10 research outputs found
Solvent Effects upon Guest Binding and Dynamics of a Fe<sup>II</sup><sub>4</sub>L<sub>4</sub> Cage
Solvent-dependent host–guest
chemistry and favoring of otherwise
disfavored conformations of large guests has been achieved with an
adaptive, self-assembled Fe<sup>II</sup><sub>4</sub>L<sub>4</sub> coordination
cage. Depending on the counterion, this face-capped tetrahedral capsule
is soluble either in water or in acetonitrile and shows a solvent-dependent
preference for encapsulation of certain classes of guest molecules.
Quantitative binding studies were undertaken, revealing that both
aromatic and aliphatic guests bind in water, whereas only aliphatic
guests bind in acetonitrile. The flexibility of its subcomponent building
blocks allows this cage to expand or contract upon guest binding,
as studied by VT-NMR, thereby ensuring strong binding of both small
and large guests. Upon encapsulation, large guest molecules can adopt
conformations which are not thermodynamically favored in the free
state. In addition, the chirotopic inner phase of the cage renders
enantiotopic guest proton signals diastereotopic in specific cases
Synthesis and Cavity Size Effect of Pd-Containing Macrocycle Catalyst for Efficient Intramolecular Hydroamination of Allylurethane
Palladium-containing macrocycle catalysts
(<b>PdMCs</b>)
with different ring sizes ranging from 24 to 30 members were synthesized.
The intramolecular hydroamination of an allylurethane (<b>AU</b>) catalyzed by <b>PdMCs</b> proceeded efficiently to afford
the corresponding oxazolidinone (<b>OZ</b>) in 95% isolated
yield. The dependence of the hydroamination of <b>AU</b> to <b>OZ</b> on the cavity size indicated that the reaction rate was
clearly controlled by both substrate uptake and product release steps
Solvent Effects upon Guest Binding and Dynamics of a Fe<sup>II</sup><sub>4</sub>L<sub>4</sub> Cage
Solvent-dependent host–guest
chemistry and favoring of otherwise
disfavored conformations of large guests has been achieved with an
adaptive, self-assembled Fe<sup>II</sup><sub>4</sub>L<sub>4</sub> coordination
cage. Depending on the counterion, this face-capped tetrahedral capsule
is soluble either in water or in acetonitrile and shows a solvent-dependent
preference for encapsulation of certain classes of guest molecules.
Quantitative binding studies were undertaken, revealing that both
aromatic and aliphatic guests bind in water, whereas only aliphatic
guests bind in acetonitrile. The flexibility of its subcomponent building
blocks allows this cage to expand or contract upon guest binding,
as studied by VT-NMR, thereby ensuring strong binding of both small
and large guests. Upon encapsulation, large guest molecules can adopt
conformations which are not thermodynamically favored in the free
state. In addition, the chirotopic inner phase of the cage renders
enantiotopic guest proton signals diastereotopic in specific cases
Isolation of Hypervalent Group-16 Radicals and Their Application in Organic-Radical Batteries
Using
a newly prepared tridentate ligand, we isolated hypervalent
sulfur and selenium radicals for the first time and characterized
their structures. X-ray crystallography, electron spin resonance spectroscopy,
and density functional theory calculations revealed a three-coordinate
hypervalent structure. Utilizing the reversible redox reactions between
hypervalent radicals and the corresponding anions bearing Li<sup>+</sup>, we developed organic radical batteries with these compounds as
cathode-active materials. Furthermore, an all-radical battery, with
these compounds as the cathode and a silyl radical as the anode, was
developed that exhibited a practical discharge potential of ∼1.8
V and stable cycle performance, demonstrating the potential of these
