Data in Brief

Uranium (U) and arsenic (As) are both ubiquitous contaminants in the American southwest, posing risks to humans, animals, and the environment. Depleted uraniums (DU) chronic effects and mechanisms of toxicity are incompletely understood. Differential gene expression of concomitant exposures to identify markers of toxicity have not been undertaken until now. Continuous low-dose, high-dose, and concomitant exposures are investigated using the larval zebrafish (Danio rerio), with exposure paradigms lasting from embryo collection until sampling at 5 days post fertilization (dpf). Herein, we describe overall differential gene expression with counts and pathway enrichment statistics using both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The raw dataset has been deposited in NCBIs Gene Expression Omnibus (GEO) repository [1] under the accession number GSE319292 [2]. O_TBL View this table: org.highwire.dtl.DTLVardef@9b121aorg.highwire.dtl.DTLVardef@c17073org.highwire.dtl.DTLVardef@1bdc2b9org.highwire.dtl.DTLVardef@13b130aorg.highwire.dtl.DTLVardef@15f1d22_HPS_FORMAT_FIGEXP M_TBL C_TBL VALUE OF THE DATAO_LIUranyl nitrate (UN), a water-soluble depleted uranium species, and sodium arsenite (As) are both ubiquitous contaminants in the American southwest, posing risks to humans, animals, and the environment. The United States Environmental Protection Agency (EPA) has set maximum contaminant limits (MCL) of 30 ppb U atoms and 10 ppb As atoms, respectively. C_LIO_LIThese data show differentially expressed genes (DEGs) from larval zebrafish exposed to 1 or 10 {micro}M As, 30 or 300 {micro}g/L UN, or 1 {micro}M As and 30 {micro}g/L UN in combination. Concentrations were specifically chosen based on environmental relevance. C_LIO_LIGene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of up- and down-regulated DEGs are provided to understand the molecular mechanisms of uranium toxicity and inform future studies. C_LIO_LIThese data should be used for biomarker identification and mechanistic interrogation of single and combinatorial exposures of environmentally relevant compounds at realistic exposure levels. C_LI

Back to the 1990 the single step method developed by Chomczynski and Sacchi for RNA isolation was extended for sequential isolation of RNA, DNA and proteins from a same sample. Although the quality of the extracted RNA turned compatible with RNA-Seq analyses, the extraction of the protein fraction from the same sample was time-consuming and resulting in low yield and quality of proteins not compatible with LC-MS proteomic analyses. Here we report a novel procedure by isolating in parallel the protein fraction and the RNA fraction from the same exact minute mosquito samples. We provide evidence that each cognate fractions are compatible with LC-MS proteomic analysis on the one hand and RNA-Seq analysis on the other hand. This protocol is simple, time efficient and adequate for studies involving limited sample size and could be applied easily to a broad range of animal and human samples.

There is growing interest in the therapeutic potential of 5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) for psychiatric disorders. While 5-MeO-DMT can be chemically synthesized, the parotoid gland secretions of Incilius alvarius (also known as the Colorado River or Sonoran Desert toad) contain 5-MeO-DMT and other molecules including bufotenine, bufagenins, bufotoxins, and indole alkylamines that may have individual clinical utility or act as entourage molecules to enhance the activity of 5-MeO-DMT. Incilius alvarius is currently under severe ecological pressure due to demand for natural 5-MeO-DMT and habitat loss. We established a cell line from tissue obtained by wedge biopsy of the Incilius alvarius parotoid gland and confirmed the cell-based biosynthesis of 5-MeO-DMT by LC-MS/MS. Cell-based biosynthesis of Incilius alvarius parotoid gland secretions is a potentially cruelty-free and sustainable source of naturally derived 5-MeO-DMT for research and drug development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/492789v3_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@163bfc6org.highwire.dtl.DTLVardef@1c36601org.highwire.dtl.DTLVardef@15ded62org.highwire.dtl.DTLVardef@18bbea8_HPS_FORMAT_FIGEXP M_FIG C_FIG

Investigating the divergence time between different populations has been of fundamental interest in evolution biology. In this study, we reanalysed the mitochondrial and Y chromosome DNA of the 1000 Genomes Project, and revealed that most single nucleotide polymorphisms (SNPs) are specific to minority and would be classified as low-frequency mutations. Using these polymorphisms, we recalculated the divergence time of different populations by direct comparison between individuals and the out-group.

