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Sixty-four phenols grouped as nitrated, bromo, amino, methyl, chloro-phenols, and cresols, and thirty-eight organic acids grouped as mono-carboxylic and dicarboxylic are analyzed in forty-two fog samples collected in the Alsace region between 2015 and 2021 to check their atmospheric behavior. Fogwater samples are collected using the Caltech Active Strand Cloudwater Collector (CASCC2), extracted using liquid–liquid extraction (LLE) on a solid cartridge (XTR Chromabond), and then analyzed using gas chromatography coupled with mass spectrometry (GC-MS). The results show the high capability of phenols and acids to be scavenged by fogwater due to their high solubility. Nitro-phenols and mono-carboxylic acids have the highest contributions to the total phenolic and acidic concentrations, respectively. 2,5-dinitrophenol, 3-methyl-4-nitrophenol, 4-nitrophenol, and 3,4-dinitrophenol have the highest concentration, originating mainly from vehicular emissions and some photochemical reactions. The top three mono-carboxylic acids are hexadecenoic acid (C16), eicosanoic acid (C18), and dodecanoic acid (C12), whereas succinic acid, suberic acid, sebacic acid, and oxalic acid are the most concentrated dicarboxylic acids, originated either from atmospheric oxidation (mainly secondary organic aerosols (SOAs)) or vehicular transport. Pearson’s correlations show positive correlations between organic acids and previously analyzed metals (p < 0.05), between mono- and dicarboxylic acids (p < 0.001), and between the analyzed acidic compounds (p < 0.001), whereas no correlations are observed with previously analyzed inorganic ions. Total phenolic and acidic fractions are found to be much higher than those observed for pesticides, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) measured at the same region due to their higher scavenging by fogwater.

Abstract Deciduous trees exhibit a spectacular phenomenon of autumn senescence driven by the seasonality of their growth environment, yet there is no consensus which external or internal cues trigger it. Senescence starts at different times in European aspen (Populus tremula L.) genotypes grown in same location. By integrating omics studies, we demonstrate that aspen genotypes utilize similar transcriptional cascades and metabolic cues to initiate senescence, but at different times during autumn. The timing of autumn senescence initiation appeared to be controlled by two consecutive “switches”; 1) first the environmental variation induced the rewiring of the transcriptional network, stress signalling pathways and metabolic perturbations and 2) the start of senescence process was defined by the ability of the genotype to activate and sustain stress tolerance mechanisms mediated by salicylic acid. We propose that salicylic acid represses the onset of leaf senescence in stressful natural conditions, rather than promoting it as often observed in annual plants.

Abstract Ionizing radiation is known to be DNA damaging and mutagenic, however less is known about which mutational footprints result from exposures of human cells to different types of radiation. We were interested in the mutagenic effects of particle radiation exposures on genomes of various human cell types, in order to gauge the genotoxic risks of galactic cosmic radiation, and of certain types of tumor radiotherapy. To this end, we exposed cultured cell lines from the human blood, breast and lung to fractionated proton and alpha particle (helium nuclei) beams at doses sufficient to considerably affect cell viability. Whole-genome sequencing revealed that mutation rates were not overall markedly increased upon proton and alpha exposures. However, there were modest changes in mutation spectra and distributions, such as the increases in clustered mutations and of certain types of indels and structural variants. The spectrum of mutagenic effects of particle beams may be cell-type and/or genetic background specific. Overall, the mutational effects of repeated exposures to proton and alpha radiation on human cells in culture appear subtle, however further work is warranted to understand effects of long-term exposures on various human tissues.

