Radiosynthesis and in vivo evaluation of [11C]MP-10 as a PET probe for imaging PDE10A in rodent and non-human primate brain

2-((4-(1-[(11)C]Methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl)-quinoline (MP-10), a specific PDE10A inhibitor (IC(50)=0.18 nM with 100-fold selectivity over other PDEs), was radiosynthesized by alkylation of the desmethyl precursor with [(11)C]CH(3)I, ～45% yield, >92% radiochemical purity, >370 GBq/μmol specific activity at end of bombardment (EOB). Evaluation in Sprague-Dawley rats revealed that [(11)C]MP-10 had highest brain accumulation in the PDE10A enriched-striatum, the 30 min striatum: cerebellum ratio reached 6.55. MicroPET studies of [(11)C]MP-10 in monkeys displayed selective uptake in striatum. However, a radiolabeled metabolite capable of penetrating the blood-brain-barrier may limit the clinical utility of [(11)C]MP-10 as a PDE10A PET tracer.     

Chemical and enzyme-assisted syntheses of norbuprenorphine-3-β-D-glucuronide

Norbuprenorphine-3-β-d-glucuronide (nBPN-3-β-d-G, 1) is a major phase II metabolite of buprenorphine, a pharmaceutical used for the treatment of opioid addiction. The pharmacological activity of compound 1 is not clear because investigations have been limited by the lack of chemically pure, well characterized 1 in sufficient quantities for in vitro and in vivo experiments. This work describes two concise, new methods of synthesis of 1, a chemical and an enzyme-assisted synthesis. The chemical synthesis used a strategy based on a combination of Koenig-Knorr coupling and amino-silyl protection. The enzyme-assisted synthesis used dog liver to convert the substrate norbuprenorphine (nBPN, 2) to 1. Both methods provided 1, characterized by (1)H NMR and tandem mass spectrometry, with purity >96%. The fractional yield of the enzyme-assisted synthesis was greater than that of the chemical synthesis (67% vs 5.3%), but due to larger reaction volumes, the chemical synthesis afforded greater amounts of total 1.     

三江平原不同群落小叶章种群生物量及氮、磷营养结构动态

对三江平原典型草甸和沼泽化草甸两个群落的优势植物小叶章的生物量、结构动态、不同生长阶段各器官的氮、磷含量和储量动态以及氮、磷养分限制状况进行了研究.结果表明,二者各器官生物量差异显著,但均符合模式Y=A+B_1t+B_2t2+B_3t3;二者地上各器官生物量均为单峰型,且峰值出现的时间相差15 d左右;F/C 均小于1且前者明显大于后者;二者地上各器官的全氮和全磷含量在生长季均单调下降,且叶＞叶鞘＞茎,根中全氮变化基本一致,但全磷变化差别很大;二者各器官“三氮”含量特别是NH₄⁺-N和NO₃^--N含量变化较大,且NH₄⁺-N/NO₃^--N＞1;根是二者氮、磷的重要储库,而茎、叶和叶鞘的氮、磷储量波动较大;两种小叶章的氮/磷＜14,表明氮是影响二者生长的限制性养分,但其对于前者的限制性程度要高于后者.     

Decomposition and nutrient dynamics of marsh litter in the Sanjiang Plain, Northeast China

