Regulation of c-Myc Expression by Ahnak Promotes Induced Pluripotent Stem Cell Generation

We have previously reported that Ahnak-mediated TGFβ signaling leads to down-regulation of c-Myc expression. Here, we show that inhibition of Ahnak can promote generation of induced pluripotent stem cells (iPSC) via up-regulation of endogenous c-Myc. Consistent with the c-Myc inhibitory role of Ahnak, mouse embryonic fibroblasts from Ahnak-deficient mouse (Ahnak^−/− MEF) show an increased level of c-Myc expression compared with wild type MEF. Generation of iPSC with just three of the four Yamanaka factors, Oct4, Sox2, and Klf4 (hereafter 3F), was significantly enhanced in Ahnak^−/− MEF. Similar results were obtained when Ahnak-specific shRNA was applied to wild type MEF. Of note, expressionof Ahnak was significantly induced during the formation of embryoid bodies from embryonic stem cells, suggesting that Ahnak-mediated c-Myc inhibition is involved in embryoid body formation and the initial differentiation of pluripotent stem cells. The iPSC from 3F-infected Ahnak^−/− MEF cells (Ahnak^−/−-iPSC-3F) showed expression of all stem cell markers examined and the capability to form three primary germ layers. Moreover, injection of Ahnak^−/−-iPSC-3F into athymic nude mice led to development of teratoma containing tissues from all three primary germ layers, indicating that iPSC from Ahnak^−/− MEF are bona fide pluripotent stem cells. Taken together, these data provide evidence for a new role for Ahnak in cell fate determination during development and suggest that manipulation of Ahnak and the associated signaling pathway may provide a means to regulate iPSC generation.     

祁连山青海云杉林群落结构的空间异质性

以动态监测样地(340 m×300 m)的网格(5 m×5 m)为基本单元,选择5个群落结构属性变量,采用分形几何学和地统计学方法对祁连山大野口流域青海云杉林群落结构的空间异质性进行研究.结果表明: 青海云杉林5个结构属性的变异程度大小依次为:密度＞平均冠幅＞显著度＞盖度＞平均树高,变异系数为43.7%～79.6%.Moran I系数表明,各个结构属性均有不同程度的空间自相关性,自相关大小顺序为:密度＞平均树高＞盖度＞平均冠幅＞显著度,变化范围为-0.047～0.382.指数理论变异函数模型能很好地拟合不同结构属性的空间变异,变程为24.6～68.1 m,各属性变量的结构比除盖度表现为中等空间相关,其他指标均为强烈空间相关,各属性指标分维数接近2,空间依赖性较小.植被密度和盖度空间分布呈带状结构和斑块结构叠加的特点,其他指标呈较强的斑块状空间结构,密度和盖度对平均冠幅、显著度和平均树高有一定的空间依赖性.青海云杉林群落结构空间异质性适宜的采样间隔和采样面积分别为10 m和0.5 hm².     

大肠杆菌棉子糖操纵子α—半乳糖苷酶表达的调节控制

The alpha-galactosidase, coded for by the first structural gene rafA in the plasmid determined raf operon was an inducible enzyme. In contrast to lac or mel operon, raf operon has more strict structural specificity for inducers. The enzyme can be induced by melibiose and raffinose, or weakly by D-galactose, but not by structurally related sugars such as lactose, PNPG etc.. The alpha-galactosidase forming capacity as function of growth curve reached a single peak at the end of the logarithmic phase of the growth. The structure and regulation of raf operon is similar to those of lac operon. The repressormor-mediated negative control plays a major role in the regulation of raf operon, and cAMP-CAP mediated positive control is also involved in the regulation. When 0.4% glucose was added into the medium with other carbon sources, the expression of the enzyme was repressed by 2-3 fold. Transient catabolite repression has been observed neither in inducible nor constitutive alpha-galactosidase expression. Based on alpha-galactosidase assay, in mutant strains CA8306(cya) and CA8445 (cya, crp) the expression level of raf operon was only 9% and 2.5% of that in wild type strain respectively. The glucose effect or the repression in cya mutant can be abolished by 1-5 mmol cAMP. The constitutive alpha-galactosidase expression in cya and cry double mutant (CA8445) remains repressible by glucose, but irreversible by cAMP, suggesting cAMP-CAP complex is not the exclusive mediator of the catablite repression.(ABSTRACT TRUNCATED AT 250 WORDS)     

