CHL1 Is Expressed and Functions as a Malignancy Promoter in Glioma Cells.

The cell adhesion molecule with homology to L1CAM (close homolog of L1) (CHL1) is a member of the cell adhesion molecule L1 (L1CAM) gene family. Although CHL1 expression and function have been reported in several tumors, the roles of CHL1 in the development of glioma remain unclear. In the present study, we investigated the effects of CHL1 on proliferation indexes and activation of Akt1 and Erk signaling by siRNA in U-87 MG human glioblastoma and human U251 and SHG-44 glioma cells. We found that siRNA targeting CHL1 significantly down-regulated the expression of CHL1 mRNA and protein accompanied by reduced cell proliferation and transmigration invasion in all three cell lines. Down-regulating CHL1 expression also reduced cell survival, as measured by the Bax/Bcl-2 ratio, and increased activation of caspase-3. In subcutaneous U-87 MG cell xenograft tumors in nude mice, intratumoral administration of siRNA targeting CHL1 treatment significantly down-regulated CHL1 expression in vivo, accompanied by increased levels of activated caspase-3. Our combined results confirmed for the first time that in contrast to findings about CHL1 in most other cancer types, CHL1 functions in promoting cell proliferation, metastasis and migration in human glioma cells both in vitro and in vivo. These results indicate that CHL1 is a therapeutic target in the clinical management of glioma/glioblastoma.

Differential changes in Neuregulin-1 signaling in major brain regions in a lipopolysaccharide-induced neuroinflammation mouse model.

Neuregulin 1 (Nrg1) is involved in multiple biological processes in the nervous system. The present study investigated changes in Nrg1 signaling in the major brain regions of mice subjected to lipopolysaccharide (LPS)-induced neuroinflammation. At 24 h post­intraperitoneal injection of LPS, mouse brain tissues, including tissues from the cortex, striatum, hippocampus and hypothalamus, were collected. Reverse transcription­polymerase chain reaction was used to determine the expression of Nrg1 and its receptors, Neu and ErbB4, at the mRNA level. Western blotting was performed to determine the levels of these proteins and the protein levels of phosphorylated extracellular signal-regulated kinases (Erk)1/2 and Akt1. Immunohistochemical staining was utilized to detect the levels of pNeu and pErbB4 in these regions. LPS successfully induced sites of neuroinflammation in these regions, in which changes in Nrg1, Neu and ErbB4 at the mRNA and protein levels were identified compared with controls. LPS induced a reduction in pNeu and pErbB4 in the striatum and hypothalamus, although marginally increased pErbB4 levels were found in the hippocampus. LPS increased the overall phosphorylation of Src but this effect was reduced in the hypothalamus. Moreover, increased phosphorylation of Akt1 was found in the striatum and hippocampus. These data suggest diverse roles for Nrg1 signaling in these regions during the process of neuroinflammation.

L1 modulates PKD1 phosphorylation in cerebellar granule neurons.

The neural cell adhesion molecule L1 (L1CAM) is crucial for the development of the nervous system, with an essential role in regulating multiple cellular activities. Protein kinase D1 (PKD1) serves as a key kinase given its diverse array of functions within the cell. Here, we investigated various aspects of the functional relationship between L1 and phosphorylated PKD1 (pPKD1) in cerebellar granule neurons. To study the relationship between L1 and PKD1 phosphorylation, human cerebellar tissue microarrays were subject to immunofluorescence staining. We observed a positive correlation between L1 protein levels and PKD1 phosphorylation. In addition, L1 also co-localized with pPKD1. To analyze the regulatory role of L1 on PKD1 phosphorylation, primary mouse cerebellar granule neurons were treated with various concentrations of rL1 for 48 h. Using Western blot, we revealed that L1 significantly increased PKD1 phosphorylation compared with vehicle control, with the maximal effect observed at 5 nM. ERK1/2 phosphorylation was significantly increased by 2.5 nM and 10nM L1, with no apparent change in SRC phosphorylation. However, SRC expression was markedly reduced by 10nM rL1. AKT1 expression and phosphorylation levels were significantly increased by rL1, with the maximal effect observed at 2.5 and 5 nM, respectively. Our combined data revealed a positive relationship between L1 and pPKD1 in both cultured cerebellar neurons and human cerebellar tissue, suggesting that L1 functions in the modulation of PKD1 phosphorylation.

China's postgraduate education practices and its academic impact on publishing: is it proportional?

Though postgraduate education started before the founding of new China in 1949, it was not until the implementation of the policy reform and the opening-up in 1978 that China's postgraduate productivity began to take off. Since the introduction of Regulations of the People's Republic of China on Academic Degrees in 1981, the number of graduate students enrolled each year has increased 50 times since 1978. China is now the second largest producer of publications indexed by the database of Science Citation Index (SCI) (Web of Science™, Thomson Reuters), which reflects great strides being made in the postgraduate education. In this paper, we discuss the relationship between the increasingly high enrollments of graduate students and the quantity (the number) and quality (the academic impact and the originality) of their publications, to see whether there is a correlation.