Understanding the errors of SHAPE-directed RNA structure modeling

Single-nucleotide-resolution chemical mapping for structured RNA is being rapidly advanced by new chemistries, faster readouts, and coupling to computational algorithms. Recent tests have shown that selective 2'-hydroxyl acylation by primer extension (SHAPE) can give near-zero error rates (0-2%) in modeling the helices of RNA secondary structure. Here, we benchmark the method using six molecules for which crystallographic data are available: tRNA(phe) and 5S rRNA from Escherichia coli, the P4-P6 domain of the Tetrahymena group I ribozyme, and ligand-bound domains from riboswitches for adenine, cyclic di-GMP, and glycine. SHAPE-directed modeling of these highly structured RNAs gave an overall false negative rate (FNR) of 17% and a false discovery rate (FDR) of 21%, with at least one helix prediction error in five of the six cases. Extensive variations of data processing, normalization, and modeling parameters did not significantly mitigate modeling errors. Only one varation, filtering out data collected with deoxyinosine triphosphate during primer extension, gave a modest improvement (FNR = 12%, and FDR = 14%). The residual structure modeling errors are explained by the insufficient information content of these RNAs' SHAPE data, as evaluated by a nonparametric bootstrapping analysis. Beyond these benchmark cases, bootstrapping suggests a low level of confidence (<50%) in the majority of helices in a previously proposed SHAPE-directed model for the HIV-1 RNA genome. Thus, SHAPE-directed RNA modeling is not always unambiguous, and helix-by-helix confidence estimates, as described herein, may be critical for interpreting results from this powerful methodology.Comment: Biochemistry, Article ASAP (Aug. 15, 2011

Geophysical Investigation of the Moon

No abstract availabl

Lunar Seismology Enabled by a Lunar Orbital Platform-Gateway

No abstract availabl

DNA methylation in insects

Cytosine DNA methylation has been demonstrated in numerous eukaryotic organisms and has been shown to play an important role in human disease. The function of DNA methylation has been studied extensively in vertebrates, but establishing its primary role has proved difficult and controversial. Analysing methylation in insects has indicated an apparent functional diversity that seems to argue against a strict functional conservation. To investigate this hypothesis, we here assess the data reported in four different insect species in which DNA methylation has been analysed more thoroughly: the fruit fly Drosophila melanogaster, the cabbage moth Mamestra brassicae, the peach-potato aphid Myzus persicae and the mealybug Planococcus citri

The Polarization of Ambient Noise on Mars

Seismic noise recorded at the surface of Mars has been monitored since February 2019, using the InSight seismometers. This noise can reach −200 dB. It is 500 times lower than on Earth at night and it increases of 30 dB during the day. We analyze its polarization as a function of time and frequency in the band 0.03–1 Hz. We use the degree of polarization to extract signals with stable polarization independent of their amplitude and type of polarization. We detect polarized signals at all frequencies and all times. Glitches correspond to linear polarized signals which are more abundant during the night. For signals with elliptical polarization, the ellipse is in the horizontal plane below 0.3 Hz. In the 0.3-1Hz high frequency band (HF) and except in the evening, the ellipse is in the vertical plane and the major axis is tilted. While polarization azimuths are different in the two frequency bands, they both vary as a function of local hour and season. They are also correlated with wind direction, particularly during the daytime. We investigate possible aseismic and seismic origins of the polarized signals. Lander or tether noise can be discarded. Pressure fluctuations transported by wind may explain part of the HF polarization but not the tilt of the ellipse. This tilt can be obtained if the source is an acoustic emission coming from high altitude at critical angle. Finally, in the evening when the wind is low, the measured polarized signals may correspond to the seismic wavefield of the Mars background noise

SEIS: Insight's Seismic Experiment for Internal Structure of Mars.

By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01&nbsp;Hz to 50&nbsp;Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1&nbsp;sps and a continuous compound VBB/SP vertical axis at 10&nbsp;sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1&nbsp;Hz and ∼ 200 000 at 0.1&nbsp;Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution.Electronic supplementary materialThe online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users

Diagnosing Schistosomiasis by Detection of Cell-Free Parasite DNA in Human Plasma

Bilharzia (schistosomiasis) occurs in the tropics and subtropics and is one of the most important parasite diseases of humans. It is caused by flukes residing in the vessels of the gut or bladder, causing fever, pain, and bleeding. Bladder cancer or esophageal varices may follow. Diagnosis is difficult, requiring detection of parasite eggs in stool, urine, or gut/bladder biopsies. In this paper, we introduce a fundamentally new way of diagnosing bilharzia from the blood. It has been known for almost 20 years that patients with cancer have tumor-derived DNA circulating in their blood, which can be used for diagnostic purposes. During pregnancy, free DNA from the fetus can be detected in motherly blood, which can be used for diagnosing a range of fetal diseases and pregnancy-associated complications. We found that parasite DNA can be detected in the same way in the blood of patients with bilharzia. In patients with early disease, diagnosis was possible earlier than with any other test. DNA could be detected in all patients with active disease in our study. Patients after treatment had significantly lower parasite DNA concentrations and turned negative 1–2 years after treatment. Future studies should implement the method in large cohorts of patients and should define criteria for the confirmation of the success of treatment by comparing the concentration of fluke DNA before and after therapy

