) NK cells were correlated significantly with the values of body mass index in patients. Moreover, the frequencies of spontaneous and inducible CD107a(+), but not IFN-γ-secreting, NK cells in patients were significantly higher than those in the controls (P < 0.004, P < 0.0001). Our data indicated that a higher frequency of activated NK cells may participate in the obesity-related chronic inflammation involved in the pathogenesis of T2DM.

PURPOSE: To understand the role of mitochondrial DNA (mtDNA) mutations in patients with polycystic ovary syndrome (PCOS). METHODS: A total of 57 women with PCOS and 38 controls were recruited in this study, mutational analysis of mitochondrial genome was performed using polymerase chain reaction and under a direct sequence analysis. RESULTS: Sequence characterization of mitochondrial genome showed a distinct set of polymorphisms mainly focused on oxidative phosphorylation (OXPHOS) complex, in addition, six variants in mitochondrial tRNA genes, including tRNA(Gln), tRNA(Cys), tRNA(Asp), tRNA(Lys), tRNA(Arg) and tRNA(Glu) were also identified in PCOS patients. Interestingly, these variants occurred at highly conserved nucleotides of corresponding tRNAs, which are important for tRNA stability level and biochemical function. CONCLUSIONS: Mutations in mtDNA, especially the OXPHOS complex and tRNAs, may be associated with PCOS patients, thus, our results shed new insight into the pathogenesis of PCOS.