The litterbag technique was used to study the decomposition and nutrient dynamics of marsh litter in the four communities, Carex pseudocuraica (C.pa), C. lasiocarpa (C.la), Deyeuxia angustifolia (D.aa), and D. angustifolia-Shrub (D.aa-Srb), in Sanjiang Plain, Northeast China. Decomposition was divided into two periods in the first year, with the mass loss ranging from 11.7% to 31.4% of the initial mass during summer and autumn, accounting for more than 75% of the annual loss. The decomposition rates ranged from 0.000 612 to 0.000 945 d^?1 depending on the depth of the flooding and its duration, and differed significantly in each community. The litter decomposed faster in communities with deeper and perennial flooding than in those with shallow and seasonal flooding. The initial ratios of C:N and C:P were also different among the four litter types, but these differences had no impact on the decomposition rates, suggesting that the main factor influencing the decomposition rates of marsh litter was the flooding status rather than the litter quality. The N concentrations in C.pa and C.la almost continuously increased over time, with their final values being 2.8 and 2.4 times higher than the initial ones, respectively. However, the nutrient dynamics in D.aa and D.aa-Srb offered another pattern, sharply falling in the first month and then gradually rising, with the values at the end of the experiment being close to those at the beginning. The litter accumulated substantial amounts of N in C.pa and C.la, while net N release from the litter was observed in both D.aa and D.aa-Srb. The difference may be caused by microorganisms' demand for nutrition, and then limited by the C:N ratios of litter and the availability of nitrogen from the soil and marsh water. In contrast with N dynamics, P concentrations of all the litter types apparently decreased during the first month, and then continued to decline in C.pa, remained constant in C.la and D.aa and increased slightly in D.aa-Srb. At the end of the experiment, the P concentrations decreased, respectively, by 56%, ?5%, 47% and 24% of the initial values of C.la, C. pa, D.aa and D.aa-Srb. The net P release was observed in all marsh litter over 480 days of decomposition and the intensity of the P release was different amongst communities, which may be regulated by ratios of initial C:P. The results suggested that in the marsh with the N limitation, litter tended to accumulate N and release P during decomposition and the intensity of accumulation or release was closely related to the initial C:N and C:P ratios.     

三江平原泥炭中营养元素垂直分布特征

采用冬季采样、现场分层的方法,系统地研究了三江平原河床．河漫滩型泥炭地和谷底洼地型泥炭地中常量营养元素N、P、Mg、Ca、Fe和微量营养元素Cu、Zn、Mn、B的垂直分布特征．结果表明,总N在泥炭表层富集,总P在草根层富集,其含量随剖面深度的增加而降低,Zn、Mn、B、Mg、Fe表现出草根层富集和淤泥质亚粘土潜育层急剧积累,Ca元素含量在剖面各层次中分布较均匀．某些营养元素间具有显著的相关性．     

A novel deletion mutation,c.1296delT in the BCOR gene,is associated with oculo-facio-cardio-dental syndrome

The purpose of the present study was to analyze the clinical phenotypes of a girl with oculo-facio-cardio-dental(OFCD)syndrome and to identify the potential pathogenic mutation responsible for her disease. The patient underwent detailed clinical examinations and phenotype data were collected over a follow-up period of 9 years. Mutation analysis of the candidate gene BCOR was performed with polymerase chain reaction and Sanger sequencing. BCOR of 60 unrelated normal individuals were also sequenced as a control group. Clinical phenotyping and follow-up study results indicate that this patient had multiple system anomalies including ocular, facial, cardiac, dental, and limb malformations. In addition, papilloma of the choroid plexus was identified, which represents the first report of this phenotype in an OFCD patient. A novel deletion mutation, c.1296 delT in exon4 of the BCOR gene, was identified in this patient and was not found in her parents or in 60 normal unrelated individuals. This deletion was a frameshift mutation and is proposed to encode a premature stop codon, thus producing a truncated protein. Our patient fitted the diagnostic criteria for OFCD syndrome and we report the first papilloma of the choroid plexus in an OFCD patient, expanding the recognized phenotypic spectrum of this disease. Meanwhile, we identified a novel deletion mutation that may cause OFCD syndrome.     

