几种生化信号物质对双壳类催产效应的研究

采用个体注射的方法，研究不同的信号物质（五羟色胺、肾上腺素、去甲肾上腺素、多巴胺、Ｔ－氨基丁酸ＧＡＢＡ、溴化乙酰胆碱）对双壳类催产的效应。结果表明：所选用的六种物质中，只有五羟色胺能有效地诱导菲律宾蛤仔（Ｒｕｄｉｔａｐｅｓ ｐｈｉｌｉｐ－ｐｉｎａｒｕｍ）、栉孔扇贝（Ｃｈｌａｍｙｓ ｆａｒｒｅｒｉ）、贻贝（Ｍｙｔｉｌｕｓ ｅｄｕｌｉｓ）的精卵排放。五羟色胺作用的有效浓度范围为１０－３～１０－７ｍｏｌ／Ｌ，最佳作用浓度为１０－４ｍｏｌ／Ｌ。五羟色胺诱导的精卵排放具有作用潜伏期短（绝大部分在 ３０ｍｉｎ以内）、同步性高的特点，为贝 类配子的人工操作创造了条件。

蓝牙通信恒电位仪式电-生化信号读取电路设计

以微处理器为控制核心,设计了一种可通过手机等移动智能终端控制的,应用于生化检测中三电极体系的恒电位仪式读取电路系统。该系统集恒电位仪电路、滤波电路、I/V转换电路、蓝牙通信控制终端等于一体,小型便携,无线遥控,操作方便。测试结果与LK2006A测试结果对比,绝对误差小于0.04%。

吮吸压力与生化刺激下单细胞动力学响应的微流控研究

目的单细胞动力学探究力学和生化因素对细胞结构和功能及整体行为的影响,可比经典的单细胞生物学提供更全面的动态信息。基于微流控技术对力学和生化信号组合刺激下的单细胞动力学响应进行高通量的检测与分析。方法结合水动力学原理,优化设计可用于大量单细胞稳定捕获、且能定量加载相同动态力学与生化刺激的微流控阵列。

整合素和细胞骨架在细胞力传导中的作用

整合素和细胞骨架在力信号转化为细胞内生化信号 ,进而引发相应的生理或病理反应中起着重要作用。同时 ,细胞外基质 (ECM ) -整合素 -细胞骨架 (CSK)轴系统与膜离子通道。

细菌运动中的物理生物学

细菌是一个包含从分子到宏观多尺度多系统强烈耦合的复杂生物体系.细菌的运动行为在每一个时空尺度都蕴含有丰富的生物和物理学现象.例如,细菌对氧气和很多化合物有很强的应激反应;细菌体内信号传感网络会影响细菌鞭毛马达的转动;纳米尺度的细菌鞭毛马达转动会影响细菌在界面附近的游动、趋化性、积聚、黏附、飞速旋转;单个细菌的活跃状态和环境的物理化学性质又会影响细菌部落的生长过程.微生物膜在空间中的扩张会形成丰富多彩的宏观自组织斑图.细菌运动的物理生物学涉及到力学、流体和统计物理等多个学科的研究范畴.本文分别介绍细菌鞭毛马达、细菌微生物膜的集群运动、细菌在界面的运动以及细菌趋化性和生化信号传感等方面的若干最新研究进展.

美曲普汀对肥胖2型糖尿病患者的作用研究

美曲普汀可改善脂肪营养不良患者的代谢，但对于患有2型糖尿病的肥胖患者该药物的有效性尚未被证实。最近有学者就此问题开展了一项随机、双盲、包含安慰剂对照的试验研究，时间为期16周，研究过程中包括对相关生化信号的详细检验。患者在使用美曲普汀16周后，

Role of transforming growth factor-beta1-smad signal transduction pathway in patients with hepatocellular carcinoma