Botanical dietary supplements (like wheat, barley, teff, oats, white lupin, pumpkin seed, and chickpeas) may contain trace amounts of toxicants in addition to important micronutrients. Developing and validating a reliable protocol for the simultaneous quantification of Cu, Fe, Zn, Mo, Se, Mn, Pb, Al, Ni, and Cr using a PerkinElmer (NexIONTM2000 model) quadrupole ICP MS (including a He collision and reaction cell when needed) with closed vessel microwave digestion using (HNO3 + H2O2) was the aim of this study.The method was subsequently utilized in a sample survey, and the outcomes were evaluated against WHO/JECFA standards. From five study regions, twenty-seven farm-collected botanical powder samples representing seven species were acquired. To create one composite per species, field subsamples were cleaned, air dried, ground, and blended (nine subsamples per botanical: three grabs from each of three farms). HNO3/H2O2 was used to digest aliquots (0.250-0.500gm) in closed microwave containers. Internal standards, multi-point external calibration, procedural blanks, verified reference materials, matrix spikes, and duplicates were all used in ICP MSs multi-element quantitation. Method LODs/LOQs, accuracy (CRM recoveries), and precision (RSD) were calculated.The technique produced low LODs that were suitable for dietary evaluation (typical LOD ranges: Cu, Fe, Zn, Mn, Ni, Cr (0.001-0.01) mg/kg; Mo, Se, Pb, Al (0.002-0.05) mg/kg. For the majority of analytes, within-run RSDs were less than 5%, while CRM recoveries ranged from 88.9 to 110%. The concentrations of essential elements varied greatly (average mg/kg: Fe (280.7{+/-}25.6); Zn (6.0{+/-}0.541); Cu (2.8{+/-}0.269); Mn (398.3{+/-}23.8); {micro}gm/kg: Se (0.061{+/-}0.006); Mo (1.0 {+/-}0.022). Although some composites approached or exceeded conservative intake thresholds for Pb and Al under high consumption scenarios, toxic elements were generally low (mean mg/kg: Pb (0.062{+/-}0.007); Al(185.2{+/-}18.5); Ni(1.6{+/-}0.163); Cr(1.8{+/-}0.171).For the simultaneous nutritional and contaminant profiling of supplements derived from cereals and those not, the validated ICP- MS workflow with microwave HNO3 and H2O2 digestion is suitable. Accurate labeling and consumer safety can be supported by routine screening and supply chain controls.

Assessing how much of the variability in blood plasma proteins is due to genetic or environmental factors is essential for advancing personalized medicine. While large-scale studies have established SNP-based heritability (SNP-h2) estimates for plasma proteins, less is known about the proportion of total genetic effects on protein variability. We applied quantitative genetic twin models to estimate the heritability of 2,321 plasma proteins and to assess the proportion of heritability accounted for by SNP-h2 estimates. Olink proteomics data were generated for 401 twins aged 56-70, including 196 complete same-sex twin pairs. On average, 40% of protein variability was attributable to genetic effects. Twin-based heritability estimates were highly correlated with published SNP-h2 estimates from the UK Biobank (Spearman coefficient: r=0.80). However, on average, only half of the total heritability was covered by SNP-h2, and the other half, representing one-fifth of total protein phenotypic variability, remains missing.

Dunaliella tertiolecta is a marine microalgae that has been studied extensively as a potential carbon-neutral biofuel source [1]. Microalgae oil contains high quantities of energy-rich fatty acids and lipids, but is not yet commercially viable as an alternative fuel. Carefully optimised growth conditions, and more recently, algal-bacterial co-cultures have been explored as a way of improving the yield of Dunaliella tertiolecta microalgae oils. The relationship between the host microalgae and bacterial co-cultures is currently poorly understood. Here, a complete workflow is proposed to analyse the global metabolomic profile of co-cultured Dunaliella tertiolectra and Phaeobacter italicus R11, which will enable researchers to explore the chemical nature of this relationship in more detail. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/461748v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@18c3cb0org.highwire.dtl.DTLVardef@1e48735org.highwire.dtl.DTLVardef@68a98borg.highwire.dtl.DTLVardef@15306bc_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA method for direct microalgae sample introduction is proposed. C_LIO_LIAdvanced chemometric tools can extract, useful and discriminating metabolomic features even from very noisy complex datasets. C_LI