materials for use in metal-free batteries that can replace conventional
Li-ion batteries where Li is used in the metal form
<i>Zfat</i>-Deficiency Results in a Loss of CD3ζ Phosphorylation with Dysregulation of ERK and Egr Activities Leading to Impaired Positive Selection
<div><p>The human <i>ZFAT</i> gene was originally identified as a susceptibility gene for autoimmune thyroid disease. Mouse Zfat is a critical transcriptional regulator for primitive hematopoiesis and required for peripheral T cell homeostasis. However, its physiological roles in T cell development remain poorly understood. Here, we generated <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> mice and demonstrated that T cell-specific <i>Zfat</i>-deletion in <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> mice resulted in a reduction in the number of CD4<sup>+</sup>CD8<sup>+</sup>double-positive (DP) cells, CD4<sup>+</sup>single positive cells and CD8<sup>+</sup>single positive cells. Indeed, in <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> DP cells, positive selection was severely impaired. Defects of positive selection in <i>Zfat</i>-deficient thymocytes were not restored in the presence of the exogenous TCR by using TCR-transgenic mice. Furthermore, <i>Zfat</i>-deficient DP cells showed a loss of CD3ζ phosphorylation in response to T cell antigen receptor (TCR)-stimulation concomitant with dysregulation of extracellular signal-related kinase (ERK) and early growth response protein (Egr) activities. These results demonstrate that Zfat is required for proper regulation of the TCR-proximal signalings, and is a crucial molecule for positive selection through ERK and Egr activities, thus suggesting that a full understanding of the precise molecular mechanisms of Zfat will provide deeper insight into T cell development and immune regulation.</p></div
<i>Zfat-</i>deficiency impaired CD3ζ phosphorylation with defects in ERK1/2 activation.
<p>Immunoblots for phosphorylated or total protein of ERK, MEK1/2, c-Raf, Zap70, PLCγ1, CD3ζ and Lck before or at the indicated time points after the stimulation with cross-linking anti-CD3ε antibody in thymocytes from the indicated genotypes. The values below each image represent the relative ratio of the amount of phosphorylated protein to total protein. Data are representative of three independent experiments.</p
TCR-stimulation induced Egr expressions were impaired in the <i>Zfat</i>-deficient DP thymocytes.
<p>(A)Immunoblots for Egr1, Egr2 and Egr3 before or at the indicated time points after the stimulation with plate-bound anti-CD3ε and anti-CD28 antibodies in DP cells from the indicated genotypes. Actin was used as a loading control. Data are representative of three independent experiments. (B) Immunoblots for Egr1, Egr2 and Egr3 in DP cells from the indicated genotypes before or at the indicated time points after the stimulation with plate-bound anti-CD3ε and anti-CD28 antibodies under the condition with U0126 in DMSO or with DMSO alone. Actin was used as a loading control. Data are representative of three independent experiments. (C, D) Quantitative RT-PCR analysis of <i>Egr1</i>, <i>Egr2</i> and <i>Egr3</i> expression before (C) or at the indicated time points after the stimulation with anti-CD3ε and anti-CD28 antibodies (D) in DP cells from <i>Zfat</i><sup>f/f</sup> and <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> mice. The relative expression for each gene was normalized by the expression of <i>Actb</i>. The results are presented as the value relative to the unstimulated DP cells from <i>Zfat</i><sup>f/f</sup> mice. The data are the mean ± s.d.; n.s., not significant.</p
Impaired positive selection in <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> thymus.
