High-order harmonic generation using a high-repetition-rate turnkey laser

We generate high-order harmonics at high pulse repetition rates using a turnkey laser. High-order harmonics at 400 kHz are observed when argon is used as target gas. In neon we achieve generation of photons with energies exceeding 90 eV ($\sim$13 nm) at 20 kHz. We measure a photon flux of 4.4$\cdot10^{10}$ photons per second per harmonic in argon at 100 kHz. Many experiments employing high-order harmonics would benefit from higher repetition rates, and the user-friendly operation opens up for applications of coherent extreme ultra-violet pulses in new research areas

The metaRbolomics Toolbox in Bioconductor and beyond

Metabolomics aims to measure and characterise the complex composition of metabolites in a biological system. Metabolomics studies involve sophisticated analytical techniques such as mass spectrometry and nuclear magnetic resonance spectroscopy, and generate large amounts of high-dimensional and complex experimental data. Open source processing and analysis tools are of major interest in light of innovative, open and reproducible science. The scientific community has developed a wide range of open source software, providing freely available advanced processing and analysis approaches. The programming and statistics environment R has emerged as one of the most popular environments to process and analyse Metabolomics datasets. A major benefit of such an environment is the possibility of connecting different tools into more complex workflows. Combining reusable data processing R scripts with the experimental data thus allows for open, reproducible research. This review provides an extensive overview of existing packages in R for different steps in a typical computational metabolomics workflow, including data processing, biostatistics, metabolite annotation and identification, and biochemical network and pathway analysis. Multifunctional workflows, possible user interfaces and integration into workflow management systems are also reviewed. In total, this review summarises more than two hundred metabolomics specific packages primarily available on CRAN, Bioconductor and GitHub

Modeling Meets Metabolomics-The WormJam Consensus Model as Basis for Metabolic Studies in the Model Organism Caenorhabditis elegans.

Metabolism is one of the attributes of life and supplies energy and building blocks to organisms. Therefore, understanding metabolism is crucial for the understanding of complex biological phenomena. Despite having been in the focus of research for centuries, our picture of metabolism is still incomplete. Metabolomics, the systematic analysis of all small molecules in a biological system, aims to close this gap. In order to facilitate such investigations a blueprint of the metabolic network is required. Recently, several metabolic network reconstructions for the model organism Caenorhabditis elegans have been published, each having unique features. We have established the WormJam Community to merge and reconcile these (and other unpublished models) into a single consensus metabolic reconstruction. In a series of workshops and annotation seminars this model was refined with manual correction of incorrect assignments, metabolite structure and identifier curation as well as addition of new pathways. The WormJam consensus metabolic reconstruction represents a rich data source not only for in silico network-based approaches like flux balance analysis, but also for metabolomics, as it includes a database of metabolites present in C. elegans, which can be used for annotation. Here we present the process of model merging, correction and curation and give a detailed overview of the model. In the future it is intended to expand the model toward different tissues and put special emphasizes on lipid metabolism and secondary metabolism including ascaroside metabolism in accordance to their central role in C. elegans physiology

Quality assurance and quality control reporting in untargeted metabolic phenotyping: mQACC recommendations for analytical quality management

Background Demonstrating that the data produced in metabolic phenotyping investigations (metabolomics/metabonomics) is of good quality is increasingly seen as a key factor in gaining acceptance for the results of such studies. The use of established quality control (QC) protocols, including appropriate QC samples, is an important and evolving aspect of this process. However, inadequate or incorrect reporting of the QA/QC procedures followed in the study may lead to misinterpretation or overemphasis of the findings and prevent future metanalysis of the body of work. Objective The aim of this guidance is to provide researchers with a framework that encourages them to describe quality assessment and quality control procedures and outcomes in mass spectrometry and nuclear magnetic resonance spectroscopy-based methods in untargeted metabolomics, with a focus on reporting on QC samples in sufficient detail for them to be understood, trusted and replicated. There is no intent to be proscriptive with regard to analytical best practices; rather, guidance for reporting QA/QC procedures is suggested. A template that can be completed as studies progress to ensure that relevant data is collected, and further documents, are provided as on-line resources. Key reporting practices Multiple topics should be considered when reporting QA/QC protocols and outcomes for metabolic phenotyping data. Coverage should include the role(s), sources, types, preparation and uses of the QC materials and samples generally employed in the generation of metabolomic data. Details such as sample matrices and sample preparation, the use of test mixtures and system suitability tests, blanks and technique-specific factors are considered and methods for reporting are discussed, including the importance of reporting the acceptance criteria for the QCs. To this end, the reporting of the QC samples and results are considered at two levels of detail: “minimal” and “best reporting practice” levels