Anthelmintic resistance in equine parasite Parascaris univalens, compromises ivermectin (IVM) effectiveness and necessitates an in-depth understanding of its resistance mechanisms. Most research, primarily focused on holistic gene expression analyses, may overlook vital tissue-specific responses and often limit the scope of novel genes. This study leveraged gene co-expression network analysis to elucidate tissue-specific transcriptional responses and to identify core genes implicated in the IVM response in P. univalens. Adult worms (n = 28) were exposed to 10-11 M and 10-9 M IVM in vitro for 24 hours. RNA-sequencing examined transcriptional changes in the anterior end and intestine. Differential expression analysis revealed pronounced tissue differences, with the intestine exhibiting substantially more IVM-induced transcriptional activity. Gene co-expression network analysis identified seven modules significantly associated with the response to IVM. Within these, 219 core genes were detected, largely expressed in the intestinal tissue and spanning diverse biological processes with unspecific patterns. After 10-11 M IVM, intestinal tissue core genes showed transcriptional suppression, cell cycle inhibition, and ribosomal alterations. Interestingly, genes PgR028_g047 (sorb-1), PgB01_g200 (gmap-1) and PgR046_g017 (col-37 & col-102) switched from downregulation at 10-11 M to upregulation at 10-9 M IVM. The 10-9 M concentration induced expression of cuticle and membrane integrity core genes in the intestinal tissue. No clear core gene patterns were visible in the anterior end after 10-11 M IVM. However, after 10-9 M IVM, the anterior end mostly displayed downregulation, indicating disrupted transcriptional regulation. One interesting finding was the non-modular calcium-signaling gene, PgR047_g066 (gegf-1), which uniquely connected 71 genes across four modules. These genes were enriched for transmembrane signaling activity, suggesting that PgR047_g066 (gegf-1) could have a key signaling role. By unveiling tissue-specific expression patterns and highlighting biological processes through unbiased core gene detection, this study reveals intricate IVM responses in P. univalens. These findings suggest alternative drug uptake of IVM and can guide functional validations to further IVM resistance mechanism understanding.

Abstract Gonorrhea is a sexually transmitted infection for which antibiotic treatment options have declined due to increasing antibiotic resistance. Zoliflodacin, an investigational oral spiropyrimidinetrione antibiotic with activity against Neisseria gonorrhoeae strains that are multidrug‐resistant, including to third‐generation cephalosporins, is in phase III development for uncomplicated gonorrhea. This phase I, parallel, open‐label, randomized, crossover study in healthy adults evaluated the effect of food on the pharmacokinetics of single 3 or 4 g doses of zoliflodacin administered as granules for oral suspension in the fasted state or after consumption of a standardized high‐fat meal. Forty‐seven out of 48 randomized subjects completed the study. Oral administration of zoliflodacin with food delayed the absorption rate, compared with fasted state, with time to maximum concentration (Tmax) increasing from 3 to 6 h for the 3 g dose, and 2.5 to 4 h for the 4 g dose, but had no impact on the elimination of zoliflodacin. The maximum concentration (Cmax) and area under the plasma concentration‐time curve from time 0 to 24 h (AUC(0–24)) significantly increased with food by 52% and 94% for the 3 g dose, and by 89% and 108% for the 4 g dose. Forty‐two percent of participants reported a total of 34 treatment‐emergent adverse events (TEAEs), which were all considered mild in severity. Headache was the most common TEAE (22/48 subjects, 45.8%) and the only TEAE reported in more than one subject. In conclusion, administration of single 3 and 4 g doses of zoliflodacin as granules for oral suspension, with a high‐fat meal was well‐tolerated and resulted in statistically significant increases in peak and overall systemic exposure to zoliflodacin.

Abstract Single spin-defects in 2D transition-metal dichalcogenides are natural spin-photon interfaces for quantum applications. Here we report high-field magneto-photoluminescence spectroscopy from three emission lines (Q1, Q2, and Q*) of He-ion induced sulfur vacancies in monolayer MoS2. Analysis of the asymmetric PL lineshapes in combination with the diamagnetic shift of Q1 and Q2 yields a consistent picture of localized emitters with a wave function extent of ~3.5 nm. The distinct valley-Zeeman splitting in out-of-plane B-fields and the brightening of dark states through in-plane B-fields necessitates spin-valley selectivity of the defect states and lifted spin-degeneracy at zero field. Comparing our results to ab initio calculations identifies the nature of Q1 and Q2 and suggests that Q* is the emission from a chemically functionalized defect. Analysis of the optical degree of circular polarization reveals that the Fermi level is a parameter that enables the tunability of the emitter. These results show that defects in 2D semiconductors may be utilized for quantum technologies.

