第831回千葉医学会例会・第15回千葉大学放射線医学教室例会

Figure S2. All a-DMRs within (1) genomic location. Top: a-DMRs (purple), gene, DHS clusters, transcription factor ChIP-seq, ChromHMM segmentation, combined segmentation and conservation; and (2) scatterplot: x-axis = Age, y-axis = Normalised methylation. (PDF 34909 kb

Late Devonian closure of the North Qilian Ocean: evidence from detrital zircon U–Pb geochronology and Hf isotopes in the eastern North Qilian Orogenic Belt

<div><p>The closure age of the North Qilian Ocean, which lay between the Alashan Terrane and Central Qilian Block during the early Palaeozoic, is intensely debated. This article presents a provenance study of detrital materials from three Upper Devonian sedimentary formations in the Pingchuan area of Gansu Province in the eastern North Qilian Orogenic Belt (NQOB), to constrain the tectonic evolution of the belt. U–Pb dating and Lu–Hf isotopic studies were conducted on detrital zircons from samples of sedimentary rocks. Four age populations of U–Pb zircon ages are defined as: 0.5–0.4 Ga (peak at 472 Ma); 0.8–1.3 Ga (peaks at 960 Ma and 1102 Ma); 1.8–2.1 Ga (two prominent peaks at 1963 Ma and 2045 Ma, and two subordinate peaks at 1816 Ma and 2168 Ma); and 2.4–2.5 Ga (peak at 2495 Ma). Zircons with U–Pb age spectra of 1.8–2.1 Ga and their corresponding εHf(t) values are markedly different from those of the North China Block, Dunhuang Terrane, and Central Qilian Block, but have a strong similarity to zircons from the Alashan Terrane. Furthermore, zircons with ages ranging from 1.8 to 2.1 Ga are reported for the first time in early Palaeozoic strata of the eastern NQOB. The presence of Alashan-derived clasts in the Upper Devonian strata in the NQOB indicates that the sediments were deposited after amalgamation between the Alashan and Qilian terranes. Combined with previous geochronological and geochemical data from the early Palaeozoic igneous and sedimentary rocks, we propose that the closure of the North Qilian Ocean occurred in the Late Devonian. The similar age spectra of detrital zircons from sediments of the Alashan, Cathaysia, and Australia imply that the Alashan–Qilian–Qaidam block was probably located in the periphery of Gondwana in the early Palaeozoic.</p></div

Cyclic AMP signalling pathways in the regulation of uterine relaxation-0

<p><b>Copyright information:</b></p><p>Taken from "Cyclic AMP signalling pathways in the regulation of uterine relaxation"</p><p>http://www.biomedcentral.com/1471-2393/7/S1/S10</p><p>BMC Pregnancy and Childbirth 2007;7(Suppl 1):S10-S10.</p><p>Published online 1 Jun 2007</p><p>PMCID:PMC1892051.</p><p></p>l cyclase (ADCY) which converts ATP to cAMP. The levels of cAMP are tightly regulated by phosphodiesterases (PDE), especially PDE4 isoforms. It is thought that cAMP induces uterine relaxation via activation of a specific protein kinase (PRKA) which phosphorylates and inhibits myosin light chain kinase (MYLK). PRKA may also oppose the effect of stimulatory receptors which operate through the phospholipase C (PLC)/calcium pathway. However the precise targets for PRKA phosphorylation in human myometrium are under investigation ( stimulation, inhibition

Covalent cum Noncovalent Functionalizations of Carbon Nanotubes for Effective Reinforcement of a Solution Cast Composite Film

