LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism, lipid transport and oxidative stress response'.
Answer: Amphotericin B is increasingly used in treatment of leishmaniasis. Here, fourteen independent lines of Leishmania mexicana and one L. infantum line were selected for resistance to either amphotericin B or the related polyene antimicrobial, nystatin. Sterol profiling revealed that, in each line, the predominant ergostane-type sterol of wild-type cells was replaced by other sterol species. Broadly, two different profiles emerged among the resistant lines. Whole genome sequencing then showed that these distinct profiles were due either to mutations in the sterol methyl transferase (C24SMT) gene locus or the sterol C5 desaturase (C5DS) gene. In three lines an additional deletion of the miltefosine transporter was found. Differences in sensitivity to amphotericin B were apparent, depending on whether cells were grown in HOMEM, supplemented with foetal bovine serum, or a serum free defined medium (DM). These differences appeared to relate to the presence of lipids in the former. Metabolomic analysis after exposure to AmB showed that a large increase in glucose flux via the pentose phosphate pathway preceded cell death in cells sustained in HOMEM but not DM, indicating the oxidative stress was more significantly induced under HOMEM conditions. Several of the lines were tested for ability to infect macrophages and replicate as amastigote forms, alongside their ability to establish infections in mice. While several lines showed reduced virulence, at least one AmB resistant line displayed heightened virulence in mice whilst retaining its resistance phenotype, emphasising the risks of resistance emerging to this critical drug.
Question: Write a study description for the study titled 'Metabolome and transcriptome combined profiling reveals fluconazole resistance mechanisms of Trichosporon asahii and role of farnesol in fluconazole tolerance'.
Answer: Trichosporon asahii is a basidiomycete yeast that is pathogenic to humans and animals, and fluconazole-resistant strains have recently increased. Farnesol secreted by fungi is a factor that causes variations in fluconazole resistance; however, few studies have explored the underlying mechanisms. Therefore, this study aims to delineate the fluconazole resistance mechanisms of T. asahii and explore farnesol’s effects on these processes. A comparative metabolome-transcriptome analysis of untreated fluconazole-sensitive (YAN), fluconazole-resistant (PB) T. asahii strains and 25 μM farnesol-treated strains (YAN-25 and PB-25, respectively) was performed. The membrane lipid-related genes and metabolites were upregulated in the PB vs YAN and PB-25 vs PB comparisons. Farnesol demonstrated strain-dependent mechanisms underlying fluconazole tolerance between the YAN and PB strains, and upregulated and downregulated efflux pumps in PB-25 and YAN-25 strains, respectively. Membrane lipid-related metabolites were highly correlated with transporter-coding genes. Fluconazole resistance in T. asahii was induced by membrane lipid bio-synthesis activation. Farnesol inhibited fluconazole resistance in the sensitive strain, but enhanced resistance in the resistant strain by upregulating efflux pump genes and membrane lipids. This study offers valuable insights into the mechanisms underlying fungal drug resistance and provides guidance for future research aimed at developing more potent antifungal drugs for clinical use.
Question: Write a study description for the study titled 'Metabolic consequences of cobalamin scarcity in diatoms as revealed through metabolomics (Thalassiosira pseudonana study)'.
Answer: Diatoms perform about 20% of photosynthesis on earth, play a crucial role in forming the base of the marine food web, and sequester anthropogenic carbon into the deep ocean through the biological pump. In some areas of the ocean, diatom growth is limited by the organic micronutrient cobalamin (vitamin B12). Cobalamin affects phytoplankton growth rate and biomass yield, though the consequences of cobalamin limitation are not well understood on the biochemical level. In a controlled laboratory setting, we grew two diatoms, Thalassiosira pseudonana and Navicula pelliculosa, under cobalamin limited and replete conditions to elucidate changes in metabolite pools under cobalamin limitation. Using targeted and untargeted metabolomics, we show that the cobalamin-dependent T. pseudonana experienced a metabolic cascade under cobalamin limitation that a ects the central methionine cycle, the transsulfuration pathway, and the composition of its osmolyte pools. N. pelliculosa, a cobalamin-independent diatom, also showed evidence for changes in the methionine cycle when grown without cobalamin, though to a lesser extent than what we observed in T. pseudonana. In both diatoms the concentration of 5'-methylthioadenosine decreased when limited for cobalamin, suggesting a disruption in the diatoms' polyamine biosynthesis. Furthermore, two acylcarnitines and adenosyl cobalamin accumulated in T. pseudonana under cobalamin limitation, suggesting the use of an adenosylcobalamin-dependent enzyme, methylmalonyl CoA mutase. Overall, these changes in metabolite pools yield insight into the metabolic consequences of cobalamin limitation in diatoms and suggest that cobalamin starvation may have consequences for microbial interactions that are based on metabolite production by phytoplankton.  Thalassiosira pseudonana protocols and data are reported in the current study MTBLS703.  Navicula pelliculosa protocols and data are reported in MTBLS708.