The good insulation properties and the low carbon footprint of vegetal concretes make them promising materials whose use tends to grow continuously. To produce optimized building materials, a better understanding of the interfacial transition zone (ITZ) between vegetal particles and cement paste in terms of the reactions involved and the size of the impacted surface was investigated. This research led to the setting of a reliable visual test to observe ITZ, which enables the monitoring of its appearance and development. Different combinations of vegetal particles and cement pastes were tested to compare the formed ITZ: hemp, rapeseed, and bamboo into Portland and Prompt cement. Finally, a clear link was drawn between the sugar concentration and the size of ITZ. Thanks to image analysis, it was shown that ITZ is due to physico-chemical reactions, with the extraction of free saccharide molecules from the vegetal and water suction followed by their release into the cement paste.

The use of fluoroquinolone antibiotics was legally restricted by the European Commission in March 2019. Since the extender for rabbit semen Galap® contained this antibiotic, it became necessary to modify it. The purpose of this study was to search for another molecule, based on its antimicrobial activity and also on the conservation, motility and fertility of semen diluted with the new extender. Several bacterial strains were isolated from 10 poor-quality ejaculates, including Enterococcus spp., Staphylococcus aureus and Proteus spp. They were then tested for antimicrobial susceptibility. Out of 15 antibiotics evaluated, gentamicin was the one targeting such bacteria. In vivo tests were then carried out to assess the effects of this antibiotic change on sperm parameters. Up to 26 pools of good quality semen (total motility >70%) were diluted in original Galap® or in this extender with gentamicin. Ejaculates were analysed on the day (D) of collection and up to 6 d of storage at +17°C. After 24 h storage, the motility in the new extender was reduced by 7.7% compared to the original; this decrease did not worsen by storing. After 6 d of storage, no difference between the two media was detected. A total of 360 females were then inseminated with pools of 4 to 5 good quality semen diluted 1:10 in both extenders, following the routine protocol of rabbit semen processing centres. There was no difference in female fertility or prolificacy between both formulations. In conclusion, these preliminary results suggest that the addition of gentamicin to this extender is useful and also has no adverse effect on fertility or prolificacy.

Gene regulatory and gene co-expression networks are powerful research tools for identifying biological signal within high-dimensional gene expression data. In recent years, research has focused on addressing shortcomings of these techniques with regard to the low signal-to-noise ratio, non-linear interactions and dataset dependent biases of published methods. Furthermore, it has been shown that aggregating networks from multiple methods provides improved results. Despite this, few useable and scalable software tools have been implemented to perform such best-practice analyses. Here, we present Seidr (stylized Seiðr), a software toolkit designed to assist scientists in gene regulatory and gene co-expression network inference. Seidr creates community networks to reduce algorithmic bias and utilizes noise corrected network backboning to prune noisy edges in the networks.Using benchmarks in real-world conditions across three eukaryotic model organisms, Saccharomyces cerevisiae, Drosophila melanogaster, and Arabidopsis thaliana, we show that individual algorithms are biased toward functional evidence for certain gene-gene interactions. We further demonstrate that the community network is less biased, providing robust performance across different standards and comparisons for the model organisms.Finally, we apply Seidr to a network of drought stress in Norway spruce (Picea abies (L.) H. Krast) as an example application in a non-model species. We demonstrate the use of a network inferred using Seidr for identifying key components, communities and suggesting gene function for non-annotated genes.