Psychedelic compounds have gained renewed interest for their potential therapeutic applications, but their metabolism and effects on complex biological systems remain poorly understood. Here, we present a systematic characterization of LSD metabolites in the model organism Caenorhabditis elegans using state-of-the-art analytical techniques. By employing ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS), we identified and quantified a range of LSD metabolites, shedding light on their metabolic pathways and offering insights into their pharmacokinetics. Our study demonstrates the suitability of C. elegans as a valuable model system for investigating the metabolism of psychedelic compounds and provides a foundation for further research on the therapeutic potential of LSD. These findings contribute to the growing body of knowledge in the field and highlight the importance of advanced analytical methodologies in elucidating the effects of psychedelic substances on biological systems.

Ascosphaera apis is an entomopathogenic fungus that exclusively infects honeybee larvae, resulting in chalkbrood disease, a widespread fungal disease damaging the beekeeping industry all over the world. In this article, purified mycelia (Aam) and spores (Aas) of A. apis pure culture under lab condition were sequenced using PacBio Sequel platform. In total, 13,302,489 and 9,911,345 subreads were yielded from Aam and Aas, respectively; 394,142 and 274,928 circular consensus sequence (CCS) reads were identified as being full-length non-chimeric (FLNC) reads, with a mean length of 2820 bp and 2602 bp, respectively. Furthermore, 174,095 and 103,845 corrected isoforms were identified, with a N50 length of 3543 bp and 3262 bp, respectively. The reported full-length transcriptome data of A. apis mycelium and spore will provide a valuable resource for improvement of genome and transcriptome annotations as well as better understanding of transcript structure such as alternative splicing and polyadenylation. Value of the dataO_LICurrent dataset offers a set of high-quality full-length transcripts of A. apis. C_LIO_LIThe data can facilitate the improvement of A. apis genome and transcriptome annotations. C_LIO_LIThis dataset benefits further exploration of alternative splicing and polyadenylation of A. apis mRNAs. C_LI

The Solve-RD project brings together clinicians, scientists, and patient representatives from 51 institutes spanning 15 countries to collaborate on genetically diagnosing ("solving") rare diseases (RDs). The project aims to significantly increase the diagnostic success rate by co-analysing data from thousands of RD cases, including phenotypes, pedigrees, exome/genome sequencing and multi-omics data. Here we report on the data infrastructure devised and created to support this co-analysis. This infrastructure enables users to store, find, connect, and analyse data and metadata in a collaborative manner. Pseudonymised phenotypic and raw experimental data are submitted to the RD-Connect Genome-Phenome Analysis Platform and processed through standardised pipelines. Resulting files and novel produced omics data are sent to the European Genome-phenome Archive, which adds unique file identifiers and provides long-term storage and controlled access services. MOLGENIS "RD3" and Cafe Variome "Discovery Nexus" connect data and metadata and offer discovery services, and secure cloud-based "Sandboxes" support multi-party data analysis. This proven infrastructure design provides a blueprint for other projects that need to analyse large amounts of heterogeneous data.

Favipiravir (FAV; T-705) has been approved for use as an anti-influenza therapeutic and has reports against a wide range of viruses (e.g., Ebola virus, rabies and norovirus). Most recently FAV has been reported to demonstrate activity against SARS-CoV-2. Repurposing opportunities have been intensively studied with only limited success to date. If successful, repurposing will allow interventions to become more rapidly available than development of new chemical entities. Pre-clinical and clinical investigations of FAV require robust, reproducible and sensitive bioanalytical assay. Here, a liquid chromatography tandem mass spectrometry assay is presented which was linear from 0.78-200 ng/mL Accuracy and precision ranged between 89% and 110%, 101% and 106%, respectively. The presented assay here has applications in both pre-clinical and clinical research and may be used to facilitate further investigations into the application of FAV against SARS-CoV-2.