Question: Write a study description for the study titled 'A Multi-Omics Analysis of Glycine max Leaves Reveals Alteration in Flavonoid and Isoflavonoid Metabolism Upon Ethylene and Abscisic Acid Treatment'.
Answer: Phytohormones are central to plant growth and development. Despite the advancement in our knowledge of hormone signaling, downstream targets, and their interactions upon hormones action remain largely fragmented, especially at the protein and metabolite levels. With an aim to get new insight into the effects of two hormones, ethylene (ET) and abscisic acid (ABA), this study utilizes an integrated proteomics and metabolomics approach to investigate their individual and combined (ABA+ET) signaling in soybean leaves. Targeting low-abundance proteins, our previously established protamine sulfate precipitation method was applied, followed by label-free quantification of identified proteins. A total of 4129 unique protein groups including 1083 differentially modulated in one (individual) or other (combined) treatments were discerned. Functional annotation of the identified proteins showed an increased abundance of proteins related to the flavonoid and isoflavonoid biosynthesis and MAPK signaling pathway in response to ET treatment. HPLC analysis showed an accumulation of isoflavones (genistin, daidzein, and genistein) upon ET treatment, in agreement with the proteomics results. A metabolome analysis assigned 79 metabolites and further confirmed the accumulation of flavonoids and isoflavonoids in response to ET. A potential cross-talk between ET and MAPK signaling, leading to the accumulation of flavonoids and isoflavonoids in soybean leaves is suggested.
Question: Write a study description for the study titled 'Root hair developmental regulators orchestrate drought induced microbiome changes and affect the interactions with stress alleviating Rhizobiaceae'.
Answer: Drought is one of the most severe abiotic stresses. However, there is a lack of genetic evidence regarding whether and how plants coordinate the dynamic assembly of the microbiome in response to drought. Through the use of mutants with enhanced or reduced root hair densities (rsl2 rsl4, hairless mutant; Col-0, wild type; gl2, hairy mutant), we discovered that regulators of root hair development also influence changes in the root microbiome under drought conditions. The abundance of Rhizobiaceae, a specific group of microorganisms, was significantly affected by mutations related to root hair development. Since mutations in root hair-related genes can affect transportation and metabolic functions in the root microbiome, we performed non-targeted metabolomics analysis to investigate potential metabolic cues associated with changes in the root microbiome during drought. Our results revealed significant differences in the composition of root metabolites among these genotypes. The overall abundance of amino acids, flavonoids and indoles or their derivatives gradually increased from the rsl2 rsl4 mutant to the gl2 mutant. Subsequently, we identified differentially abundant metabolites (DMs) based on their variable importance in projection scores (VIP > 1.0) and fold changes (log2FC > 0) in relative abundances. Enrichment analysis was further conducted based on these DMs in the rsl2 rsl4 and gl2 mutants. Consistent with the increased content of flavonoids, the DMs in the roots of the gl2 mutant were enriched in metabolites associated with flavonoid biosynthesis. Flavonoids are well-known for their ability to induce the expression of rhizobia nodulation genes and the attraction of rhizobia towards the roots. In our study, several flavonoid molecules, including tangeretin, glyceollin, quercetin and gallocatechin, were found to be enriched in the roots of the gl2 mutant compared to those of the Col-0 wild type. We will further investigate whether there is a specific association between specific metabolites and microorganisms in the Rhizobiaceae family.
