Public Health Perspectives on Dioxin Risks: Two Decades of Evaluations

The paper provides an overview of approaches to dioxin risk assessment employed by different agencies worldwide over the past 20 years. Our insights regarding understanding of the toxicity of dioxins have advanced tremendously in recent years; however, important data gaps still exist. More information on topics such as mechanism of interaction, effects at low levels of exposure, interspecies differences, and sensitive populations is needed. Some differences exist between USEPA's approach to dioxin assessment and that of other health organizations around the world. The authors conclude that USEPA's reassessment of dioxin and related compounds may place too much confidence in the ability to accurately predict cancer risks at low doses. Further, it is important to derive health-based guidance values for noncancer end points especially in accordance with emerging reports that reproductive and developmental end points are very sensitive to dioxins. A worldwide convergence on the health assessment value being around 1 to 4?pg/kg/day is noted.     

放射线引导下经椎间盘入路内脏大小神经毁损术治疗上腹部癌痛的临床分析

目的:观察放射线引导下经椎间盘入路毁损内脏神经治疗上腹部癌痛的疗效及安全性。方法:选择上腹部癌痛患者26例,在放射线引导下经T11~12椎间盘入路穿刺,注射无水乙醇5.0 mL毁损内脏大、小神经,观察穿刺成功率,并记录术前、术后1天、1周、2周、1月、2月的疼痛强度(NRS评分)、生活质量评分(QOL),阿片类药物的用量以及手术不良反应的发生情况。结果:所有患者均穿刺到位,无严重并发症出现。和术前相比,术后各时点的NRS评分、每日吗啡消耗量下降,QOL评分增加(P0.05)。其中,6例患者发生暂时性腹泻,一周内恢复;5例患者出现不同程度的腹背部烧灼感,未经特殊处理24 h后症状消失。结论:在放射线引导下经椎间盘入路毁损内脏神经治疗上腹部癌痛的操作简单,疗效好,可显著提高患者的生活质量,且安全性高。     

The Dream Will Tell: Militant Muslim Dreaming in the Context of Traditional and Contemporary Islamic Dream Theory and Practice.

Al-Qaeda and Taliban leadership and membership appear to have been motivated, inspired, and guided by certain dreams. Their understanding of dreams seems to draw at least partly on traditional and contemporary Islamic dream theories. If this hypothesis is correct, then there is a need for the urgent study of Islamic Jihadist political/religious conversion and guidance dreams across the Middle East. The dream-as experienced, reported, and interpreted-is now a significant aspect of the global conflict between Al-Qaeda and its associates versus the core value system of Western civilization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of a novel member of murine semaphorin family

Semaphorin gene family contains a large number of secreted and transmembrane proteins, and some of them are functioning as the repulsive and attractive cues of the axon guidance during development. Here we report murine orthologues of a novel member of class 6 semaphorin gene, semaphorin 6D (Sema6D), mapped on the chromosome 2. Sema6D is mainly expressed in the brain and lung, and the ubiquitous expression in the brain continues from embryonic late stage to adulthood, as determined by Northern blot and in situ hybridization. We also found that Sema6D has five different splicing variants, and the expression patterns of individual isoforms differ depending on the tissues. Thus, Sema6D may play important roles in various functions including the axon guidance during development and neuronal plasticity.     

Ectoderm removal prevents cutaneous nerve formation and perturbs sensory axon growth in the chick hindlimb

Target tissues are thought to provide important cues for growing axons, yet there is little direct evidence that they are essential for axonal pathfinding. Here we examined whether target ectoderm is necessary for the formation of cutaneous nerves, and for the normal growth and guidance of cutaneous axons as they first enter the limb plexus. To do this, we removed a patch of ectoderm from the chick hindlimb at various times during early axon outgrowth. We find there is a critical period when cutaneous nerve formation requires target ectoderm. When the ectoderm is absent during this time, axons progress into the limb more slowly and, although a few sensory axons occasionally diverge a short distance from the plexus, they do not form a discrete nerve that travels to the skin. A few days later, when the nerve pattern is mature, axons normally destined for the 'deprived' cutaneous nerve are not segregated appropriately within the plexus. Some cutaneous axons are instead misdirected along an inappropriate cutaneous nerve, while others have seemingly failed to reach their correct target, or a suitable alternative, and died. These results demonstrate that the target ectoderm is necessary for normal sensory axon growth and guidance in the hindlimb.     

