Mutations in cadherin 23 affect tip links in zebrafish sensory hair cells

Hair cells have highly organized bundles of apical projections, or stereocilia, that are deflected by sound and movement. Displacement of stereocilia stretches linkages at the tips of stereocilia that are thought to gate mechanosensory channels. To identify the molecular machinery that mediates mechanotransduction in hair cells, zebrafish mutants were identified with defects in balance and hearing. In sputnik mutants, stereociliary bundles are splayed to various degrees, with individuals displaying reduced or absent mechanotransduction. Here we show that the defects in sputnik mutants are caused by mutations in cadherin 23 (cdh23). Mutations in Cdh23 also cause deafness and vestibular defects in mice and humans, and the protein is present in hair bundles. We show that zebrafish Cdh23 protein is concentrated near the tips of hair bundles, and that tip links are absent in homozygous sputnik(tc317e) larvae. Moreover, tip links are absent in larvae carrying weak alleles of cdh23 that affect mechanotransduction but not hair bundle integrity. We conclude that Cdh23 is an essential tip link component required for hair-cell mechanotransduction.     

Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities

Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.     

Diversity and dispersal interactively affect predictability of ecosystem function

Theory and small-scale experiments predict that biodiversity losses can decrease the magnitude and stability of ecosystem services such as production and nutrient cycling. Most of this research, however, has been isolated from the immigration and emigration (dispersal) processes that create and maintain diversity in nature. As common anthropogenic drivers of biodiversity change--such as habitat fragmentation, species introductions and climate change--are mediated by these understudied processes, it is unclear how environmental degradation will affect ecosystem services. Here we tested the interactive effects of mobile grazer diversity and dispersal on the magnitude and stability of ecosystem properties in experimental seagrass communities that were either isolated or connected by dispersal corridors. We show that, contrary to theoretical predictions, increasing the number of mobile grazer species in these metacommunities increased the spatial and temporal variability of primary and secondary production. Moreover, allowing grazers to move among and select patches reduced diversity effects on production. Finally, effects of diversity on stability differed qualitatively between patch and metacommunity scales. Our results indicate that declining biodiversity and habitat fragmentation synergistically influence the predictability of ecosystem functioning.     

bFGF和NGF对小鼠免疫细胞功能的影响

目的：探讨碱性成纤维细胞生长因子(bFGF)和神经生长因子(NGF)对免疫功能的影响。方法：通过小鼠巨噬细胞吞噬。溶血空斑形成细胞(PFC)和脾细胞增殖等实验,观察bFGF和NGF对正常小鼠免疫细胞功能的影响。结果：一定剂量的啪F、NGF对小鼠免疫细胞功能有较明显的促进作用,且表现具有协同促进效应,而同剂量的NGF对免疫功能的促进作用略强于bFGF。此外,bFGF、NGF还能协同促进活化淋巴细胞分泌sIL-2R。结论：一定剂量的bFGF、NGF表现出较明显的免疫促进作用,并存在协同效应。     

Research progress in gecko locomotion and biomimetic gecko-robots

Geckos are known for their excellent ability to climb walls and run on ceilings. Previous studies of the gecko’s locomotive and adhesive mechanisms, its neuro-sensory and neuro-modulatory systems, its fabrication of artificial setae array, and other related developments, have inspired further research on gecko-based and gecko-like robots. Key research findings in this area are reviewed in the present paper.     

Nucleosome positioning can affect the function of a cis-acting DNA element in vivo

Positioning of nucleosomes has been proposed as one mechanism whereby the activity of DNA is regulated: cis-acting elements located in linker DNA might be more accessible for interaction with trans-acting protein factors than they would be if they were directly associated with histones in nucleosome core particles. The eleven base pairs constituting the autonomously replicating sequence (ARS) of the high-copy-number TRP1ARS1 plasmid of Saccharomyces cerevisiae are located in a linker region near the edge of a positioned nucleosome and form an origin of replication. Could nucleosome positioning render the ARS accessible for interaction with the proteins necessary for its function? I have tested this hypothesis by making deletions and an insertion to move the ARS into the nucleosome DNA and then examining the effects on ARS function. There is a marked decrease in copy number when the ARS is moved into the central DNA region of the nucleosome core particle, a region known to differ in structure and stability from the peripheral segments of nucleosome DNA.     

Research progress in gecko locomotion and biomimetic gecko-robots

Geckos are known for their excellent ability to climb walls and run on ceilings. Previous studies of the gecko's locomotive and adhesive mechanisms, its neuro-sensory and neuro-modulatory systems, its fabrication of artificial setae array, and other related developments, have inspired further research on gecko-based and gecko-like robots. Key research findings in this area are reviewed in the present paper.     

