A platform for controlled drug delivery using a conductive‐polymer substrate has been created. Through the incorporation of biotin into the conductive polymer polypyrrole (PPy) and the subsequent attachment of the desired drug molecule (such as nerve growth factor, NGF) via a streptavidin linker, an applied potential can trigger release of the drug from the polymer surface (see figure).

The incidence of lung diseases and cancer caused by cigarette smoke is increasing. The molecular mechanisms of gene regulation induced by cigarette smoke that ultimately lead to cancer remain unclear. This report describes a novel long noncoding RNA (lncRNA) that is induced by cigarette smoke extract (CSE) both in vitro and in vivo and is elevated in numerous lung cancer cell lines. We have termed this lncRNA the smoke and cancer-associated lncRNA-1 (SCAL1). This lncRNA is located in chromosome 5, and initial sequencing analysis reveals a transcript with four exons and three introns. The expression of SCAL1 is regulated transcriptionally by nuclear factor erythroid 2-related factor (NRF2), as determined by the small, interfering RNA (siRNA) knockdown of NRF2 and kelch-like ECH-associated protein 1 (KEAP1). A nuclear factor erythroid-derived 2 (NF-E2) motif was identified in the promoter region that shows binding to NRF2 after its activation. Functionally, the siRNA knockdown of SCAL1 in human bronchial epithelial cells shows a significant potentiation of cytotoxicity induced by CSE in vitro. Altogether, these results identify a novel and intriguing new noncoding RNA that may act downstream of NRF2 to regulate gene expression and mediate oxidative stress protection in airway epithelial cells.Keywords: lincRNA; cancer; smoke; NRF2; epigenetics Recent advances in sequencing technology have revealed that significant numbers of noncoding RNAs are expressed and have significant functions in regulating gene expression. Noncoding RNAs have been classified according to size as either microRNAs (less than 200 base pairs) to long noncoding RNAs (greater than 200 base pairs; lncRNAs). LncRNAs have been further subdivided, based on their location relative to coding genes. Native antisense transcripts overlap with coding genes, intronic lncRNAs are expressed from the introns of coding genes, and long intergenic noncoding RNAs (lincRNAs) are found in the genome between coding genes (1). Unlike micro-RNAs, lncRNAs are much less well characterized, and how they function in biology and gene regulation remains an active area of investigation.Using gain and loss of function approaches, the function of individual lncRNAs are gradually being elucidated. X-inactive specific transcript (XIST), one of the earliest identified lncRNAs, plays an essential role in sex-specific imprinting by epigenetically silencing one of the two X chromosomes in female zygotes through the recruitment of polycomb repressor complexes (PRC2) (2). Other lncRNAs, such as HOX antisense intergenic RNA (HOTAIR) and P21-associated ncRNA DNA damage activated (PANDA), have also been found to regulate the chromatin state through their effects on the PRC2 complex (3, 4). Beyond its novelty in regulating important biological functions through epigenetic mechanisms, emerging evidence suggests that lncRNAs are associated with and may cause diseases such as cancer. Abnormal expressions of lncRNAs have been associated with cancers of the lung and breast (5, 6). Specific lnc...

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(2012) Dose-dependent differential mRNA target selection and regulation by let-7a-7f and miR-17-92 cluster microRNAs, RNA Biology, 9

The action of many extracellular guidance cues on axon pathfinding requires Ca2+ influx at the growth cone (Hong et al., 2000; Nishiyama et al., 2003; Henley and Poo, 2004), but how activation of guidance cue receptors leads to opening of plasmalemmal ion channels remains largely unknown. Analogous to the chemotaxis of amoeboid cells (Parent et al., 1998; Servant et al., 2000), we found that a gradient of chemoattractant triggered rapid asymmetric PI(3,4,5)P3 accumulation at the growth cone’s leading edge, as detected by the translocation of a GFP-tagged binding domain of Akt in Xenopus laevis spinal neurons. Growth cone chemoattraction required PI(3,4,5)P3 production and Akt activation, and genetic perturbation of polarized Akt activity disrupted axon pathfinding in vitro and in vivo. Furthermore, patch-clamp recording from growth cones revealed that exogenous PI(3,4,5)P3 rapidly activated TRP (transient receptor potential) channels, and asymmetrically applied PI(3,4,5)P3 was sufficient to induce chemoattractive growth cone turning in a manner that required downstream Ca2+ signaling. Thus, asymmetric PI(3,4,5)P3 elevation and Akt activation are early events in growth cone chemotaxis that link receptor activation to TRP channel opening and Ca2+ signaling. Altogether, our findings reveal that PI(3,4,5)P3 elevation polarizes to the growth cone’s leading edge and can serve as an early regulator during chemotactic guidance.