Stochastic aspects of biological locomotion

Various aspects of random walks undertaken by motile bacteria and migrating leukocytes are discussed, including the motions of these cells when responding to gradients of chemoattractants. Brief reference also is made to studies of particle movements within the cytoplasm of eucaryotic cells.Presented at the Symposium on Random Walks, Gaithersburg, MD, June 1982.     

眶额叶区多巴胺对胃运动的影响及其机制研究

通过大鼠眶额叶微量注射给药,记录胃内压(Intragastric pressure,IGP),观察胃运动变化的方法,研究了眶额叶多巴胺(dopamine,DA)对胃运动调节的神经机制.结果显示,眶额叶注射DA10μg,胃内压显著升高;眶额叶单独注射DA D1受体阻断剂SCH 2μg(SCH23390,SCH),胃内压降低.眶额叶注射SCH 2μg,能阻断DA升高胃内压的作用;眶额叶注射利陪酮(Risperidon)2μg,可升高胃内压,增强胃运动.但利陪酮却不能阻断DA升高胃内压的作用;切断双侧膈下迷走神经,眶额叶注射DA增加胃内压的作用被消除.以上各组中胃收缩频率均无明显变化.实验结果表明,眶额叶内DA能增大胃内压,增强胃运动,DA对胃内压及胃运动的增强作用主要是通过D1受体介导,经过迷走神经传出.     

北极狐精液冷冻和解冻对精子活力的影响

对9－10月龄的后备北极公狐的精液进行了冷冻观测,结果表明：I号稀释液经冷冻保存（－196℃）3年,其解冻活率达45％．5％葡萄糖作为解冻液明显好于葡－柠解冻液,2．9％柠檬酸钠液不适于北极狐冷冻精 液,干解冻优于湿解冻。     

SMI测试系统研究

建立了一个由光路、模拟信号提取电路以及信号处理电路等组成的精子活动度测试系统;对照国外测试实验,进行了一系列确认实验,验证了本测试系统的实用性和可行性。     

Subdiffraction‐Resolution Fluorescence Microscopy of Myosin–Actin Motility

Subdiffraction‐resolution imaging by subsequent localization of single photoswitchable molecules can achieve a spatial resolution in the range of ～20 nm with moderate excitation intensities, but have so far been too slow for imaging faster dynamics in biology. Herein, we introduce a novel approach for video‐like subdiffraction microscopy based on rapid and reversible photoswitching of commercially available organic carbocyanine fluorophores. With the present concept, we demonstrate in vitro studies on the motility of fluorophore‐labeled actin filaments along myosin II. Actin filaments were densely labeled with carbocyanine fluorophores, and the gliding velocity adjusted by the concentration of ATP. At imaging frame rates of ～100 Hz, only 100 consecutive frames are sufficient to generate a single high‐resolution image of moving actin filaments with a lateral resolution of ～30 nm. A video‐like sequence is generated from individual reconstructed images by additionally applying a sliding window algorithm. We measured velocities of individual actin filaments of up to ～0.18 μm s^?1, observed strong bending and disruption of filaments as well as locally immobile fragments.     

Inhibitors of Bacterial Swarming Behavior

Bacteria can migrate in groups of flagella-driven cells over semisolid surfaces. This coordinated form of motility is called swarming behavior. Swarming is associated with enhanced virulence and antibiotic resistance of various human pathogens and may be considered as favorable adaptation to the diverse challenges that microbes face in rapidly changing environments. Consequently, the differentiation of motile swarmer cells is tightly regulated and involves multi-layered signaling networks. Controlling swarming behavior is of major interest for the development of novel anti-infective strategies. In addition, compounds that block swarming represent important tools for more detailed insights into the molecular mechanisms of the coordination of bacterial population behavior. Over the past decades, there has been major progress in the discovery of small-molecule modulators and mechanisms that allow selective inhibition of swarming behavior. Herein, an overview of the achievements in the field and future directions and challenges will be presented.     

