Nucleolar silver-stained granules in maturing erythroid and granulocytic cells

Summary Human and rabbit erythroid and granulocytic precursors in bone marrow have been investigated to provide information concerning the number of nucleolar silverstained granules (SSGs), which represent active interphasic nucleolar organizer regions (NORs). The differentiation and maturation of precursor cells of both investigated cell lines are characterized by a gradual decrease in number of nucleolar SSGs. In advanced maturation stages of erythroblasts or granulocytes, which are known to lose the capacity to divide, the number of nucleolar SSGs is smaller than the reported average or maximal values of NORs determined for human or rabbit cells. Since committed stem cells from both cell lines contain several times the number of nucleolar SSGs than the last dividing maturation and differentiation stages, the number of active parts of interphasic NORs in committed stem cells seems to be increased and might represent a stock for the later stages. In addition, the number of nucleolar SSGs appear to be a very convenient marker of nucleolar biosynthetic activity in individual differentiating and maturing blood cells. The differences between erythroid and granulocytic stem cells with respect to the number of nucleolar SSGs disappear during the course of further differentiation and maturation.     

Ligand Binding to Anion-binding Exosites Regulates Conformational Properties of Thrombin

Thrombin participates in coagulation, anticoagulation, and initiation of platelet activation. To fulfill its diverse roles and maintain hemostasis, this serine protease is regulated via the extended active site region and anion-binding exosites (ABEs) I and II. For the current project, amide proton hydrogen-deuterium exchange coupled with MALDI-TOF mass spectrometry was used to characterize ligand binding to individual exosites and to investigate the presence of exosite-active site and exosite-exosite interactions. PAR3(44–56) and PAR1(49–62) were observed to bind to thrombin ABE I and then to exhibit long range effects over to ABE II. By contrast, Hirudin(54–65) focused more on ABE I and did not transmit influences over to ABE II. Although these three ligands were each directed to ABE I, they did not promote the same conformational consequences. d-Phe-Pro-Arg-chloromethyl ketone inhibition at the thrombin active site led to further local and long range consequences to thrombin-ABE I ligand complexes with the autolysis loop often most affected. When Hirudin(54–65) was bound to ABE I, it was still possible to bind GpIbα(269–286) or fibrinogen γ′(410–427) to ABE II. Each ligand exerted its predominant influences on thrombin and also allowed interexosite communication. The results obtained support the proposal that thrombin is a highly dynamic protein. The transmission of ligand-specific local and long range conformational events is proposed to help regulate this multifunctional enzyme.     

高原鼢鼠对低氧高二氧化碳环境适应的相关血液生理指标的季节变化

高原鼢鼠是终生生活于地下封闭洞道中的一种啮齿动物。为了探讨高原鼢鼠对低氧和高二氧化碳环境的适应机制,对春、夏和秋三季高原鼢鼠血液生理指标以及心肌和骨骼肌肌红蛋白含量进行了测定。春、夏和秋季高原鼢鼠动脉血和静脉血pH值分别为7.44±0.09、7.44±0.05、7.51±0.07和7.17±0.05、7.29±0.07、7.35±0.08,动脉血pH在不同季节没有显著性差异,静脉血pH春季显著低于夏季和秋季。动脉和静脉血二氧化碳分压(Pco2)分别为47.81±14.50mmHg、55.10±13.50mmHg、53.00±10.81mmHg和75.17±31.09mmHg、75.40±20.21mmHg、80.00±17.44mmHg,没有季节性差异;动脉和静脉血氧分压(Po2)分别为76.17±33.24mmHg、78.90±16.61mmHg、88.67±24.94mmHg和7.34±4.07mmHg、10.60±2.76mmHg、10.33±3.56mmHg,没有季节性差异;动脉和静脉血血氧饱和度(SaO2)分别为92.71%±5.00%、94.70%±3.65%、96.00%±4.38%和4.27%±3.03%、9.01%±5.26%、9.67%±6.02%,动脉血SaO2没有季节性差异,而静脉血SaO2春季显著低于夏季和秋季。血液红细胞数(RBC)、血红蛋白(Hb)和红细胞压积(HCT),从春季到冬季依次增加,并具有显著性差异,血清诱导型一氧化氮合成酶(iNOS)活力随着夏季洞道中二氧化碳浓度的增加而显著提高。心肌和骨骼肌肌红蛋白(Mb)含量春季显著高于夏季和秋季,红细胞内2,3-二磷酸甘油酸(2,3-DPG)含量秋季显著高于春季和夏季。上述结果表明:随着洞道中氧气和二氧化碳浓度的季节波动,高原鼢鼠通过调节氧转运有关的功能蛋白含量以及氧代谢有关的生理机制维持组织的氧平衡。     

