Development of high blood pressure in spontaneously hypertensive rats is delayed by treatment with cyclosporin at an early age

In spontaneously hypertensive rats the effect of the T-cell inhibitor cyclosporin was studied at different ages. If treatment was started at the age of 2 weeks the development of hypertension was delayed, but the ultimate level of blood pressure was not affected. These results indicate the involvement of immune mechanisms in the early development of hypertension in spontaneously hypertensive rats.     

Portability of paddle motif function and pharmacology in voltage sensors

Voltage-sensing domains enable membrane proteins to sense and react to changes in membrane voltage. Although identifiable S1-S4 voltage-sensing domains are found in an array of conventional ion channels and in other membrane proteins that lack pore domains, the extent to which their voltage-sensing mechanisms are conserved is unknown. Here we show that the voltage-sensor paddle, a motif composed of S3b and S4 helices, can drive channel opening with membrane depolarization when transplanted from an archaebacterial voltage-activated potassium channel (KvAP) or voltage-sensing domain proteins (Hv1 and Ci-VSP) into eukaryotic voltage-activated potassium channels. Tarantula toxins that partition into membranes can interact with these paddle motifs at the protein-lipid interface and similarly perturb voltage-sensor activation in both ion channels and proteins with a voltage-sensing domain. Our results show that paddle motifs are modular, that their functions are conserved in voltage sensors, and that they move in the relatively unconstrained environment of the lipid membrane. The widespread targeting of voltage-sensor paddles by toxins demonstrates that this modular structural motif is an important pharmacological target.     

基于DEM-CFD耦合的新型CAE软件系统设计

基于离散元法和计算流体动力学方法, 设计一种流固耦合及流动过程分析软件, 实现了与三维计算机辅助设计软件的集成, 从而开发出一种集设计与性能分析评价为一体的新型计算机辅助工程软件--AgriDEM, 并通过实例验证了该软件的可行性和有效性.     

Reverse breeding in Arabidopsis thaliana generates homozygous parental lines from a heterozygous plant

Traditionally, hybrid seeds are produced by crossing selected inbred lines. Here we provide a proof of concept for reverse breeding, a new approach that simplifies meiosis such that homozygous parental lines can be generated from a vigorous hybrid individual. We silenced DMC1, which encodes the meiotic recombination protein DISRUPTED MEIOTIC cDNA1, in hybrids of A. thaliana, so that non-recombined parental chromosomes segregate during meiosis. We then converted the resulting gametes into adult haploid plants, and subsequently into homozygous diploids, so that each contained half the genome of the original hybrid. From 36 homozygous lines, we selected 3 (out of 6) complementing parental pairs that allowed us to recreate the original hybrid by intercrossing. In addition, this approach resulted in a complete set of chromosome-substitution lines. Our method allows the selection of a single choice offspring from a segregating population and preservation of its heterozygous genotype by generating homozygous founder lines.     

Prevention of cisplatin-induced ototoxicity by the inhibition of gap junctional intercellular communication in auditory cells

Cis-diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic drug for cancer therapy. However, most patients treated with cisplatin are at a high risk of ototoxicity, which causes severe hearing loss. Inspired by the “Good Samaritan effect” or “bystander effect” from gap junction coupling, we investigated the role of gap junctions in cisplatin-induced ototoxicity as a potential therapeutic method. We showed that connexin 43 (Cx43) was highly expressed in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, mediating cell–cell communication. The viability of HEI-OC1 cells was greatly decreased by cisplatin treatment, and cisplatin-treated HEI-OC1 cells showed lower Cx43 expression compared to that of untreated HEI-OC1 cells. In particular, high accumulation of Cx43 was observed around the nucleus of cisplatin-treated cells, whereas scattered punctuate expression of Cx43 was observed in the cytoplasm and membrane in normal cells, suggesting that cisplatin may interrupt the normal gap junction communication by inhibiting the trafficking of Cx43 to cell membranes in HEI-OC1 cells. Interestingly, we found that the inhibition of gap junction activity reduced cisplatin-induced apoptosis of auditory hair cells. Cx43 siRNA- or 18α-GA-treated HEI-OC1 cells showed higher cell viability compared to control HEI-OC1 cells during cisplatin treatment; this was also supported by fluorescence recovery after photobleaching studies. Inhibition of gap junction activity reduced recovery of calcein acetoxymethyl ester fluorescence compared to control cells. Additionally, analysis of the mechanisms involved demonstrated that highly activate extracellular signal-regulated kinase and protein kinase B, combined with inhibition of gap junctions may promote cell viability during cisplatin treatment.     

基于时—频分析的步态模式自动分类

针对不同路况和运动模式下的高维、非线性、强耦合和高时变下肢加速度信号的识别问题,提出了一种基于时--频分析的步态模式自动分类方案.利用三轴加速度传感器采集运动时小腿在矢状面、冠状面和横切面的加速度信号,利用五阶Daubechies小波基对其进行特征提取,并采用线性判别式分析进行降维,最后利用决策树和支持向量机对得到的精简步态特征进行模式分类.实验结果显示两种分类器的总体分类准确率均达到90%以上,个别步态分类可达到100%,验证了特征提取和降维方法的合理性和有效性.     

A radioimmunoassay of vasopressin. A note on pituitary vasopressin content in brattleboro rats

Zusammenfassung Die Empfindlichkeit und Zuverlässigkeit eines neu entwickelten Radioimmunotests für Vasopressin wurde durch Messungen des Vasopressinspiegels im Hypophysenhinterlappen von homozygoten und heterozygoten Ratten für angeborenen Diabetes insipidus geprüft und eine gute Korrelation zwischen dem biologisch und radioimmunologisch gemessenen Vasopressingehalt der Hypophyse nachgewiesen.     

Structure of the CED-4-CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans

Interplay among four genes--egl-1, ced-9, ced-4 and ced-3--controls the onset of programmed cell death in the nematode Caenorhabditis elegans. Activation of the cell-killing protease CED-3 requires CED-4. However, CED-4 is constitutively inhibited by CED-9 until its release by EGL-1. Here we report the crystal structure of the CED-4-CED-9 complex at 2.6 A resolution, and a complete reconstitution of the CED-3 activation pathway using homogeneous proteins of CED-4, CED-9 and EGL-1. One molecule of CED-9 binds to an asymmetric dimer of CED-4, but specifically recognizes only one of the two CED-4 molecules. This specific interaction prevents CED-4 from activating CED-3. EGL-1 binding induces pronounced conformational changes in CED-9 that result in the dissociation of the CED-4 dimer from CED-9. The released CED-4 dimer further dimerizes to form a tetramer, which facilitates the autoactivation of CED-3. Together, our studies provide important insights into the regulation of cell death activation in C. elegans.