AIM： To explore the role of transforming growth factorbeta1 （TGF-β1）-smad signal transduction pathway in patients with hepatocellular carcinoma. METHODS： Thirty-six hepatocellular carcinoma specimens were obtained from Qidong Liver Cancer Institute and Department of Pathology of the Second Affiliated Hospital of Nanjing Medical University. All primary antibodies （polyclonal antibodies） to TGF-β1, type H Transforming growth factor-beta receptor （TβR-Ⅱ）, nuclear factor-kappaB （NF-KB）, CD34, smad4 and smad7, secondary antibodies and immunohistochemical kit were purchased from Zhongshan Biotechnology Limited Company （Beijing, China）. The expressions of TGF-β1, TβR-Ⅱ, NF- KB, smad4 and smad7 proteins in 36 specimens of hepatocellular carcinoma （HCC） and its adjacent tissue were separately detected by immunohistochemistry to observe the relationship between TGF-β1 and TβR-Ⅱ, between NF-KB and TGF-β1, between smad4 and smad7 and between TGF-β1 or TβR-Ⅱ and microvessel density （MVD）. MVD was determined by labelling the vessel endothelial cells with CD34. RESULTS： The expression of TGF-β1, smad7 and MVD was higher in HCC tissue than in adjacent HCC tissue （P〈0.01, P〈0.05,P〈0.01 respectively）. The expression of TβR-Ⅱ and smad4 was lower in HCC tissue than in its adjacent tissue （P〈0.01, P〈0.05 respectively）. The expression of TGF-β1 protein and NF-KB protein was consistent in HCC tissue. The expression of TGF-β1 and MVD was also consistent in HCC tissue. The expression of TIER- Ⅱ was negatively correlated with that of MVD in HCC tissue. CONCLUSION： The expressions of TGF-IB1, TβR- Ⅱ, NF-KB, smad4 and smad7 in HCC tissue, which are major up and down stream factors of TGF-β1-smad signal transduction pathway, are abnormal. These factors are closely related with NVD and may play an important role in HCC angiogenesis. The inhibitory action of TGF-β1 is weakened in hepatic carcinoma cells because of abnormality of TGF-β1 receptors （such as TIBR- Ⅱ） and postreceptors （such as smad4 and smad7）. NF-KB may cause activation and production of TGF-β1.

Tetrandrine inhibits activation of rat hepatic stellate cells in vitro via transforming growth factor-β signaling

AIM: To investigate the effect of various concentrations of tetrandrine on activation of quiescent rat hepatic stellate cells (HSCs) and transforming growth factor-β (TGF-β) signaling in vitro.METHODS: HSCs were isolated from rats by in situperfusion of liver and 18% Nycodenz gradient centrifugation, and primarily cultured on uncoated plastic plates for 24 hwith DMEM containing 20% fetal bovine serum (FBS/DMEM) before the culture medium was substituted with 2% FBS/DMEM for another 24 h. Then, the HSCs were cultured in 2% FBS/DMEM with tetrandrine (0.25, 0.5, 1,2 mg/L, respectively). Cell morphological features were observed under an inverted microscope, smooth muscleα-actin (α-SMA) was detected by immunocytochemistry and image analysis system, laminin (LN) and type Ⅲprocollagen (PCⅢ) in supernatants were determined byradioimmunoassay. TGF-β1 mRNA, Smad 7 mRNA and Smad 7 protein were analyzed with RT-PCR and Western blotting, respectively.RESULTS: Tetrandrine at the concentrations of 0.25-2 mg/L prevented morphological transformation of HSC from the quiescent state to the activated one, while α-SMA, LN and PCⅢ expressions were inhibited. As estimated by gray values, the expression of α-SMA in tetrandrine groups (0.25, 0.5, 1, 2 mg/L) was reduced from 21.3% to 42.2%(control: 0.67, tetrandrine groups: 0.82, 0.85, 0.96, or 0.96, respectively, which were statistically different from the control, P＜0.01), and the difference was more significant in tetrandrine at 1 and 2 mg/L. The content of LN in supernatants was significantly decreased in tetrandrine groups to 58.5%, 69.1%, 65.8% or 60.0% that of the control respectively, and that of PCⅢ to 84.6%, 81.5%,75.7% or 80.7% respectively (P＜0.05 vs control), with no significant difference among tetrandrine groups. RTPCR showed that TGF-β1 mRNA expression was reduced by tetrandrine treatments from 56.56% to 87.90% in comparison with the control, while Smad 7 mRNA was increased 1.4-4.8 times. The TGF-β1 mRNA and Smad 7 mRNA expression was in a significant negative correlation (r= -0.755, P＜0.01), and both were significantly correlated with α-SMA protein expression (r = -0.938, P＜0.01;r = 0.938, P＜0.01, respectively). The up-regulation of Smad 7 protein by tetrandrine (1 mg/L)was confirmed by Western blotting as well.CONCLUSION: Tetrandrine has a direct inhibiting effect on the activation of rat HSCs in culture. It up-regulates the expression of Smad 7 which in turn blocks TGF-β1 expression and signaling.