Although carbon nanotubes have impressive tensile properties, exploiting these properties in composites, especially those made by the common solution casting technique, seems to be elusive thus far. The reasons could be partly due to the poor nanotube dispersion and the weak nanotube/matrix interface. To solve this dual pronged problem, we combine noncovalent and covalent functionalizations of nanotubes in a single system by the design and application of a novel dispersant, hydroxyl polyimide-<i>graft</i>-bisphenol A diglyceryl acrylate (PI_OH-BDA), and use them with epoxidized single-walled carbon nanotubes (O-SWNTs). Our novel PI_OH-BDA dispersant functionalizes the nanotubes noncovalently to achieve good dispersion of the nanotubes because of the strong π–π interaction due to main chain and steric hindrance of the BDA side chain. PI_OH-BDA also functionalizes O-SWNTs covalently because it reacts with epoxide groups on the nanotubes, as well as the cyanate ester (CE) matrix used. The resulting solution-cast CE composites show 57%, 71%, and 124% increases in Young’s modulus, tensile strength, and toughness over neat CE. These values are higher than those of composites reinforced with pristine SWNTs, epoxidized SWNTs, and pristine SWNTs dispersed with PI_OH-BDA. The modulus and strength increase per unit nanotube weight fraction, i.e., d<i>E</i>/d<i>W</i>_NT and dσ/d<i>W</i>_NT, are 175 GPa and 7220 MPa, respectively, which are significantly higher than those of other nanotube/thermosetting composites (22–70 GPa and 140–3540 MPa, respectively). Our study indicates that covalent cum noncovalent functionalization of nanotubes is an effective tool for improving both the nanotube dispersion and nanotube/matrix interfacial interaction, resulting in significantly improved mechanical reinforcement of the solution-cast composites

Optimized Fragmentation for Quantitative Analysis of Fucosylated N‑Glycoproteins by LC-MS-MRM

Quantitative analysis of site specific glycoforms of proteins is technically challenging but highly desirable; resolution of the fucosylated glycoforms is of particular interest due to their biological importance. In this study, we developed a sensitive and specific LC-MS-MRM quantification method that distinguishes the outer arm and core fucosylated configurations of the N-glycopeptides. We take advantage of limited fragmentation of the glycopeptides at low collision energy CID to produce linkage-specific Y-ions. We select these informative ions as MRM transitions for the quantification of the outer arm and total fucosylation of 12 fucosylated glycoforms of 9 glycopeptides in 7 plasma proteins. Our workflow showed improved sensitivity and specificity of quantification of the glycopeptides compared to oxonium ion transitions which allowed us to quantify the glycoforms directly in plasma or serum without fractionation of the samples or glycopeptide enrichment. A pilot study of fucosylation in liver cirrhosis of the HCV and NASH etiologies confirms the quantitative capabilities of the method and shows that liver cirrhosis is consistently associated with increased outer arm fucosylation of majority of the analyzed proteins. The results show that the outer arm fucosylation of the A2G2F1 glycoform of the VDKDLQSLEDILHQVENK peptide of fibrinogen increases greater than 10-fold in the HCV and NASH patients compared to healthy controls

Improving Mechanoluminescent Sensitivity of 1,2-Dioxetane-Containing Thermoplastic Polyurethanes by Controlling Energy Transfer across Polymer Chains

1,2-Dioxetane was found as a mechanoluminescent probe when it was covalently linked into a polymer backbone. To bring about a further leap in sensitivity without sacrificing thermal stability of this mechanophore is highly desirable while a great challenge. Herein, we presented a new strategy to improve the mechanoluminescent sensitivity of 1,2-dioxetane-containing polyurethanes (PUs) by incorporating fluorescent dyes as the repeating units into the main chains of PUs. This approach provides simplified procedures to obtain mechanoluminescent films with high quality and increased amount of acceptor units. Compared to the same mechanophore-containing polymer with physically incorporated fluorophores, the two kinds of PUs not only exhibited enhanced light intensity and tunable emission colors but also displayed much lower force threshold upon deformation due to the efficient energy transfer. By virtue of these advantages, the current work will promise an invaluable tool to study failure mechanisms of thermoplastic elastomers at molecular level with unprecedented resolution

A Novel Polyimide Dispersing Matrix for Highly Electrically Conductive Solution-Cast Carbon Nanotube-Based Composite

