Structural interaction and functional regulation of polycystin-2 by filamin

Filamins are important actin cross-linking proteins implicated in scaffolding, membrane stabilization and signal transduction, through interaction with ion channels, receptors and signaling proteins. Here we report the physical and functional interaction between filamins and polycystin-2, a TRP-type cation channel mutated in 10-15% patients with autosomal dominant polycystic kidney disease. Yeast two-hybrid and GST pull-down experiments demonstrated that the C-termini of filamin isoforms A, B and C directly bind to both the intracellular N- and C-termini of polycystin-2. Reciprocal co-immunoprecipitation experiments showed that endogenous polycystin-2 and filamins are in the same complexes in renal epithelial cells and human melanoma A7 cells. We then examined the effect of filamin on polycystin-2 channel function by electrophysiology studies with a lipid bilayer reconstitution system and found that filamin-A substantially inhibits polycystin-2 channel activity. Our study indicates that filamins are important regulators of polycystin-2 channel function, and further links actin cytoskeletal dynamics to the regulation of this channel protein.     

Exosomes derived from imatinib-resistant chronic myeloid leukemia cells mediate a horizontal transfer of drug-resistant trait by delivering miR-365

Chronic myeloid leukemia (CML) is a malignant disorder of hematopoietic stem/progenitor cells. Majority of patients can be effectively treated with tyrosine kinase inhibitors (TKIs) such as imatinib, but a portion of patients will develop drug resistance. Accumulated evidences have identified exosomes in cancer as promoters of tumor progression. Herein, we found that exosomes derived from imatinib resistant CML cells can be internalized into sensitive CML cells and confer drug-resistance traits. We also demonstrated a significant higher level of miR-365 in exosomes derived from drug-resistant CML cells compared with those from sensitive ones using microarray and qRT-PCR. The imatinib sensitive CML cells transfected with pre-miR-365 displayed lower chemosensitivity and apoptosis rate compared with controls. We further confirmed that exosomal transfer of miR-365 induced drug resistance by inhibiting expression of pro-apoptosis protein in sensitive CML cells. In conclusion, our study reveals that exosomes mediate a horizontal transfer of drug-resistant trait in chronic myeloid leukemia cell by delivering miR-365.     

兔在体膀胱储尿期和排尿期对胆碱能递质响应差异

目的:探讨胆碱能递质对在体膀胱的储尿和排尿影响的差异及特点.方法:提高或降低节后胆碱能兴奋性,分别检测充盈期膀胱内压和排液速度.结果:胆碱能兴奋和胆碱能抑制剂对充盈期膀胱内压影响均不甚明显;胆碱能兴奋使膀胱排液速度明显加快,胆碱能抑制可使排液速度明显减慢.结论:储尿期和排尿期的膀胱对胆碱能递质有不同的响应特性,后者的响应高于前者.     

Steroidal saponins from the rhizomes of Paris delavayi

Two new steroidal saponins, padelaosides A (1) and B (2), along with two other known steroidal saponins (3 and 4) were isolated from the rhizomes of Paris delavayi. Their structures were elucidated by 1D and 2D NMR techniques, HRFTMS, physical data and chemical methods. The two different absolute configurations of fucose, assigned as l and d that were found on compounds 1 and 2, respectively, were simultaneously reported in a natural medicine for the first time.     

大肠杆菌细胞外膜渗透性与脂多糖结构的关系

细胞外膜是大肠杆菌的半透膜屏障, 其主要成分是脂多糖。选取并构造共9种具有不同脂多糖结构的大肠杆菌, 用于考察脂多糖结构对细胞外膜渗透性的影响。从9种菌株中提取出脂多糖和类脂A, 并且用薄层层析色谱和离子源质谱来鉴定其结构。用N-苯基-1-萘胺作为荧光探针来测定细胞外膜渗透性大小。野生型大肠杆菌表现出最小的渗透性, 因敲除或表达某些基因而导致脂多糖结构改变的突变株均表现出较高的渗透性。脂多糖上的磷酸基团、脂肪酸链和多糖链的改变都影响了大肠杆菌的渗透性, 其中多糖链长度的改变对渗透性影响最大, 其次是脂肪酸链的数目变化。实验结果表明渗透性和脂多糖的结构具有较强的相关性。     

Electrochemical sensor based on nitrogen doped graphene: simultaneous determination of ascorbic acid, dopamine and uric acid