The associated regulators and signal pathway in rIL-16/CD4 mediated growth regulation in Jurkat cells

IL-16 is a ligand and chemotactic factor for CD4+ T cells. IL-16 inhibits the CDS mediated lymphocyte activation and proliferation. The effects of IL-16 on the target cells are dependent on the cell type, the presence of co-activators etc. To understand the regulation function and mechanism of IL-16 on target cells, we used a 130 a.a. recombinant IL-16 to study its effects on the growth of Jurkat T leukemia cells in vitro. We found that the rIL-16 stimulated the proliferation of Jurkat cells at low dose (10-9M), but inhibited the growth of the cells at higher concentration (10-5M). Results showed that 10-5 M of rIL-16 treatment induced an enhanced apoptosis in Jurkat cells. The treatment blocked the expression of FasL, but up-regulated the c-myc and Bid expression in the cells. Pre-treatment of PKC inhibitor or MEK1 inhibitor markedly increased or decreased the rIL-16 induced growth-inhibiting effects on Jurkat cells, respectively. The results suggested that the rIL-16 might be a regulator for the growth or apoptosis of Jurkat cells at a dose-dependent manner. The growth-inhibiting effects of rIL-16 might be Fas/FasL independent, but, associated with the activation of PKC, up-regulated expression of c-Myc and Bid, and the participation of the ERK signal pathway in Jurkat cells.

Wnt5a Signaling A New and Attractive Target for Specific Anticancer Therapy

Wnt signaling has been shown to engage a multifunctional pathway that is involved in the regulation of a wide variety of normal and pathologic processes, including embryogenesis, differentiation and tumorigenesis. Recent studies have demonstrated that Wnt5a expression is frequently seen in various human cancers. In contrast to the transforming members of the Wnt family, shown to be upregulated in many cancers, the role of Wnt5a is still controversial in its expression in different tumors. There is increasing evidence that Wnt5a has tumor suppressor function in some malignancies, and in addition, it elicits promigratory and proinvasive effects via the planar cell polarity pathway, which suggests that Wnt5a might be an effective marker for the progression and prognosis of tumors. Obviously, the outcome of Wnt5a signaling is dependent on a multitude of variables, ranging from receptors, downstream effectors and inhibitors, to external influences coming from the tumor microenvironment. This review will focus on the role of Wnt5a signaling and, as a consequence, provide an outline describing the expression and functions of Wnt5a in cancer progression.

骨组织应力转导过程中主要信号通路的研究进展

细胞感受机械改变，将其转化为生化信号，最终引起细胞变化的过程，称为应力转导^[1]。其过程受到一系列信号通路的影响和调节，机制尚不十分明确。应力转导对活体组织的结构和功能具有重要意义，特别是在骨组织中。骨组织在不断的更新重建中，应力刺激可以引发骨组织表达特殊的生化信号，调节其生长和功能。机械刺激增强时，

Study on the Expression and Significance of TGF-β1, p-ERK1/2and K-ras in Colorectal Cancer Using Tissue Microarray Technique

OBJECTIVE This study aimed to explore the expression and significance of transforming growth factor β1（TGF-β1）,extracellular signal-regulated kinases 1/2 （ERK1/2）, and K-ras in colorectal cancer （CRC） using tissue microarray technology.METHODS The expressions of TGF-β1, ERK1/2, and K-ras in colon cancer cells taken from the specimens of 92 CRC patients （stage Ⅰ： 16 cases, stage Ⅱ： 28 cases, stage Ⅲ： 24 cases, and stage Ⅳ：24 cases） were analyzed using tissue microarray technology and immunohistochemistry, and compared with those of 20 normal colon tissue samples.RESULTS High immunoreactive scores （IRS） of TGF-β1,p-ERK1/2, and K-ras protein in CRC were obtained, which were 66.3% （61/92）, 59.8% （55/92）, and 48.9% （45/92）, respectively, and those in normal epithelial cells of colon were 10% （2/20）, 20% （4/20）, and 30% （6/20）, respectively （P 〈 0.05）. The expressions of TGF-β1 and ERK1/2 in CRC at stage Ⅰwere 37.5% and 31.3%,respectively, and those in CRC at stage Ⅳ were 83.3% and79.3%, respectively, with statistically significant differences. No significant relationship was found between K-ras expression and tumor stages （P〉0.05）.CONCLUSION High level expressions of TGF-β1 and ERK1/2 are closely related to the clinical stages of colon cancer and crosstalk may exist between the 2 signal pathways.