Oxford Nanopore Technology (ONT) based methylation sequencing is increasingly recognized for its rapid and accurate classification of brain tumors. A process that is crucial for optimal patient treatment. However, widespread clinical utility is currently limited by the need for fresh-frozen biopsies and not the standard-of-care formalin-fixed, paraffin-embedded (FFPE) samples. Our study explores the impact of FFPE on DNA methylation and presents a developed and validated protocol for ONT-based FFPE tumor classification. We present a practical solution for precise brain tumor diagnoses in routine clinical settings and facilitating timely treatment decisions at the point of care and without interfering with operating room standards.

The Swedish Phenylketonuria (PKU) screening biobank contains neonatal blood spots from over five million individuals born in Sweden since 1975, offering a unique research resource. While its value has been proven in several research areas, such as genetics, the feasibility of DNA methylation studies using archived dried blood spots remains uncertain. Here, we selected samples from seven random individuals born between 1985 and 2003 to evaluate the performance of the Illumina Infinium MethylationEPIC v2.0 array on DNA extracted from PKU blood spots. Despite DNA input quantities as low as 19.2 ng, probe call rates remained exceptionally high (mean 99.76% at p<0.01), with robust methylation site coverage across all samples. These findings challenge conventional assumptions about the DNA quantity and quality required for methylation arrays and demonstrate that decades-old neonatal blood spots can yield high-quality epigenetic data.

The source of almost all of the lead (Pb) found in meat from carcasses of wild-shot small game animals is often thought to be small embedded fragments of the lead shotgun pellets usually used by hunters to kill them. Available circumstantial evidence supports this conjecture, but an unknown proportion of the lead in game meat might be biologically-incorporated and absorbed by the game animal from ingested shotgun pellets and other environmental sources, such as soil and residues from mining. A critical test comparing lead concentrations in meat from animals known to have been killed using different types of shotgun ammunition has not been performed until now. We compared lead concentrations in samples of edible meat from carcasses of 27 wild-shot common pheasants (Phasianus colchicus) from which only lead shotgun pellets were recovered post mortem with concentrations for 20 birds from which only iron pellets were recovered. Shotgun pellets were removed from the meat samples before analysis. The mean concentration of lead was about 30 times greater in the meat of pheasants shot with lead than those shot with iron and was similar to mean concentrations of lead reported previously from Europe-wide samples of meat from wild-shot small game animals, including pheasants, killed using unknown types of ammunition. These results support the hypothesis that changing the type of shotgun ammunition in use for hunting from lead to iron would greatly reduce the concentration of lead in meat from wild-shot small game.

SARS-CoV-2 was first detected in Sudan on 13th March 2020. Here, we describe the genomic epidemiology of SARS-CoV-2 in Sudan between May 2020 and April 2022 to understand the introduction and transmission of SARS-CoV-2 variants in the country. A total of 667 SARS-CoV-2 positive samples were successfully sequenced using the nCoV-19 Artic protocol on the Oxford Nanopore Technology ([&ge;]70% genome completeness). The genomes were compared with a select contemporaneous global dataset to determine genetic relatedness and estimate import/export events. The genomes were classified into 37 Pango lineages within the ancestral strain (107 isolates across 13 Pango lineages), Eta variant of interest (VOI) (78 isolates in 1 lineage), Alpha variant of concern (VOC) (10 isolates in 2 lineages), Beta VOC (26 isolates in 1 lineage), Delta VOC (171 isolates across 8 lineages) and Omicron VOC (242 isolates across 12 lineages). We estimated a total of 144 introductions of the observed variants from different countries across the globe. Multiple introductions of the Eta VOI, Beta VOC and Omicron VOC were observed in Sudan mainly from Europe and Africa. These findings suggest a need for continuous genomic surveillance of SARS-CoV-2 to monitor their introduction and spread consequently inform public health measures to combat SARS-CoV-2 transmission.

