The observation of the non-Keplerian behavior of propeller structures in Saturn’s outer A ring raises the question: how does the propeller respond to the wandering of the central embedded moonlet? Here, we study numerically how the structural imprint of the propeller changes for a libration of the moonlet. It turns out that the libration induces an asymmetry in the propeller, which depends on the libration period and amplitude of the moonlet. Further, we study the dependence of the asymmetry on the libration period and amplitude for a moonlet with a 400 m Hill radius, which is located in the outer A ring. This allows us to apply our findings to the largest known propeller Blériot, which is expected to be of a similar size. For Blériot, we can conclude that, supposing the moonlet is librating with the largest observed period of 11.1 yr and an azimuthal amplitude of about 1845 km, a small asymmetry should be measurable but depends on the moonlet’s libration phase at the observation time. The longitude residuals of other trans-Encke propellers (e.g., Earhart) show amplitudes similar to Blériot, which might allow us to observe larger asymmetries due to their smaller azimuthal extent, allowing us to scan the whole gap structure for asymmetries in one observation. Although the librational model of the moonlet is a simplification, our results are a first step toward the development of a consistent model for the description of the formation of asymmetric propellers caused by a freely moving moonlet.

One of the biggest successes of the Cassini mission is the detection of small moons (moonlets) embedded in Saturn's rings which cause S-shaped density structures in their close vicinity, called propellers (Spahn and Sremcevic 2000; Tiscareno et al. 2006; Sremcevic et al. 2007). Here, we present isothermal hydrodynamic simulations of moonlet-induced propellers in Saturn's A ring which denote a further development of the original model (Spahn and Sremcevic 2000). We find excellent agreement between these new hydrodynamic and corresponding N-body simulations. Furthermore, the hydrodynamic simulations confirm the predicted scaling laws (Spahn and Sremcevic 2000) and the analytical solution for the density in the propeller gaps (Sremcevic et al. 2002). Finally, this mean field approach allows us to simulate the pattern of the giant propeller Bleriot, which is too large to be modeled by direct N-body simulations. Our results are compared to two stellar occultation observations by the Cassini Ultraviolet Imaging Spectrometer (UVIS), that intersect the propeller Bleriot. Best fits to the UVIS optical depth profiles are achieved for a Hill radius of 590 m, which implies a moonlet diameter of about 860 m. Furthermore, the model favours a kinematic shear viscosity of the surrounding ring material of $\nu_0 = 340$ cm^2/s, a dispersion velocity in the range of 0.3 cm/s $< c_0 <$ 1.5 cm/s, and a fairly high bulk viscosity $7 < \xi_0/\nu_0 < 17$. These large transport values might be overestimated by our isothermal ring model and should be reviewed by an extended model including thermal fluctuations.

In this work, we model the radial density profile of the outer A ring of Saturn observed with Cassini cameras (Tiscareno & Harris 2018): An axisymmetric diffusion model has been developed, accounting for the outward viscous flow of the ring material, and the counteracting inward drift caused by resonances of the planet's large outer moons. It has been generally accepted that the 7:6 resonance of Janus alone confines the outer A ring which, however, was disproved by Tajeddine et al. (2017). We show that the step-like density profile of the outer A ring is predominantly defined by the discrete first-order resonances of Janus, the 5:3 second-order resonance of Mimas, and the overlapping resonances of Prometheus and Pandora.

Saturn’s main ring system is associated with a set of small moons that either are embedded within it or interact with the rings to alter their shape and composition. Five close flybys of the moons Pan, Daphnis, Atlas, Pandora, and Epimetheus were performed between December 2016 and April 2017 during the ring-grazing orbits of the Cassini mission. Data on the moons’ morphology, structure, particle environment, and composition were returned, along with images in the ultraviolet and thermal infrared. We find that the optical properties of the moons’ surfaces are determined by two competing processes: contamination by a red material formed in Saturn’s main ring system and accretion of bright icy particles or water vapor from volcanic plumes originating on the moon Enceladus.