Mixed signals in trends of variance in high-elevation tree ring chronologies

Increases in climate variability, including extremes, may be expected with anthropogenic climate change, but some evidence is contrary. The issue is important because the consequences of variability can be critical for ecosystems. It has long been known and often rehearsed that ecological consequences of increased variability may be greater than those that result from expected changes in mean temperature and precipitation. Tree rings have been useful indicators of ecological response to climate change and used as proxies for climate variability;work in the Rocky Mountains, USA, has been particularly informative. Chronologies from two high elevation species ranging over 2500 km were analyzed for changes in variance through time. These spatially extensive and disaggregated tree ring records do not show a consistent pattern of change in variance over the past 500 or 100 years; heteroscedasticity has recently been greater. A lack of consistent response in growth over a period encompassing changes in mean climate indicates that mountain environments, with inconsistent trends in temperature and precipitation,may be too complex to act as sentinels.

化学中的计算——DNA计算的发展与模型概述

电子计算机的发展给人类社会进步带来了极大的推动作用,但是随着电子计算机制造工艺趋于极限,人们迫切需要找到一种新的计算体系来满足日益增长的计算需求。DNA计算因其超强的信息存储、大规模的并行计算能力和超低的能耗而受到了广泛的关注。自1994年Adleman博士在实验室利用DNA完成了一个6顶点哈密尔顿路求解问题开始,各种计算模型纷纷涌现。本文首先对DNA计算的基本原理和实验操作手段进行了简单的介绍,然后对DNA相关的理论进行了阐述,包括DNA计算中序列编码设计的理论、DNA计算模型复杂度分析与通用计算能力的证明;在此基础上,对突破性的DNA计算模型进行了概括,进而根据实验操作的具体手段将所有已知模型进行了分类,按照类别进行了综述,并随后挑选了该类别中经典的模型进行更为直观的分析。更进一步,在文章的最后,结合笔者的工作对DNA计算领域的前景进行了展望。

Ontogenetic shift in response to prey-derived chemical cues in prairie rattlesnakes Crotalus viridis viridis

Snakes often have specialized diets that undergo a shift from one prey type to another depending on the life stage of the snake. Crotalus viridis viridis （prairie rattlesnake） takes different prey at different life stages, and neonates typically prey on ectotherms, while adults feed almost entirely on small endotherms. We hypothesized that elevated rates of tongue flicking to chemical stimuli should correlate with particular prey consumed, and that this response shifts from one prey type to another as in- dividuals age. To examine if an ontogenetic shift in response to chemical cues occurred, we recorded the rate of tongue flicking for 25 neonate, 20 subadult, and 20 adult （average SVL = 280.9, 552, 789.5 mm, respectively） wild-caught C. v. viridis to chemi- cal stimuli presented on a cotton-tipped applicator; water-soluble cues from two ectotherms （prairie lizard, Sceloporus undulatus, and house gecko, Hemidactylusfrenatus）, two endotherms （deer mouse, Peromyscus maniculatus and lab mouse, Mus musculus）, and water controls were used. Neonates tongue flicked significantly more to chemical cues of their common prey, S. undulatus, than to all other chemical cues; however, the response to this lizard＇s chemical cues decreased in adult rattlesnakes. Subadults tongue flicked with a higher rate of tongue flicking to both S. undulatus and P. maniculatus than to all other treatments, and adults tongue flicked significantly more to P. maniculatus than to all other chemical cues. In addition, all three sub-classes demonstrated a greater response for natural prey chemical cues over chemical stimuli of prey not encountered in the wild （M. musculus and H. frenatus）. This shift in chemosensory response correlated with the previously described ontogenetic shifts in C. v. viridis diet. Be-cause many vipers show a similar ontogenetic shift in diet and venom composition, we suggest that this shift in prey cue dis- crimination is likely a general phenomenon among viperid snakes.