Axon guidance processes in the retinotectal and vomeronasal projection are controlled by Eph receptor tyrosine kinases and ephrins

The Eph family of receptor tyrosine kinases and their ‘ligands’, the ephrins, have been shown to play key roles in a number of different developmental processes such as cell migration, boundary formation, axon guidance, synapse formation and vasculogenesis. Here, we summarize recent findings derived from investigating the role of the EphA family during development of the retinotectal and vomeronasal projection uncovering a role of ephrin-A molecules as axon guidance receptors.     

肌球蛋白X在细胞运动中的作用

肌球蛋白X(myosin X,Myo X)是一类尾部具有MyTH4(myosin tail homology 4,MyTH4)和FERM(band4.1/ezrin/radixin/moesin,FERM)结构域的非传统型肌球蛋白,广泛分布于脊椎动物细胞中.近几年的研究表明,Myo X尾部结构域能够与众多的信号分子相互作用,参与调节从丝状伪足形成到胞质分裂等多种细胞运动过程,但其具体的调控机制目前尚不完全清楚.Myo X作为一类连接细胞膜与细胞骨架的动力蛋白分子,它的研究越来越受到人们的关注,其功能的揭示将为进一步阐明细胞多种运动机制提供理论依据.     

Cellular responses to extracellular guidance cues

Extracellular guidance cues have a key role in orchestrating cell behaviour. They can take many forms, including soluble and cell‐bound ligands (proteins, lipids, peptides or small molecules) and insoluble matrix substrates, but to act as guidance cues, they must be presented to the cell in a spatially restricted manner. Cells that recognize such cues respond by activating intracellular signal transduction pathways in a spatially restricted manner and convert the extracellular information into intracellular polarity. Although extracellular cues influence a broad range of cell polarity decisions, such as mitotic spindle orientation during asymmetric cell division, or the establishment of apical–basal polarity in epithelia, this review will focus specifically on guidance cues that promote cell migration (chemotaxis), or localized cell shape changes (chemotropism).     

Error correction during guidance of pioneer axons in the leg of the cockroach embryo

Axons of the Til and Fe2 pioneer neurons in the legs of insect embryos possess separate and highly stereotyped proximal projections towards the CNS. However, quantitative analyses of deviations from the standard paths during the period of axon growth indicate that transient errors occur unexpectedly often. The distribution of legs with axons following deviant paths among the embryos analyzed is used to determine whether these errors are caused by random developmental noise or by non-random genetic or environmental factors. During the formation of the Til pathway all the errors are characterized by defasciculation of the 2 axons, occur with an average incidence of 7% and are statistically shown to be randomly caused. In comparison, during the formation of the Fe2 pathway the errors are characterized by both defasciculation and elongation in an inappropriate distal direction, occur with an incidence of 16%, and as revealed by statistical analyses, are caused by a non-random factor. Therefore, during pathfinding by these 2 pairs of axons there is a need for error-correcting mechanisms to insure the stereotypy of the final projections. These error-correcting mechanisms are suggested to have properties similar to those producing canalization as proposed by Waddington.     

Regulation of cell adhesion to collagen via β1 integrins is dependent on interactions of filamin A with vimentin and protein kinase C epsilon

Cell adhesion and spreading on collagen, which are essential processes for development and wound healing in mammals, are mediated by β1 integrins and the actin and intermediate filament cytoskeletons. The mechanisms by which these separate cytoskeletal systems interact to regulate β1 integrins and cell spreading are poorly defined. We previously reported that the actin cross-linking protein filamin A binds the intermediate filament protein vimentin and that these two proteins co-regulate cell spreading. Here we used deletional mutants of filamin A to define filamin A-vimentin interactions and the subsequent phosphorylation and re-distribution of vimentin during cell spreading on collagen. Imaging of fixed and live cell preparations showed that phosphorylated vimentin is translocated to the cell membrane during spreading. Knockdown of filamin A inhibited cell spreading and the phosphorylation and re-distribution of vimentin. Knockdown of filamin A and/or vimentin reduced the cell surface expression and activation of β1 integrins, as indicated by immunoblotting of plasma membrane-associated proteins and shear force assays. In vitro pull-down assays using filamin A mutants showed that both vimentin and protein kinase C? bind to repeats 1-8 of filamin A. Reconstitution of filamin-A-deficient cells with full-length filamin A or filamin A repeats 1-8 restored cell spreading, vimentin phosphorylation, and the cell surface expression of β1 integrins. We conclude that the binding of filamin A to vimentin and protein kinase Cε is an essential regulatory step for the trafficking and activation of β1 integrins and cell spreading on collagen.