TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma

Toll-like receptors (TLRs) through innate immune system recognize pathogen associated molecular patterns and play an important role in host defense against bacteria, fungi and viruses. TLR-7 is responsible for sensing single stranded nucleic acids of viruses but its activation has been shown to be protective in mouse models of asthma. The NADPH oxidase (NOX) enzymes family mainly produces reactive oxygen species (ROS) in the lung and is involved in regulation of airway inflammation in response to TLRs activation. However, NOX-4 mediated signaling in response to TLR-7 activation in a mouse model of allergic asthma has not been explored previously. Therefore, this study investigated the role TLR-7 activation and downstream oxidant–antioxidant signaling in a murine model of asthma. Mice were sensitized with ovalbumin (OVA) intraperitoneally and treated with TLR-7 agonist, resiquimod (RSQ) intranasally before each OVA challenge from days 14 to 16. Mice were then assessed for airway reactivity, inflammation, and NOX-4 and nuclear factor E2-related factor 2 (Nrf2) related signaling [inducible nitric oxide synthase (iNOS), nitrotyrosine, lipid peroxides and copper/zinc superoxide dismutase (Cu/Zn SOD)]. Treatment with RSQ reduced allergen induced airway reactivity and inflammation. This was paralleled by a decrease in ROS which was due to induction of Nrf2 and Cu/Zn SOD in RSQ treated group. Inhibition of MyD88 reversed RSQ-mediated protective effects on airway reactivity/inflammation due to reduction in Nrf2 signaling. SOD inhibition produced effects similar to MyD88 inhibition. The current study suggests that TLR-7 agonist is beneficial and may be developed into a therapeutic option in allergic asthma.     

Strontium isotope record of the Hygophum hygomii otoliths from the European middle Miocene

⁸⁷Sr/⁸⁶Sr values from otoliths of the worldwide-distributed fish Hygophum hygomii are used for the purpose of isotope chemostratigraphy. In order to evaluate the potential of H. hygomii otoliths for strontium (Sr) isotopic studies, we first compare the ⁸⁷Sr/⁸⁶Sr ratio of current representatives of the species with that of modern sea water. Then, three fossil otoliths of H. hygomii collected in middle Miocene sediments of the Aquitaine Basin (Lafaurie locality, SW France) and the Carpathian Foredeep of the Central Paratethys (Brno-Kralovo Pole locality, SE Czech Republic) are analysed. The age inferred from the ⁸⁷Sr/⁸⁶Sr ratio at Lafaurie places the two analysed otoliths within the time interval of 15.5–15.1 Ma. This time interval matches the published early Langhian age obtained from the ⁸⁷Sr/⁸⁶Sr ratio of bivalves measured at the same locality. At the Brno-Kralovo Pole, the ⁸⁷Sr/⁸⁶Sr ratio of the analysed otolith returns a wider timespan of 14.78–13.10 Ma, falling into an interval of poor time resolution of the ⁸⁷Sr/⁸⁶Sr chemostratigraphy. Comparisons with published biostratigraphic and paleoclimatic data suggest that the analysed fossil otoliths of H. hygomii were mineralized during the late part of the Langhian, at ∼14.2 Ma. This work represents a first attempt to use otoliths for ⁸⁷Sr/⁸⁶Sr chemostratigraphy, and indicates that such a use may represent a powerful tool for testing stratigraphic correlations in the future.     

Molecular dynamics simulations on the conformational transitions from the GA98 (GA88) to GB98 (GB88) proteins

We performed conventional and targeted molecular dynamics simulations to address the dynamic transition mechanisms of the conformational transitions from the G_A98 protein with only 1 mutation of Leu45Tyr to G_B98 and from the G_A88 protein with 7 mutations of Gly24Ala, Ile25Thr, Ile30Phe, Ile33Tyr, Leu45Tyr, Ile49Thr, and Leu50Lys to G_B88. The results show that the conformational transition mechanism from the mutated 3α G_A98 (G_A88) state to the α+4β G_B98 (G_B88) state via several intermediate conformations involves the bending of loops at the N and C termini firstly, the unfolding of αA and αC, then the traversing of αB, and the formation of the 4β layer with the conversion of the hydrophobic core. The bending of loops at the N and C termini and the formation of the crucial transition conformation with the full unfolded structure are key factors in their transition processes. The communication of the interaction network, the bending directions of loops, and the traversing site of αB in the transition of G_A98 to G_B98 are markedly different from those in G_A88 to G_B88 because of the different mutated residues. The analysis of the correlations and the calculated mass center distances between some segments further supported their conformational transition mechanisms. These results could help people to better understand the Paracelsus challenge. Copyright © 2016 John Wiley & Sons, Ltd.     

