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Transforming growth factor-β ( TGF-β) plays central roles in endothelial-mesenchymal transition (End MT) involved in development and pathogenesis. Although End MT and epithelial-mesenchymal transition are similar processes, roles of micro RNAs in End MT are largely unknown. Here, we report that constitutively active micro RNA-31 (miR-31) is a positive regulator of TGF-β-induced End MT. Although the expression is not induced by TGF-β, miR-31 is required for induction of mesenchymal genes including α- SMA, actin reorganization and MRTF-A activation during End MT. We identified VAV3, a regulator of actin remodeling and MRTF-A activity, as a miR-31 target. Global transcriptome analysis further showed that miR-31 positively regulates End MT-associated unique secretory phenotype (End MT- SP) characterized by induction of multiple inflammatory chemokines and cytokines including CCL17, CX3 CL1, CXCL16, IL-6 and Angptl2. As a mechanism for this phenomenon, TGF-β and miR-31 suppress Stk40, a negative regulator of NF-κB pathway. Interestingly, TGF-β induces alternative polyadenylation ( APA)-coupled miR-31-dependent Stk40 suppression without concomitant miR-31 induction, and APA-mediated exclusion of internal poly(A) sequence in Stk40 3′ UTR enhances target efficiency of Stk40. Finally, miR-31 functions as a molecular hub to integrate TGF-β and TNF-α signaling to enhance End MT. These data confirm that constitutively active micro RNAs, as well as inducible micro RNAs, serve as phenotypic modifiers interconnected with transcriptome dynamics during End MT. [ABSTRACT FROM AUTHOR]

Asymmetric selection of single-stranded guide RNAs from double-stranded RNA precursors is crucial in RNA silencing-mediated gene regulation. However, the precise mechanisms of small-RNA asymmetry are unclear, especially because asymmetric selection can still occur when the putative asymmetry sensors Drosophila R2D2 and mammalian Dicer are depleted. Here we report a direct contribution of mammalian Argonaute 2 (Ago2) to microRNA (miRNA) asymmetry. Ago2 selects strands with 5′-uridine or 5′-adenosine and thermodynamically unstable 5′ ends in parallel through its two sensor regions, which contact the 5′ nucleobases and 5′-phosphates of prospective guide strands. Hence, miRNA asymmetry shows superposed patterns reflecting 5′-end nucleotide identity ('digital' pattern) and thermodynamic stability ('analog' pattern). Furthermore, we demonstrate that cancer-associated miRNA variations reprogram asymmetric selection. Finally, our study presents a model of this universal principle, to aid in comprehensive understanding of miRNA function and development of new RNA-silencing therapies in precision medicine. [ABSTRACT FROM AUTHOR]

Abstract: Properties of solution-processed organic photodetectors with iridium (Ir) complexes doped in fluorene-type conjugated polymer, poly(dioctylfluorene-co-benzothiadiazole) [F8BT] as a host were investigated. F8BT devices had blue sensitivity. Ir complexes as triplet materials can enhance the incident-photon-to-current conversion efficiency (IPCE) of the devices when their triplet levels are lower than the lowest excited singlet states (S1) of the host and higher than the lowest excited triplet states (T1) of the host. A bilayer F8BT device utilizing solution-processable starburst molecular and tris(2-phenylpyridine)iridium(III) [Ir(ppy)3] as a hole transporting layer and a dopant, respectively, showed larger photocurrent than an non-doped bilayer device under high applied voltage. For the bilayer device with Ir(ppy)3, a cut-off frequency of more than 10MHz was observed under forward bias of 5V and clear response pulses at 10MHz were received using a sinusoidal modulated laser light illumination. [Copyright &y& Elsevier]

Lymphatic vessels (LVs) play critical roles in the maintenance of fluid homeostasis and in pathological conditions, including cancer metastasis. Although mutations in ALK1, a member of the trans- forming growth factor (TGF)-β/bone morphogenetic protein (BMP) receptor family, have been linked to hereditary hemorrhagic tel- angiectasia, a human vascular disease, the roles of activin recep- tor-like kinase 1 (ALK-1) signals in LV formation largely remain to be elucidated. We show that ALK-1 signals inhibit LV formation, and LV5 were enlarged in multiple organs in AIkl-depleted mice. These inhibitory effects of ALK-1 signaling were mediated by BMP- 9, which decreased the number of cultured lymphatic endothetial cells. Bmp9-deficient mouse embryos consistently exhibited en- larged dermal LV5. BMP-9 also inhibited LV formation during inflam- mation and tumorigenesis. BMP-9 downregulated the expression of the transcription factor prospero-related homeobox 1, which is nec- essary to maintain lymphatic endothelial cell identity. Furthermore, silencing prospero-related homeobox 1 expression inhibited lym- phatic endothelial cell proliferation. Our findings reveal a unique molecular basis for the physiological and pathological roles of BMP-9IALK-1 signals in LV formation. [ABSTRACT FROM AUTHOR]