Challenges and perspectives for naming lipids in the context of lipidomics

Introduction: Lipids are key compounds in the study of metabolism and are increasingly studied in biology projects. It is a very broad family that encompasses many compounds, and the name of the same compound may vary depending on the community where they are studied. Objectives: In addition, their structures are varied and complex, which complicates their analysis. Indeed, the structural resolution does not always allow a complete level of annotation so the actual compound analysed will vary from study to study and should be clearly stated. For all these reasons the identification and naming of lipids is complicated and very variable from one study to another, it needs to be harmonized. Methods & Results: In this position paper we will present and discuss the different way to name lipids (with chemoinformatic and semantic identifiers) and their importance to share lipidomic results. Conclusion: Homogenising this identification and adopting the same rules is essential to be able to share data within the community and to map data on functional networks

Workshop on Assessing the Impact of Fishing on Oceanic Carbon (WKFISHCARBON; outputs from 2023 meeting)

Rapports Scientifiques du CIEM. Volume 6, nº 12The Workshop on Assessing the Impact of Fishing on Oceanic Carbon (WKFISHCARBON) was set up to provide ICES and stakeholders with a summary of knowledge on the role of fishing in the process of carbon budgets, sequestration and footprint in the ocean. The workshop addressed the potential impact of fishing on the biological carbon pump (BCP), the possible impacts of bottom trawling on carbon stores in the seabed, as well as considering emissions from fishing vessels. The overall aim was to generate proposals on how to develop an ICES approach to fishing and its role in the ocean carbon budget, and to develop a roadmap for a way forward. The main findings were that knowledge of the BCP in the open ocean was reasonably well developed, but that key gaps existed. In particular, information on the biomass of mesopelagic fish and other biota, and of some of the key processes e.g. fluxes and fish bioenergetics. Knowledge is much weaker for the BCP in shelf seas, where the bulk of fishing occurs. In particular, while biomass of fish was often well quantified, unlike the open ocean, the understanding of the important processes was lacking, particularly for the fate of faecal pellets and deadfall at the seabed. There is extensive scientific knowledge of the impact of fishing on the seabed, but what is un-clear is what it means for seabed carbon storage. There have been numbers of studies, which give a very divided view on this. There has also been open controversy about this in the literature. Physical disturbance to the seabed from fishing can affect sediment transport and has the potential to facilitate remineralization, but precise impacts will depend on habitat, fishing métier, and other environmental factors. From this, it is clear that more research is needed to resolve the controversy, and to quantify the impacts from different fishing gears and on different substrates or habitats in terms of carbon storage. There has been much more research on minimizing fuel use by fishing vessels, and hence emissions, but this has mainly focused on fuel efficiency, fuel use per unit of landed catch, and less on the total emissions. Baselines for fuel use are available at the global level, but are lacking at the national and vessel level. There is a need for standardization of methodologies and protocols, and for improving the uptake of fuel conservation measures by industry, as well as for improving the uptake of existing and potential fuel conservation and efficiency measures by industry. Finally, a roadmap was proposed to develop research and synthesis, on the understandings of the processes involved, the metrics and how to translate this into possible advice for policy-makers. To that end, a further workshop was proposed in 2024.info:eu-repo/semantics/publishedVersio

Clearance of apoptotic cells: implications in health and disease

Recent advances in defining the molecular signaling pathways that regulate the phagocytosis of apoptotic cells have improved our understanding of this complex and evolutionarily conserved process. Studies in mice and humans suggest that the prompt removal of dying cells is crucial for immune tolerance and tissue homeostasis. Failed or defective clearance has emerged as an important contributing factor to a range of disease processes. This review addresses how specific molecular alterations of engulfment pathways are linked to pathogenic states. A better understanding of the apoptotic cell clearance process in healthy and diseased states could offer new therapeutic strategies

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo