[Vaccinovigilance: Adverse reaction reports of animal vaccines in 2020].

The aim of the vigilance system in Switzerland is the evaluation and classification of reported suspected adverse reactions of immunological veterinary medicines (IVMP), including suspected lack of expected efficacy. The Institute of Virology and Immunology (IVI) is the competent authority for marketing authorizations of immunological veterinary medicinal products in Switzerland and responsible for the vaccinovigilance system. In 2020, 130 adverse reaction reports were received (5% less compared to 2019). The reports mainly concerned dogs (41%) and cats (25%) followed by cattle (18%) and horses (7%). Many of the reports in dogs involved the application of combined vaccines against canine distemper, hepatitis, parvovirosis and parainfluenza in combination with canine leptospira components, in cats against cat flu and feline panleukopenia in combination with feline leukaemia virus infection. Causality assessments were done according to the international ABON system. In 27% of the reported cases, the causality assessments between the vaccination and the reaction described were evaluated as being probable (ABON A), in 44% as possible (ABON B)

Making food systems safer: Time to curb use of highly hazardous pesticides

Use of synthetic chemical pesticides has expanded widely. These insecti-cides, herbicides, and fungicides have helped to boost crop production, but at a major cost – one whose full extent remains unknown. Many commonly used pesticides – especially in developing countries – are now considered “highly hazardous” by experts due to their proven or likely harms to nature and people.1 Evidence from farms in the global South confirms heavy use of pesticides, including substances banned elsewhere. Farmers and nearby communities face the most direct health threats. This policy brief outlines key harms and research findings, high-lights alternatives to pesticide-intensive agricultural practices, and calls for phasing out the riskiest substances – in line with human rights and proper application of the precautionary principle

Structure calculation, refinement and validation using CcpNmr Analysis

CcpNmr Analysis provides a streamlined pipeline for both NMR chemical shift assignment and structure determination of biological macromolecules. In addition, it encompasses tools to analyse the many additional experiments that make NMR such a pivotal technique for research into complex biological questions. This report describes how CcpNmr Analysis can seamlessly link together all of the tasks in the NMR structure-determination process. It details each of the stages from generating NMR restraints [distance, dihedral,hydrogen bonds and residual dipolar couplings (RDCs)],exporting these to and subsequently re-importing them from structure-calculation software (such as the programs CYANA or ARIA) and analysing and validating the results obtained from the structure calculation to, ultimately, the streamlined deposition of the completed assignments and the refined ensemble of structures into the PDBe repository. Until recently, such solution-structure determination by NMR has been quite a laborious task, requiring multiple stages and programs. However, with the new enhancements to CcpNmr Analysis described here, this process is now much more intuitive and efficient and less error-prone

Large Interferometer For Exoplanets (LIFE): VIII. Where is the phosphine? Observing exoplanetary PH3 with a space based MIR nulling interferometer

Phosphine could be a key molecule in the understanding of exotic chemistry happening in (exo)planetary atmospheres. While it has been detected in the Solar System's giant planets, it has not been observed in exoplanets yet. In the exoplanetary context however it has been theorized as a potential biosignature molecule. The goal of our study is to identify which illustrative science cases for PH3 chemistry are observable with a space-based mid-infrared nulling interferometric observatory like the LIFE (Large Interferometer For Exoplanets) concept. We identified a representative set of scenarios for PH3 detections in exoplanetary atmospheres varying over the whole dynamic range of the LIFE mission. We used chemical kinetics and radiative transfer calculations to produce forward models of these informative, prototypical observational cases for LIFEsim, our observation simulator software for LIFE. In a detailed, yet first order approximation it takes a mission like LIFE: (i) about 1h to find phosphine in a warm giant around a G star at 10 pc, (ii) about 10 h in H2 or CO2 dominated temperate super-Earths around M star hosts at 5 pc, (iii) and even in 100h it seems very unlikely that phosphine would be detectable in a Venus-Twin with extreme PH3 concentrations at 5 pc. Phosphine in concentrations previously discussed in the literature is detectable in 2 out of the 3 cases and about an order of magnitude faster than comparable cases with JWST. We show that there is a significant number of objects accessible for these classes of observations. These results will be used to prioritize the parameter range for the next steps with more detailed retrieval simulations. They will also inform timely questions in the early design phase of a mission like LIFE and guide the community by providing easy-to-scale first estimates for a large part of detection space of such a mission.Comment: In press. Accepted for publication in Astrobiology on 02 November 2022. 26 pages, 5 figures and 8 table

