Inhibition of parathormone-stimulated bone resorption by type I interferon

The effect of Type I interferon on bone resorption was studied by measuring its effect on parathormone-stimulated calcium release from neonatal murine calvaria in vitro. A pure human recombinant leukocyte interferon hybrid of the A and D subtypes was used, which has high antiviral activity on mouse cells. Calcium release was inhibited in a dose dependent fashion with 50% inhibition at about 10(-10) M or 600 U/ml, and the inhibition was reversible. The presence of interferon was required before or during the activation phase of the resorptive response, when the formation of osteoclasts from precursor cells would occur. When added to actively resorbing bone it had no effect. The data suggest that Type I interferon can inhibit the parathormone-regulated development of active osteoclasts, possibly by inhibiting osteoclast precursor differentiation.     

Metal-directed affinity labeling of zinc(II), cobalt(II) and cadmium(II) horse liver alcohol dehydrogenases

The active site metal in horse liver alcohol dehydrogenase has been studied by metal-directed affinity labeling of the native zinc(II) enzyme and that substituted with cobalt(II) or cadmium(II). Reversible binding of bromoimidazolyl propionic acid to the cobalt enzyme blueshifts the visible absorption band originating from the catalytic cobalt atom at 655 to 630 nm. Binding of imidazole to the cobalt(II) enzyme redshifts the 655 nm band to 667 nm. Addition of bromoimidazolyl propionic acid blueshifts this 667 nm band back to 630 nm. This proves direct binding of the label to the active site metal in competition with imidazole. The affinity of the label for the reversible binding site in the three enzymes follows the order Zn ? Cd ? Co. After reversible complex formation, bromoimidazolyl propionic acid alkylates cysteine-46, one of the protein ligands to the active site metal. The nucleophilic reactivity of this metal-mercaptide bond in each reversible complex follows the order Co ? Zn ? Cd.     

Further characterization and thiophosphorylation of smooth muscle myosin

(i) Myosin from chicken gizzards was purified by a modification of an earlier procedure (M. N. Malik, 1978,Biochemistry17, 27–32). When this myosin, as well as that prepared by the method of A. Sobieszek and R. D. Bremel (1975,Eur. J. Biochem.55, 49–60), was analyzed by gradient slab gel using the discontinuous buffer system of Neville (1971,J. Biol. Chem.246, 6328–6334), a closely spaced doublet in the heavy chain and four light chains were observed as opposed to one heavy chain and two light chains with the method of Weber and Osborn (1969, J. Biol. Chem.244, 4406–4412). These findings raise the possibility of the existence of myosin isoenzymes in smooth muscle. (ii) The purified gizzard myosin was found to be free of kinase and phosphatase. Phosphorylation or thiophosphorylation of myosin was observed only by exogenously adding kinase. A maximum of 1.2 mol of ³²P/mol of myosin and 2.3 mol of ³⁵S/mol of myosin were obtained. The actin-activated ATPase activity depended upon the extent of thiophosphorylation of myosin; a four- to fivefold increase in the activity was observed when myosin was fully thiophosphorylated. Thiophosphorylated myosin was found to be more stable than phosphorylated myosin.     

Comparison of steady-state kinetics of thiophosphorylated versus unphosphorylated smooth muscle myosin

(i) The steady-state kinetic data obtained with purified gizzard and uterus smooth muscle myosins indicated the presence of a plateau region on the substrate-saturation curves. Hill plots of these data provided evidence for mixed positive and negative cooperative interactions. In contrast, when gizzard myosin was prepared according to the method of A. Sobieszek and R.D. Bremel (1975, Eur. J. Biochem.55, 49–60), the saturation curve in the presence of CaATP was hyperbolic and no cooperativity of the binding site(s) was discerned. However, in the presence of MgATP although the curve appeared hyperbolic the Hill plot of the data was biphasic with negative cooperativity at low MgATP concentration, (ii) When thiophosphorylated gizzard myosin was used for kinetic analysis, the plateau region in the presence of MnATP was eliminated from the saturation curve and this curve became hyperbolic. However, in the presence of MgATP, although the plateau was almost eliminated, the saturation curve was still biphasic with either no or greatly reduced negative cooperativity of binding sites at low MgATP concentrations but positive cooperativity of binding at high MgATP concentrations. In addition, the thiophosphorylation of myosin also increased the K_m and V of MgATP and MnATP, thus indicating weaker affinity for these substrates with thiophosphorylated myosin. (iii) Gizzard myosin also hydrolyzed other nucleotides (the order of rates being CTP = ITP > ATP = UTP > GTP), therefore saturation kinetics using different nucleotides as substrates was also carried out. The saturation curves with each nucleotide were different i.e., hyperbolic with CTP, sigmoid with GTP, hyperbolic with biphasic Hill plot with ITP, and possessing plateau with UTP. In addition, it was observed that the kinetic pattern with each nucleotide was very sensitive to temperature and pH.     

1,6-Diamino-2,5-anhydro-1,6-dideoxy-dl-glucitol and some derivatives thereof

1,6-Diamino-2,5-anhydro-1,6-dideoxy-dl-glucitol dihydrochloride and some derivatives were synthesized from 3,5-di-O-acetyl-1,6-dibromo-1,6-dideoxy-d-mannitol. Introduction of the 2,5-anhydro ring and subsequent replacement of the terminal bromine atoms by azide gave low yields of the diazide; therefore, a reverse reaction-sequence was applied. The azido groups were reduced with hydrogen sulfide-pyridine, and the amino groups formed were methylated by using formaldehyde-formic acid and subsequently treating with borohydride. According to ¹³C-n.m.r. investigations, the symmetrically substituted, 2,5-anhydroglucitol derivatives are present mainly in the ⁴T₃ [“north” (N) type of twist] conformation, whereas the analogous l-iditol derivatives mainly adopt the ³T₄ [“south” (S)] type. The different quaternary salts obtained on methylation of the corresponding 1,6-bis(dimethylamino)derivatives with methyl iodide (aiming at the structure of epi-muscarine) showed no muscarine-like, biological activity.     

