In Vivo Ligands of MDA5 and RIG-I in Measles Virus-Infected Cells

RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) play a major role in the innate immune response against viral infections and detect patterns on viral RNA molecules that are typically absent from host RNA. Upon RNA binding, RLRs trigger a complex downstream signaling cascade resulting in the expression of type I interferons and proinflammatory cytokines. In the past decade extensive efforts were made to elucidate the nature of putative RLR ligands. In vitro and transfection studies identified 5'-triphosphate containing blunt-ended double-strand RNAs as potent RIG-I inducers and these findings were confirmed by next-generation sequencing of RIG-I associated RNAs from virus-infected cells. The nature of RNA ligands of MDA5 is less clear. Several studies suggest that double-stranded RNAs are the preferred agonists for the protein. However, the exact nature of physiological MDA5 ligands from virus-infected cells needs to be elucidated. In this work, we combine a crosslinking technique with next-generation sequencing in order to shed light on MDA5-associated RNAs from human cells infected with measles virus. Our findings suggest that RIG-I and MDA5 associate with AU-rich RNA species originating from the mRNA of the measles virus L gene. Corresponding sequences are poorer activators of ATP-hydrolysis by MDA5 in vitro, suggesting that they result in more stable MDA5 filaments. These data provide a possible model of how AU-rich sequences could activate type I interferon signaling

Quality Assessment of Photogrammetric Methods—A Workflow for Reproducible UAS Orthomosaics

Unmanned aerial systems (UAS) are cost-effective, flexible and offer a wide range of applications. If equipped with optical sensors, orthophotos with very high spatial resolution can be retrieved using photogrammetric processing. The use of these images in multi-temporal analysis and the combination with spatial data imposes high demands on their spatial accuracy. This georeferencing accuracy of UAS orthomosaics is generally expressed as the checkpoint error. However, the checkpoint error alone gives no information about the reproducibility of the photogrammetrical compilation of orthomosaics. This study optimizes the geolocation of UAS orthomosaics time series and evaluates their reproducibility. A correlation analysis of repeatedly computed orthomosaics with identical parameters revealed a reproducibility of 99% in a grassland and 75% in a forest area. Between time steps, the corresponding positional errors of digitized objects lie between 0.07 m in the grassland and 0.3 m in the forest canopy. The novel methods were integrated into a processing workflow to enhance the traceability and increase the quality of UAS remote sensing.This research was funded by the Hessian State Ministry for Higher Education, Research and the Arts, Germany, as part of the LOEWE priority project Nature 4.0—Sensing Biodiversity. The grassland study was funded by the Spanish Science Foundation FECYT-MINECO through the BIOGEI (GL2013- 49142-C2-1-R) and IMAGINE (CGL2017-85490-R) projects, and by the University of Lleida; and supported by a FI Fellowship to C.M.R. (2019 FI_B 01167) by the Catalan Government

Application of the LymphGen classification tool to 928 clinically and genetically-characterised cases of diffuse large B cell lymphoma (DLBCL).

We recently published results of targeted sequencing applied to 928 unselected cases of DLBCL registered in the Haematological Malignancy Research Network (HMRN) registry (1). Clustering allowed us to resolve five genomic subtypes. These subtypes shared considerable overlap with those proposed in two independent genomic studies(2, 3), suggesting the potential to use genetics to stratify patients by both risk and biology. In the original studies, clustering techniques were applied to sample cohorts to reveal molecular substructure, but left open the challenge of how to classify an individual patient. This was addressed by the LymphGen classification tool (4). LymphGen assigns an individual case to one of six molecular subtypes. The tool accommodates data from exome or targeted sequencing, either with or without copy number variant (CNV) data. Separate gene expression data allows classification of a seventh, MYC-driven subtype defined by a double hit (DHL) or molecular high-grade (MHG) gene expression signature(5-7).HR was funded by a studentship from the Medical Research Council. DH was supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/M008584/1). The Hodson laboratory receives core funding from Wellcome and MRC to the Wellcome-MRC Cambridge Stem Cell Institute and core funding from the CRUK Cambridge Cancer Centre. HMRN is supported by BCUK 15037 and CRUK 18362

Visible photodissociation spectroscopy of PAH cations and derivatives in the PIRENEA experiment

The electronic spectra of gas-phase cationic polycyclic aromatic hydrocarbons (PAHs), trapped in the Fourier Transform Ion Cyclotron Resonance cell of the PIRENEA experiment, have been measured by multiphoton dissociation spectroscopy in the 430-480 nm spectral range using the radiation of a mid-band optical parametric oscillator laser. We present here the spectra recorded for different species of increasing size, namely the pyrene cation (C16H10+), the 1-methylpyrene cation (CH3-C16H9+), the coronene cation (C24H12+), and its dehydrogenated derivative C24H10+. The experimental results are interpreted with the help of time-dependent density functional theory calculations and analysed using spectral information on the same species obtained from matrix isolation spectroscopy data. A kinetic Monte Carlo code has also been used, in the case of pyrene and coronene cations, to estimate the absorption cross-sections of the measured electronic transitions. Gas-phase spectra of highly reactive species such as dehydrogenated PAH cations are reported for the first time