First Focal Mechanisms of Marsquakes

Since February 2019, NASA's InSight lander is recording seismic signals on the planet Mars, which, for the first time, allows to observe ongoing tectonic processes with geophysical methods. A number of Marsquakes have been located in the Cerberus Fossae graben system in Elysium Planitia and further west, in the Orcus Patera depression. We present a first study of the focal mechanisms of three well-recorded events (S0173a, S0183a, S0235b) to determine the processes dominating in the source region. We infer for all three events a predominantly extensional setting. Our method is adapted to the case of a single, multicomponent receiver and based on fitting waveforms of P and S waves against synthetic seismograms computed for the initial crustal velocity model derived by the InSight team. We explore the uncertainty due to the single-station limitation and find that even data recorded by one station constrains the mechanisms (reasonably) well. For the events in the Cerberus Fossae region (S0173a, S0235b) normal faulting with a relatively steep dipping fault plane is inferred, suggesting an extensional regime mainly oriented E-W to NE-SW. The fault regime in the Orcus Patera region is not determined uniquely because only the P wave can be used for the source inversion. However, we find that the P and weak S waves of the S0183a event show similar polarities to the event S0173, which indicates similar fault regimes

The Far Side of Mars: Two Distant Marsquakes Detected by InSight

For over three Earth years the Marsquake Service has been analyzing the data sent back from the Seismic Experiment for Interior Structure¿the seismometer placed on the surface of Mars by NASA¿s InSight lander. Although by October 2021, the Mars seismic catalog included 951 events, until recently all these events have been assessed as lying within a radius of 100° of InSight. Here we report two distant events that occurred within days of each other, located on the far side of Mars, giving us our first glimpse into Mars¿ core shadow zone. The first event, recorded on 25 August 2021 (InSight sol 976), shows clear polarized arrivals that we interpret to be PP and SS phases at low frequencies and locates to Valles Marineris, 146° ± 7° from InSight. The second event, occurring on 18 September 2021 (sol 1000), has significantly more broadband energy with emergent PP and SS arrivals, and a weak phase arriving before PP that we interpret as Pdiff¿. Considering uncertain pick times and poorly constrained travel times for Pdiff¿, we estimate this event is at a distance between 107° and 147° from InSight. With magnitudes of MMaw 4.2 and 4.1, respectively, these are the largest seismic events recorded so far on Mars.Anna C. Horleston, Jessica C. E. Irving,and Nicholas A. Teanby are funded by the UKSA under Grant Numbers ST/R002096/1, ST/W002523/1, and ST/W002515/1.Nikolaj L. Dahmen, Cecilia Duran, Géraldine Zenhäusern, andSimon C. Stähler would like to acknowledge support from Eidgenössische Technische Hochschule (ETH) through the ETH+ funding scheme (ETH+02 19-1: “Planet Mars”). The French coauthors acknowledge the funding support provided by CNES and the Agence Nationale de la Recherche (ANR-19-CE31-0008-08 MAGIS) for SEIS operation and SEIS Science analysis. Alexander E. Stott acknowledges the French Space Agency CNES and ANR (ANR-19-CE31-0008-08). Caroline Beghein and Jiaqi Li were supported by NASA InSight Participating Scientist Program (PSP) Grant Number 80NSSC18K1679. This article is InSight Contribution Number 236

Evaluation of Chikungunya Diagnostic Assays: Differences in Sensitivity of Serology Assays in Two Independent Outbreaks

Chikungunya is a mounting public health concern in many parts of the world. Definitive diagnosis is critical in differentiating the diseases, especially in dengue endemic areas. There are some commercial chikungunya kits and published molecular protocols available, but no comprehensive comparative evaluation of them was performed. Using sera collected in outbreaks caused by two variants of Chikungunya virus (A226 and 226V), we tested 2 commercial IgM tests (CTK lateral flow rapid test and EUROIMMUN IFA) alongside our in-house IgM assays (using both variants of the virus). Sensitivities of 2 published PCR protocols were also evaluated based on RNA standards derived from cell-cultured viruses. The commercial assays had different performances in each outbreak, with CTK's lateral flow test having the best performance in the first outbreak and EUROIMMUN IFA being more sensitive in the second outbreak. Use of the current circulating virus in a test assay improves sensitivity of the MAC-ELISAs. For PCR, a probe-based real time RT-PCR method was found to be 10 times more sensitive than the SYBR Green method. Despite this, the latter protocol is found to be more suitable and cost-effective for our diagnostic laboratory. This evaluation demonstrates the importance of appraisal of commercial kits and published protocols before application of a diagnostic tool in the clinical and operational setting