Movement of a spherical cell in capillaries using a boundary element method

This study aims to investigate the translation and rotation of a spherical particle in capillaries and overcomes limitations in previous studies by using a boundary element method. The capillary, a straight cylindrical tube, is filled with a Newtonian viscous fluid. A spherical particle is arbitrarily positioned in the capillary either co-centrically or eccentrically and is free to translate and rotate. Flow in the capillary is first assumed to be caused solely by the movement of the sphere under the gravity. When a steady state is reached, the net force and torque on the sphere are zero. The translating velocity and rotation of the particle are calculated from equilibrium equations. For a co-centric sphere, our result agrees to Bohlin's analytical solution (Bohlin, 1960) and the difference is less than 1%. For an eccentrically positioned sphere in the tube, there are no analytical solutions unless the eccentricity is infinitesimal. Results by boundary element method (BEM) give an improved estimations on the velocity and rotation of the sphere than earlier results by a boundary singularity method (BSM), particularly when the clearance between the tube and the sphere becomes small. Movement of a spherical particle in a capillary driven by a pressure gradient is further investigated, which has closer relevance to movement of blood cells in capillaries. The current study using BEM enables investigation on cell movement in close proximities of the capillary wall.     

Spatial targeting of type II protein kinase A to filopodia mediates the regulation of growth cone guidance by cAMP

The second messenger cyclic adenosine monophosphate (cAMP) plays a pivotal role in axonal growth and guidance, but its downstream mechanisms remain elusive. In this study, we report that type II protein kinase A (PKA) is highly enriched in growth cone filopodia, and this spatial localization enables the coupling of cAMP signaling to its specific effectors to regulate guidance responses. Disrupting the localization of PKA to filopodia impairs cAMP-mediated growth cone attraction and prevents the switching of repulsive responses to attraction by elevated cAMP. Our data further show that PKA targets protein phosphatase-1 (PP1) through the phosphorylation of a regulatory protein inhibitor-1 (I-1) to promote growth cone attraction. Finally, we find that I-1 and PP1 mediate growth cone repulsion induced by myelin-associated glycoprotein. These findings demonstrate that the spatial localization of type II PKA to growth cone filopodia plays an important role in the regulation of growth cone motility and guidance by cAMP.     

Virus-specific CD8+ T cells in the liver: armed and ready to kill

Influenza A virus infection of C57BL/6 mice is a well-characterized model for studying CD8+ T cell-mediated immunity. Analysis of primary and secondary responses showed that the liver is highly enriched for CD8+ T cells specific for the immunodominant H2D(b)NP(366-374) (D(b)NP(366)) epitope. Functional analysis established that these liver-derived virus-specific CD8+ T cells are fully competent cytotoxic effectors and IFN-gamma secretors. In addition, flow cytometric analysis of early apoptotic cells showed that these influenza-specific CD8+ T cells from liver are as viable as those in the spleen, bronchoalveolar lavage, mediastinal lymph nodes, or lung. Moreover, cytokine profiles of the influenza-specific CD8+ T cells recovered from different sites were consistent with the bronchoalveolar lavage, rather than liver population, being the most susceptible to activation-induced cell death. Importantly, adoptively transferred influenza virus-specific CD8+ T cells from the liver survived and were readily recalled after virus challenge. Together, these results show clearly that the liver is not a "graveyard" for influenza virus-specific CD8+ T cells.     

白藜芦醇以Caspase依赖和非依赖两种方式导致Jurkat细胞死亡

应用形态学观察、流式细胞仪检测、Western印迹和DNA凝胶电泳等方法研究白藜芦醇对Jurkat细胞的作用。发现白藜芦醇处理组中细胞有皱缩、出泡、染色质边集等现象,但染色质浓缩呈散在团块状且不致密。细胞质结构疏松,线粒体肿胀,脊消失。少见凋亡小体。在白藜芦醇处理组,Western印迹可检测到弱的17kDacaspase-3条带,DNA凝胶电泳可以检测到梯状DNA和弥散条带;流式细胞仪在白藜芦醇处理组检测到大量PI单阳性细胞和少量膜联蛋白V单阳性细胞。Z-VAD-FMK干预后可以发现细胞死亡率降低,同时该组梯状DNA消失,但是大分子量弥散DNA条带依然可以检测到。结果表明白藜芦醇可以通过caspase依赖和非依赖途径导致Jurkat细胞死亡。此分子机制的明确将为白藜芦醇应用于临床白血病的治疗打下理论基础。     

