Quartets for stringed instruments: K.80, 155, 156, 157, 158, 159, 160, 168, 170, 171, 172, 173.

G major, K.80.--D major, K.155.--G major, K.156.--C major, K.157.--F major, K.158.--B♭ major, K.159.--E♭ major, K.160.--F major, K.168.--A major, K.169.--C major, K.170.--E♭ major, K.171.--B♭ major, K.172.--D minor, K.173.

MicroRNA-155 promotes resolution of hypoxia-inducible factor 1α activity during prolonged hypoxia

The hypoxia-inducible factor (HIF) is a key regulator of the transcriptional response to hypoxia. While the mechanism underpinning HIF activation is well understood, little is known about its resolution. Both the protein and the mRNA levels of HIF-1a (but not HIF-2a) were decreased in intestinal epithelial cells exposed to prolonged hypoxia. Coincident with this, microRNA (miRNA) array analysis revealed multiple hypoxiainducible miRNAs. Among these was miRNA-155 (miR-155), which is predicted to target HIF-1a mRNA. We confirmed the hypoxic upregulation of miR-155 in cultured cells and intestinal tissue from mice exposed to hypoxia. Furthermore, a role for HIF-1a in the induction of miR-155 in hypoxia was suggested by the identification of hypoxia response elements in the miR-155 promoter and confirmed experimentally. Application of miR-155 decreased the HIF-1a mRNA, protein, and transcriptional activity in hypoxia, and neutralization of endogenous miR-155 reversed the resolution of HIF-1a stabilization and activity. Based on these data and a mathematical model of HIF-1a suppression by miR-155, we propose that miR-155 induction contributes to an isoform-specific negative-feedback loop for the resolution of HIF-1a activity in cells exposed to prolonged hypoxia, leading to oscillatory behavior of HIF-1a-dependent transcription. © 2011, American Society for Microbiology.

Cocaine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells by Suppressing microRNA-155

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers.

(Tables 4-5, page 160) REE contents in ferromanganese concretions from the Gulf of Bothnia and the Barents Sea

Ferromanganese concretions from the Svalbard shelf in the Barents Sea show slightly convex shale-normalized REE patterns with no Eu anomalies. Concretions from the Gulf of Bothnia, northern part of the Baltic Sea, exhibit an enrichment of light REE and negative Eu anomalies. This difference is interpreted as a consequence of different conveyor mechanisms of the REE to the sediment. It is suggested that dissolving biogenic debris contributes to the convex pattern obtained in the Barents Sea, whereas an inorganic suspended fraction with scavenged REE is the main carrier in the Gulf of Bothnia. During oxic diagenesis in the sediment, the scavenged REE are set free into the porewater and contribute to the distribution pattern in concretions found in the Gulf of Bothnia. Small Mn-rich spheroidal concretions are enriched two to five times in REE compared to average shale, whereas Mn-poor flat concretions are low in REE. Specific surface area of the concretion and the depth of burial in the oxidized surface sediment are two factors that strongly affect the enrichment of the REE. Weak Ce anomalies are present in the analysed concretions and a redox level dependence is seen.