草甸湿地土壤溶解有机碳淋溶动态及其影响因素

采用土柱淋溶试验研究了草甸湿地有机土层（2～13 cm）DOC的淋溶动态,并探讨了土壤呼吸、NH₄⁺产生速率和淋溶液pH与DOC生成速率的关系.试验第一周,小叶章湿草甸（Ⅺ）和小叶章沼泽化草甸（Ⅻ）土壤DOC的释放速率经历了一个快速下降的过程,而后达到平稳水平,其DOC的释放动态可用一次指数衰减方程进行描述（R²>0.96,P<0.05）.整个试验期间（35 d）,两种草甸湿地土壤DOC的累积释放量分别为2109（Ⅺ）和506.58 μgC·g^-1（Ⅻ）,CO₂的累积释放量为679.64（Ⅺ）和455.54 μgC·g^-1（Ⅻ）,表明Ⅺ的低DOC释放可能与高CO₂释放所造成的微生物碳源受限有关.DOC的释放速率与NH₄⁺的生成速率呈显著正相关（r_Ⅺ=0.886,P<0.05;r_Ⅻ=0.972,P<0.01）,而与淋溶液pH无相关性.多元回归分析表明,草甸湿地DOC的生成主要受土壤氮矿化潜势制约（P<0.05）.     

Metabolic response to MMS-mediated DNA damage in Saccharomyces cerevisiae is dependent on the glucose concentration in the medium

Maintenance and adaptation of energy metabolism could play an important role in the cellular ability to respond to DNA damage. A large number of studies suggest that the sensitivity of cells to oxidants and oxidative stress depends on the activity of cellular metabolism and is dependent on the glucose concentration. In fact, yeast cells that utilize fermentative carbon sources and hence rely mainly on glycolysis for energy appear to be more sensitive to oxidative stress. Here we show that treatment of the yeast Saccharomyces cerevisiae growing on a glucose-rich medium with the DNA alkylating agent methyl methanesulphonate (MMS) triggers a rapid inhibition of respiration and enhances reactive oxygen species (ROS) production, which is accompanied by a strong suppression of glycolysis. Further, diminished activity of pyruvate kinase and glyceraldehyde-3-phosphate dehydrogenase upon MMS treatment leads to a diversion of glucose carbon to glycerol, trehalose and glycogen accumulation and an increased flux through the pentose-phosphate pathway. Such conditions finally result in a significant decline in the ATP level and energy charge. These effects are dependent on the glucose concentration in the medium. Our results clearly demonstrate that calorie restriction reduces MMS toxicity through increased respiration and reduced ROS accumulation, enhancing the survival and recovery of cells.     

Evaluation of the eco-environmental frangibility in west Jilin Province based on the matter-element model

The west Jilin Province is a typical area in the ecotone between agriculture and animal husbandry, with a frangible eco-environment. With respect to the three aspects of water resource, natural disasters and land degradation, 10 indices were selected to establish a matter-element model for the assessment of eco-environmental frangibility in the west Jilin Province. The results indicate that during 1985-2000, Qian’an, Fuyu, and Changling had the least frangibility (level I), followed by Da’an and Qianguo (level II), and Taobei, Zhenlai, Taonan, and Tongyu had the highest frangibility (level III). On the whole, the counties in Songyuan city were less frangible than those in Baicheng city. Different counties had different frangibilities to environmental factors, e.g., Da’an and Tongyu were frangible in water resource conditions; Taobei, Zhenlai, Taonan, Tongyu and Qian’an suffered most from natural disasters; while Taobei, Taonan and Qianguo were threatened by severe land degradation. __________ Translated from Chinese Journal of Ecology, 2007, 26(2): 291–295 [译自: 生态学杂志]     

The Effects of Temperature and pH on Secondary Structure and Antioxidant Activity of Crocodylus siamensis Hemoglobin

Crocodylus siamensis hemoglobin (cHb) was purified by gel filtration chromatography and visualized by SDS-PAGE. Effects of temperature and pH on secondary structure and conformation changes of cHb were studied using circular dichroism spectropolarimeter and fourier transform infrared spectrophotometer. The secondary structure of intact cHb was mainly α-helices. cHb was not heat stable when heated at 65 °C and cooled down to original temperature, indicating the irreversible unfolding process. The stability of cHb at different pH ranging from 2.5 to 10.5 was determined. The maximum value of the α-helix content was found at pH 3.5 and tended to decrease at strong acid and strong base. The antioxidant activities of heat treated cHb and cHb in solution with pH range 2.5 to 10.5 were tested by DPPH radical scavenging assay. cHb at pH 4.5, having highest β-turn structure, showed highest radical scavenging activity. In contrast to pH, heat had no effect on antioxidant activity of cHb.