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) exist in the atmosphere in the vapor and particulate phases, as well as in solubilized form in fog/rain/cloud waters. In the current paper, fogwater samples are collected during 42 events between 2015 and 2021 at four different sites (Strasbourg, Geispolsheim, Erstein, Cronenbourg) in the Alsace region. Organics are extracted using liquid–liquid extraction (LLE) supported on a solid cartridge (XTR Chromabond), and then analyzed by gas chromatography–tandem mass spectrometry (GC-MS/MS). The total PAHs and PCBs concentrations in fog samples vary between 0.58 and 6.7 µg L−1 (average of 2.70 µg L−1), and 0.14 and 15.5 µg L−1 (average of 2.75 µg L−1). Low-molecular-weight (LMW) PAHs are predominant and highly detectable compared to high-molecular-weight (HMW) PAHs, while pentachloro-biphenyls are the dominant PCB congener. The PAHs and PCBs concentrations have increased over the sampling years at all sites, except for a slight decrease in PCBs level at Geispolsheim. A diagnostic ratio (DR) and principal component analysis (PCA) are applied to suggest potential contamination sources at Strasbourg metropolitan. Their results reveal that PAHs derive from a mixture of pyrogenic activities, while PCBs mainly come from industrial activities. The results also reveal, in some cases, inter-site variability for simultaneous and successive fog events.

Studies concerning fog water have been rapidly increasing due to its negative impacts on different environmental processes. However, fog water harvesting has become beneficial in various countries to overcome water scarcity. Accurate fog forecasting remains a challenging issue due to its spatio-temporal variability and uncertainties despite the development and efforts made to understand its chemistry and microphysics. The literature proved that the decrease in fog frequency over time in most countries is mainly attributed to the improvement in air quality or the change in regional climatic conditions. The current fog review summarizes its different types and collectors, life cycle, and impacts, the effects of aerosols, and the latest results concerning its forecast challenges and frequency. It also highlights the major chemical processes along with the main field studies performed on fog water. The aim of this work is not to provide a criticism about fog but to present a general comprehensive review of its physical and chemical aspects covering up to 330 research and review papers aimed to serve as a basis for new challenges and findings about fog water.

The enteric nervous system (ENS), sometimes referred to as a “second brain” is a quasi-autonomous nervous system, made up of interconnected plexuses organized in a mesh-like network lining the gastrointestinal tract. Originally described as an actor in the regulation of digestion, bowel contraction, and intestinal secretion, the implications of the ENS in various central neuropathologies has recently been demonstrated. However, with a few exceptions, the morphology and pathologic alterations of the ENS have mostly been studied on thin sections of the intestinal wall or, alternatively, in dissected explants. Precious information on the three-dimensional (3-D) architecture and connectivity is hence lost. Here, we propose the fast, label-free 3-D imaging of the ENS, based on intrinsic signals. We used a custom, fast tissue-clearing protocol based on a high refractive-index aqueous solution to increase the imaging depth and allow us the detection of faint signals and we characterized the autofluorescence (AF) from the various cellular and sub-cellular components of the ENS. Validation by immunofluorescence and spectral recordings complete this groundwork. Then, we demonstrate the rapid acquisition of detailed 3-D image stacks from unlabeled mouse ileum and colon, across the whole intestinal wall and including both the myenteric and submucosal enteric nervous plexuses using a new spinning-disk two-photon (2P) microscope. The combination of fast clearing (less than 15 min for 73% transparency), AF detection and rapid volume imaging [less than 1 min for the acquisition of a z-stack of 100 planes (150*150 μm) at sub-300-nm spatial resolution] opens up the possibility for new applications in fundamental and clinical research.