Saturn's main rings are composed of >95% water ice, and the nature of the remaining few percent has remained unclear. The Cassini spacecraft's traversals between Saturn and its innermost D ring allowed its cosmic dust analyzer (CDA) to collect material released from the main rings and to characterize the ring material infall into Saturn. We report the direct in situ detection of material from Saturn's dense rings by the CDA impact mass spectrometer. Most detected grains are a few tens of nanometers in size and dynamically associated with the previously inferred "ring rain." Silicate and water-ice grains were identified, in proportions that vary with latitude. Silicate grains constitute up to 30% of infalling grains, a higher percentage than the bulk silicate content of the rings.

Among the great discoveries of the Cassini mission are the propeller-shaped structures created by small moonlets embedded in Saturn's dense rings. We analyze images of the sunlit side of Saturn's outer A ring, which show the propeller Bleriot with clearly visible partial propeller gaps. By determining radial brightness profiles at different azimuthal locations, we obtain the evolution of the gap minimum downstream of the moonlet. From the radial separation of the partial propeller gaps we estimate the Hill radius of Bleriot to be about 400m. Further, we fit the analytic solution from Sremcevic et al. (2002) describing the azimuthal evolution of the surface mass density in the propeller gap region to the azimuthal gap evolution obtained from Cassini images. From these fits, we estimate a kinematic shear viscosity in the range of 60 cm$^2$/s to 100 cm$^2$/s in Bleriot's ring region. These values are consistent with the parametrization given by Daisaka et al. (2001) and agree well with values estimated for the Encke gap edge (Tajeddine et al. 2017; Graetz et al. 2018).

The reconstruction of the orbital evolution of the propeller structure Blériot orbiting in Saturn’s A ring from recurrent observations in Cassini ISS images yielded a considerable offset motion from the expected Keplerian orbit. This offset motion can be composed by three sinusoidal harmonics with amplitudes and periods of 1845, 152, 58 km and 11.1, 3.7, and 2.2 years, respectively. In this paper we present results from N -body simulations, where we integrated the orbital evolution of a moonlet, which is placed at the radial position of Blériot under the gravitational action of the Saturnian satellites. Our simulations yield that, especially the gravitational interactions with Prometheus, Pandora, and Mimas are forcing the moonlet to librate with the right frequencies, but the libration amplitudes are too small to explain the observations. Thus, further mechanisms are needed to explain the amplitudes of the forced librations—e.g., moonlet–ring interactions. Here, we develop a model, where the moonlet is allowed to be slightly displaced with respect to its created gaps breaking the point symmetry and causing a repulsive force in this way. As a result, the evolution of the moonlet’s longitude can be described by a harmonic oscillator. In the presence of external forcing by the outer moons, the libration amplitudes get the more amplified the closer the forcing frequency is to the eigenfrequency of the disturbed propeller oscillator. Applying our model to Blériot, it is possible to reproduce a libration period of 13 years with an amplitude of about 2000 km.

Mature thrombin activatable fibrinolysis inhibitor (TAFIa) is a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation of fibrin clots and may help to prevent thrombosis. Applying a lead finding approach based on literature-mining, we discovered that anabaenopeptins, cyclic peptides produced by cyanobacteria, were potent inhibitors of TAFIa with IC50 values as low as 1.5 nM. We describe the isolation and structure elucidation of 20 anabaenopeptins, including 13 novel congeners, as well as their pronounced structure-activity relationships (SAR) with respect to inhibition of TAFIa. Crystal structures of the anabaenopeptins B, C and F bound to the surrogate protease carboxypeptidase B revealed the binding modes of these large (~850 Da) compounds in detail and explained the observed SAR, i.e. the strong dependence of the potency on a basic (Arg, Lys) exocyclic residue that addressed the S1’ binding pocket, and a broad tolerance towards substitutions in the pentacyclic ring that acted as a plug of the active site.

Microbial natural products are a rich source of bioactive molecules to serve as drug leads and/or biological tools. We investigated a little-explored myxobacterial genus, Nannocystis sp., and discovered a novel 21-membered macrocyclic scaffold that is composed of a tripeptide and a polyketide part with an epoxyamide moiety. The relative and absolute configurations of the nine stereocenters was determined by NMR spectroscopy, molecular dynamics calculations, chemical degradation, and X-ray crystallography. The compound, named nannocystin A (1), was found to inhibit cell proliferation at low nanomolar concentrations through the early induction of apoptosis. The mode of action of 1 could not be matched to that of standard drugs by transcriptional profiling and biochemical experiments. An initial investigation of the structure-activity relationship based on seven analogues demonstrated the importance of the epoxide moiety for high activity.

