Inference of single-cell phylogenies from lineage tracing data using Cassiopeia.

The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia

Differential replication of pathogenic and nonpathogenic strains of West Nile virus within astrocytes

The severity of West Nile virus (WNV) infection in immunocompetent animals is highly strain dependent, ranging from avirulent to highly neuropathogenic. Here, we investigate the nature of this strain-specific restriction by analyzing the replication of avirulent (WNV-MAD78) and highly virulent (WNV-NY) strains in neurons, astrocytes, and microvascular endothelial cells, which comprise the neurovascular unit within the central nervous system (CNS). We demonstrate that WNV-MAD78 replicated in and traversed brain microvascular endothelial cells as efficiently as WNV-NY. Likewise, similar levels of replication were detected in neurons. Thus, WNV-MAD78's nonneuropathogenic phenotype is not due to an intrinsic inability to replicate in key target cells within the CNS. In contrast, replication of WNV-MAD78 was delayed and reduced compared to that of WNV-NY in astrocytes. The reduced susceptibility of astrocytes to WNV-MAD78 was due to a delay in viral genome replication and an interferon-independent reduction in cell-to-cell spread. Together, our data suggest that astrocytes regulate WNV spread within the CNS and therefore are an attractive target for ameliorating WNV-induced neuropathology

Alp7/TACC-Alp14/TOG generates long-lived, fast-growing MTs by an unconventional mechanism

Alp14 is a TOG-family microtubule polymerase from S. pombe that tracks plus ends and accelerates their growth. To interrogate its mechanism, we reconstituted dynamically unstable single isoform S. pombe microtubules with full length Alp14/TOG and Alp7, the TACC-family binding partner of Alp14. We find that Alp14 can drive microtubule plus end growth at GTP-tubulin concentrations at least 10-fold below the usual critical concentration, at the expense of increased catastrophe. This reveals Alp14 to be a highly unusual enzyme that biases the equilibrium for the reaction that it catalyses. Alp7/TACC enhances the effectiveness of Alp14, by increasing its occupancy. Consistent with this, we show in live cells that Alp7 deletion produces very similar MT dynamics defects to Alp14 deletion. The ability of Alp7/14 to accelerate and bias GTP-tubulin exchange at microtubule plus ends allows it to generate long-lived, fast-growing microtubules at very low cellular free tubulin concentrations

Tidal friction in close-in satellites and exoplanets. The Darwin theory re-visited

This report is a review of Darwin's classical theory of bodily tides in which we present the analytical expressions for the orbital and rotational evolution of the bodies and for the energy dissipation rates due to their tidal interaction. General formulas are given which do not depend on any assumption linking the tidal lags to the frequencies of the corresponding tidal waves (except that equal frequency harmonics are assumed to span equal lags). Emphasis is given to the cases of companions having reached one of the two possible final states: (1) the super-synchronous stationary rotation resulting from the vanishing of the average tidal torque; (2) the capture into a 1:1 spin-orbit resonance (true synchronization). In these cases, the energy dissipation is controlled by the tidal harmonic with period equal to the orbital period (instead of the semi-diurnal tide) and the singularity due to the vanishing of the geometric phase lag does not exist. It is also shown that the true synchronization with non-zero eccentricity is only possible if an extra torque exists opposite to the tidal torque. The theory is developed assuming that this additional torque is produced by an equatorial permanent asymmetry in the companion. The results are model-dependent and the theory is developed only to the second degree in eccentricity and inclination (obliquity). It can easily be extended to higher orders, but formal accuracy will not be a real improvement as long as the physics of the processes leading to tidal lags is not better known.Comment: 30 pages, 7 figures, corrected typo

Surface albedo changes with time on Titan’s possible cryovolcanic sites: Cassini/VIMS processing and geophysical implications

We present a study on Titan’s possibly cryovolcanic and varying regions as suggested from previous studies [e.g. 1;2;7]. These regions, which are potentially subject to change over time in brightness and are located close to the equator, are Tui Regio, Hotei Regio, and Sotra Patera. We apply two methods on Cassini/VIMS data in order to retrieve their surface properties and monitor any temporal variations. First, we apply a statistical method, the Principal Component Analysis (PCA) [3;4] where we manage to isolate regions of distinct and diverse chemical composition called ‘Region of interest – RoI’. Then, we focus on retrieving the spectral differences (with respect to the Huygens landing site albedo) among the RoIs by applying a radiative transfer code (RT) [5;3]. Hence, we are able to view the dynamical range and evaluate the differences in surface albedo within the RoIs of the three regions. In addition, using this double procedure, we study the temporal surface variations of the three regions witnessing albedo changes with time for Tui Regio from 2005-2009 (darkening) and Sotra Patera from 2005-2006 (brightening) at all wavelengths [3]. The surface albedo variations and the presence of volcanic-like features within the regions in addition to a recent study [6] that calculates Titan's tidal response are significant indications for the connection of the interior with the cryovolcanic candidate features with implications for the satellite’s astrobiological potential

The Europa Clipper Gravity and Radio Science Investigation

The primary objective of the Europa Clipper mission is to assess the habitability of Europa, an overarching goal that rests on improving our understanding of Europa’s interior structure, composition, and geologic activity. Here we describe the Gravity and Radio Science (G/RS) investigation. The primary measurement, the gravitational tidal Love number k2 , will be an independent diagnostic of the presence of a global subsurface ocean, but G/RS will make a number of other key measurements related to Europa’s deep interior, silicate mantle-ocean interface, ice shell, ionosphere, and plasma environment. Although radio science is common to many missions, Europa Clipper’s orbit and spacecraft configuration during flybys present special challenges for the design of this experiment. The information obtained through G/RS will be complementary to the measurements by the other instruments onboard Europa Clipper, and their combined analysis will refine the geophysical understanding of Europa necessary to best assess its potential habitability