Estimation of interdomain flexibility of N-terminus of factor H using residual dipolar couplings

Characterization of segmental flexibility is needed to understand the biological mechanisms of the very large category of functionally diverse proteins, exemplified by the regulators of complement activation, that consist of numerous compact modules or domains linked by short, potentially flexible, sequences of amino acid residues. The use of NMR-derived residual dipolar couplings (RDCs), in magnetically aligned media, to evaluate interdomain motion is established but only for two-domain proteins. We focused on the three N-terminal domains (called CCPs or SCRs) of the important complement regulator, human factor H (i.e. FH1-3). These domains cooperate to facilitate cleavage of the key complement activation-specific protein fragment, C3b, forming iC3b that no longer participates in the complement cascade. We refined a three-dimensional solution structure of recombinant FH1-3 based on nuclear Overhauser effects and RDCs. We then employed a rudimentary series of RDC datasets, collected in media containing magnetically aligned bicelles (disk-like particles formed from phospholipids) under three different conditions, to estimate interdomain motions. This circumvents a requirement of previous approaches for technically difficult collection of five independent RDC datasets. More than 80% of conformers of this predominantly extended three-domain molecule exhibit flexions of < 40 °. Such segmental flexibility (together with the local dynamics of the hypervariable loop within domain 3), could facilitate recognition of C3b via initial anchoring and eventual reorganization of modules to the conformation captured in the previously solved crystal structure of a C3b:FH1-4 complex

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

Watson–Crick and Sugar-Edge Base Pairing of Cytosine in the Gas Phase: UV and Infrared Spectra of Cytosine·2-Pyridone

While keto-amino cytosine is the dominant species in aqueous solution, spectroscopic studies in molecular beams and in noble gas matrices show that other cytosine tautomers prevail in apolar environments. Each of these offers two or three H-bonding sites (Watson–Crick, wobble, sugar-edge). The mass- and isomer-specific S1 ← S0 vibronic spectra of cytosine·2-pyridone (Cyt·2PY) and 1-methylcytosine·2PY are measured using UV laser resonant two-photon ionization (R2PI), UV/UV depletion, and IR depletion spectroscopy. The UV spectra of the Watson–Crick and sugar-edge isomers of Cyt·2PY are separated using UV/UV spectral hole-burning. Five different isomers of Cyt·2PY are observed in a supersonic beam. We show that the Watson–Crick and sugar-edge dimers of keto-amino cytosine with 2PY are the most abundant in the beam, although keto-amino-cytosine is only the third most abundant tautomer in the gas phase. We identify the different isomers by combining three different diagnostic tools: (1) methylation of the cytosine N1–H group prevents formation of both the sugar-edge and wobble isomers and gives the Watson–Crick isomer exclusively. (2) The calculated ground state binding and dissociation energies, relative gas-phase abundances, excitation and the ionization energies are in agreement with the assignment of the dominant Cyt·2PY isomers to the Watson–Crick and sugar-edge complexes of keto-amino cytosine. (3) The comparison of calculated ground state vibrational frequencies to the experimental IR spectra in the carbonyl stretch and NH/OH/CH stretch ranges strengthen this identification

Large Interferometer For Exoplanets (LIFE): II. Signal simulation, signal extraction, and fundamental exoplanet parameters from single-epoch observations

peer reviewedContext. The Large Interferometer For Exoplanets (LIFE) initiative is developing the science and a technology road map for an ambitious space mission featuring a space-based mid-infrared (MIR) nulling interferometer in order to detect the thermal emission of hundreds of exoplanets and characterize their atmospheres. Aims. In order to quantify the science potential of such a mission, in particular in the context of technical trade-offs, an instrument simulator is required. In addition, signal extraction algorithms are needed to verify that exoplanet properties (e.g., angular separation and spectral flux) contained in simulated exoplanet data sets can be accurately retrieved. Methods. We present LIFEsim, a software tool developed for simulating observations of exoplanetary systems with an MIR space-based nulling interferometer. It includes astrophysical noise sources (i.e., stellar leakage and thermal emission from local zodiacal and exozodiacal dust) and offers the flexibility to include instrumental noise terms in the future. Here, we provide some first quantitative limits on instrumental effects that would allow the measurements to remain in the fundamental noise limited regime. We demonstrate updated signal extraction approaches to validating signal-to-noise ratio (S/N) estimates from the simulator. Monte Carlo simulations are used to generate a mock survey of nearby terrestrial exoplanets and determine to which accuracy fundamental planet properties can be retrieved. Results. LIFEsim provides an accessible way to predict the expected S/N of future observations as a function of various key instrument and target parameters. The S/Ns of the extracted spectra are photon noise dominated, as expected from our current simulations. Signals from multi-planet systems can be reliably extracted. From single-epoch observations in our mock survey of small (R < 1.5 REarth) planets orbiting within the habitable zones of their stars, we find that typical uncertainties in the estimated effective temperature of the exoplanets are ≲10%, for the exoplanet radius ≲20%, and for the separation from the host star ≲2%. Signal-to-noise-ratio values obtained in the signal extraction process deviate by less than 10% from purely photon-counting statistics-based S/Ns. Conclusions. LIFEsim has been sufficiently well validated so that it can be shared with a broader community interested in quantifying various exoplanet science cases that a future space-based MIR nulling interferometer could address. Reliable signal extraction algorithms exist, and our results underline the power of the MIR wavelength range for deriving fundamental exoplanet properties from single-epoch observations.Large Interferometer For Exoplanets (LIFE

13C-direct detected NMR experiments for the sequential J-based resonance assignment of RNA oligonucleotides

We present here a set of 13C-direct detected NMR experiments to facilitate the resonance assignment of RNA oligonucleotides. Three experiments have been developed: (1) the (H)CC-TOCSY-experiment utilizing a virtual decoupling scheme to assign the intraresidual ribose 13C-spins, (2) the (H)CPC-experiment that correlates each phosphorus with the C4′ nuclei of adjacent nucleotides via J(C,P) couplings and (3) the (H)CPC-CCH-TOCSY-experiment that correlates the phosphorus nuclei with the respective C1′,H1′ ribose signals. The experiments were applied to two RNA hairpin structures. The current set of 13C-direct detected experiments allows direct and unambiguous assignment of the majority of the hetero nuclei and the identification of the individual ribose moieties following their sequential assignment. Thus, 13C-direct detected NMR methods constitute useful complements to the conventional 1H-detected approach for the resonance assignment of oligonucleotides that is often hindered by the limited chemical shift dispersion. The developed methods can also be applied to large deuterated RNAs

Cys-Ph-TAHA: a lanthanide binding tag for RDC and PCS enhanced protein NMR

Here we present Cys-Ph-TAHA, a new nonadentate lanthanide tag for the paramagnetic labelling of proteins. The tag can be easily synthesized and is stereochemically homogenous over a wide range of temperatures, yielding NMR spectra with a single set of peaks. Bound to ubiquitin, it induced large residual dipolar couplings and pseudocontact shifts that could be measured easily and agreed very well with the protein structure. We show that Cys-Ph-TAHA can be used to label large proteins that are biochemically challenging such as the Lac repressor in a 90 kDa ternary complex with DNA and inducer