<p>(A, B) A scheme of the intermediates of positive selection defined by changes in expression of TCRβ and CD69: TCRβ<sup>int</sup>CD69<sup>+</sup>(P-I), TCRβ<sup>hi</sup>CD69<sup>+</sup>(P-II) and TCRβ<sup>hi</sup>CD69<sup>−</sup> (P-III) are generated sequentially as shown by arrows (A, left). Flow cytometry analysis of the surface expression of CD69 and TCRβ on total thymocytes (A) or DP cells (B) from the indicated genotypes at 6 to 7 weeks of age. The numbers indicate the proportion of the gated area. Data are representative of three independent experiments. (C-E) Surface expression of TCRβ on DP cells (C), CD45 on DP cells (D) or CD5 on DP, CD4<sup>+</sup>CD8<sup>−</sup>TCRβ<sup>+</sup>or CD4<sup>−</sup>CD8<sup>+</sup>TCRβ<sup>+</sup>cells (E) from <i>Zfat</i><sup>f/f</sup> (gray-filled) and <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> (black line) mice at 6 to 7 weeks of age. Data are representative of three independent experiments. (F, G) Flow cytometry analysis for the surface expression of CD4 and CD8 on the thymocytes and total numbers of CD4<sup>+</sup>CD8<sup>int</sup>, CD8SP or CD4SP cells from OT-I <i>Zfat</i><sup>f/f</sup> (black bar) and OT-I <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> mice (white bar) (F) or from OT-II <i>Zfat</i><sup>f/f</sup> (black bar) and OT-II <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> mice (white bar) (G). The numbers indicate the proportion of the gated area. The data are the mean ± standard deviation (s.d.); <i>n</i> = 3; ** P<0.01. Data are representative of three independent experiments.</p
Reduction in the number of thymocytes and peripheral T cells in <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> mice.
<p>(A) An immunoblot of Zfat in nuclear (N) or cytoplasmic (C) fractions of thymocytes from <i>Zfat</i><sup>f/f</sup> and <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> mice. CREB1 and PLCγ1 were used as controls of nuclear and cytoplasmic fractions, respectively. (B) An immunoblot of Zfat in DN1 and DN2 (DN1,2: CD4<sup>−</sup>CD8<sup>−</sup>CD44<sup>+</sup>), DN3 (CD4<sup>−</sup>CD8<sup>−</sup>CD25<sup>+</sup>CD44<sup>−</sup>), DN4 (CD4<sup>−</sup>CD8<sup>−</sup>CD25<sup>−</sup>CD44<sup>−</sup>) or DP thymocytes from <i>Zfat</i><sup>f/f</sup> and <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> mice. Actin was used as a loading control. (C) Flow cytometry analysis of the surface expression of CD4 and CD8 on thymocytes from <i>Zfat</i><sup>f/f</sup> (top) and <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> (bottom) mice at 6 to 7 weeks of age. Data are representative of three independent experiments. (D) Total numbers of thymocytes, thymic DP, DN, CD4SP or CD8SP cells from <i>Zfat</i><sup>f/f</sup> (black bars) and <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> (white bars) mice at 6 to 7 weeks of age. The data are the mean ± standard deviation (s.d.); <i>n</i> = 6; * <i>P</i><0.05; ** <i>P</i><0.01; n.s., not significant. (E) Flow cytometry analysis of TCRβ<sup>+</sup>T cells and B220<sup>+</sup>B cells (left) or CD4<sup>+</sup>and CD8<sup>+</sup>T cells (right) in the spleen and LNs of <i>Zfat</i><sup>f/f</sup> (top) and <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> (bottom) mice. Data are representative of three independent experiments. (F) Total numbers of CD4<sup>+</sup>T, CD8<sup>+</sup>T or B220<sup>+</sup>B cells in the spleen from <i>Zfat</i><sup>f/f</sup> (black bars) and <i>Zfat</i><sup>f/f</sup>-<i>LckCre</i> (white bars) mice. The data are the mean ± s.d.; <i>n</i> = 6; ** <i>P</i><0.01; n.s., not significant.</p
Additional file 1: Figure S1. of Clarithromycin attenuates IL-13–induced periostin production in human lung fibroblasts
Expression of IL-4Rα and IL-13Rα1 in MRC5 cells. (A) Cell surface expression of IL-4Rα and IL-13Rα1 was assessed by flow cytometry. Mean fluorescent intensities (MFI) of the stained cells are shown. (B) Expression of mRNA of the indicated genes was assessed by quantitative RT-PCR. Fold changes over vehicle are shown. Black columns, clarithromycin (CAM); gray columns, vehicle. Statistical analyses were performed using Bonferroni’s multiple comparison test. P values of 0.05 or less were regarded significant. NS, not significant; MFI, mean fluorescent intensity. (PPT 121 kb