For the purpose of Covid-19 antibody testing, the human plasma samples acquired over a period of 310 days from August 18, 2021, to June 22, 2022, were subjected to DIA LC-MS proteome analysis. This process led to the acquisition of a quantitative protein profile and allowed for the validation of the temporal behavior of expressed proteins within the samples. A total of 1502 proteins were identified from the plasma samples. Before vaccination, after the first dose, after the second dose, and during the period after contracting the novel coronavirus, protein quantification values during each event interval were compared. Despite minimal changes observed before and after Covid-19 vaccination, notable proteins exhibiting distinct high-expression and low-expression patterns were identified after contracting the novel coronavirus infection.

SummaryThe ever-growing genetic cohorts lead to an increase in scale of molecular Quantitative Trait Loci (QTL) studies, creating opportunities for more extensive two samples Mendelian randomization (MR) investigations aiming to identify causal relationships between molecular traits and diseases. This increase led to the identification of multiple causal candidates and potential drug targets over time. However, the increase in scale of such studies and higher dimension multi-omic data come with computational challenges. We present "LArge SCAle MOLecular Mendelian Randomization with Julia" (LaScaMolMR.jl), an open-sourced integrated Julia package optimized for Omic-wide Mendelian Randomization (OWMR) Studies. This versatile package eliminates the two-language problem and implements fast algorithms for instrumental variable selection approaches with both cis and trans instruments and performs the most popular regression estimators for MR studies with molecular exposures. It reduces the compute time via meta-programming allowing easy deployment of multi-threaded approach and the internalization of linkage disequilibrium investigation of potential instrumental variables. Via its integrated approach and high-computational performance, LaScaMolMR.jl allows users who have minimal programming experience to perform large scale OWMR studies. Implementation and availabilityLaScaMolMR is freely available at github.com/SamuelMathieu-code/LaScaMolMR.jl.

Hypoxia in disease describes persistent low oxygen conditions, observed in a range of pathologies, including cancer. In the discovery of biomarkers in biological models, pathophysiological traits present a source of translatable metabolic products for the diagnosis of disease in humans. Part of the metabolome is represented by its volatile, gaseous fraction; the volatilome. Human volatile profiles, such as those found in breath, are able to diagnose disease, however accurate volatile biomarker discovery is required to target reliable biomarkers to develop new diagnostic tools. Using custom chambers to control oxygen levels and facilitate headspace sampling, the MDA-MB-231 breast cancer cell line was exposed to hypoxia (1% oxygen) for 24 hours. The maintenance of hypoxic conditions in the system was successfully validated over this time period. Targeting and non-targeting gas chromatography mass spectrometry approaches revealed four significantly altered volatile organic compounds when compared to control cells. Three compounds were actively consumed by cells: methyl chloride, acetone and n-Hexane. Cells under hypoxia also produced significant amounts of styrene. This work presents a novel methodology for identification of volatile metabolisms under controlled gas conditions with novel observations of volatile metabolisms by breast cancer cells.

Wastewater was screened for the presence of functionally significant mutations in SARS-CoV-2 associated with emerging variants of concern (VOC) by ddPCR, and results accorded with sequencing of clinical samples from the same region. We propose that PCR-based screening of wastewater can provide a powerful tool for rapid and inexpensive screening of large population segments for VOC-associated mutations and can hone complementary sampling and sequencing of direct (human) test material to track emerging VOC.

Loose Anagen Hair Syndrome is a form of non-scarring alopecia marked by easily and painlessly pluckable terminal hair during its active growth - anagen - phase. This condition is believed to result from poor hair shaft anchoring within the follicle due to premature keratinization. Our research identified the likely pathogenic c.296C>T (p.T99I) variant in KRT32, which was found to co-segregate with the disorder in a large family with autosomal dominant loose anagen hair syndrome. This study aimed to explore the role of KRT32, previously unassociated with loose anagen hair, in hair anchorage and assess the functional impact of the p.T99I variant. We hypothesized that the p.T99I variant reduces KRT32s binding affinity to KRT82, disrupting the intermediate filament structure in the hair shaft cuticle and leading to weak anagen hair anchorage. To test this hypothesis, we conducted a protein-protein interaction assay using far western blotting and performed in silico intermediate filament network segmentation analysis on high-resolution fluorescent microscopy images. Our results revealed a decreased binding affinity of KRT32T99I for KRT82 compared to KRT32WT, along with significant differences in segment count and filament brightness (thickness) between the two groups.