小胶质细胞在神经病理性疼痛中的作用

神经病理性疼痛对患者的生理和心理健康都有着极大的影响。近几年来的研究表明,外周神经炎症或损伤激活的小胶质细胞通过表达及释放一系列介质分子,在神经病理性疼痛的产生和传递通路中发挥重要的调制作用。激活的小胶质细胞与神经元之间信息交互传递从而影响痛敏行为的这一崭新模式极大地推进了人们对于疼痛的理解。同时也为以小胶质细胞作为靶点,开辟镇痛药物治疗的新方法提供了理论依据。     

Blocking BE301622 gene expression by RNAi initiates differentiation of neural stem cells in rat

Neural stem cells (NSCs) are capable of differentiating into neurons, astrocytes and oligodendrocytes. However, the molecular mechanisms regulating NSCs differentiation are not well understood. Our previous research by microarray analysis certified that a lot of genes are differentially expressed in the course of NSC differentiation. In this study we report the function of one of these genes, BE301622, by RNAi techniques. To silence the BE301622 gene, a long, double-stranded RNA (dsRNA) was synthesized by using a kit (Ambion T7 MegaScript) and transformed into NSCs. Expression of mRNA was tested through RT-PCR. The result showed the expression of BE301622 gene was specificially suppressed. This finding effectively validated that BE301622 is involved in the differentiation of NSCs.     

Genetic relationships among Chinese pigs and other pig populations from Hunan Province, China

In this study, protein-level polymorphisms of transferrin, pre-albumin, hemopexin, ceruloplasmin and amylase were investigated in Hunan native pigs and Large Yorkshire pigs collected from Hunan (a province of China), allowing calculations of allele frequencies, average heterozygosities, inbreeding coefficients and genetic distances. The genetic relationship between Southeast Asian native pigs and American pigs was more distant than those among Southeast Asian native pig breeds. The genetic relationship between Southeast Asian native pig breeds and Hampshire pigs was the most distant.     

Modulation of the chemokines KC and MCP-1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice

Activation of the aryl hydrocarbon receptor (AhR) by TCDD may lead to the induction of proinflammatory cytokines in various cell types and organs such as liver leading to active chronic inflammation. Here we studied the expression of the chemokines keratinocyte chemoattractant (KC) and monocyte chemoattractant protein 1 (MCP-1) in different organs of mice after exposure to TCDD. TCDD exposure led to an early and clear induction of KC in liver and spleen on day 1 which was sustained over a period of 10 days. The level of MCP-1 mRNA was induced by TCDD on day 1 in spleen, lung, kidney, and liver, which was further increased at day 7. Increase of KC and MCP-1 at day 7 in liver, thymus, kidney, adipose, and heart was associated with elevated levels of the macrophage marker F4/80, indicating the infiltration of macrophages in these organs. Induction of KC requires a functional AhR since mice with a mutation in the AhR nuclear localization domain (AhR(nls)) were found to be resistant to TCDD-induced expression of KC. These results are the first showing the induction of the chemokines KC and MCP-1 in multiple organs of mice associated with an increase of the macrophage marker F4/80 indicating the involvement in TCDD's inflammatory response like infiltration of macrophages.     

Isolation and identification of mesenchymal stem cells from human lipoma tissue

Lipoma is a benign neoplasm of normal fat cells that appears as a soft, movable swelling, often with a slight yellowish coloration. Human mesenchymal stem cells (MSCs) that have been isolated from bone marrow, blood, and other adult tissues including adipose tissue have the potential to be useful candidates for therapy. No literature had reported about stem cells from lipoma tissue. Here, a new cell culture method is described and utilized to greatly accelerate the growth rate and prolong the lifespan of lipoma-derived MSCs. Cells produced in early cultures display characteristics similar to those previously reported for multipotential stem cells, including a high frequency of anchorage-independent growth in soft agar and a lack of gap junctional intercellular communication in cell types with serpiginous morphology. These cells can differentiate into adipocytes, osteoblasts, and chondrocytes after induction. In conclusion, lipoma-derived stem cells possessing the characteristics of MSCs are described for the first time.