Gadolinium-promoted angiogenesis involves the activation of PKCα/β_2 and MAPKs in human umbilical vein endothelial cells

Gadolinium has been widely used as a contrast agent for magnetic resonance imaging in clinical practice. Recently, it was reported that gadolinium is involved in nephrogenic systemic fibrosis, although the exact mechanism by which gadolinium triggers nephrogenic systemic fibrosis remains unclear. In this study, we show that gadolinium chloride （GdC13） induced human umbilical vein endothelial cells （HUVECs） to migrate in Matrigel and tubulogenesis during wound healing. Chick chorioallantoic membrane assay confirmed that GdC13 stimulates angiogenesis. Under the optimal angiogenic concentration of GdC13 （1 0 ~tM）, intracellular calcium concentration and reactive oxygen species generation were elevated. Moreover, western blotting results indicate that in cells treated with GdC13, Ca2＋-dependent PKCa/132 was phosphorylated, and MAPKs pathways were also activated. Taken together, GdC13 has a potential effect on angiogenesis in HUVECs, and the possible mechanisms may involve oxidative stress and calcium-related signalin~ pathways.

Targeting stem cell signaling pathways for drug discovery:advances in the Notch and Wnt pathways

Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions.In stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are responsible for the regulation of pluripotency and differentiation.During embryonic development,these pathways govern cell fate specifications as well as the formation of tissues and organs.In adulthood,their normal functions are important for tissue homeostasis and regeneration,whereas aberrations result in diseases,such as cancer and degenerative disorders.In complex biological systems,stem cell signaling pathways work in concert as a network and exhibit crosstalk,such as the negative crosstalk between Wnt and Notch.Over the past decade,genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways.Indeed,discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry.Remarkable progress has been made and several promising drug candidates have entered into clinical trials.This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.

SREBP-1 is a novel mediator of TGFβ1 signaling in mesangial cells

Glomerular matrix accumulation is a hallmark of diabetic nephropathy. Recent studies showed that overexpression of the transcription factor SREBP-1 induces glomerutoscterosis. TGFI31 is a key profibrotic mediator of glomerutoscterosis, but whether SREBP-1 regulates its effects is unknown. In kidney mesangial cells and in vivo, TGFβI activates SREBP-1. This requires SCAPo SIP0 and PI3K/Akt signaling, but is independent of Smad3. Activation of the TGFβ1-responsive reporter plasmid p3TP-lux requires SREBP-la, but not SREBP-lc, binding to an E-box adjacent to a Smad-binding element. SREBP-la overexpression atone activates p3TP-tux. Smad3 is required for SREBP-la transcriptional activation and TGFβ induces association between the two transcription factors. SREBP-la K333 acetylation by the acetyltransferase CBP is required for Smad3 association and SREBP-1 transcriptional activity, and is also required for Smad3 transcriptional activity. Thus, both Smad3 and SREBP-la activation cooperatively regulate TGFβ transcriptional responses. SREBP-1 inhibition provides a novel therapeutic strategy for diabetic kidney disease.

Transportation of dynamic biochemical signals in non-reversing oscillatory flows in blood vessels

Biological processes and behaviors of endothelial cells on the inner surfaces of blood vessels are regulated by the stimulation from biochemical signals contained in the blood.In this paper,the transportation of dynamic biochemical signals in non-reversing oscillatory flows in blood vessels is analyzed by numerically solving a nonlinear governing equation for the time-dependent Taylor-Aris dispersion.Results show that the nonlinear frequency-amplitude modulation of the transportation of biochemical signals is more(less) significant when the frequency of an oscillatory flow is close to(higher than) that of an oscillatory signal.Under steady flow,the transfer function for the signal transmission system is obtained,showing that the system is a low-pass filter.Lower inner radius or higher center-line velocity of a blood vessel increases the cutoff frequency of the transportation system.These results suggest the possibility and condition for the 'remote' transmission of low-frequency dynamic biochemical signals in pulsatile blood flows.

Evolutionary ecology of chemosensation and its role in sensory drive

All behaviors of an organism are rooted in sensory processing of signals from its environment, and nat ural selection shapes sensory adaptations to ensure successful detection of cues that maximize fitness. Sensory drive, or divergent selection for efficient signal transmission among heterogeneous environ ments, has been a useful hypothesis for describing sensory adaptations, but its current scope has pri marily focused on visual and acoustic sensory modalities. Chemosensation, the most widespread sensory modality in animals that includes the senses of smell and taste, is characterized by rapid evolu tion and has been linked to sensory adaptations to new environments in numerous lineages. Yet, olfac tion and gustation have been largely underappreciated in light of the sensory drive hypothesis. Here, we examine why chemosensory systems have been overlooked and discuss the potential of chemo sensation to shed new insight on the sensory drive hypothesis and vice versa. We provide suggestions for developing a framework to better incorporate studies of chemosensory adaptation that have the po tential to shape a more complete, coherent, and holistic interpretation of the sensory drive.