Resonance Lifetimes from Complex Densities

The ab-initio calculation of resonance lifetimes of metastable anions challenges modern quantum-chemical methods. The exact lifetime of the lowest-energy resonance is encoded into a complex "density" that can be obtained via complex-coordinate scaling. We illustrate this with one-electron examples and show how the lifetime can be extracted from the complex density in much the same way as the ground-state energy of bound systems is extracted from its ground-state density

Non-zero temperature transport near quantum critical points

We describe the nature of charge transport at non-zero temperatures ($T$) above the two-dimensional ($d$) superfluid-insulator quantum critical point. We argue that the transport is characterized by inelastic collisions among thermally excited carriers at a rate of order $k_B T/\hbar$. This implies that the transport at frequencies $\omega \ll k_B T/\hbar$ is in the hydrodynamic, collision-dominated (or `incoherent') regime, while $\omega \gg k_B T/\hbar$ is the collisionless (or `phase-coherent') regime. The conductivity is argued to be $e^2 / h$ times a non-trivial universal scaling function of $\hbar \omega / k_B T$, and not independent of $\hbar \omega/k_B T$, as has been previously claimed, or implicitly assumed. The experimentally measured d.c. conductivity is the hydrodynamic $\hbar \omega/k_B T \to 0$ limit of this function, and is a universal number times $e^2 / h$, even though the transport is incoherent. Previous work determined the conductivity by incorrectly assuming it was also equal to the collisionless $\hbar \omega/k_B T \to \infty$ limit of the scaling function, which actually describes phase-coherent transport with a conductivity given by a different universal number times $e^2 / h$. We provide the first computation of the universal d.c. conductivity in a disorder-free boson model, along with explicit crossover functions, using a quantum Boltzmann equation and an expansion in $\epsilon=3-d$. The case of spin transport near quantum critical points in antiferromagnets is also discussed. Similar ideas should apply to the transitions in quantum Hall systems and to metal-insulator transitions. We suggest experimental tests of our picture and speculate on a new route to self-duality at two-dimensional quantum critical points.Comment: Feedback incorporated into numerous clarifying remarks; additional appendix discusses relationship to transport in dissipative quantum mechanics and quantum Hall edge state tunnelling problems, stimulated by discussions with E. Fradki

Age, extent and carbon storage of the central Congo Basin peatland complex

Peatlands are carbon-rich ecosystems that cover just three per cent of Earth's land surface, but store one-third of soil carbon. Peat soils are formed by the build-up of partially decomposed organic matter under waterlogged anoxic conditions. Most peat is found in cool climatic regions where unimpeded decomposition is slower, but deposits are also found under some tropical swamp forests. Here we present field measurements from one of the world's most extensive regions of swamp forest, the Cuvette Centrale depression in the central Congo Basin. We find extensive peat deposits beneath the swamp forest vegetation (peat defined as material with an organic matter content of at least 65 per cent to a depth of at least 0.3 metres). Radiocarbon dates indicate that peat began accumulating from about 10,600 years ago, coincident with the onset of more humid conditions in central Africa at the beginning of the Holocene. The peatlands occupy large interfluvial basins, and seem to be largely rain-fed and ombrotrophic-like (of low nutrient status) systems. Although the peat layer is relatively shallow (with a maximum depth of 5.9 metres and a median depth of 2.0 metres), by combining in situ and remotely sensed data, we estimate the area of peat to be approximately 145,500 square kilometres (95 per cent confidence interval of 131,900-156,400 square kilometres), making the Cuvette Centrale the most extensive peatland complex in the tropics. This area is more than five times the maximum possible area reported for the Congo Basin in a recent synthesis of pantropical peat extent. We estimate that the peatlands store approximately 30.6 petagrams (30.6 × 10(15) grams) of carbon belowground (95 per cent confidence interval of 6.3-46.8 petagrams of carbon)-a quantity that is similar to the above-ground carbon stocks of the tropical forests of the entire Congo Basin. Our result for the Cuvette Centrale increases the best estimate of global tropical peatland carbon stocks by 36 per cent, to 104.7 petagrams of carbon (minimum estimate of 69.6 petagrams of carbon; maximum estimate of 129.8 petagrams of carbon). This stored carbon is vulnerable to land-use change and any future reduction in precipitation