2D-3D异质结结构中的紧凑集成电路

通过时域有限差分方法,详细地分析了2D-3D异质结结构中密度集成光学器件的传输特性。在三层2D结构中,分别引入了不同设计结构的波分复用器,通过调整结构参数实现了集成光路中每个器件、每个端口的波长选择特性,如B₁端口的输出频率为0.404[c/a],B₂端口为0.408[c/a],B₃端口为0.386[c/a],B₄端口为0.388[c/a],B₅端口为0.390[c/a],B₆端口为0.394[c/a],B₈端口为0.392[c/a],B₉端口为0.409[c/a]。更重要的是,此结构实现了多个器件沿堆叠方向的密度集成,集成器件的总尺寸为0.3 mm×0.3 mm×0.14 mm。这些研究结果可为紧凑集成电路的设计提供重要的理论指导。     

SKF83959调节大鼠的自发活动和焦虑行为

为了探讨多巴胺D1类受体激动剂SKF83959在动物自发活动、焦虑情绪和学习记忆方面的作用,将3月龄雄性大鼠随机分为给药组和空白对照组,分别腹腔注射1.0mg/kgSKF83959或等体积PBS缓冲液后,进行行为学测试.实验结果显示,与对照组相比,SKF83959注射后的大鼠在开放场测试中水平方向活动次数和总活动时间显著增加;在高架十字迷宫中给药组大鼠在闭臂区的停留时间更长,总穿臂次数和开臂、闭臂进臂次数也都减少.在恐惧性条件学习中,SKF83959处理组大鼠的记忆能力与对照组大鼠之间没有明显差异.结果提示,SKF83959能够提高大鼠的活动量,增加大鼠的焦虑情绪行为,而对大鼠恐惧记忆没有明显影响.     

Testis determination requires insulin receptor family function in mice

In mice, gonads are formed shortly before embryonic day 10.5 by the thickening of the mesonephros and consist of somatic cells and migratory primordial germ cells. The male sex-determining process is set in motion by the sex-determining region of the Y chromosome (Sry), which triggers differentiation of the Sertoli cell lineage. In turn, Sertoli cells function as organizing centres and direct differentiation of the testis. In the absence of Sry expression, neither XX nor XY gonads develop testes, and alterations in Sry expression are often associated with abnormal sexual differentiation. The molecular signalling mechanisms by which Sry specifies the male pathway and models the undifferentiated gonad are unknown. Here we show that the insulin receptor tyrosine kinase family, comprising Ir, Igf1r and Irr, is required for the appearance of male gonads and thus for male sexual differentiation. XY mice that are mutant for all three receptors develop ovaries and show a completely female phenotype. Reduced expression of both Sry and the early testis-specific marker Sox9 indicates that the insulin signalling pathway is required for male sex determination.     

野木瓜注射液及其提取物对脊髓神经元的氧化保护和生长促进

研究野木瓜注射液(IS)及其提取物(AI)对氧化损伤脊髓神经元的保护和对未损伤脊髓神经元生长的影响.方法:通过MTT法和细胞外液LDH漏出量的测定检测IS对未损伤的脊髓神经元细胞存活率的影响;建立H2O2氧化损伤模型,通过MTT法、胞内SOD活力和细胞外液LDH漏出量的测定研究IS对H2O2氧化损伤脊髓神经元的细胞保护作用;运用激光共聚焦显微镜研究氧化受损及IS保护对脊髓神经元胞浆内Ca2+浓度变化的影响.结果表明:当浓度为100～200 mg/L时,IS能显著地促进离体培养的小鼠脊髓神经元氧化受损的修复,神经元存活率得到显著的提高,胞内SOD活力显著地增加和LDH漏出量显著地减少,同时胞内Ca2+超载显著地被抑制;未受损的脊髓神经元在200 mg/L IS作用下LDH漏出量显著地减少,细胞存活率显著地提高;AI3对能显著地提高氧化受损脊髓神经元的存活率.     

3G移动通信系统共存干扰分析与滤波电路设计

讨论了3G移动通信技术的发展,并就我国TD-SCDMA标准的技术特点作了分析.由于WCDMA与TD-SCDMA混合组网时,临近频率存在系统干扰问题.在对此问题进行分析和研究的基础上,提出了解决的方法,并设计了两款滤波电路用于减少系统间的信号干扰.     

小檗碱对小鼠体内抑菌作用的研究

目的:研究小檗碱对抑制小鼠体内沙门氏菌感染的效果.方法:通过将60只SPF级昆明小鼠随机等分为4组,每组15只.按体重计算1-3组小鼠分别按照低剂量(0.01 g/kg)、中剂量(0.02g/kg)、高剂量(0.03g/kg)灌胃小檗碱0.2 mL,第4组为空白对照组灌胃生理盐水,给药七天后皮下注射沙门氏菌(2.3× 108CFU)建立人工感染小鼠模型,并观察小鼠临床表现与死亡情况.结果:各剂量药物组对抑制小鼠体内沙门氏菌感染效果明显,其中高剂量组使小鼠死亡率下降60％左右.各药物组均显著延长感染小鼠的存活时间,其中高、中剂量组与空白对照组差异极显著(P＜0.01).结论:此研究证明小檗碱对革兰氏阴菌感染小鼠体有很好的抑菌效果,并具有一定量效关系.     

灵芝多糖对小鼠体液免疫功能的影响

目的:研究灵芝多糖(GLB7)对小鼠特异性体液免疫功能调节的影响。方法:实验小鼠分成4组,分别经胃灌注不同剂量灵芝多糖,每天1次,连续14d,对照组小鼠用等量蒸馏水代替。在实验第10、24d用羊红细胞(SRBC)免疫小鼠,分别于免疫后第5d进行抗体生成细胞(AFC)检测和血清抗SRBC抗体凝集效价测定。结果:灵芝多糖喂药后2周,高、中、低3个剂量组小鼠抗体生成细胞以及高剂量组小鼠血清溶血素(抗体积数)与对照组比较均有显著性差异(P<0 01;P<0 05);喂药后4周,高、中、低3个剂量组小鼠抗体生成细胞以及小鼠血清溶血素(抗体积数)与对照组比较均无显著性差异(P>0 05)。结论:灵芝多糖能提高小鼠的B细胞产生特异性抗体的能力。