Question: Write a study description for the study titled 'Release of Ecologically Relevant Metabolites by the Cyanobacterium, Synechococcus elongatus CCMP 1631'.
Answer: Phytoplankton are known to release organic compounds that fuel secondary production by heterotrophic bacteria. Here we show that an abundant marine cyanobacterium, Synechococcus elongatus, contributes a variety of nitrogen-rich and sulfur-containing compounds to dissolved organic matter. A combination of targeted and untargeted metabolomics and genomic tools was used to characterize the intracellular and extracellular metabolites of S. elongatus. Aromatic compounds such as 4-hydroxybenzoic acid and phenylalanine, as well as nucleosides (e.g., thymidine, 5’-methylthioadenosine, xanthosine), the organosulfur compound 3-mercaptopropionate, and the plant auxin indole 3-acetic acid, were detected in the extracellular metabolites at multiple time points during the growth of S. elongatus. Further, the amino acid kynurenine was found to accumulate in the media even though it was not included in the predicted metabolome of S. elongatus. This suggests that not all metabolites produced by an organism can be predicted from its genome sequence. Some metabolites may be products of non-enzymatic reactions and are likely excreted into the environment as waste. The compounds described herein provide excellent targets for quantitative analysis in field settings to assess the source and lability of dissolved organic matter in situ.
Question: Write a study description for the study titled 'A metabolite roadmap of the wood-forming tissue in Populus tremula (UPLC-MS assay; Wood ring and extraxylary tissue)'.
Answer: Wood, or secondary xylem, is the product of xylogenesis, a developmental process that begins with the proliferation of cambial derivatives and ends with mature xylem fibers and vessels with lignified secondary cell walls. Fully mature xylem has undergone a series of cellular processes, including cell division, cell expansion, secondary wall formation, lignification and programmed cell death. A complex network of interactions between transcriptional regulators and signal transduction pathways controls wood formation. However, the role of metabolites during this developmental process has not been comprehensively characterized. To evaluate the role of metabolites during wood formation, we performed a high spatial resolution metabolomics study of the wood-forming zone of Populus tremula, including laser dissected aspen ray and fiber cells. We show that metabolites show specific patterns within the wood-forming zone, following the differentiation process from cell division to cell death. The data from profiled laser dissected aspen ray and fiber cells suggests that these two cell types host distinctly different metabolic processes. Furthermore, by integrating previously published transcriptomic and proteomic profiles generated from the same trees, we provide an integrative picture of molecular processes, for example, deamination of phenylalanine during lignification is of critical importance for nitrogen metabolism during wood formation.UPLC-MS assay of Wood ring and extraxylary tissue is reported in the current study MTBLS1797.GC-MS assay of Wood ring and extraxylary tissue is reported in MTBLS1796.UPLC-MS assay of Wood fibre and ray cell tissue is reported in MTBLS1831.
Question: Write a study description for the study titled '13C glucose labelling studies using 2D NMR is a useful tool for determining ex vivo whole organ metabolism during hypothermic machine perfusion of kidneys'.
Answer: Background: The aim of this study is to determine the feasibility of using Nuclear Magnetic Resonance (NMR) tracer studies (13C-enriched glucose) to detect ex vivo de novo metabolism in the perfusion fluid and cortical tissue of porcine kidneys during hypothermic machine perfusion (HMP). Methods: Porcine kidneys (n=6) were subjected to 24hrs of HMP using the Organ Recovery Systems LifePort Kidney perfusion device. Glucose, uniformly enriched with the stable isotope 13C ([U-13C] glucose) was incorporated into KPS-1-like perfusion fluid at a concentration of 10 mM. Analysis of perfusate was performed using both 1D 1H and 2D 1H,13C Heteronuclear single quantum coherence NMR spectroscopy (HSQC). The metabolic activity was then studied by quantifying the proportion of key metabolites containing 13C in both perfusate and tissue samples. Results: There was significant enrichment of 13C in a number of central metabolites present in both the perfusate and tissue extracts and was most pronounced for lactate and alanine. The total amount of enriched lactate (per sample) in perfusion fluid increased during HMP (31.1 ± 12.2 nmol at 6 hrs vs 93.4 ± 25.6 nmol at 24 hrs p<0.01). The total amount of enriched alanine increased in a similar fashion (1.73 ± 0.89 nmol at 6hrs vs 6.80 ± 2.56 nmol at 24hrs (p<0.05). In addition, small amounts of enriched acetate and glutamic acid was evident in some samples. Conclusions: This study conclusively demonstrates that de novo metabolism occurs during HMP and highlights active metabolic pathways in this hypothermic, hypoxic environment. While the majority of the 13C-enriched glucose is metabolised into glycolytic endpoint metabolites such as lactate, the presence of non-glycolytic pathway derivatives suggests that metabolism during HMP is more complex than previously thought. Isotopic labelled ex vivo organ perfusion studies using 2D-NMR are feasible and informative.
