Aims. Solar Orbiter, the first mission of ESA’s Cosmic Vision 2015–2025 programme and a mission of international collaboration between ESA and NASA, will explore the Sun and heliosphere from close up and out of the ecliptic plane. It was launched on 10 February 2020 04:03 UTC from Cape Canaveral and aims to address key questions of solar and heliospheric physics pertaining to how the Sun creates and controls the Heliosphere, and why solar activity changes with time. To answer these, the mission carries six remote-sensing instruments to observe the Sun and the solar corona, and four in-situ instruments to measure the solar wind, energetic particles, and electromagnetic fields. In this paper, we describe the science objectives of the mission, and how these will be addressed by the joint observations of the instruments onboard. Methods. The paper first summarises the mission-level science objectives, followed by an overview of the spacecraft and payload. We report the observables and performance figures of each instrument, as well as the trajectory design. This is followed by a summary of the science operations concept. The paper concludes with a more detailed description of the science objectives. Results. Solar Orbiter will combine in-situ measurements in the heliosphere with high-resolution remote-sensing observations of the Sun to address fundamental questions of solar and heliospheric physics. The performance of the Solar Orbiter payload meets the requirements derived from the mission’s science objectives. Its science return will be augmented further by coordinated observations with other space missions and ground-based observatories.

The CafA protein, which was initially described as having a role in either Escherichia coli cell division or chromosomal segregation, has recently been shown to be required for the maturation of the 5-end of 16 S rRNA. The sequence of CafA is similar to that of the N-terminal ribonucleolytic half of RNase E, an essential E. coli enzyme that has a central role in the processing of rRNA and the decay of mRNA and RNAI, the antisense regulator of ColE1-type plasmids. We show here that a highly purified preparation of CafA is sufficient in vitro for RNA cutting. We detected CafA cleavage of RNAI and a structured region from the 5-untranslated region of ompA mRNA within segments cleavable by RNaseE, but not CafA cleavage of 9 S RNA at its "a" RNase E site. The latter is consistent with the finding that the generation of 5 S rRNA from its 9 S precursor can be blocked by inactivation of RNase E in cells that are wild type for CafA. Interestingly, however, a decanucleotide corresponding in sequence to the a site of 9 S RNA was cut efficiently indicating that cleavage by CafA is regulated by the context of sites within structured RNAs. Consistent with this notion is our finding that although 23 S rRNA is stable in vivo, a segment from this RNA is cut efficient by CafA at multiple sites in vitro. We also show that, like RNase E cleavage, the efficiency of cleavage by CafA is dependent on the presence of a monophosphate group on the 5-end of the RNA. This finding raises the possibility that the context dependence of cleavage by CafA may be due at least in part to the separation of a cleavable sequence from the 5-end of an RNA. Comparison of the sites surrounding points of CafA cleavage suggests that this enzyme has broad sequence specificity. Together with the knowledge that CafA can cut RNAI and ompA mRNA in vitro within segments whose cleavage in vivo initiates the decay of these RNAs, this finding suggests that CafA may contribute at some point during the decay of many RNAs in E. coli.The overproduction of CafA (1-3) under conditions of slow growth has been shown to cause the formation of chained cells and minicells. The presence of the latter has been interpreted as evidence for CafA either enhancing the rate of cell division and/or inhibiting chromosome partitioning after replication (4). Electron microscopic examination of the chained cells revealed axial filamentous bundles, termed cytoplasmic axial filaments (hence the designation CafA), running through the center of their cytoplasms. Furthermore, the cytoplasmic axial filaments appear to be composed almost entirely of CafA (5). This finding combined with the phenotype of cells overproducing CafA has led to the proposal that in normal cells these filaments in an unbundled form may have a role as cytoskeletal-like elements in either cell division or chromosome segregation (4).The sequence of CafA has 34% similarity with the N-terminal nucleolytic domain of RNase E (6), an essential Escherichia coli ribonuclease that is required for the generation of 5 S rRNA from a 9...

The HIV-1 trans-activation responsive element (TAR) RNA 59-residue stem-loop interacts with the HIV trans-activator protein Tat and other cellular factors to stimulate transcriptional elongation from the viral long terminal repeat (LTR). Inhibition of these interactions blocks full-length HIV transcription and hence replication. We have found that three types of 12-residue oligonucleotide analogues, namely, a 2'-O-methyl oligoribonucleotide (OMe), a chimeric oligonucleotide containing 7xOMe and 5x5-methyl C locked nucleic acid (LNA) residues, and a peptide nucleic acid (PNA), inhibit Tat-dependent in vitro transcription in HeLa cell nuclear extract equally efficiently (50% inhibition at 100-200 nM) and sequence specifically. The results are correlated with surprisingly similar binding strengths to a model 39-residue TAR under transcription conditions. A 12-mer containing 11 contiguous LNA residues was less effective in both Tat-dependent transcription inhibition and TAR 39 binding. Anti-TAR 3'-carboxyfluorescein- (FAM-) labeled OMe and OMe/LNA chimeric 12-mers were also efficient Tat-dependent in vitro transcription inhibitors as were 3'-FAM-labeled OMe oligonucleotides containing some phosphorothioate (PS) linkages. By use of a HeLa cell line containing stably integrated plasmids expressing firefly luciferase under HIV-LTR/Tat dependence as well as a Renilla luciferase constitutive control, we showed submicromolar, selective, dose-dependent, and sequence-dependent intracellular inhibition of Tat-TAR trans activation by the anti-TAR 3'-FAM 12-residue 7xOMe/5xLNA oligonucleotide when delivered by cationic lipid. No intracellular activity was observed for the corresponding anti-TAR 3'-FAM OMe 12-mer. An alternating PS-containing 3'-FAM OMe 12-mer oligonucleotide exhibited partial inhibition of trans-activation activity, but this was correlated with a similar effect on control gene expression, suggesting nonspecific inhibition.