基于“管制平衡”的草原生态补偿政策参与式干预发展评价研究

从整体性治理理论视角出发,深入分析了草原生态补偿政策实施过程中的管制与治理维度,认为草原生态补偿政策是一个"管制平衡"导向型政策,进而提出从"参与式干预发展"的角度对该政策的实施效果进行综合性评价。基于内蒙古锡林郭勒典型草原的一个纯牧业嘎查(村庄)的案例研究,将参与式干预发展评价(PADev)方法的应用进行了详细呈现,并获得了兼具"形成性"和"主体间性"的综合性评价结论与发现。为验证PADev的适合性和科学性,从"元评价"的角度,进一步呈现了基于生态调研和抽样社会调查的评价,作为PADev方法的"验证性"评价。案例研究发现,草原生态补偿政策的地位和作用体现在"草-畜-人"历史性(长达35年,从1983年牲畜承包开始)发展变迁的结构关系中,从政策作用的末端来评价生态补偿政策所产生的生态效益,比较难以直接确定其因果关系,但从基于制度变迁的路径依赖及未来发展的角度,政府主导的生态补偿政策将积极地促进牧民们的自主整合和适应市场的发展,以及"生态载畜量"和"实际载畜量"的收敛趋同。     

青藏高原重大建设工程生态修复综合效益评估指标体系

青藏高原作为我国重要的生态屏障和战略资源基地,兼顾经济社会的发展和生态环境的保护,是当前区域发展的主要目标。为实现该目标,国家先后开展了多项推动当地经济发展的重大建设工程项目,并在项目开展的过程中,针对出现的生态问题,实施了一系列的生态修复措施。目前针对青藏高原重大建设工程生态修复的研究,在多工程类型修复效益的融合,以及宏观空间布局尺度上对生态修复成效的评估还相对较少,并且缺乏统一的评价标准。故本研究选取青藏高原道路、水电和矿产开发三类典型的重大建设工程,结合区域及工程特点,通过文献调研、业界专家咨询等方法手段,以生态修复后的生态系统结构、质量和服务为核心架构,筛选能够综合客观的反映该地区生态修复效益的具体指标,最终构建系统、合理和科学的青藏高原重大建设工程生态修复综合效益评估指标体系。该评估指标体系涉及生态系统结构、质量和服务三大指标类别,包括10个主题指标,21个具体指标。以期为青藏高原重大建设工程生态修复效益的总体认知和长期监测,以及未来生态修复工程的制定、建设工程的布局及其他生态系统管理措施的实施,和未来生态修复评估的相关研究提供科学参考和理论支撑。     

旅游生态系统能值研究进展

能值分析是以能值为基准,通过能值转换率,有效测度与评价生态系统及经济系统中不同类型的物质流、能量流、货币流及其相互关系的方法。旅游生态系统是特殊类型的人地关系地域系统,是以旅游活动为中心的"自然、经济、社会、旅游"复合系统,利用能值方法进行旅游能值研究可以为旅游可持续发展提供科学建议。通过对国内外相关研究重要文献的梳理,从旅游能值研究尺度与类型角度,分析了国内外相关研究进展,并通过与农业、工业系统的能值研究对比分析,目前研究在理论推进、要素选择、指标构建、方法集成等4个方面,旅游生态系统能值研究存在特殊性,并从理论、方法、内容等3个角度,提出了今后旅游能值研究的方向,以期推动旅游系统能值研究的深入。     

PBL教学模式在病原生物学理论教学中的应用

PBL 教学法是一种源自西方,近年来引入我国全新教学模式,它主要培养学生的自学能力,发展学生综合思考能力和解决实际问题能.本文作者总结了中国医科大学病原生物学教研室三年来在理论课教学中采用PBL教学模式的实践经验,通过样本成绩分析证明了 PBL 教学方法对于提高学生综合思考能力很有帮助,同时在意见反馈结果中也显示学生对于 PBL 教学模式有很高的热情,可以很好地发挥学生的主观能动性.     

基于可持续发展目标的资源型城市可持续发展评价技术及应用——以湖南省郴州市为例

资源型城市作为我国重要战略保障基地,面临较为突出的不可持续问题,定量化开展可持续发展水平监测评估是推动其绿色转型发展、激活再生动力的重要途径。基于联合国可持续发展目标体系(SDGs),结合行星边界理论,从资源型城市可持续发展特征出发,建立了由2个系统、4个支柱、12个领域和48项指标组成的资源型城市可持续发展评价指标体系。借鉴全球SDGs监测评估实践经验,考虑指标属性,综合确定各指标的阈值,并采用改进的离差标准化、障碍度分析及耦合协调度分析等方法建立综合评价技术体系。以拥有“有色金属之乡”称号的郴州市国家可持续发展议程创新示范区为评价对象,对其2005—2019年连续15年的可持续发展水平进行实证分析。结果表明：(1)郴州市可持续发展水平整体上呈现稳步上升趋势,得分由0.398上升到0.610。(2)4个支柱中,自然资源支柱的得分进步幅度最大,高达71.3%,说明郴州市已经逐步提高对资源利用效率的重视,同时意识到挖掘替代资源的重要性,资源保障与利用能力不断提升;而发展动力支柱得分始终处于较弱或中等水平,已成为制约郴州市可持续发展和绿色转型的主要因素,其中科技创新驱动是该支柱发展关键障碍...