Question: Write a study description for the study titled 'The efflux pump ABCC1/MRP1 constitutively restricts PROTAC sensitivity in cancer cells'.
Answer: Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that induce selective protein degradation by linking an E3 ubiquitin ligase enzyme to a target protein. This approach allows scope for targeting “undruggable” proteins and several PROTACs have reached the stage of clinical candidates. However, the roles of cellular transmembrane transporters in PROTAC uptake and efflux remain underexplored. Here, we utilized transporter-focused genetic screens to identify the ATP binding cassette transporter ABCC1/MRP1 as a key PROTAC resistance factor. Unlike the previously identified inducible PROTAC exporter ABCB1/MDR1, ABCC1 is highly expressed among cancers of various origins and constitutively restricts PROTAC bioavailability. Moreover, in a genome-wide PROTAC resistance screen, we identified candidates involved in processes such as ubiquitination, mTOR signaling and apoptosis as genetic factors involved in PROTAC resistance. In summary, our findings reveal ABCC1 as a crucial constitutively active efflux pump limiting PROTAC efficacy in various cancer cells, offering insights for overcoming drug resistance.
Question: Write a study description for the study titled 'Mannitol mediates the mummification behavior of Thitarodes xiaojinensis larvae infected with Ophiocordyceps sinensis'.
Answer: Parasites can facilitate their own spread and reproduction by manipulating insect hosts behavior, as seen in the interaction between Thitarodes xiaojinensis and Ophiocordyceps sinensis. Infection by O. sinensis leads to the mummification of T. xiaojinensis larvae, but the underlying mechanisms remain mysterious. To uncover this parasitic relationship, metabolites were analyzed in infected and mummified larvae of T. xiaojinensis in this study. Significant changes were found in phenotype, fungal morphology in hemocoel, larval hardness, and mannitol metabolites in infected, mummified 0 h larvae and larvae 5 days after mummification behavior. Surprisingly, the occurrence of mummification behavior was accompanied by fungal dimorphism, as well as the absence of mannitol in both infected and non-infected larvae, until the initial accumulation of mannitol and the expression of mannitol-associated genes occurred at the time of mummification behavior. The presence of mannitol may promote fungal dimorphism to mediate changes in fungal toxicity or resistance, leading to the end of the fungus-insect coexistence period and the incidence of mummification behavior. Furthermore, mannitol injections increase the mummification rate of the infected larvae without significant difference from the normal mummification phenotype. This finding suggests the importance of mannitol in the mummification of host larvae infected with O. sinensis.
Question: Write a study description for the study titled 'Metabolomic analysis of riboswitch containing E. coli recombinant expression system'.
Answer: In this study we have employed metabolomics approaches to understand the metabolic effects of producing enhanced green fluorescent protein (eGFP) as a recombinant protein in Escherichia coli cells. This metabolic burden analysis was performed against a number of recombinant expression systems and control strains and included: (i) standard transcriptional recombinant expression control system BL21(DE3) with the expression plasmid pET-eGFP, (ii) the recently developed dual transcriptional–translational recombinant expression control strain BL21(IL3), with pET-eGFP, (iii) BL21(DE3) with an empty expression plasmid pET, (iv) BL21(IL3) with an empty expression plasmid, and (v) BL21(DE3) without an expression plasmid; all strains were cultured under various induction conditions. The growth profiles of all strains together with the results gathered by the analysis of the Fourier transform infrared (FT-IR) spectroscopy data, identified IPTG-dependent induction as the dominant factor hampering cellular growth and metabolism, which was in general agreement with the findings of GC-MS analysis of cell extracts and media samples. In addition, the exposure of host cells to the synthetic inducer ligand, pyrimido[4,5-d] pyrimidine-2,4-diamine (PPDA), of the orthogonal riboswitch containing expression system (BL21(IL3)) did not display any detrimental effects, and its detected levels in all the samples were at similar levels, emphasising the inability of the cells to metabolise PPDA. The overall results obtained in this study suggested that although the BL21(DE3)-EGFP and BL21(IL3)-EGFP strains produced comparable levels of recombinant eGFP, the presence of the orthogonal riboswitch seemed to be moderating the metabolic burden of eGFP production in the cells enabling higher biomass yield, whilst providing a greater level of control over protein expression.
