Background: MicroRNA (miR) dysregulation is found in Alzheimer disease (AD). A disintegrin and metalloprotease 10 (ADAM10) prevents generation of amyloid ␤ (A␤) and decrease AD pathology. Results: miR-144 suppresses ADAM10 expression and is up-regulated by activator protein-1. Conclusion: miR-144 is a negative regulator of ADAM10 and may be involved in AD pathogenesis. Significance:The first work to demonstrate the function of miRNA-144 and its regulation in the pathogenesis of AD.

Background The anionic toxicity of plants under salt stress is mainly caused by chloride (Cl − ). Thus Cl − influx, transport and their regulatory mechanisms should be one of the most important aspects of plant salt tolerance studies, but are often sidelined by the focus on sodium (Na + ) toxicity and its associated adaptations. Plant chloride channels (CLCs) are transport proteins for anions including Cl − and nitrate (NO 3 − ), and are critical for nutrition uptake and transport, adjustment of cellular turgor, stomatal movement, signal transduction, and Cl − and NO 3 − homeostasis under salt stress. Results Among the eight soybean CLC genes, the tonoplast-localized c2 has uniquely different transcriptional patterns between cultivated soybean N23674 and wild soybean BB52. Using soybean hairy root transformation, we found that GsCLC-c2 over-expression contributed to Cl − and NO 3 − homeostasis, and therefore conferred salt tolerance, through increasing the accumulation of Cl − in the roots, thereby reducing their transportation to the shoots where most of the cellular damages occur. Also, by keeping relatively high levels of NO 3 − in the aerial part of the plant, GsCLC-c2 could reduce the Cl − /NO 3 − ratio. Wild type GsCLC-c2, but not its mutants ( S184P , E227V and E294G ) with mutations in the conserved domains, is able to complement Saccharomyces cerevisiae △gef1 Cl − sensitive phenotype. Using two-electrode voltage clamp on Xenopus laevis oocytes injected with GsCLC-c2 cRNA, we found that GsCLC-c2 transports both Cl − and NO 3 − with slightly different affinity, and the affinity toward Cl − was pH-independent. Conclusion This study revealed that the expression of GsCLC-c2 is induced by NaCl-stress in the root of wild soybean. The tonoplast localized GsCLC-c2 transports Cl − with a higher affinity than NO 3 − in a pH-independent fashion. GsCLC-c2 probably alleviates salt stress in planta through the sequestration of excess Cl − into the vacuoles of root cells and thus preventing Cl ...

Although cyclophilin A (CypA) has been reported to be over-expressed in cancer cells and solid tumors, its expression and role in glioblastomas have not been studied. Herein, we show that expression of CypA in human glioblastoma cell lines and tissues is significantly higher than in normal human astrocytes and normal counterparts of brain tissue. To determine the role of over-expressed CypA in glioblastoma, stable RNA interference (RNAi)-mediated knockdown of CypA (CypA KD) was performed in gliobastoma cell line U87vIII (U87MG · ΔEGFR). CypA KD stable single clones decrease proliferation, infiltration, migration, and anchorage-independent growth in vitro and with slower growth in vivo as xenografts in immunodeficient nude mice. We have also observed that knockdown of CypA inhibits expression of interleukin-8 (IL-8), a tumorigenic and proangiogenic cytokine. Conversely, enforced expression of CypA in the CypA KD cell line, Ud-12, markedly enhanced IL-8 transcripts and restored Ud-12 proliferation, suggesting that CypA-mediated IL-8 production provides a growth advantage to glioblastoma cells. CypA knockdown-mediated inhibition of IL-8 is due to reduced activity of NF-κB, which is one of the major transcription factors regulating IL-8 expression. These results not only establish the relevance of CypA to glioblastoma growth in vitro and in vivo, but also suggest that small interfering RNA-based CypA knockdown could be an effective therapeutic approach against glioblastomas.

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