Parasitic nematodes pose a significant threat to human and animal health, as well as cause economic losses in the agricultural sector. The use of anthelmintic drugs, such as Ivermectin (IVM), to control these parasites has led to widespread drug resistance. Identifying genetic markers of resistance in parasitic nematodes can be challenging, but the free-living nematode Caenorhabditis elegans provides a suitable model. In this study, we aimed to analyze the transcriptomes of adult C. elegans worms of the N2 strain exposed to the anthelmintic drug Ivermectin (IVM), and compare them to those of the resistant strain DA1316 and the recently identified Abamectin Quantitative Trait Loci (QTL) on chromosome V. We exposed pools of 300 adult N2 worms to IVM (10-7 and 10-8 M) for 4 hours at 20°C, extracted total RNA and sequenced it on the Illumina NovaSeq6000 platform. Differentially expressed genes (DEGs) were determined using an in-house pipeline. The DEGs were compared to genes from a previous microarray study on IVM-resistant C. elegans and Abamectin-QTL. Our results revealed 615 DEGs (183 up-regulated and 432 down-regulated genes) from diverse gene families in the N2 C. elegans strain. Of these DEGs, 31 overlapped with genes from IVM-exposed adult worms of the DA1316 strain. We identified 19 genes, including the folate transporter (folt-2) and the transmembrane transporter (T22F3.11), which exhibited an opposite expression in N2 and the DA1316 strain and were deemed potential candidates. Additionally, we compiled a list of potential candidates for further research including T-type calcium channel (cca-1), potassium chloride cotransporter (kcc-2), as well as other genes such as glutamate-gated channel (glc-1) that mapped to the Abamectin-QTL.

Pulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: "type I LCNECs" with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and "type II LCNECs" enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1high/DLL3high/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1low/DLL3low/NOTCHhigh, and an upregulation of immune-related pathways. In conclusion, LCNECs comprise two molecularly defined subgroups, and distinguishing them from SCLC may allow stratified targeted treatment of high-grade neuroendocrine lung tumors.

Abstract Background Affordable high-throughput DNA and RNA sequencing technologies are allowing genomic analysis of plant and animal populations and as a result empowering new systems genetics approaches to study complex traits. The availability of intuitive tools to browse and analyze the resulting large-scale genetic and genomic datasets remain a significant challenge. Furthermore, these integrative genomics approaches require innovative methods to dissect the flow and interconnectedness of biological information underlying complex trait variation. The Plant Genome Integrative Explorer (PlantGenIE.org) is a multi-species database and domain that houses online tools for model and woody plant species including Eucalyptus. Since the Eucalyptus Genome Integrative Explorer (EucGenIE) is integrated within PlantGenIE, it shares genome and expression analysis tools previously implemented within the various subdomains (ConGenIE, PopGenIE and AtGenIE). Despite the success in setting up integrative genomics databases, online tools for systems genetics modelling and high-resolution dissection of complex trait variation in plant populations have been lacking. Results We have developed qtlXplorer ( https://eucgenie.org/QTLXplorer ) for visualizing and exploring systems genetics data from genome-wide association studies including quantitative trait loci (QTLs) and expression-based QTL (eQTL) associations. This module allows users to, for example, find co-located QTLs and eQTLs using an interactive version of Circos, or explore underlying genes using JBrowse. It provides users with a means to build systems genetics models and generate hypotheses from large-scale population genomics data. We also substantially upgraded the EucGenIE resource and show how it enables users to combine genomics and systems genetics approaches to discover candidate genes involved in biotic stress responses and wood formation by focusing on two multigene families, laccases and peroxidases. Conclusions qtlXplorer adds a new dimension, population genomics, to the EucGenIE and PlantGenIE environment. The resource will be of interest to researchers and molecular breeders working in Eucalyptus and other woody plant species. It provides an example of how systems genetics data can be integrated with functional genetics data to provide biological insight and formulate hypotheses. Importantly, integration within PlantGenIE enables novel comparative genomics analyses to be performed from population-scale data.

