Identification and molecular characterization of two closely related G protein-coupled receptors activated by prokineticins/endocrine gland vascular endothelial growth factor

We previously described two mammalian secreted proteins, prokineticin 1 and prokineticin 2, that potently contract gastrointestinal smooth muscle. Prokineticin 1 has also been shown to promote angiogenesis by stimulating proliferation, migration, and fenestration of endocrine organ-derived endothelial cells. Here we report the cloning and characterization of two closely related G protein-coupled receptors as receptors for prokineticins. Expression of prokineticin receptors in heterologous systems shows that these receptors bind to and are activated by nanomolar concentrations of recombinant prokineticins. Activation of prokineticin receptors leads to mobilization of calcium, stimulation of phosphoinositide turnover, and activation of p44/p42 MAPK signaling pathways that are consistent with the effects of prokineticins on smooth muscle contraction and angiogenesis. mRNA expression analysis reveals that prokineticin receptors are expressed in gastrointestinal organs, endocrine glands, and other tissues.     

Rab31 promotes the invasion and metastasis of cervical cancer cells by inhibiting MAPK6 degradation

Persistent infection with high-risk human papillomavirus (HPV) is the main risk factor for cervical cancer. Our mass spectrometry data showed that the Ras-associated binding protein Rab31 was upregulated by HPV; however, little is known regarding the role of Rab31 in the metastasis of cervical cancer cells. In this study, we showed that Rab31 was highly expressed in cervical cancer tissues and cells, and both HPV E6 and E7 promoted the expression of Rab31. Rab31 knockdown inhibited while Rab31 overexpression promoted the migration and invasion capabilities of cervical cancer cells. Additionally, Rab31 knockdown inhibited the epithelial-mesenchymal transition (EMT) and cytoskeletal rearrangement in cervical cancer cells. Furthermore, Rab31 interacted with mitogen-activated protein kinase 6 (MAPK6), and Rab31 knockdown inhibited the expression of MAPK6, which was mainly localized in the cytoplasm. More importantly, Rab31 knockdown promoted and Rab31 overexpression inhibited MAPK6 degradation. Accordingly, MAPK6 overexpression restored the decreased migration potential caused by Rab31 knockdown. Finally, a xenograft mouse model showed that Rab31 knockdown in cervical cancer cells led to reduced tumor growth and impaired lung and liver metastasis in vivo. In conclusion, Rab31 plays a crucial role in cervical cancer metastasis by inhibiting MAPK6 degradation. Thus, Rab31 may serve as a novel therapeutic target to manage cervical cancer.     

Redox regulation of plant stem cell fate

Despite the importance of stem cells in plant and animal development, the common mechanisms of stem cell maintenance in both systems have remained elusive. Recently, the importance of hydrogen peroxide (H₂O₂) signaling in priming stem cell differentiation has been extensively studied in animals. Here, we show that different forms of reactive oxygen species (ROS) have antagonistic roles in plant stem cell regulation, which were established by distinct spatiotemporal patterns of ROS‐metabolizing enzymes. The superoxide anion () is markedly enriched in stem cells to activate WUSCHEL and maintain stemness, whereas H₂O₂ is more abundant in the differentiating peripheral zone to promote stem cell differentiation. Moreover, H₂O₂ negatively regulates biosynthesis in stem cells, and increasing H₂O₂ levels or scavenging leads to the termination of stem cells. Our results provide a mechanistic framework for ROS‐mediated control of plant stem cell fate and demonstrate that the balance between and H₂O₂ is key to stem cell maintenance and differentiation.     

Dual regulation of glycogen synthase kinase-3beta by the alpha1A-adrenergic receptor

Catecholamines, acting through adrenergic receptors, play an important role in modulating the effects of insulin on glucose metabolism. Insulin activation of glycogen synthesis is mediated in part by the inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3). In this study, catecholamine regulation of GSK-3beta was investigated in Rat-1 fibroblasts stably expressing the alpha1A-adrenergic receptor. Treatment of these cells with either insulin or phenylephrine (PE), an alpha1-adrenergic receptor agonist, induced Ser-9 phosphorylation of GSK-3beta and inhibited GSK-3beta activity. Insulin-induced GSK-3beta phosphorylation is mediated by the phosphatidylinositol 3-kinase/Akt signaling pathway. PE treatment does not activate phosphatidylinositol 3-kinase or Akt (Ballou, L. M., Cross, M. E., Huang, S., McReynolds, E. M., Zhang, B. X., and Lin, R. Z. (2000) J. Biol. Chem. 275, 4803-4809), but instead inhibits insulin-induced Akt activation and GSK-3beta phosphorylation. Experiments using protein kinase C (PKC) inhibitors suggest that phorbol ester-sensitive novel PKC and G? 6983-sensitive atypical PKC isoforms are involved in the PE-induced phosphorylation of GSK-3beta. Indeed, PE treatment of Rat-1 cells increased the activity of atypical PKCzeta, and expression of PKCzeta in COS-7 cells stimulated GSK-3beta Ser-9 phosphorylation. In addition, PE-induced GSK-3beta phosphorylation was reduced in Rat-1 cells treated with a cell-permeable PKCzeta pseudosubstrate peptide inhibitor. These results suggest that the alpha1A-adrenergic receptor regulates GSK-3beta through two signaling pathways. One pathway inhibits insulin-induced GSK-3beta phosphorylation by blocking insulin activation of Akt. The second pathway stimulates Ser-9 phosphorylation of GSK-3beta, probably via PKC.     