Nitrogen doped graphene (NG) was prepared by thermally annealing graphite oxide and melamine mixture. After characterization by atomic force microscopy and X-ray photoelectron spectroscopy etc., the electrochemical sensor based on NG was constructed to simultaneously determine small biomolecules such as ascorbic acid (AA), dopamine (DA) and uric acid (UA). Due to its unique structure and properties originating from nitrogen doping, NG shows highly electrocatalytic activity towards the oxidation of AA, DA and UA. The electrochemical sensor shows a wide linear response for AA, DA and UA in the concentration range of 5.0×10(-6) to 1.3×10(-3)M, 5.0×10(-7) to 1.7×10(-4)M and 1.0×10(-7) to 2.0×10(-5)M with detection limit of 2.2×10(-6)M, 2.5×10(-7)M and 4.5×10(-8)M at S/N=3, respectively. These results demonstrate that NG is a promising candidate of advanced electrode material in electrochemical sensing and other electrocatalytic applications.     

山西翅果油树上三种重要鳞翅目害虫的形态和分子鉴定及生活史观察

[目的]明确山西翅果油树Elaeagnus mollis上发生危害的3种鳞翅目害虫形态鉴定特征及生活史特性,并基于mtDNA COI基因DNA条形码对这3个种进行快速物种识别鉴定.[方法]通过观察山西翅果油树上3种鳞翅目害虫成虫外部形态和解剖拍照雌、雄性外生殖器特征,利用PCR扩增对待测样本COI基因DNA条形码序列进...     

Effects of inter-annual landscape change on interactions between cereal aphids and their natural enemies

The agricultural intensification and the subsequent habitat changes in agroecosystem can strongly affect biological control services. We here examine the influence of inter-annual landscape change in wheat field area on interactions of cereal aphids and their natural enemies, as well as the efficacy of biological control using data collected from a 4-year experiment in Northwest China. Two hypotheses were tested. (i) Population densities decline following an inter-annual expansion of wheat crop proportion cover due to dilution and crowding effects. (ii) Species that are specialists or at higher trophic levels are more sensitive to bottom-up disturbance by inter-annual change in percent cover of wheat crop. Results showed the population densities of one cereal aphid (Macrosiphum avenae), one parasitic wasp (Aphidius avenae), two specialist predators (ladybirds: Hippodamia variegata and H. tredecimpunctata) and one hyperparasitic wasp (Pachyneuron aphidis) declined following the expansion of wheat crop areas, supporting the predictions of inter-annual dilution and crowding effects. In contrast, the populations of one cereal aphid (Schizaphis graminum), one parasitic wasp (A. gifuensis), two generalist predators (spiders: Pardosa astrigera; carabid beetles: Chlaenius pallipes), and two hyperparasitic wasps (Asaphes suspensus, and Alloxysta sp.) did not respond to inter-annual landscape change. The two hypotheses were partially supported but with noticeable exceptions, and the bio-control efficiency declined with the increase of the proportion cover of wheat field in agricultural landscape. Overall, different responses of cereal aphids and their natural enemies make it difficult but still possible to optimize inter-annual landscape change for enhancing the parasitism rate and predator-prey ratio.     

Endothelin-1 in paraventricular nucleus modulates cardiac sympathetic afferent reflex and sympathetic activity in rats

Background

Cardiac sympathetic afferent reflex (CSAR) is a positive-feedback, sympathoexcitatory reflex. Paraventricular nucleus (PVN) is an important component of the central neurocircuitry of the CSAR. The present study is designed to determine whether endothelin-1 (ET-1) in the PVN modulates the CSAR and sympathetic activity, and whether superoxide anions are involved in modulating the effects of ET-1 in the PVN in rats.

Methodology/Principal Findings

In anaesthetized Sprague–Dawley rats with cervical vagotomy and sinoaortic denervation, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. The CSAR was evaluated by the responses of the RSNA and MAP to epicardial application of capsaicin. Microinjection of ET-1 into the bilateral PVN dose-dependently enhanced the CSAR, increased the baseline RSNA and MAP. The effects of ET-1 were blocked by PVN pretreatment with the ET_A receptor antagonist BQ-123. However, BQ-123 alone had no significant effects on the CSAR, the baseline RSNA and MAP. Bilateral PVN pretreatment with either superoxide anion scavenger tempol or polyethylene glycol-superoxide dismutase (PEG-SOD) inhibited the effects of ET-1 on the CSAR, RSNA and MAP. Microinjection of ET-1 into the PVN increased the superoxide anion level in the PVN, which was abolished by PVN pretreatment with BQ-123. Epicardial application of capsaicin increased superoxide anion level in PVN which was further enhanced by PVN pretreatment with ET-1.

Conclusions

Exogenous activation of ET_A receptors with ET-1 in the PVN enhances the CSAR, increases RSNA and MAP. Superoxide anions in PVN are involved in the effects of ET-1 in the PVN.