Cyclic biphalin analogues with a novel linker lead to potent agonist activities at mu,delta, and kappa opioid receptors

In an effort to improve biphalin’s potency and efficacy at the µ-(MOR) and δ-opioid receptors (DOR), a series of cyclic biphalin analogues 1–5 with a cystamine or piperazine linker at the C-terminus were designed and synthesized by solution phase synthesis using Boc-chemistry. Interestingly, all of the analogues showed balanced opioid agonist activities at all opioid receptor subtypes due to enhanced κ-opioid receptor (KOR) activity. Our results indicate that C-terminal flexible linkers play an important role in KOR activity compared to that of the other cyclic biphalin analogues with a hydrazine linker. Among them, analogue 5 is a potent (Ki?=?0.27, 0.46, and 0.87?nM; EC₅₀?=?3.47, 1.45, and 13.5?nM at MOR, DOR, and KOR, respectively) opioid agonist with high efficacy. Based on the high potency and efficacy at the three opioid receptor subtypes, the ligand is expected to have a potential synergistic effect on relieving pain and further studies including in vivo tests are worthwhile.     

On the causes of trends in the seasonal amplitude of atmospheric CO2

No consensus has yet been reached on the major factors driving the observed increase in the seasonal amplitude of atmospheric CO₂ in the northern latitudes. In this study, we used atmospheric CO₂ records from 26 northern hemisphere stations with a temporal coverage longer than 15 years, and an atmospheric transport model prescribed with net biome productivity (NBP) from an ensemble of nine terrestrial ecosystem models, to attribute change in the seasonal amplitude of atmospheric CO₂. We found significant (p < .05) increases in seasonal peak‐to‐trough CO₂ amplitude (AMP_P‐T) at nine stations, and in trough‐to‐peak amplitude (AMP_T‐P) at eight stations over the last three decades. Most of the stations that recorded increasing amplitudes are in Arctic and boreal regions (>50°N), consistent with previous observations that the amplitude increased faster at Barrow (Arctic) than at Mauna Loa (subtropics). The multi‐model ensemble mean (MMEM) shows that the response of ecosystem carbon cycling to rising CO₂ concentration (eCO₂) and climate change are dominant drivers of the increase in AMP_P‐T and AMP_T‐P in the high latitudes. At the Barrow station, the observed increase of AMP_P‐T and AMP_T‐P over the last 33 years is explained by eCO₂ (39% and 42%) almost equally than by climate change (32% and 35%). The increased carbon losses during the months with a net carbon release in response to eCO₂ are associated with higher ecosystem respiration due to the increase in carbon storage caused by eCO₂ during carbon uptake period. Air‐sea CO₂ fluxes (10% for AMP_P‐T and 11% for AMP_T‐P) and the impacts of land‐use change (marginally significant 3% for AMP_P‐T and 4% for AMP_T‐P) also contributed to the CO₂ measured at Barrow, highlighting the role of these factors in regulating seasonal changes in the global carbon cycle.     

