Understanding the Role of Dicer in Astrocyte Development

The Dicer1 allele is used to show that microRNAs (miRNAs) play important roles in astrocyte development and functions. While it is known that astrocytes that lack miRNAs are dysregulated, the in vivo phenotypes of these astrocytes are not well understood. In this study, we use Aldh1l1-EGFP transgene, a marker of astrocytes, to characterize mouse models with conditional Dicer1 ablation (via either human or mouse GFAP-Cre). This transgene revealed novel features of the defective astrocytes from the absence of miRNA. Although astrocyte miRNAs were depleted in both lines, we found histological and molecular differences in the Aldh1l1-EGFP cells between the two Cre lines. Aldh1l1-EGFP cells from hGFAP-Cre mutant lines displayed up-regulation of Aldh1l1-EGFP with increased proliferation and a genomic profile that acquired many features of wildtype primary astrocyte cultures. In the young mGFAP-Cre mutant lines we found that Aldh1l1-EGFP cells were disorganized and hyperproliferative in the developing cerebellum. Using the Aldh1l1-EGFP transgene, our work provides new insights into the roles of miRNAs in astrocyte development and the features of astrocytes in these two mouse models.     

Impact of Conditional miRNA126 Overexpression on Apoptosis-Resistant Endothelial Cell Production

The activation of endothelial cells is essential to repair damage caused by atherosclerosis via endothelial cell proliferation and migration. Overexpression of VEGF (vascular endothelial growth factor) and the downstream gene, B-cell lymphoma-2 (BCL-2) could result in apoptosis-resistant endothelial cells, which are responsible for aggravated hyperplasia and instable plaques generation. Previous studies have shown that miRNA126 could regulate the expression of VEGF. Here, we verified the existence of a miRNA126 binding site in VEGF’s 3’UTR. Additionally, VEGF regulated BCL-2 expression via AP1 (Activator Protein 1) binding site in BCL-2’s promoter. Next, we established an apoptosis-resistant endothelial cell line and constructed a lentiviral vector to express miRNA126 under the control of the BCL-2 promoter to investigate whether conditional expression of miRNA126 could modulate VEGF and BCL-2 expression in apoptosis-resistant endothelial cells. This lentiviral system specifically expressed miRNA126 in cells with high BCL-2 levels, downregulated VEGF expression, inhibited MAPK pathway activation and downregulated BCL-2 expression via suppression of AP1, and as a whole, reduced apoptosis-resistant endothelial cells, while the effects of miRNA126 on normal endothelial cells were relatively small. Our results demonstrate that conditional miRNA126 overexpression under the control of the downstream BCL-2 promoter provides a flexible regulatory strategy for reducing the apoptosis-resistant endothelial cells without having a significant impact on normal endothelial cells.     

Splenic gene expression profiling in White Leghorn layer inoculated with the Salmonella enterica serovar Enteritidis

Salmonella enterica serovar Enteritidis (SE) is a foodborne pathogen that can threaten human health through contaminated poultry products. Live poultry, chicken eggs and meat are primary sources of human salmonellosis. To understand the genetic resistance of egg‐type chickens in response to SE inoculation, global gene expression in the spleen of 20‐week‐old White Leghorn was measured using the Agilent 4 × 44 K chicken microarray at 7 and 14 days following SE inoculation (dpi). Results showed that there were 1363 genes significantly differentially expressed between inoculated and non‐inoculated groups at 7 dpi (I7/N7), of which 682 were up‐regulated and 681 were down‐regulated genes. By contrast, 688 differentially expressed genes were observed at 14 dpi (I14/N14), of which 371 were up‐regulated genes and 317 were down‐regulated genes. There were 33 and 28 immune‐related genes significantly differentially expressed in the comparisons of I7/N7 and I14/N14 respectively. Functional annotation revealed that several Gene Ontology (GO) terms related to immunity were significantly enriched between the inoculated and non‐inoculated groups at 14 dpi but not at 7 dpi, despite a similar number of immune‐related genes identified between I7/N7 and I14/N14. The immune response to SE inoculation changes with different time points following SE inoculation. The complicated interaction between the immune system and metabolism contributes to the immune responses to SE inoculation of egg‐type chickens at 14 dpi at the onset of lay. GC, TNFSF8, CD86, CD274, BLB1 and BLB2 play important roles in response to SE inoculation. The results from this study will deepen the current understanding of the genetic response of the egg‐type chicken to SE inoculation at the onset of egg laying.     

A new genus of Coelotinae (Araneae,Agelenidae) from southern China

One new genus of the spider subfamily Coelotinae, Flexicoelotes gen. n., with five new species is described from southern China: Flexicoelotes huyunensis sp. n. (female), Flexicoelotes jiaohanyanensis sp. n. (male and female), Flexicoelotes jinlongyanensis sp. n. (male and female), Flexicoelotes pingzhaiensis sp. n. (female), Flexicoelotes xingwangensis sp. n. (male and female).     

A New Pathway for Senescence Regulation

<正>Research concerning senescence has become a hotspot since the conception of‘cellular senescence’was put forward by Drs.Hayflick and Moorhead over five decades ago[1].Recently,a paper published in Science by Kang and colleagues,which this article aims to comment on,provides evidence of a new pathway involved in senescence[2].Senescence is a physiological and pathological process induced by numerous factors,during which cell growth ceases     

Statistical Inference Methods for Two Crossing Survival Curves: A Comparison of Methods

A common problem that is encountered in medical applications is the overall homogeneity of survival distributions when two survival curves cross each other. A survey demonstrated that under this condition, which was an obvious violation of the assumption of proportional hazard rates, the log-rank test was still used in 70% of studies. Several statistical methods have been proposed to solve this problem. However, in many applications, it is difficult to specify the types of survival differences and choose an appropriate method prior to analysis. Thus, we conducted an extensive series of Monte Carlo simulations to investigate the power and type I error rate of these procedures under various patterns of crossing survival curves with different censoring rates and distribution parameters. Our objective was to evaluate the strengths and weaknesses of tests in different situations and for various censoring rates and to recommend an appropriate test that will not fail for a wide range of applications. Simulation studies demonstrated that adaptive Neyman’s smooth tests and the two-stage procedure offer higher power and greater stability than other methods when the survival distributions cross at early, middle or late times. Even for proportional hazards, both methods maintain acceptable power compared with the log-rank test. In terms of the type I error rate, Renyi and Cramér—von Mises tests are relatively conservative, whereas the statistics of the Lin-Xu test exhibit apparent inflation as the censoring rate increases. Other tests produce results close to the nominal 0.05 level. In conclusion, adaptive Neyman’s smooth tests and the two-stage procedure are found to be the most stable and feasible approaches for a variety of situations and censoring rates. Therefore, they are applicable to a wider spectrum of alternatives compared with other tests.