血管成形术介入治疗糖尿病下肢血管病变的临床效果分析

目的:探讨经皮腔内血管成形术(PTA)联合支架植入术治疗糖尿病下肢血管病变的临床效果及安全性。方法:选择2008年3月至2011年12月在我院内分泌科接受治疗的2型糖尿病合并糖尿病足的患者36例,将其随机分为观察组(19例)和对照组(17例)。观察组19例患者中,14例行PTA术,4例行PTA+腔内支架植入术,1例行截肢术;对照组17例患者,全部采用传统方法进行治疗。观察和比较两组患者术后的糖尿病下肢血管病变的特点、临床效果及并发症的发生情况。结果:观察组19例患者,共40条靶血管,实施PTA手术的成功率为87.5%。采用两种治疗方法 2周或4周后,患者的临床症状和体征均得到一定程度的缓解,且均未观察到明显的不良反应。与对照组相比,接受介入治疗的患者,其临床症状的缓解率明显升高,其中在2周时介入治疗对麻木和紫绀症状的缓解尤其显著,和对照组之间有统计学差异(P0.05)。结论:血管成形术介入治疗糖尿病下肢血管病变是一种安全可靠的方法,治疗效果好,安全性高,值得临床推广。     

黑龙江省野生东北虎调查管理信息系统的构建

文章以黑龙江省野生东北虎（Panthera tigris altaica）野外调查数据为基础,利用地理信息系统技术、计算机技术与野生动物资源调查管理技术,构建了黑龙江省野生东北虎调查管理信息系统。主要运用面向对象程序设计语言C#和ArcGIS Engine嵌入式组件技术以及SQL Server数据库技术,设计并构建东北虎调查管理系统,实现了对野生东北虎调查数据的图形可视化操作管理。同时,结合研究区域内的自然因素和人文因素对调查资源进行动态的空间分析,及时准确地反映出东北虎的种群数量和空间变化规律,并制作出相应的分类专题图及野外分布信息统计图表等。该管理信息系统将有助于野生东北虎种群及栖息地调查数据与资料的科学管理,对于推动我国野生东北虎就地保护和科学管理具有重要意义。     

Influence of solids retention time on membrane fouling: characterization of extracellular polymeric substances and soluble microbial products

The objective of this study was to investigate the influence of solids retention time (SRT) on membrane fouling and the characteristics of biomacromolecules. Four identical laboratory-scale membrane bioreactors (MBRs) were operated with SRTs for 10, 20, 40 and 80 days. The results indicated that membrane fouling occurred faster and more readily under short SRTs. Fouling resistance was the primary source of filtration resistance. The modified fouling index (MFI) results suggested that the more ready fouling at short SRTs could be attributed to higher concentrations of soluble microbial products (SMP). Fourier transform infrared (FTIR) spectra indicated that the SRT had a weak influence on the functional groups of the total extracellular polymeric substances (TEPS) and SMP. However, the MBR under a short SRT had more low-molecular-weight (MW) compounds (<1 kDa) and fewer high-MW compounds (>100 kDa). Aromatic protein and tryptophan protein-like substances were the dominant groups in the TEPS and SMP, respectively.     

柑橘全爪螨空间格局与抽样技术的研究

本应用空间分布型统计参数IwaoM-X模型中α,β及6个聚集指标分析了柑橘全爪螨的空间格局,并对抽样技术进行了探讨。结果表明,柑橘全爪螨的空间格局为聚集型;田间的抽样部位是上、中、下三部的叶片。提出了估算柑橘全爪螨在不同虫口密度下的理论抽样数。     

应用光敏生物素标记核酸探针鉴定分枝杆菌的研究

用光敏生物素标记非结核分枝杆菌临床分离株及标准分枝杆菌全染色体ＤＮＡ制成探针,与已知标准牛分枝杆菌（ＢＣＧ株）及不同种的非结核分枝杆菌ＤＮＡ杂交,可快速将分支杆菌鉴定到种,同时以大肠埃希氏菌做阴性对照,显示良好的特异性和准确性。此种方法具有鉴定速度快、操作简便、稳定性好及对人体无害等特点,适用于结核杆菌和非结核分枝杆菌的菌种鉴定。     

ROS-Mediated Autophagy Induced by Dysregulation of Lipid Metabolism Plays a Protective Role in Colorectal Cancer Cells Treated with Gambogic Acid

Gambogic acid (GA), the main active component of gamboge resin, has potent antitumor activity both in vivo and in vitro. However, the underlying molecular mechanisms remain unclear. In this study, we found that GA could initiate autophagy in colorectal cancer cells, and inhibition of the autophagy process accelerated the effect of proliferative inhibition and apoptotic cell death induced by GA, implying a protective role of autophagy. Two-dimensional electrophoresis-based proteomics showed that GA treatment altered the expression of multiple proteins involved in redox signaling and lipid metabolism. Functional studies revealed that GA-induced dysregulation of lipid metabolism could activate 5-lipoxygenase (5-LOX), resulting in intracellular ROS accumulation, followed by inhibition of Akt-mTOR signaling and autophagy initiation. Finally, results using a xenograft model suggested ROS-induced autophagy protect against the antitumor effect of GA. Taken together, these data showed new biological activities of GA against colorectal cancer underlying the protective role of ROS-induced autophagy. This study will provide valuable insights for future studies regarding the anticancer mechanisms of GA.