The Interface Region Imaging Spectrograph (IRIS) small explorer spacecraft provides simultaneous spectra and images of the photosphere, chromosphere, transition region, and corona with 0.33 -0.4 arcsec spatial resolution, two-second temporal resolution, and 1 km s −1 velocity resolution over a field-of-view of up to 175 arcsec × 175 arcsec. . IRIS is sensitive to emission from plasma at temperatures between 5000 K and 10 MK and will advance our understanding of the flow of mass and energy through an interface region, formed by the chromosphere and transition region, between the photosphere and corona. This highly structured and dynamic region not only acts as the conduit of all mass and energy feeding into the corona and solar wind, it also requires an order of magnitude more energy to heat than the corona and solar wind combined. The IRIS investigation includes a strong numerical modeling component based on advanced radiative-MHD codes to facilitate interpretation of observations of this complex region. Approximately eight Gbytes of data (after compression) are acquired by B. De Pontieu (B) ·Harvard-Smithsonian Astrophysical Observatory, 60 Garden Street, Cambridge, MA 02138, USA

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tRNA-derived small RNAs (tsRNAs; also called tRNA-derived fragments (tRFs)) are an abundant class of small non-coding RNAs whose biological roles are not well defined. We show that inhibition of a specific tsRNA, LeuCAG3′tsRNA, induces apoptosis in rapidly dividing cells in vitro and in a patient-derived orthotopic hepatocellular carcinoma model in mice. This tsRNA binds at least two ribosomal protein mRNAs (for RPS28 and RPS15) to enhance their translation. Reduction of RPS28 mRNA translation blocks pre-18S ribosomal RNA processing, resulting in a decrease in the number of 40S ribosomal subunits. These data establish another post-transcriptional mechanism that can fine-tune gene expression during different physiological states and provide a potential new target for treating cancer.

Site-specific gene addition can allow stable transgene expression for gene therapy. When possible, this is preferred over the use of promiscuously integrating vectors, which are sometimes associated with clonal expansion1 and oncogenesis2. Site-specific endonucleases that can induce high rates of targeted genome editing are finding increasing applications in biological discovery and gene therapy3. However, two safety concerns persist: (1) endonuclease-associated adverse effects, both on4 and off-target5,6; and (2) oncogene activation caused by promoter integration, even without nucleases7. Here, we perform recombinant adeno-associated virus (rAAV) mediated promoterless gene targeting without nucleases and demonstrate amelioration of the bleeding diathesis in haemophilia B mice. In particular, we target a promoterless human coagulation factor IX (hF9) gene to the liver-expressed albumin (Alb) locus. hF9 is targeted, along with a preceding 2A-peptide coding sequence, to be integrated just upstream to the Alb stop codon. While hF9 is fused to Alb at the DNA and RNA levels, two separate proteins are synthesized by way of ribosomal skipping. Thus, hF9 expression is linked to robust hepatic albumin expression without disrupting it. We injected an AAV8-hF9 vector into neonatal and adult mice and achieved on-target integration into ~0.5% of the albumin alleles in hepatocytes. We established that hF9 was produced only from on-target integration, and ribosomal skipping was highly efficient. Stable hF9 plasma levels at 7–20% of normal were obtained, and treated factor IX deficient mice had normal coagulation times. In conclusion, transgene integration as a 2A-fusion to a highly expressed endogenous gene may obviate the requirement for nucleases and/or vector-borne promoters. This method may allow for safe and efficacious gene targeting in both infants and adults by greatly diminishing off-target effects while still providing therapeutic levels of expression from integration.