Question: Write a study description for the study titled 'Extensive PFAS accumulation by human gut bacteria'.
Answer: Per- and polyfluoroalkyl Substances (PFAS) – the so-called ‘forever chemicals’ – are a major cause of environmental and health concern due to their toxicity and long-term persistence. Yet, no efficient mechanisms for their removal have been identified. Here we report the potential of microbial strains to bioaccumulate PFAS compounds.
Question: Write a study description for the study titled 'Groundwater metabolome responds to recharge in fractured sedimentary strata'.
Answer: Understanding biogeochemical conversions of dissolved organic matter (DOM) in aquifers is paramount for the effective management of groundwater supplies. On its passage through the critical zone, DOM is subject to biogeochemical conversions and therefore carries cross-habitat information useful for monitoring and predicting the stability of groundwater ecosystem services. Groundwater metabolomics assesses this information. However, challenges arise from insufficient knowledge on groundwater metabolite composition and dynamics, and the necessity to maintain analytical conditions for long-term monitoring. We explored fractured sedimentary bedrock by 5-year untargeted metabolomics monitoring for oxic perched and anoxic phreatic sites along a hillslope recharge area, to evaluate DOM as groundwater tracer. Dimension reduction by principal component analysis revealed that metabolome dissimilarities between distant wells coincide with transient cross-stratal flow indicated by groundwater levels and environmental tracers. The metabolome was highly variable lacking seasonal patterns, and did not segregate by geographic location of sampling wells thus ruling out surface vegetation or (agricultura) land use as driving factor. The metabolome time series provide detailed insights into subsurface responses to recharge dynamics. Metabolomics monitoring provides information on groundwater flows, and allows concluding about below ground ecology and water quality evolution, required to understand the impact of interannual wet-dry cycles.
Question: Write a study description for the study titled 'Metabolomic and physiological analysis of bud differentiation in dense apple (Malus × domestica Borkh.) orchards following thinning and reshaping'.
Answer: BACKGROUND: In China, a majority of apple orchards were initially planted under arboriculture. Noteworthy, as the trees age, there is an increase in the number of branches and the degree of orchard depression and deterioration of the canopy light conditions. This phenomenon results in in blockage of bud differentiation, causing yield decrease and overall deterioration in fruit quality. Intercropping is an effective strategy for addressing the issue of orchard depression. However, the impact of intercropping on bud differentiation remains unclear. This study thus analyzed the physiological and metabolic aspects of flower bud differentiation after thinning and reshaping an overcrowded orchard. METHODS: A series of physiological and metabolomic analyses were conducted on terminal flower bud samples collected during early (T1) and late (T2) bud differentiation following thinning and reshaping alongside their controls CK1 and CK2. RESULTS: The T1 group had significantly higher amounts of sucrose, glucose, fructose and sorbitol compared to its control. Metabolomic analyses yielded 845 metabolites. Among these metabolites, 72 were significantly different in CK1 vs T1. In contrast, 73 metabolites were different in CK2 vs T2, while 26 metabolites were common between the two comparison groups. CK1 vs T1 and CK2 vs T2 had 20 and 16 enhanced metabolic pathways, respectively. Bud differentiation was closely associated with the phenylpropane and flavonoid biosynthesis pathways. CONCLUSIONS: Thinning and reshaping of the apple orchard improved light penetration and increased the content of coumarins and eriodictyol, thereby promoting flower bud differentiation. This study provides new insights into how orchard management practices, such as thinning, pruning and shaping, promote flower bud development in apple trees.