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In a runoff irrigation system in Northern Kenya, we studied the nutrient interactions of sole cropped and alley cropped Sorghum bicolor (L.) Moench and Acacia saligna (Labill.) H.L. Wendl. The trees were pruned once before the cropping season and the biomass was used as fodder for animals. The nutrient contents in leaf tissue, soil and soil solution were monitored and the uptake of applied tracers (¹⁵N, Sr) was followed. The grain yield of alley cropped sorghum was similar to or slightly higher than in monoculture and did not decrease near the tree-crop interface. Foliar N and Ca contents of the crop were higher in the agroforestry combination than in monoculture, corresponding to higher soil N and Ca contents. Soil solution and soil mineral N dynamics indicate an increase of N under the tree row and unused soil N at the topsoil in the alley of the sole cropped trees as well as below 60 cm depth in the crop monoculture. The N use efficiency of the tree+crop combination was higher than the sole cropped trees or crops. Competition was observed for Zn and Mn of both tree and crop whereas for Ca only the tree contents decreased. P, K, Mg and Fe dynamics were not affected by alley cropping at our site. The lower uptake of applied Sr by trees in alley cropping compared to those of the monoculture stand suggested a lower competitiveness of the acacia than sorghum, which did not show lower Sr contents when intercropped. The study showed the usefulness of combining soil and plant analyses together with tracer techniques identifying nutrient competition, nutrient transfer processes and the complementary use of soil nutrients, as the main features of the tree-crop combination. This revised version was published online in June 2006 with corrections to the Cover Date.     

Tunable warm white light emission and energy transfer of Dy3+ co-doped Sr2LaZrO5.5:Eu3+ phosphors

Eu³⁺,Dy³⁺ co-doped Sr₂LaZrO_5.5-based phosphors were prepared through a sol–gel method. Through characterization, it was found that the Sr₂LaZrO_5.5-based fluorescent powder co-doped with Eu³⁺ and Dy³⁺ had a cubic structure. At an excitation wavelength of 290 nm, the substrate Sr₂LaZrO_5.5 exhibited strong blue emission at 468 nm, and the Sr₂LaZrO_5.5:18%Eu³⁺ phosphor exhibited a strong red emission peak at 612 nm. When the doping amount of Dy³⁺ was 5, 8, 12, 15, or 18%, the Sr₂LaZrO_5.5:18%Eu³⁺ phosphor changed from an orange-red light, to a warm white light, and to a cold white light. According to the emission spectra, the emission intensities of the substrates Sr₂LaZrO_5.5 and Sr₂LaZrO_5.5:Eu³⁺ decreased with increasing Dy³⁺ concentration, confirming the energy transfer between the host Sr₂LaZrO_5.5-Eu³⁺,Dy³⁺, and resulting in a lower CCT value, with significantly improved white light emission.     

RNA干扰NUP88基因对人乳腺癌MCF-7细胞生长及侵袭力的影响

目的： 构建重组慢病毒介导的NUP88-shRNA载体,通过RNAi技术分别观察沉默NUP88后对MCF-7增殖,粘附,侵袭和转移情况的影响,为乳腺癌的临床基因治疗寻找新的靶点。方法： 构建NUP88重组慢病毒表达载体,包装后检测滴度,以最佳复感染指数转染乳腺癌MCF-7细胞,利用RT-PCR和Western blot检测各组MCF-7细胞中mRNA和蛋白的表达效率;MTT法和流式细胞仪检测法,检测NUP88基因被干扰后对MCF-7细胞增殖和凋亡的影响;细胞侵袭实验检测NUP88基因被干扰后对MCF-7侵袭力的影响。结果 四组病毒及一组阴性对照均构建成功,滴度均为4E+8TU/ml;RT-PCR和Western blot检测,结果表明：经NUP88-shRNA转染的MCF-7细胞组NUP88 mRNA和蛋白质的表达与经阴性转染组和空白MCF-7细胞组相比,差异明显具有统计学意义（P<0.01）;测定NUP88-shRNA1组沉默效率最高,沉默率可达到86%;MTT法结果表明：实验组经NUP88-shRNA1慢病毒转染后细胞增殖程度显著减少,与空白组和对照组相比有显著性差异（P<0.05）。流式细胞仪检测三组MCF-7细胞凋亡结果表明：实验组经慢病毒转染后细胞凋亡率显著增加,与对照组和空白组相比有显著性差异（P<0.05）;细胞侵袭实验表明：在肿瘤细胞常规培养24h后,实验组与空白组和阴性对照组比较,穿膜细胞数量明显减少,具有显著性差异（P<0.05） 结论： NUP88重组慢病毒可以通过RNAi成功抑制MCF-7中NUP88基因的表达,并能显著抑制其增殖及远处的侵袭能力。     