Multiwalled carbon nanotubes (MWNTs) have high intrinsic conductivities and are thought to be ideal fillers for electrically conductive composites. However, so far, simple solution casting or blending of nanotubes has not been highly successful in producing highly conductive composites, because of the poor dispersion and low loading of the nanotubes. We show that, by using a novel poly(amic acid) (PAA) containing a rigid backbone with hydroxyl pendant groups, as both the nanotube dispersant and the matrix precursor, we can increase the nanotube content in the solution-cast polyimide (PI)-based composite to as high as 30 wt % and achieve ultrahigh composite electrical conductivity as well as high mechanical properties. The electrical conductivity of the MWNT/PI composites reaches a value of 38.8 S cm–1 at a nanotube loading of 30 wt % and the MWNT concentration for achieving the percolation threshold of conductivity of the composites is 0.48 wt %. These are, respectively, the highest and among the lowest reported values for any conventional solution-processed nanotube composites. The 30 wt % MWNTs composite has a higher Young’s modulus (9.43 ± 0.14 GPa) and tensile strength (179.2 ± 9.7 MPa) than other nanotube-reinforced polyimide composites. The high conductivity, as well as tensile properties, of the composite films is attributed to the good nanotube dispersion and strong nanotube–polymer interfacial adhesion achieved through use of a single polymer to perform the dual functions of nanotube dispersant and matrix precursor. The excellent properties, combined with the facile conventional solution-casting technique, make this MWNT/PI composite film a promising material for many potential applications. We have also demonstrated that uniform MWNT(30 wt %)/PI composite coatings can be deposited onto glass and aluminum substrates

Extraction and Quantitation of Ketones and Aldehydes from Mammalian Cells Using Fluorous Tagging and Capillary LC-MS

The extraction and quantitation of carbonyl metabolites from cell lysate was accomplished using a carbonyl-reactive fluorous tag and capillary liquid chromatography coupled to mass spectrometry (capLC-MS). Selective fluorous tagging for ketones and aldehydes provided a 30-fold increase in sensitivity using electrospray ionization MS. Separation of fluorous tagged carbonyl resulted in good separation of all components, and tandem MS was able to differentiate structural carbonyl isomers. The average limit of detection for carbonyl standards was 37 nM (range 1.5–250 nM), with linearity of <i>R</i>² > 0.99. Reproducibility for metabolites in cell lysate averaged 9% RSD. Human aortic endothelial cells (HAECs) were exposed to varying levels of glucose, and their carbonyl metabolite levels were quantified. Significant metabolite changes were seen in glycolysis and the propanoate pathway from a glucose challenge. Using an untargeted approach, 120 carbonyl metabolites were found to change in hyperglycemic HAECs. From this list of compounds, multiple metabolites from the pentose phosphate and tryptophan metabolic pathways were discovered. This system provides excellent sensitivity and quantitation of carbonyl metabolites without the need for isotope standards or labels

Improving Mechanoluminescent Sensitivity of 1,2-Dioxetane-Containing Thermoplastic Polyurethanes by Controlling Energy Transfer across Polymer Chains

1,2-Dioxetane was found as a mechanoluminescent probe when it was covalently linked into a polymer backbone. To bring about a further leap in sensitivity without sacrificing thermal stability of this mechanophore is highly desirable while a great challenge. Herein, we presented a new strategy to improve the mechanoluminescent sensitivity of 1,2-dioxetane-containing polyurethanes (PUs) by incorporating fluorescent dyes as the repeating units into the main chains of PUs. This approach provides simplified procedures to obtain mechanoluminescent films with high quality and increased amount of acceptor units. Compared to the same mechanophore-containing polymer with physically incorporated fluorophores, the two kinds of PUs not only exhibited enhanced light intensity and tunable emission colors but also displayed much lower force threshold upon deformation due to the efficient energy transfer. By virtue of these advantages, the current work will promise an invaluable tool to study failure mechanisms of thermoplastic elastomers at molecular level with unprecedented resolution