Cyano Enone-Bearing Triterpenoid Soloxolone Methyl Inhibits Epithelial-Mesenchymal Transition of Human Lung Adenocarcinoma Cells In Vitro and Metastasis of Murine Melanoma In Vivo

Introduction of α-cyano α,β-unsaturated carbonyl moiety into natural cyclic compounds markedly improves their bioactivities, including inhibitory potential against tumor growth and metastasis. Previously, we showed that cyano enone-bearing derivatives of 18βH-glycyrrhetinic (GA) and deoxycholic acids displayed marked cytotoxicity in different tumor cell lines. Moreover, GA derivative soloxolone methyl (SM) was found to induce ER stress and apoptosis in tumor cells in vitro and inhibit growth of carcinoma Krebs-2 in vivo. In this work, we studied the effects of these compounds used in non-toxic dosage on the processes associated with metastatic potential of tumor cells. Performed screening revealed SM as a hit compound, which inhibits motility of murine melanoma B16 and human lung adenocarcinoma A549 cells and significantly suppresses colony formation of A549 cells. Further study showed that SM effectively blocked transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) of A549 cells: namely, inhibited TGF-β-stimulated motility and invasion of tumor cells as well as loss of their epithelial characteristics, such as, an acquisition of spindle-like phenotype, up- and down-regulation of mesenchymal (vimentin, fibronectin) and epithelial (E-cadherin, zona occludens-1 (ZO-1)) markers, respectively. Network pharmacology analysis with subsequent verification by molecular modeling revealed that matrix metalloproteinases MMP-2/-9 and c-Jun N-terminal protein kinase 1 (JNK1) can be considered as hypothetical primary targets of SM, mediating its marked anti-EMT activity. The inhibitory effect of SM on EMT revealed in vitro was further confirmed in a metastatic model of murine B16 melanoma: SM was found to effectively block metastatic dissemination of melanoma B16 cells in vivo, increase expression of E-cadherin and suppress expression of MMP-9 in lung metastatic foci. Altogether, our data provided valuable information for a better understanding of the antitumor activity of cyano enone-bearing semisynthetic compounds and revealed SM as a promising anti-metastatic drug candidate.     

Nonlinear dynamics of cell migration in anisotropic microenvironment

Cell migration in anisotropic microenvironment plays an important role in the development of normal tissues and organs as well as neoplasm progression, e.g., osteogenic differentiation of embryonic stem cells was facilitated on stiffer substrates, indicating that the mechanical signals greatly affect both early and terminal differentiation of embryonic stem cells. However, the effect of anisotropy on cell migration dynamics, in particular, in terms of acceleration profiles which is important for recognizing dynamics modes of cell migration and analyzing the regulation mechanisms of microenvironment in mechanical signal transmission, has not been systematically investigated. In this work, we firstly rigorously investigate and quantify the differences between persistent random walk and anisotropic persistent random walk models based on the analysis of cell migration trajectories and velocity auto-covariance function, both qualitatively and quantitatively. Secondly, we introduce the concepts of positive and negative anisotropy based on the motility parameters to study the effect of anisotropy on acceleration profiles, especially the nonlinear decrease and non-monotonic behaviors. We particularly elaborate and discuss the mechanisms, and physical insights of non-monotonic behaviors in the case of positive anisotropy,focusing on the force exerted on migrating cells. Finally, we analyze two types of in vitro cell migration experiments and verify the universality of nonlinear decrease and the consistence of non-monotonic behaviors with numerical results.We conclude that the anisotropy of microenvironment is the cause of the non-monotonic and nonlinear dynamics, and the anisotropic persistent random walk can be as a suitable tool to analyze in vitro cell migration with different combinations of motility parameters. Our analysis provides new insights into the dynamics of cell migration in complex microenvironment,which also has implications in tissue engineering and cancer research.     

The role of the liquid crystalline state in the bundling of Salmonella enterica serovar Typhimurium flagella

Salmonella bacteria owe their motility to the rotation of bundled protein filaments known as flagella. While the method by which flagella impart motility is known, there is a scarcity of data elucidating the critical process of flagellum bundling itself. This work hypothesises the process of flagellum bundling to be an energetically driven phenomenon in which a physical state transition drives the formation of the flagellum bundle at the surface of a Salmonella cell. In vitro analysis of intact flagella, detached and purified from Salmonella enterica serovar Typhimurium cells, with cross-polarised light microscopy demonstrates a transition from an isotropic to mesophasic suspension at physiologically relevant concentrations. We believe the state transition of flagellum suspensions to the liquid crystalline state directs the formation of the flagellum bundle and thus plays a role in Salmonella motility that, until this point, has been sparsely investigated.