Benzimidazole (BZ) drugs are frequently used to treat infections with the equine ascarid Parascaris univalens due to increasing resistance to macrocyclic lactones and pyrantel. Benzimidazole resistance is rare in ascarids in contrast to strongyle parasites where this resistance is widespread. In strongyles, single nucleotide polymorphisms (SNPs) at codons 167, 198 and 200 in a β-tubulin gene have been correlated to BZ resistance, but little is known about the β-tubulin genes and their possible involvement in BZ resistance in P. univalens and other ascarids. Previously two β-tubulin genes have been identified in P. univalens. In this study, we present five additional β-tubulin genes as well as the phylogenetic relationship of all seven genes to β-tubulins of other clade III and V nematodes. In addition, the efficacy of fenbendazole for treatment of P. univalens on a Swedish stud farm was studied in 2019 and 2020 using faecal egg count reduction test. Reductions varied from 73% to 88%, indicating the presence of a resistant P. univalens population on the farm. The emergence of BZ resistance emphasizes the need for development of molecular markers for rapid and more sensitive detection of resistant populations. We therefore investigated whether possible SNPs at positions 167, 198 or 200 in any of the β-tubulin genes could be used to distinguish between resistant and susceptible P. univalens populations. Amplicon sequencing covering the mutation sites 167, 198 and 200 in all seven β-tubulin genes revealed an absence of SNPs in both resistant and susceptible populations, suggesting that the mechanism behind BZ resistance in ascarids is different from that in strongyle nematodes and the search for a molecular marker for BZ resistance in P. univalens needs to continue.

Abstract Background Intermixing of genomes through meiotic reassortment and recombination of homologous chromosomes is a unifying theme of sexual reproduction in eukaryotic organisms and is considered crucial for their adaptive evolution. Previous studies of the budding yeast species Saccharomycodes ludwigii suggested that meiotic crossing over might be absent from its sexual life cycle, which is predominated by fertilization within the meiotic tetrad. Results We demonstrate that recombination is extremely suppressed during meiosis in Sd. ludwigii. DNA double-strand break formation by the conserved transesterase Spo11, processing and repair involving interhomolog interactions are required for normal meiosis but do not lead to crossing over. Although the species has retained an intact meiotic gene repertoire, genetic and population analyses suggest the exceptionally rare occurrence of meiotic crossovers in its genome. A strong AT bias of spontaneous mutations and the absence of recombination are likely responsible for its unusually low genomic GC level. Conclusions Sd. ludwigii has followed a unique evolutionary trajectory that possibly derives fitness benefits from the combination of frequent mating between products of the same meiotic event with the extreme suppression of meiotic recombination. This life style ensures preservation of heterozygosity throughout its genome and may enable the species to adapt to its environment and survive with only minimal levels of rare meiotic recombination. We propose Sd. ludwigii as an excellent natural forum for the study of genome evolution and recombination rates.

Abstract Background Translation is a tightly regulated process, controlling the rate of protein synthesis in cells. Ribosome sequencing (Ribo-Seq) is a recently developed tool for studying actively translated mRNA and can thus directly address translational regulation. Ribo-Seq libraries need to be sequenced to a great depth due to high contamination by rRNA and other contaminating nucleic acid fragments. Deep sequencing is expensive, and it generates large volumes of data, making data analysis complicated and time consuming. Methods and results Here we developed a platform for Ribo-Seq library construction and data analysis to enable rapid quality assessment of Ribo-Seq libraries with the help of a small-scale sequencer. Our data show that several qualitative features of a Ribo-Seq library, such as read length distribution, P-site distribution, reading frame and triplet periodicity, can be effectively evaluated using only the data generated by a benchtop sequencer with a very limited number of reads. Conclusion Our pipeline enables rapid evaluation of Ribo-Seq libraries, opening up possibilities for optimization of Ribo-Seq library construction from difficult samples, and leading to better decision making prior to more costly deep sequencing.

Excitonic physics dominates the optical response of semiconductor monolayers but single particle band structure parameters are hard to probe experimentally. Here, spin-orbit splitting in the conduction band of monolayer WSe2 is revealed by the identification of the Rydberg series of dark excitons.

Combining magnetic and semiconducting properties in a single material offers great technological potential, all the more so if these are coupled with good optical properties. Here, Neumann et al. present a Manganese doped Ruddlesden-Popper perovskite with this trifecta of attributes.

Excitons control the optical properties of transition metal dichalcogenide monolayers. Here, the authors measure the exciton fine structure of MoS2 and MoSe2 monolayers encapsulated in hBN in magnetic fields up to 30 T, and observe a brightening of the spin-forbidden dark excitons in MoS2.