格网尺度下典型旅游城市生态服务价值估算和时空分异特征——以三亚为例

以典型旅游城市三亚市为案例地,利用2006-2018年4期Landsat遥感影像数据,借助ENVI、ArcGIS平台定量识别土地利用演变特征,在1km×1km格网尺度下估算旅游地生态系统服务价值,并结合空间探索性数据分析揭示生态系统服务价值时空分异特征及其与旅游地发展的时空耦合关系。结果表明：（1）2006-2018年间,三亚市生态系统服务价值总量呈逐年下降趋势,由6.73×10⁹元降至5.76×10⁹元,累计减少9.78×10⁸元;（2）空间格局上,三亚市呈"南低北高"空间分异格局,2006-2018年增值区域连片分布于崖州区、天涯区、吉阳区南部区域,且呈逐年减少趋势,减值区域集聚于天涯区东北部、海棠区;（3）空间集聚上,生态系统服务价值截面各年份均呈显著空间正相关且相关性先降后增。高高集聚区位于天涯区北部区域,低低集聚区分布于沿海、海湾地区;（4）旅游发展与生态系统服务价值时空演化特征关联性较强。三亚市天涯区北部林地生态环境良好,生态系统服务价值略有下降但绝对数值稳定,是生态系统服务价值主要来源;旅游发展较为迅速的三亚湾、崖州湾以及海棠湾,相对增值区域较多,但绝对生态系统服务价值损失显著,严重滞后于其他区域。     

A natural product enhances apoptosis via mitochondria/caspase-mediated pathway in HeLa cells

Cervical cancer is the fourth most lethal human malignancy and the leading cause of death among females around the world. Many antitumor agents have microbial origins. 5′-epi-SPA-6952A is a new 24-membered macrolide isolated from the cultured broth of Streptomyces diastatochromogenes. Therefore, we studied the activity and molecular mechanism of 5′-epi-SPA-6952A in human cervical carcinoma HeLa cell. The results showed that 5′-epi-SPA-6952A significantly inhibited cell proliferation and migration. In addition, 5′-epi-SPA-6952A obviously increased the production of intracellular reactive oxygen species and DNA damage in HeLa cells. Moreover, nuclear shrinkage of cells, decrease in mitochondrial membrane potential, and upregulation of Bax/Bcl-2 ratio resulted in the release of cytochrome c, and activation of caspase-9/3 was observed in HeLa cells treated with 5′-epi-SPA-6952A, which means it enhanced the intrinsic mitochondrial apoptosis. Besides, DNA-damage associated proteins poly (ADP-ribose) polymerase (PARP) and p53 were also studied, and the expressions of cleaved-PARP and p53 were drastically increased in HeLa cells treated with 5′-epi-SPA-6952A. Furthermore, we confirmed that 5′-epi-SPA-6952A affected the survival of HeLa cells by blocking cell cycle progression in the G1 phase. Taken together, the results shows that 5′-epi-SPA-6952A significantly inhibited HeLa cells proliferation via intrinsic mitochondrial apoptosis, cell cycle arrest, and blocking cell migration.     

Receptor‐like kinase OsSIK1 improves drought and salt stress tolerance in rice (Oryza sativa) plants

Receptor‐like kinases (RLKs) play essential roles in plant growth, development and responses to environmental stresses. A putative RLK gene, OsSIK1, with extracellular leucine‐rich repeats was cloned and characterized in rice (Oryza sativa). OsSIK1 exhibits kinase activity in the presence of Mn²⁺, and the OsSIK1 kinase domain has the ability to autophosphorylate and phosphorylate myelin basic protein (MBP). OsSIK1 promoter‐GUS analysis revealed that OsSIK1 is expressed mainly in the stem and spikelet in rice. The expression of OsSIK1 is mainly induced by salt, drought and H₂O₂ treatments. Transgenic rice plants with overexpression of OsSIK1 show higher tolerance to salt and drought stresses than control plants. On the contrary, the knock‐out mutants sik1‐1 and sik1‐2, as well as RNA interference (RNAi) plants, are sensitive to drought and salt stresses. The activities of peroxidase, superoxide dismutase and catalase are enhanced significantly in OsSIK1‐overexpressing plants. Also, the accumulation of H₂O₂ in leaves of OsSIK1‐overexpressing plants is much less than that of the mutants, RNAi plants and control plants, as measured by 3,3′‐diamino benzidine (DAB) staining. We also show that OsSIK1 affects stomatal density in the abaxial and adaxial leaf epidermis of rice. These results indicate that OsSIK1 plays important roles in salt and drought stress tolerance in rice, through the activation of the antioxidative system.     

