A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue

The nematode Caenorhabditis elegans is commonly used as a genetic model organism for dissecting integration of the sensory and motor systems. Despite extensive genetic and behavioural analyses that have led to the identification of many genes and neural circuits involved in regulating C. elegans locomotion behaviour, it remains unclear whether and how somatosensory feedback modulates motor output during locomotion. In particular, no stretch receptors have been identified in C. elegans, raising the issue of whether stretch-receptor-mediated proprioception is used by C. elegans to regulate its locomotion behaviour. Here we have characterized TRP-4, the C. elegans homologue of the mechanosensitive TRPN channel. We show that trp-4 mutant worms bend their body abnormally, exhibiting a body posture distinct from that of wild-type worms during locomotion, suggesting that TRP-4 is involved in stretch-receptor-mediated proprioception. We show that TRP-4 acts in a single neuron, DVA, to mediate its function in proprioception, and that the activity of DVA can be stimulated by body stretch. DVA both positively and negatively modulates locomotion, providing a unique mechanism whereby a single neuron can fine-tune motor activity. Thus, DVA represents a stretch receptor neuron that regulates sensory-motor integration during C. elegans locomotion.     

新疆温泉县卓勒萨依一带乌郎组火山岩锆石U-Pb年龄、地球化学特征及其构造意义

卓勒萨依一带的乌郎组火山岩位于温泉县城东南25km处,岩石类型主要为安山岩和流纹岩,火山岩浆具有由酸性—中性—酸性演化的特点,以裂隙式喷发类型为主。LA-ICP-MS锆石U-Pb年龄为(293±3)Ma(MSWD=0.34、Probability=0.997),时代为早二叠世早期。该火山岩里特曼指数(σ)为1.71~2.60;碱度率(AR)为2.13~2.85,K2O/Na2O比值为0.31~1.83,属钙碱性系列。Nb/Ta值为18.65~22.85,略高于原始地幔值,Zr/Hf值为28.54~41.08,与原始地幔值相近。RbN/YbN比值为9.82~20.04,大于1,属于强不相容元素富集分配形式。稀土总量∑REE为 (118.41~194.70)×10-6;(Ce/Yb)N值为2.55~3.70,(La/Yb)N值为2.98~4.17,均大于1,属于轻稀土富集型,且轻稀土分馏明显;δEu值为0.19~0.59,远小于1,显示为负铕异常,铕亏损明显。根据相关构造环境判别图解,结合火山岩的地球化学特征及其所处的区域地质背景,认为在早二叠世发生大规模的陆陆叠覆造山作用,卓勒萨依一带火山活动较强烈,所反映的构造环境为陆内岛弧造山带火山岩环境。     

Deregulated expression of c-Myc depletes epidermal stem cells

The beta-catenin/TCF signaling pathway is essential for the maintenance of epithelial stem cells in the small intestine. c-Myc a downstream target of beta-catenin/TCF (ref. 2), can induce differentiation of epidermal stem cells in vitro. To determine the role of c-Myc in epidermal stem cells in vivo, we have targeted expression of human MYC2 to the hair follicles and the basal layer of mouse epidermis using a keratin 14 vector (K14.MYC2). Adult K14.MYC2 mice gradually lose their hair and develop spontaneous ulcerated lesions due to a severe impairment in wound healing; their keratinocytes show impaired migration in response to wounding. The expression of beta1 integrin, which is preferentially expressed in epidermal stem cells is unusually low in the epidermis of K14.MYC2 mice. Label-retaining analysis to identify epidermal stem cells reveals a 75% reduction in the number of stem cells in 3-month-old K14.MYC2 mice, compared with wildtype mice. We conclude that deregulated expression of c-Myc in stem cells reduces beta1 integrin expression, which is essential to both keratinocyte migration and stem cell maintenance.     

The in vitro antiapoptotic effect of dehydroepiandrosterone sulfate in mouse thymocytes and its relation to caspase-3/caspase-6

The effects of dehydroepiandrosterone sulfate (DHEAS) on thymocyte apoptosis induced by dexamethasone (DEX) were investigated. Apoptosis was measured by using agarose gel electrophoresis of DNA, the terminal deoxynucleotidyltransferase (TdT)- mediated dUTP nick end labeling (TUNEL) assay and flow cytometry. Our results showed that preincubation with 1×10⁻⁴ M DHEAS protected thymocytes from DEX-induced apoptosis in vitro. Moreover, we found no blocking effect on the DEX-induced activation of caspase-3 and caspase-6 by the preincubation of thymocytes with DHEAS. This may be interpreted to mean that the antagonism of DHEAS to DEX-induced apoptosis is not related to the activation of these downstream caspases which play a critical role in the execution of apoptosis. Received 25 June 1999; received after revision 1 September 1999; accepted 13 September 1999