Drug-induced readthrough of premature stop codons leads to the stabilization of laminin alpha2 chain mRNA in CMD myotubes

BACKGROUND: The most common form of congenital muscular dystrophy is caused by a deficiency in the alpha2 chain of laminin-211, a protein of the extracellular matrix. A wide variety of mutations, including 20 to 30% of nonsense mutations, have been identified in the corresponding gene, LAMA2. A promising approach for the treatment of genetic disorders due to premature termination codons (PTCs) is the use of drugs to force stop codon readthrough. METHODS: Here, we analyzed the effects of two compounds on a PTC in the LAMA2 gene that targets the mRNA to nonsense-mediated RNA decay, in vitro using a dual reporter assay, as well as ex vivo in patient-derived myotubes. RESULTS: We first showed that both gentamicin and negamycin promote significant readthrough of this PTC. We then demonstrated that the mutant mRNAs were strongly stabilized in patient-derived myotubes after administration of negamycin, but not gentamicin. Nevertheless, neither treatment allowed re-expression of the laminin alpha2-chain protein, pointing to problems that may have arisen at the translational or post-translational levels. CONCLUSIONS: Taken together, our results emphasize that achievement of a clinical benefit upon treatment with novel readthrough-inducing agents would require several favourable conditions including PTC nucleotide context, intrinsic and induced stability of mRNA and correct synthesis of a full-length active protein.     

A latitudinal gradient of beta diversity for exotic vascular plant species in North America

Determining relationships between the ranges of introduced species and geographical and environmental factors is an important step in understanding the mechanisms and processes of the spread of introduced species. In this study, I examined the beta diversity and latitude relationship for all naturalized exotic species of vascular plants in North America at a continental scale. Beta diversity was calculated as the absolute value of the slope of the relationship between the natural logarithm of the Simpson index of similarity (lnS) and spatial distance between pairs of state‐level exotic floras within four latitudinal zones examined. Relative contributions of spatial distance and environmental difference to species turnover between exotic floras were examined. I found that beta diversity decreased monotonically from low to high latitudes: beta diversity for the southernmost zone was shallower than that for the northernmost zone by a factor of 2.6. Regression models of lnS in relation to spatial distance and environmental (climatic and topographical) difference for each latitudinal zone demonstrated that the explanatory power of these variables diminishes monotonically with latitude: the explained variance in lnS is 70.4%, 62.1%, 53.9%, and 33.9%, respectively, for the four latitudinal zones from south to north. For the southernmost zone, 58.3% of the variance in lnS is explained by climate variables and topography, and spatial distance explains only 2.3% of the variance. In contrast, for the northernmost zone, more than half the amount (22.5%) of the explained variance in lnS is attributable to spatial distance, and the remaining (18.9%) of the explained variance is attributable to climate variables and topography.     

Trypanosoma cruzi: the role of PGE2 in immune response during the acute phase of experimental infection

Chagas disease is characterized by cardiac lesions and a high level of PGE2. Our objective was to investigate the role of PGE2 in cardiac lesions. BALB/c mice were infected with Trypanosoma cruzi (1x10(3) trypomastigote forms) and were treated daily with PBS, meloxicam (0.5 mg/kg) or etoricoxib (0.6 mg/kg). The animals were sacrificed on the 21st day of infection and we collected the cardiac tissue and spleen cells for tissue culture. We observed that treatment with COX-2 inhibitors was able to decrease synthesis of PGE2 by spleen cells. This reduction was accompanied by reduction of the inflammatory infiltrate, parasite nets, cardiac fibrosis and fewer COX-2 positive cells in cardiac tissue obtained from these animals. In conclusion, treatment with COX-2 inhibitors, and consequent inhibition of PGE2 synthesis, was able to reduce the cardiac damage observed during the acute phase of experimental Chagas disease, thus demonstrating the involvement of this mediator in the cardiac lesion.     

Decay rates of attractive and repellent pheromones in an ant foraging trail network

Pharaoh’s ants (Monomorium pharaonis) use at least three types of foraging trail pheromone: a long-lasting attractive pheromone and two short-lived pheromones, one attractive and one repellent. We measured the decay rates of the behavioural response of ant workers at a trail bifurcation to trail substrate marked with either repellent or attractive short-lived pheromones. Our results show that the repellent pheromone effect lasts more than twice as long as the attractive pheromone effect (78 min versus 33 min). Although the effects of these two pheromones decay at approximately the same rate, the initial effect of the repellent pheromone on branch choice is almost twice that of the attractive pheromone (48% versus 25% above control). We hypothesise that the two pheromones have complementary but distinct roles, with the repellent pheromone specifically directing ants at bifurcations, while the attractive pheromone guides ants along the entire trail. Received 15 November 2007; revised 7 March 2008; accepted 18 March 2008.     

沙坡头地区人工林植物的水分生态位适宜度与种间共存机制分析

以沙坡头地区人工固沙植物为研究对象,扩展了Hutchinson提出的n维超体积生态位概念,定义固沙植物种的水分生态位适宜度是该种的最适水分生态位与现实水分资源位之间的贴近度。水分生态位适宜度的大小表示植物对土壤水分的利用程度。根据几何平行度方法建立了新的数学模型。实例计算结果表明,利用新模型计算结果比常用的百分比相似性公式计算的结果有较合理的数值分布;实验条件下的合理营林密度为5000株／hm^2,营林方式为柠条与油蒿均匀混播,此种情况下水分生态位适宜度最高,相应林木覆盖率最大。在试验条件下,油蒿和柠条纯林的水分生态位适宜度平均值低于混播下的值。关于不同种植密度下水分生态位适宜度的变化规律,呈现随密度增加先上升后下降的趋势。由于油蒿是浅根系植物,利用土壤上层水分;柠条是深根系植物．利用土壤下层水分;二者适当混播后可使土壤水分合理分配和充分利用,因此混播下具有较高的水分适宜度值,而且实验条件下能够实现稳定共存,达到较好的防风固沙效果。     

小麦籽粒中植酸、戊聚糖含量及其与相关性状关系的研究

选用不同基因型小麦,测定了籽粒中植酸、蛋白质及戊聚糖的含量,并对其进行遗传相关分析,结果表明：(1)各性状在品种间存在显著性差异,且植酸的广义遗传力比较低;(2)植酸含量与蛋白质含量呈极显著的正相关,与戊聚糖呈极显著负相关。通过对参试的18个不同基因型小麦中植酸和戊聚糖含量进行聚类分析,可以将18个基因型小麦聚为四类,并初步认为豫麦47是参试品种中最适宜于用作饲用小麦。     

具有时滞的两种群Schoener竞争模型的正周期解的存在性

应用重合度理论讨论了具有时滞的周期Schoener竞争模型,得到了系统正周期解存在的充分条件．     

具毒物影响和中立型时滞两种群竞争系统的周期正解

讨论了一类具毒物影响的中立型时滞两种群竞争系统,利用重合度理论和分析技巧建立了该系统正周期解全局存在的充分条件。