Utilization of PEI-modified Corynebacterium glutamicum biomass for the recovery of Pd(II) in hydrochloric solution

A new type of biosorbent was developed for binding anionic precious metals through cross-linking waste biomass Corynebacterium glutamicum with polyethylenimine (PEI). This biomass was evaluated for the removal and recovery of palladium and compared to commercial adsorbents, such as Amberjet 4200 Cl, Lewatit Monoplus TP 214, SPC-100, and SPS-200. The kinetic experiments revealed that the sorption equilibrium was reached with 30 min for the PEI-modified biomass. The maximum uptake of the biosorbent was 176.8 mg/g, which was calculated using the Langmuir model. The Pd(II) maximum uptake exhibited the following order: Amberjet 4200 Cl > Lewatit Monoplus TP 214 > PEI-modified biomass > SPC-100 > SPS-200. Acidified thiourea in 1.0 M HCl was used to desorb Pd(II) from all of the sorbents examined.     

In Vitro Activity of Sodium New Houttuyfonate Alone and in Combination with Oxacillin or Netilmicin against Methicillin-Resistant Staphylococcus aureus

Background

Staphylococcus aureus can cause severe infections, including bacteremia and sepsis. The spread of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for novel treatment options. Sodium new houttuyfonate (SNH) is an analogue of houttuynin, the main antibacterial ingredient of Houttuynia cordata Thunb. The aim of this study was to evaluate in vitro activity of SNH and its potential for synergy with antibiotics against hospital-associated MRSA.

Methodology

A total of 103 MRSA clinical isolates recovered in two hospitals in Beijing were evaluated for susceptibility to SNH, oxacillin, cephalothin, meropenem, vancomycin, levofloxacin, minocycline, netilmicin, and trimethoprim/sulfamethoxazole by broth microdilution. Ten isolates were evaluated for potential for synergy between SNH and the antibiotics above by checkerboard assay. Time-kill analysis was performed in three isolates to characterize the kill kinetics of SNH alone and in combination with the antibiotics that engendered synergy in checkerboard assays. Besides, two reference strains were included in all assays.

Principal Findings

SNH inhibited all test strains with minimum inhibitory concentrations (MICs) ranging from 16 to 64 µg/mL in susceptibility tests, and displayed inhibition to bacterial growth in concentration-dependent manner in time-kill analysis. In synergy studies, the combinations of SNH-oxacillin, SNH-cephalothin, SNH-meropenem and SNH-netilmicin showed synergistic effects against 12 MRSA strains with median fractional inhibitory concentration (FIC) indices of 0.38, 0.38, 0.25 and 0.38 in checkerboard assays. In time-kill analysis, SNH at 1/2 MIC in combination with oxacillin at 1/128 to 1/64 MIC or netilmicin at 1/8 to 1/2 MIC decreased the viable colonies by ≥2log₁₀ CFU/mL.

Conclusions/Significance

SNH demonstrated in vitro antibacterial activity against 103 hospital-associated MRSA isolates. Combinations of sub-MIC levels of SNH and oxacillin or netilmicin significantly improved the in vitro antibacterial activity against MRSA compared with either drug alone. The SNH-based combinations showed promise in combating MRSA.     

Design and Optimization of a Graphene Modulator Based on Hybrid Plasmonic Waveguide with Double Low-Index Slots

Plasmonics - Graphene modulators based on surface plasmonic waveguides enable a strong interaction between light and graphene because great electric field enhancement occurs in the sub-wavelength...     

天敌应激下小鼠血浆皮质酮、巨噬细胞产生NO、IL-1β水平与脑不对称性

为探讨天敌应激下脑不对称性对小鼠HPA轴活性及巨噬细胞功能的影响,通过伸爪取食法将Balb/c小鼠分为左利、右利、双利组,分别暴露在鼠类天敌——猫急性应激（45 min,1次）、慢性应激（45 min/次,每天1次,连续14天）刺激后,分别用EIA法、硝酸还原酶法、ELISA法测定了血浆皮质酮、腹腔巨噬细胞培养上清中一氧化氮（nitric oxide, NO）、IL-1β水平. a.血浆皮质酮水平：急性应激下,右利、双利组小鼠血浆皮质酮升高,右利组更为显著,左利组呈下降趋势,右利、双利组显著高于左利组及相应正常对照组（P＜0.05）;慢性应激下,右利、双利组显著高于相应正常对照组,左利、双利组也显著高于急性应激下相应组（P＜0.05）.b.NO水平：急性应激下,左利组腹腔巨噬细胞培养上清中NO无显著变化,右利、双利组呈升高趋势,右利显著高于左利（P＜0.05）;慢性应激中,三组NO水平均显著高于相应正常对照组（P＜0.05）.c.IL-1β水平：急性应激下,左利组IL-1β水平显著低于相应正常对照组,P＜0.05;慢性应激下,左利、双利组与正常对照组相比均有所降低,但无统计学意义（P＞0.05）,右利组则显著高于相应正常对照组（P＜0.05）.上述研究结果提示,小鼠在暴露于天敌——猫应激下,脑不对称可影响HPA轴活性及巨噬细胞功能.