湖南东部植被恢复对土壤有机碳矿化的影响

为阐明中亚热带植被恢复对土壤有机碳(SOC)稳定性的影响机制, 采用空间代替时间方法, 在湘东丘陵区选取檵木(Loropetalum chinense)-南烛(Vaccinium bracteatum)-杜鹃(Rhododendron simsii)灌草丛(LVR)、檵木-杉木(Cunninghamia lanceolata)-白栎(Quercus fabri)灌木林(LCQ)、马尾松(Pinus massoniana)-柯(Lithocarpus glaber)-檵木针阔混交林(PLL)、柯-红淡比(Cleyera japonica)-青冈(Cyclobalanopsis glauca)常绿阔叶林(LAG)作为一个恢复系列, 采用室内恒温培养(碱液吸收法)测定SOC矿化速率及其累积矿化量(C_m), 结合主成分和逐步回归方法分析C_m、SOC矿化率与植被因子和土壤因子的关系。结果表明: (1)不同植被恢复阶段SOC矿化速率随着培养时间呈现基本一致的变化趋势, 培养初期矿化速率较高, 且快速下降, 培养中后期缓慢下降并趋于平稳, 倒数方程能很好地拟合不同植被恢复阶段SOC矿化速率与培养时间的关系。(2)植被恢复显著提高各土层SOC矿化速率和C_m, LAG显著高于其他3个植被恢复阶段, LAG 0-40 cm土层C_m比LVR、LCQ、PLL分别高出359.06%-716.31%、112.38%-232.61%、94.40%-105.74%。(3) 4种植被恢复阶段0-10、10-20、20-30、30-40 cm土层SOC矿化率分别为2.13%-4.99%、3.42%-4.18%、4.05%-4.64%、4.02%-5.64%, 但不同植被恢复阶段之间差异不显著。(4)植被恢复过程中, C_m的变化主要受土壤全氮(TN)含量、根系生物量的驱动, 土壤TN含量、根系生物量可分别解释C_m变异的96.9%、0.9%。而土壤C:N是SOC矿化率的主要调控因子, 可单独解释SOC矿化率变异的49.4%。表明植被恢复促进了SOC矿化, 降低了SOC中矿化C的比例, 有利于提高土壤固C能力; 随着植被恢复, 土壤TN含量和根系生物量增加是影响C_m的主要因子, 而土壤SOC的质量差异是影响SOC矿化率的主要因子。     

陕北黄土高原植被生态系统水分利用效率气候时滞效应

基于月尺度气温、降水以及MODIS-GPP、MODIS-ET遥感数据,采用基于像元的时滞偏相关分析,揭示了陕北黄土高原植被生态系统水分利用效率气候时滞效应及其影响因素。结果表明:①2000—2014年,受退耕还林草生态工程和气候变化的双重影响,陕北黄土高原WUE呈波动变化趋势,2001—2003年显著下降,2003—2005年、2010—2013年显著上升。受不同植被类型的影响,年内WUE呈急速双峰、缓速双峰和单峰型3种变化状态。②陕北黄土高原WUE对降水存在明显的时滞效应,滞后时间多为3个月,人为扰动较大的I-1、I-2、Ⅱ-2生态区以及植被覆盖度较高的Ⅲ-3生态区WUE对降水的时滞响应程度明显低于其他生态区;而对气温的时滞效应较弱,仅南部的Ⅲ-2、Ⅲ-3生态区WUE对气温存在1—2个月滞后时间。③不同植被类型WUE对降水的时滞效应较明显,荒漠类植被WUE对降水时滞响应程度最强,滞后时间近3个月,针叶林时滞响应程度最弱,滞后时间为2.1个月;但对气温的时滞效应总体较弱,针叶林WUE对气温滞后时间为15 d,其余大多数植被类型WUE对气温不存在滞后时间。④WUE气候时滞效应对植被覆盖度...     

Texture of Cooked Rice Prepared from Aged Rice and Its Improvement by Reducing Agents

The textures of cooked rice prepared from aged rice grains and their improvement by reducing agents were investigated. For aged rice that was stored for 5 months without air by the operation of a vacuum packing machine, the stickiness/hardness ratio of cooked rice was as low as that of aged rice stored in air. The results of electrophoresis showed that oxidation of proteins in the former was advanced to the same degree as in the latter. The stickiness/hardness ratios of the aged rice were increased by the addition of sodium sulfite, cysteine, and dithiothreitol to the cooking water. Sodium sulfite, cysteine, and dithiothreitol cleave disulfide bonds to sulfhydryl groups. Therefore, cleaving disulfide bonds to sulfhydryl groups improved the texture. The addition of them to the cooking water also increased the extractable solids at the time of heating. Hence cleaving disulfide bonds to sulfhydryl groups must increase extractable solids. Consequently, the gelatinized paste layer thickened and the thick paste layer softened the cooked rice.     

