Cystine Deprivation Induces Oligodendroglial Death: Rescue by Free Radical Scavengers and by a Diffusible Glial Factor

Abstract: In this study we examined the effect on oligodendroglial survival of exogenous cystine deprivation. Oligodendroglia isolated from mixed glial primary cultures derived from brains of 1-day-old rats, and then grown for 3 days, were markedly dependent on extracellular cystine for survival. The EC₅₀ values for cystine for a 24-h exposure ranged from 2 to 65 µ M . After 6 h of cystine deprivation, the cellular glutathione level decreased to 21 ± 13% of the control. Free radical scavengers (α-tocopherol, ascorbate, idebenone, and N-tert -butyl-α-phenylnitrone) were protective against cystine deprivation but had no effect on the glutathione level. An iron chelator, desferrioxamine mesylate, also was protective. These findings suggest that intracellular hydroxyl radicals are important for this toxicity. In contrast to the observations in 3-day-old cultures, the dependence on exogenous cystine for cell viability was not observed consistently in oligodendroglia cultured for 6 days before the onset of cystine deprivation. Several observations suggested that this loss of cystine dependence was due to a diffusible factor. Sensitivity to the toxicity of cystine deprivation in day 6 cultures increased as the volume of medium was increased from 0.3 to 2 ml. Furthermore, preincubation of cystine-depleted medium with astrocyte cultures eliminated the toxicity of the cystine deprivation. HPLC assay of the conditioned cystine-depleted medium showed no significant change in cystine or cysteine concentration. We conclude that oligodendroglia are highly susceptible to cystine deprivation in day 3 cultures and that this susceptibility is due to the accumulation of intracellular free radicals in the setting of glutathione depletion. The resistance of day 6 oligodendroglial cultures is caused at least in part by a diffusible factor.     

陕西省新型城镇化与生态环境协调度研究

城镇化与生态环境之间相互影响、相互促进，两系统间耦合协调状态对于区域绿色可持续发展意义重大。以陕西省2005—2019年数据为例，在构建新型城镇化与生态环境系统评价指标体系的基础上结合耦合协调度模型、相对发展模型及面板向量自回归(PVAR)模型分析新型城镇化系统与生态环境系统间的耦合协调时空规律及互动关系。结果表明：(1)陕西省耦合协调度总体呈现“基本不协调—基本协调—中度协调”的演变规律。(2)各市耦合协调发展状态空间差异明显，2005年、2013年、2019年陕西省10个城市新型城镇化与生态环境耦合协调发展状态存在较大差异性，相对发展状态整体上由新型城镇化滞后状态发展为生态环境滞后状态。(3)脉冲响应图反映出新型城镇化与生态环境两系统间存在明显互动关系，前期生态环境受新型城镇化冲击的负向抑制作用，后期影响逐渐减小，受自身冲击较大，而新型城镇化发展前后期均主要受自身影响。本研究认为新型城镇化发展必须以生态为优先，在提高生态承载力的基础上，加速提升陕西省各区域空间人口等不同维度城镇化发展水平，从而实现高质量可持续的绿色发展目标。     

山岳型乡村旅游地“三生”空间演变及优化——德庆金林水乡的案例实证

以德庆县金林水乡为例,采用参与式观察和空间统计法,选取2000、2008年和2018年3个时段分析旅游发展对山岳型乡村旅游地"三生"空间的影响,并探讨了金林水乡"三生"空间的发展瓶颈及优化路径。研究发现:(1)旅游开发前,金林水乡土地结构与用地功能单一且呈片状分布;村落呈现传统乡村风貌,基础设施不健全;空间形态变化稳定,扩张缓慢。(2)旅游开发后,土地利用类型多样化,出现新型复合用地;土地功能利用复杂化,以服务旅游业为主;村庄景观风貌现代化,生活空间更加宜居。(3)旅游开发前后对比可得,土地平面占地规模化,空间用地以居民点为核心,呈圈层状向外围扩张;生产-生活-生态空间相互转化,乡村聚落重构特征较为显著;村落景观风貌的变化较大,呈现城镇化趋势。(4)金林水乡"三生"空间演化与旅游发展存在的问题表现在生产用地效率不高,生活用地质量较低,生态空间不断萎缩,在旅游产业发展上表现为旅游产品单一且缺乏创新,旅游服务功能不完善等。为此从生活空间的提质、生产空间增效、生态空间保护、旅游产业创新以及土地利用五方面提出优化建议。     

In-depth Profiling and Quantification of the Lysine Acetylome in Hepatocellular Carcinoma with a Trapped Ion Mobility Mass Spectrometer

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with limited therapeutic options. Comprehensive investigation of protein posttranslational modifications in HCC is still limited. Lysine acetylation is one of the most common types of posttranslational modification involved in many cellular processes and plays crucial roles in the regulation of cancer. In this study, we analyzed the proteome and K-acetylome in eight pairs of HCC tumors and normal adjacent tissues using a timsTOF Pro instrument. As a result, we identified 9219 K-acetylation sites in 2625 proteins, of which 1003 sites exhibited differential acetylation levels between tumors and normal adjacent tissues. Interestingly, many novel tumor-specific K-acetylation sites were characterized, for example, filamin A (K865), filamin B (K697), and cofilin (K19), suggesting altered activities of these cytoskeleton-modulating molecules, which may contribute to tumor metastasis. In addition, we observed an overall suppression of protein K-acetylation in HCC tumors, especially for enzymes from various metabolic pathways, for example, glycolysis, tricarboxylic acid cycle, and fatty acid metabolism. Moreover, the expression of deacetylase sirtuin 2 (SIRT2) was upregulated in HCC tumors, and its role of deacetylation in HCC cells was further explored by examining the impact of SIRT2 overexpression on the proteome and K-acetylome in Huh7 HCC cells. SIRT2 overexpression reduced K-acetylation of proteins involved in a wide range of cellular processes, including energy metabolism. Furthermore, cellular assays showed that overexpression of SIRT2 in HCC cells inhibited both glycolysis and oxidative phosphorylation. Taken together, our findings provide valuable information to better understand the roles of K-acetylation in HCC and to treat this disease by correcting the aberrant acetylation patterns.     