Modeling magnetospheric fields in the Jupiter system

The various processes which generate magnetic fields within the Jupiter system are exemplary for a large class of similar processes occurring at other planets in the solar system, but also around extrasolar planets. Jupiter's large internal dynamo magnetic field generates a gigantic magnetosphere, which is strongly rotational driven and possesses large plasma sources located deeply within the magnetosphere. The combination of the latter two effects is the primary reason for Jupiter's main auroral ovals. Jupiter's moon Ganymede is the only known moon with an intrinsic dynamo magnetic field, which generates a mini-magnetosphere located within Jupiter's larger magnetosphere including two auroral ovals. Ganymede's magnetosphere is qualitatively different compared to the one from Jupiter. It possesses no bow shock but develops Alfv\'en wings similar to most of the extrasolar planets which orbit their host stars within 0.1 AU. New numerical models of Jupiter's and Ganymede's magnetospheres presented here provide quantitative insight into the processes that maintain these magnetospheres. Jupiter's magnetospheric field is approximately time-periodic at the locations of Jupiter's moons and induces secondary magnetic fields in electrically conductive layers such as subsurface oceans. In the case of Ganymede, these secondary magnetic fields influence the oscillation of the location of its auroral ovals. Based on dedicated Hubble Space Telescope observations, an analysis of the amplitudes of the auroral oscillations provides evidence that Ganymede harbors a subsurface ocean. Callisto in contrast does not possess a mini-magnetosphere, but still shows a perturbed magnetic field environment. Callisto's ionosphere and atmospheric UV emission is different compared to the other Galilean satellites as it is primarily been generated by solar photons compared to magnetospheric electrons.Comment: Chapter for Book: Planetary Magnetis

Elective amputation and bionic substitution restore functional hand use after critical soft tissue injuries

Critical soft tissue injuries may lead to a non-functional and insensate limb. In these cases standard reconstructive techniques will not suffice to provide a useful outcome, and solutions outside the biological arena must be considered and offered to these patients. We propose a concept which, after all reconstructive options have been exhausted, involves an elective amputation along with a bionic substitution, implementing an actuated prosthetic hand via a structured tech-neuro-rehabilitation program. Here, three patients are presented in whom this concept has been successfully applied after mutilating hand injuries. Clinical tests conducted before, during and after the procedure, evaluating both functional and psychometric parameters, document the benefits of this approach. Additionally, in one of the patients, we show the possibility of implementing a highly functional and natural control of an advanced prosthesis providing both proportional and simultaneous movements of the wrist and hand for completing tasks of daily living with substantially less compensatory movements compared to the traditional systems. It is concluded that the proposed procedure is a viable solution for re-gaining highly functional hand use following critical soft tissue injuries when existing surgical measures fail. Our results are clinically applicable and can be extended to institutions with similar resources

Stability of Terrestrial Planets in the Habitable Zone of Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208

We have undertaken a thorough dynamical investigation of five extrasolar planetary systems using extensive numerical experiments. The systems Gl 777 A, HD 72659, Gl 614, 47 Uma and HD 4208 were examined concerning the question of whether they could host terrestrial like planets in their habitable zones (=HZ). First we investigated the mean motion resonances between fictitious terrestrial planets and the existing gas giants in these five extrasolar systems. Then a fine grid of initial conditions for a potential terrestrial planet within the HZ was chosen for each system, from which the stability of orbits was then assessed by direct integrations over a time interval of 1 million years. The computations were carried out using a Lie-series integration method with an adaptive step size control. This integration method achieves machine precision accuracy in a highly efficient and robust way, requiring no special adjustments when the orbits have large eccentricities. The stability of orbits was examined with a determination of the Renyi entropy, estimated from recurrence plots, and with a more straight forward method based on the maximum eccentricity achieved by the planet over the 1 million year integration. Additionally, the eccentricity is an indication of the habitability of a terrestrial planet in the HZ; any value of e>0.2 produces a significant temperature difference on a planet's surface between apoapse and periapse. The results for possible stable orbits for terrestrial planets in habitable zones for the five systems are summarized as follows: for Gl 777 A nearly the entire HZ is stable, for 47 Uma, HD 72659 and HD 4208 terrestrial planets can survive for a sufficiently long time, while for Gl 614 our results exclude terrestrial planets moving in stable orbits within the HZ.Comment: 14 pages, 18 figures submitted to A&

BepiColombo-Mission Overview and Science Goals

BepiColombo is a joint mission between the European Space Agency, ESA, and the Japanese Aerospace Exploration Agency, JAXA, to perform a comprehensive exploration of Mercury. Launched on 20th October 2018 from the European spaceport in Kourou, French Guiana, the spacecraft is now en route to Mercury. Two orbiters have been sent to Mercury and will be put into dedicated, polar orbits around the planet to study the planet and its environment. One orbiter, Mio, is provided by JAXA, and one orbiter, MPO, is provided by ESA. The scientific payload of both spacecraft will provide detailed information necessary to understand the origin and evolution of the planet itself and its surrounding environment. Mercury is the planet closest to the Sun, the only terrestrial planet besides Earth with a self-sustained magnetic field, and the smallest planet in our Solar System. It is a key planet for understanding the evolutionary history of our Solar System and therefore also for the question of how the Earth and our Planetary System were formed. The scientific objectives focus on a global characterization ofMercury through the investigation of its interior, surface, exosphere, and magnetosphere. In addition, instrumentation onboard BepiColombo will be used to test Einstein's theory of general relativity. Major effort was put into optimizing the scientific return of the mission by defining a payload such that individual measurements can be interrelated and complement each other.Peer reviewe