Agrobacterium bohemicum sp. nov. isolated from poppy seed wastes in central Bohemia

Two non-pathogenic strains R89-1 and R90^T isolated from poppy seed (Papaver somniferum L.) wastes were phenotypically and genotypically characterized. Multilocus sequence analysis (MLSA) was conducted with six genes (atpD, glnA, gyrB, recA, rpoB, 16S rRNA). The strains represented a new species which clustered with Agrobacterium rubi NBRC 13261^T and Agrobacterium skierniewicense Ch11^T type strains. MLSA was further accompanied by whole-genome phylogeny, in silico DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) analyses for both strains. ANI and dDDH values were deep below the species delineation threshold. Phenotypic features of the novel strains unequivocally allowed their differentiation from all other Agrobacterium species. Unlike other agrobacteria, the strains were salt sensitive and were able to biotransform morphine alkaloids. The dominant cellular fatty acids are 18:1 w7c, 16:0 and 12:0 aldehyde/16:1 iso I/14:0 3OH summed in feature 2 and the major respiratory quinine is Q-10 (87%). The DNA G + C content is 56 mol%. Microbial community analysis indicated probable association with P. somniferum plant material. Altogether, these characteristics showed that strains R90^T and R89-1 represent a new species of the genus Agrobacterium which we propose to name Agrobacterium bohemicum. The type strain of A. bohemicum is R90^T (=CCM 8736^T = DSM 104667^T).     

Whole genome DNA methylation profiling of oral cancer in ethnic population of Meghalaya,North East India reveals novel genes

Oral Squamous Cell Carcinoma (OSCC) is a serious and one of the most common and highly aggressive malignancies. Epigenetic factors such as DNA methylation have been known to be implicated in a number of cancer etiologies. The main objective of this study was to investigate physiognomies of Promoter DNA methylation patterns associated with oral cancer epigenome with special reference to the ethnic population of Meghalaya, North East India. The present study identifies 27,205 CpG sites and 3811 regions that are differentially methylated in oral cancer when compared to matched normal. 45 genes were found to be differentially methylated within the promoter region, of which 38 were hypermethylated and 7 hypomethylated. 14 of the hypermethylated genes were found to be similar to that of the TCGA-HNSCC study some of which are TSGs and few novel genes which may serve as candidate methylation biomarkers for OSCC in this poorly characterized ethnic group.     

Synthesis and evaluation of a [18F]formyl–Met–Leu–Phe derivative: A positron emission tomography imaging probe for bacterial infections

The tripeptide formyl–Met–Leu–Phe (fMLF) is a prototype of N-formylated chemotactic peptides for neutrophils owing to its ability to bind and activate the G protein-coupled formyl peptide receptor (FPR). Here, we developed an ¹⁸F-labeled fMLF derivative targeting FPR as a positron emission tomography (PET) imaging probe for bacterial infections. The study demonstrates that the fMLF derivative fMLFXYk(FB)k (X?=?Nle) has a high affinity for FPR (Ki?=?0.62?±?0.13?nM). The radiochemical yield and purity of [¹⁸F]fMLFXYk(FB)k were 16% and >96%, respectively. The in vivo biodistribution study showed that [¹⁸F]fMLFXYk(FB)k uptake was higher in the bacterial infected region than in the non-infected region. We observed considerably higher infection-to-muscle ratio of 4.6 at 60?min after [¹⁸F]fMLFXYk(FB)k injection. Furthermore, small-animal PET imaging studies suggested that [¹⁸F]fMLFXYk(FB)k uptake in the bacterial infected region was clearly visualized 60?min after injection.     

Functional Compartmentalization within Starburst Amacrine Cell Dendrites in the Retina

1. Download high-res image (153KB)
2. Download full-size image

     

向日葵茎芯多糖的提取工艺优化及其体外抗肿瘤活性研究

研究了向日葵茎芯中主要活性物质多糖的提取工艺,并对此工艺进行了优化,选取的提取方法为水提醇沉法,以多糖含量作为指标,采用单因素试验研究了提取次数、原料颗粒的大小（目数）、料液比、提取时间、提取温度对向日葵茎芯多糖含量的影响。用苯酚-硫酸法测定提取液中多糖的含量,得出向日葵茎芯中多糖的最佳提取工艺条件为：提取次数2次,原料颗粒的大小（目数）60~80目,料液比（g·mL^-1）1：50,提取时间3.0 h,提取温度90℃,在最优提取条件下,多糖的提取得率为6.56%,多糖的含量为266.03 mg·g^-1。本文也对多糖的体外抗肿瘤活性进行了研究,结果表明向日葵茎芯多糖的体外抗肿瘤活性较弱。这些条件的确定为向日葵茎芯的深入研究奠定了基础。