脑蛋白水解物对缺血性脑血管病患者血流动力学及神经功能的影响

目的:探讨脑蛋白水解物对缺血性脑血管病患者血流动力学、血脂水平及神经功能的影响。方法:92例缺血性脑血管病患者依据抽签法分作对照组与观察组,各46例,对照组采用常规治疗,观察组在常规治疗基础上结合脑蛋白水解物治疗,观察并比较两组患者的全血低切黏度、全血高切黏度、血浆黏度、红细胞压积、纤维蛋白原、总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白(LDL-C)高密度脂蛋白(HDL-C)、神经功能、脑血管储备能力、屏气指数以及临床效果。结果:治疗后,两组血流动力学均低于治疗前,且观察组低于对照组(P0.05);两组TC、TG、LDL-C均低于治疗前,且观察组低于对照组(P0.05);两组HDL-C均高于治疗前,且观察组高于对照组(P0.05);两组NIHSS均低于治疗前,且观察组低于对照组(P0.05);两组脑血管储备能力及屏气指数均高于治疗前,且观察组高于对照组(P0.05)。观察组治疗有效率高于对照组,差异具有统计学意义(P0.05)。结论:脑蛋白水解物可有效调节缺血性脑血管病患者血流动力学及血脂水平,改善神经功能。     

Assessing biodiversity loss due to land use with Life Cycle Assessment: are we there yet?

Ecosystems are under increasing pressure from human activities, with land use and land‐use change at the forefront of the drivers that provoke global and regional biodiversity loss. The first step in addressing the challenge of how to reverse the negative outlook for the coming years starts with measuring environmental loss rates and assigning responsibilities. Pinpointing the global pressures on biodiversity is a task best addressed using holistic models such as Life Cycle Assessment (LCA). LCA is the leading method for calculating cradle‐to‐grave environmental impacts of products and services; it is actively promoted by many public policies, and integrated as part of environmental information systems within private companies. LCA already deals with the potential biodiversity impacts of land use, but there are significant obstacles to overcome before its models grasp the full reach of the phenomena involved. In this review, we discuss some pressing issues that need to be addressed. LCA mainly introduces biodiversity as an endpoint category modeled as a loss in species richness due to the conversion and use of land over time and space. The functional and population effects on biodiversity are mostly absent due to the emphasis on species accumulation with limited geographic and taxonomical reach. Current land‐use modeling activities that use biodiversity indicators tend to oversimplify the real dynamics and complexity of the interactions of species among each other and with their habitats. To identify the main areas for improvement, we systematically reviewed LCA studies on land use that had findings related to global change and conservation ecology. We provide suggestion as to how to address some of the issues raised. Our overall objective was to encourage companies to monitor and take concrete steps to address the impacts of land use on biodiversity on a broader geographical scale and along increasingly globalized supply chains.     

Occurrence of bacterial indicators and bacteriophages infecting enteric bacteria in groundwater in different geographical areas

AIMS: The aim of this research was to determine the suitability of coliphages (bacteriophages) for assessing the microbial quality of groundwater. METHODS AND RESULTS: The number of several bacterial indicators (faecal coliforms, Escherichia coli, enterococci and spores of sulfite-reducing clostridia) and bacteriophages (somatic coliphages, F-specific RNA bacteriophages and bacteriophages infecting Bacteroides fragilis) were determined in groundwater of aquifers in various geographical areas. Results show that the relative abundance, determined as percentages of positive detections, of the bacterial indicators and bacteriophages varies depending on the aquifer. CONCLUSIONS: A single bacterial indicator may not be enough to assess microbiological quality in certain aquifers. One bacterial indicator and a bacteriophage parameter provide more information than two bacterial indicators. SIGNIFICANCE AND IMPACT OF THE STUDY: Coliphages (CPH) provide different information from that provided by bacterial indicators on the microbial quality of groundwater in different geographical areas. Easy, fast and inexpensive methods for the detection of CPH are feasible in both industrialized and developing countries.     