中国东方铃蟾(Bombina orientalis)皮肤中C_(-12-b)肽的分离与鉴定

东方铃蟾鲜皮的甲醇提取液,可引起大鼠离体平滑肌的收缩。此液经碱性氧化铝柱层析分离,其80%乙醇洗脱的 C 组分显示生物活性。C 组分再经葡聚糖凝胶 G-15柱分离,其活性较强的早期洗脱组分 C_(_12),可被糜蛋白酶水解灭活,但其活性并不被5-HT 拮抗剂赛庚啶[2×10~(-6)mol/L]完全拮抗。继用反相高效液相色谱(RP-HPLC)分析,见分离出的 C_(_12_h)峰与铃蟾肽~*(Bombesin,BBS)的出峰时间相同,且具相同的氨基酸组成。上述实验结果提示,C_(_12_h)肽可能就是铃蟾肽。     

普通小麦栽培品种丰抗13的4B—1D染色体易位的鉴定

通过细胞学观察,在普通小麦栽培品种“丰抗13”和“京红1号”的杂交后代中,发现有多价体出现,这就表明有染色体易位发生。为进一步弄清究竟是哪条染色体发生了易位,我们采用单体测交方法,观察鉴定所有各单体系F_1的花粉母细胞第一次减数分裂中期Ⅰ(以下简称PMCs中Ⅰ)染色体构型。从鉴定结果发现,凡2n=42的F_1 PMCs中Ⅰ出现19~Ⅱ 1~Ⅳ,而2n=41的F_1PMCs中Ⅰ的染色体构型不同,单体与易位有关的两个单体系4B和1D F_1 PMCs中的Ⅰ构型中有部分呈现为19个二价体加1个三价体,即19~Ⅱ 1~Ⅲ,没有单价体,而其余各单体系F_1 PMCs中Ⅰ构型则表现为18个二价体,1个四价体和1个单价体,即18~Ⅱ 1~Ⅰ 1~Ⅳ。因此,可以肯定“丰抗13”存在1个染色体易位,其有关染色体就是4B和1D。     

清醒狗短暂缺血心肌复灌注时舒缩功能的变化

在狗的心脏上装入微超声探头和高精度微压力传感器,手术后两星期,在清醒状态下给予左冠状动脉旋支阻断三分钟。在复灌注过程中,观察到血液动力学指标与收缩期心室壁厚度(WT)迅速恢复正常;但在 dWT/dt—WT 环形图上出现舒张早期异常相,其形状与缺血过程不同。低氧和急遽冠状动脉过度充盈可以产生此种异常图形。我们推测,心肌缺血可能促使一些产物的形成,复灌注时它使冠脉过度舒张,冠脉灌注增加,从而造成舒张早期急遽充盈而形成了此种异常的形图。     

Proteolytic processing of Blattella germanica vitellin during early embryo development

In the eggs of the cockroach Blattella germanica, vitellin (Vt) utilization is initiated 4 days postovulation by the proteolytic processing of its three subunits. These reactions yield a specific set of peptides that are consumed by the developing embryo. A yolk proteinase activity, believed central to this processing event, has been investigated. First expressed at day 3 postovulation, just prior to Vt's processing, its specific activity with synthetic substrates increased four-fold to 18-fold through day 6. In addition, a mixing experiment showed that these proteinases(s) can also process Vt's large subunits in vitro. A relationship between Vt processing and proteinase specific activity was also noted with two B. germanica translocation heterozygotes, which displayed differences in the extent of Vt processing. One group of eggs (group A) failed to process any Vt subunit. A second group (B) processed the M_r 102,000 subunit but not the M_r 95,000. A third group (C) processed their Vt normally. Proteinase specific activities in the yolk of translocant's eggs at day 6 mirrored the extent of processing, being highest in group C eggs and effectively absent from the yolk of group A eggs. Eggs defective in Vt processing also contained arrested embryos. It is concluded that the yolk proteinase activity described here participates in Vt processing at day 4 postovulation. Microscopic examination of yolk obtained from eggs of wild type females showed that, as processing began in vivo (day 4), the yolk granules also underwent an abrupt decrease in size from diameters of 15–30 μm to 3–10 μm. Yolk granules of those translocant's eggs that were defective in Vt processing did not undergo this size decrease, suggesting that granule reorganization and Vt proteolysis may be linked functionally.     

四川省米虾属一新种的描述（十足目：匙指虾科）

本文报道的刺肢米虾,新种Caridina spinipoda sp. nov。是采自四川绵竹泉水溪流中的二个雄性个体。其形状很似叶状米虾Caridina babaultioides Yu,但它第一腹肢内肢的结构非常特殊,因其周缘排列有既长又粗的刺而命名。