Migratory history of the spotted flagtail, <Emphasis Type="Italic">Kuhlia marginata</Emphasis>

The spotted flagtail, Kuhlia marginata (Kuhliidae) is commonly found in streams throughout the Ryukyu Archipelago, including Okinawa Island, Japan. Although it has been suggested that they spawn at sea, little is known about their migratory history. The aim of the study was to clarify their migration history based on otolith microchemistry analysis, size composition and the gonadal development of fish collected from the Genka River on Okinawa Island. All strontium/calcium (Sr/Ca) ratios of otoliths remained high around their cores, and then dropped rapidly at some distance from the core. The estimated standard length corresponding to decreases correlated with the size of new recruits collected in the river (ca. 20 mm in standard length: SL). Multiple increases, the sign for migrations into the high saline area, were recognized intermittently around the otolith margin. As the estimated SL at these increases in the Sr/Ca ratio occurred above the minimum maturation size (female: 95.5 mm SL; male: 83.5 mm SL), such multiple increases in Sr/Ca ratios were caused by spawning migration. Therefore, we conclude that the catadromous pattern of K. marginata is as follows; this species grows in the sea during the early life stage until ca. 20 mm SL and then grow in the freshwater area until maturation, before they migrate again to the sea for spawning. Sr/Ca ratio profiles also suggested that a large number of males did not return to the freshwater area after spawning, whereas females might spawn several times during their lives around the inshore area.     

Miocene phosphorites from the Murray Ridge, northwestern Arabian Sea

Phosphorites from the Murray Ridge, NW Arabian Sea comprise nodules, bioclasts, and bone fragments. The nodules are made up of a homogeneous, light-colored phosphate nucleus consisting of Rivulariacean filamentous cyanobacteria and a thin dark-grey colored phosphate cortex showing abundant microbial filaments and microborings. The bioclasts comprise of  14–14.5 Ma old planktonic foraminifers, accepted as the time of deposition. Spherical to ovoid-shaped apatite microparticles resembling fossil bacteria are distinct components in the bioclasts. Bone fragments exhibit apatite fillings. The nodules and bone fragments consist entirely of carbonate fluorapatite (CFA) with low Al, K, and Th concentrations suggesting absence of continental detritus. Shale-normalized REE patterns of the samples support a seawater-derived composition. The highly uniform initial _Nd values of − 4.8 to − 5.1 are interpreted as the seawater value at the onset of phosphatization  14 Ma ago. In contrast, ⁸⁷Sr/⁸⁶Sr ratios show a large range of 0.709055 to 0.709124 corresponding to unusually young stratigraphic ages of  1 to 3 Ma. The data are interpreted as evidence for post-depositional Sr exchange of the recrystallizing phosphorites with fluids isotopically not much different from modern seawater. It is concluded that the phosphorites formed under oxic, shallow-water conditions where microbial populations assimilated phosphorus primarily from seawater and mediated precipitation of CFA during early diagenesis at the sediment–water interface on different substrates.     

河西走廊西部全新世气候环境变化的元素地球化学记录

通过河西走廊西部地区条湖剖面沉积物元素地球化学分析, 结合高精度AMS-14C测年, 探讨研究区~11400-1060 cal BP期间的气候环境演变过程。研究结果显示, ~11400-9400 cal BP期间, 条湖处于高水位且流域内化学风化作用较强, 气候条件相对温暖湿润; ~9400-8100 cal BP期间, 湖泊水位下降, 化学风化作用减弱, 指示了干旱的气候条件; ~8100-5800 cal BP气候相对湿润, 其中最湿润时段出现在~8100-7200 cal BP之间; ~5800-4800 cal BP期间, 气候转干。~4800 cal BP以后人类活动增强, 导致区域荒漠化加剧。     

Thermoluminescence properties of Eu‐doped and Eu/Dy‐codoped Sr2Al2SiO7 phosphors

We report the thermoluminescence properties of Sr_1.96Al₂SiO₇:Eu_0.04 and Sr_1.92Al₂SiO₇:Eu_0.04Dy_0.04 phosphors. These phosphors were prepared by a high‐temperature solid‐state reaction method. The prepared phosphors were characterized by X‐ray diffraction. A 254 nm source was used for ultraviolet (UV) irradiation and a ⁶⁰Co source was used for γ‐irradiation. The effect of heating rate and UV‐exposure were examined. The thermoluminescence temperature shifts to higher values with increasing heating rate and thermoluminescence intensity increases with increasing UV exposure time. The trapping parameters such as activation energy (E), order of kinetics and frequency factor (s) were calculated by peak shape method. The effect of γ‐ and UV‐irradiation on thermoluminescence studies was also examined.