Psychedelic-inspired drug discovery using an engineered biosensor

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Multi-target novel neuroprotective compound ITH33/IQM9.21 inhibits calcium entry, calcium signals and exocytosis

Compound ITH33/IQM9.21 (ITH/IQM) belongs to a new family of l-glutamic acid derivatives with antioxidant and neuroprotective properties on in vitro and in vivo models of stroke. Because neuronal damage after brain ischemia is tightly linked to excess Ca²⁺ entry and neuronal Ca²⁺ overload, we have investigated whether compound ITH/IQM antagonises the elevations of the cytosolic Ca²⁺ concentrations ([Ca²⁺]_c) and the ensuing exocytotic responses triggered by depolarisation of bovine chromaffin cells. In fluo-4-loaded cell populations, ITH/IQM reduced the K⁺-evoked [Ca²⁺]_c transients with an IC₅₀ of 5.31 μM. At 10 μM, the compound decreased the amplitude and area of the Ca²⁺ transient elicited by challenging single fura-2-loaded cells with high K⁺, by 40% and 80%, respectively. This concentration also caused a blockade of K⁺-induced catecholamine release at the single-cell level (78%) and cell populations (55%). These effects are likely due to blockade of the whole-cell inward Ca²⁺ currents (IC₅₀ = 6.52 μM). At 10 μM, ITH/IQM also inhibited the Ca²⁺-dependent outward K⁺ current, leaving untouched the voltage-dependent component of I_K. The inward Na⁺ current was unaffected. Inhibition of depolarisation-elicited Ca²⁺ entry, [Ca²⁺]_c elevation and exocytosis could contribute to the neuroprotective effects of ITH/IQM in vulnerable neurons undergoing depolarisation during brain ischemia.     

实验性肾功能衰竭大鼠血浆中分子物质总量和自由基的变化研究

用腺嘌呤复制动物性慢性肾功能衰竭（ＣＲＦ）模型。观察大鼠血浆血尿素氮（ＢｕＮ）、血肌酐（Ｃｒ）、血红蛋白（Ｈｂ）、超氧化物歧化酶（ＳＯＤ）和中分子物质（ＭＭＳ）总量的变化。结果表明,ＣＲＦ大鼠血浆ＢｕＮ、Ｃｒ和ＭＭＳ总量明显升高（Ｐ〈０．０１）、Ｈｂ和ＳＯＤ含量显著降低（Ｐ〈０．０１）。提示ＣＲＦ大鼠ＭＭＳ总量升高、ＳＯＤ活性降低。     

非同位素PCR-SSCP方法的初步临床应用

单链构象多态性检测法 (PCR-SSCP)是近年发展起来的一项检测人类基因组 突变的新技术。然而,在该技术中需要使用放射性同位素标记的核苷酸或引物,从而限制 了其广泛临床研究及诊断方面的应用。本文报告一种改进的PCR-SSCP方法, 该方法不用 同位素标记引物,而直接在溴乙啶染色的聚丙烯酰胺凝胶上显示SSCP。用该方法对55例 平滑肌肉瘤p53基因第7外显子突变的检测表明,38%的瘤组织DNA存在异常的SSCP。其中10例有HaeⅢ和MspⅠ酶切位点的突变(18%), 19例有突变型p53蛋白的过度表达(9例同时有异常SSCP改变)。而p53质粒D NA,平滑肌瘤及Alzheimer病患者基因组DNA无p53基因第7外显子扩增片段的异常SSCP改变。同时,还使用该方法对临床诊断的20例Alzheimer病患者和8例健康对照进行了β-淀粉样蛋白前体基因第16和17外显子的扩增及分析,均未发现有异常SSCP改变及EcoRⅠ,BclⅠ酶切位点的突变。本研究结果提示,该非同位素PCR-SSCP方法可靠、敏感、简便、快速,具有潜在的推广价值。