AbstractBengamide, aus marinen Schwämmen stammende und als Inhibitoren der Methionin‐Aminopeptidase (MetAP) charakterisierte Naturstoffe, wurden intensiv als Wirkstoffe gegen Krebs erforscht. In einem multidisziplinären Forschungsprojekt haben wir die Bereitstellung von Bengamiden über Fermentation des terrestrischen Myxobakteriums M. virescens, die Aufklärung ihrer Biosynthese und die Optimierung ihrer Eigenschaften als Arzneistoff‐Leitstrukturen untersucht. Die Charakterisierung des Biosyntheseweges zeigte auf, dass bakterielle Resistenz gegenüber Bengamiden durch Leu154 des myxobakteriellen MetAP‐Proteins vermittelt wird, und ermöglichte den Transfer des gesamten Biosynthesegenclusters in den geeigneteren Produktionsstamm M. xanthus DK1622. Eine Kombination aus Semisynthese mikrobiell gewonnener Bengamide und Totalsynthese führte zum optimierten Derivat 8 a. Die nanomolare zelluläre Wirksamkeit und die hohe metabolische Stabilität waren mit einer verbesserten Halbwertszeit in Mäusen sowie mit Antitumor‐Effizienz in einem Melanom‐Mausmodell verbunden.

The discovery of Streptomyces -produced streptomycin founded the age of tuberculosis therapy. Despite the subsequent development of a curative regimen for this disease, tuberculosis remains a worldwide problem, and the emergence of multidrug-resistant Mycobacterium tuberculosis has prioritized the need for new drugs. Here we show that new optimized derivatives from Streptomyces -derived griselimycin are highly active against M. tuberculosis , both in vitro and in vivo, by inhibiting the DNA polymerase sliding clamp DnaN. We discovered that resistance to griselimycins, occurring at very low frequency, is associated with amplification of a chromosomal segment containing dnaN , as well as the ori site. Our results demonstrate that griselimycins have high translational potential for tuberculosis treatment, validate DnaN as an antimicrobial target, and capture the process of antibiotic pressure-induced gene amplification.

We study the vertical extent of propeller structures in Saturn's rings. Our focus lies on the gap region of the propeller and on non-inclined propeller moonlets. In order to describe the vertical structure of propellers we extend the model of Spahn and Sremcevic (2000) to include the vertical direction. We find that the gravitational interaction of ring particles with the non-inclined moonlet does not induce considerable vertical excursions of ring particles, but causes a considerable thermal motion in the ring plane. We expect ring particle collisions to partly convert the lateral induced thermal motion into vertical excursions of ring particles. For the gap region of the propeller, we calculate gap averaged propeller heights on the order of 0.7 Hill radii, which is of the order of the moonlet radius. In our model the propeller height decreases exponentially until viscous heating and collisional cooling balance. We estimate Hill radii of 370m and 615m for the propellers Earhart and Bleriot. Our model predicts about 120km for the azimuthal extent of the Earhart propeller at Saturn's 2009 equinox, being consistent with values determined from Cassini images.

The bengamides, sponge-derived natural products that have been characterized as inhibitors of methionine aminopeptidases (MetAPs), have been intensively investigated as anticancer compounds. We embarked on a multidisciplinary project to supply bengamides by fermentation of the terrestrial myxobacterium M. virescens, decipher their biosynthesis, and optimize their properties as drug leads. The characterization of the biosynthetic pathway revealed that bacterial resistance to bengamides is conferred by Leu 154 of the myxobacterial MetAP protein, and enabled transfer of the entire gene cluster into the more suitable production host M. xanthus DK1622. A combination of semisynthesis of microbially derived bengamides and total synthesis resulted in an optimized derivative that combined high cellular potency in the nanomolar range with high metabolic stability, which translated to an improved half-life in mice and antitumor efficacy in a melanoma mouse model.