LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Metabolic response to point mutations reveals principles of modulation of in vivo enzyme activity and phenotype'.
Answer: The relationship between sequence variation and phenotype is poorly understood. Here, we use metabolomic analysis to elucidate the molecular mechanism underlying the filamentous phenotype of E. coli strains that carry destabilizing mutations in dihydrofolate reductase (DHFR). We find that partial loss of DHFR activity causes reversible filamentation despite SOS response indicative of DNA damage, in contrast to thymineless death (TLD) achieved by complete inhibition of DHFR activity by high concentrations of antibiotic trimethoprim. This phenotype is triggered by a disproportionate drop in intracellular dTTP, which could not be explained by drop in dTMP based on the Michaelis-Menten-like in vitro activity curve of thymidylate kinase (Tmk), a downstream enzyme that phosphorylates dTMP to dTDP. Instead, we show that a highly cooperative (Hill coefficient 2.5) in vivo activity of Tmk is the cause of suboptimal dTTP levels. dTMP supplementation rescues filamentation and restores in vivo Tmk kinetics to Michaelis-Menten. Overall, this study highlights the important role of cellular environment in sculpting enzymatic kinetics with system-level implications for bacterial phenotype.
Question: Write a study description for the study titled 'The Immediate Metabolomic Effects of Whole Genome Duplication in the Greater Duckweed Spirodela polyrhiza'.
Answer: We use untargeted metabolomics to investigate the immediate phytochemical effects of autopolyploidy on our model system, the greater duckweed Spirodela polyrhiza, a small aquatic macrophyte from the family Lemnaceae. We compare metabolite abundances in four genetically distinct diploid-autotetraploid pairs to address potential implications for establishment and combine traditional dry mass normalization with nuclear density information to investigate the link with gene dosage. We found that autopolyploidy increases metabolite levels per cell, although there is considerable variation in the response of individual metabolites. However, the impact on metabolite level per biomass is limited because the increased cell size reduces metabolite concentration per cell. Nevertheless, whole genome duplication (WGD) still exerts a discernible quantitative and qualitative influence on the phytochemical composition of our strains, each with potential ecological implications. While some metabolite levels are consistently higher in all tetraploids, many effects are restricted to a single strain, reflecting the importance of genetic background.
Question: Write a study description for the study titled 'Untargeted Metabolomics of the enthesis interstitial fluid of wild-type and Nlrp3-/- mice with sham operation and injury post 7 days'.
Answer: In order to investigate the effect of the NLRP3 inflammasome on the regeneration of enthesis, we established an enthesis injury and repair model in wild-type and NLRP3-/- mice. The interstitial fluid of enthesis was extracted, and untargeted metabolomics was conducted to discover differential metabolites between wild-type and NLRP3-/- mice.
Question: Write a study description for the study titled 'Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice'.
Answer: Autism spectrum disorder (ASD) manifests as alterations in complex human behaviors including social communication and stereotypies. In addition to genetic risks, the gut microbiome differs between typically-developing (TD) and ASD individuals, though it remains unclear whether the microbiome contributes to symptoms. We transplanted gut microbiota from human donors with ASD and TD controls into germ-free mice, and reveal that colonization with ASD microbiota was sufficient to induce hallmark autistic behaviors. The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and affects neuronal excitability in the brain. We propose that the gut microbiome modulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD.
Question: Write a study description for the study titled 'Computational Ranking of Yerba Mate Small Molecules Based on Their Predicted Contribution to Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus'.
Answer: The aqueous extract of yerba mate, a South American tea beverage made from Ilex paraguariensis leaves, has demonstrated bactericidal and inhibitory activity against bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The gas chromatography-mass spectrometry (GC-MS) analysis of two unique fractions of yerba mate aqueous extract revealed 8 identifiable small molecules in those fractions with antimicrobial activity. For a more comprehensive analysis, a data analysis pipeline was assembled to prioritize compounds for antimicrobial testing against both MRSA and methicillin-sensitive S. aureus using forty-two unique fractions of the tea extract that were generated in duplicate, assayed for activity, and analyzed with GC-MS. As validation of our automated analysis, we checked our predicted active compounds for activity in literature references and with used authentic standards to test for antimicrobial activity. 3,4-dihydroxybenzaldehyde showed the most antibacterial activity against MRSA at low concentrations in our bioassays. In addition, quinic acid and quercetin were identified using random forests analysis and 5-hydroxy pipecolic acid was identified using linear discriminant analysis. We additionally also generated a ranked list of unidentified compounds that may contribute to the antimicrobial activity of yerba mate against MRSA. Here we utilized GC-MS data to implement an automated analysis that resulted in a ranked list of compounds that likely contribute to the antimicrobial activity of aqueous yerba mate extract against MRSA.
Question: Write a study description for the study titled 'Plasma 1H-NMR metabolic and amino acid profiles of newborn piglets from two lines divergently selected for residual feed intake'.
Answer: Together with environmental factors, physiological maturity at birth is a major determinant for neonatal survival and postnatal development in mammalian species. Maturity at birth is the outcome of complex mechanisms of intra-uterine development and maturation during the end of gestation. In pig production, piglet preweaning mortality averages 20% of the litter and thus, maturity is a major welfare and economic concern. Here, we used both targeted and untargeted metabolomic approaches to provide a deeper understanding of the maturity in a model of lines of pigs divergently selected on residual feed intake (RFI), previously shown to have contrasted signs of maturity at birth. Analyses were conducted on plasma metabolome of piglets at birth and integrated with other phenotypic characteristics associated to maturity. We confirmed proline and myo-inositol, previously described for their association with delayed growth, as potential markers of maturity. Urea cycle and energy metabolism were found more regulated in piglets from high and low RFI lines, respectively, suggesting a better thermoregulation ability for the low RFI (with higher feed efficiency) piglets.
Question: Write a study description for the study titled 'Multi‐omics analysis of xylem sap uncovers dynamic modulation of poplar defenses by ammonium and nitrate'.
Answer: Xylem sap is the major transport route for nutrients from roots to shoots. In the present study, we investigated how variations in nitrogen (N) nutrition affected the metabolome and proteome of xylem sap and the growth of the xylem endophyte Brennaria salicis, and we also report transcriptional re-wiring of leaf defenses in poplar (Populus × canescens). We supplied poplars with high, intermediate or low concentrations of ammonium or nitrate. We identified 288 unique proteins in xylem sap. Approximately 85% of the xylem sap proteins were shared among ammonium- and nitrate-supplied plants. The number of proteins increased with increasing N supply but the major functional categories (catabolic processes, cell wall-related enzymes, defense) were unaffected. Ammonium nutrition caused higher abundances of amino acids and carbohydrates, whereas nitrate caused higher malate levels in xylem sap. Pipecolic acid and N-hydroxy-pipecolic acid increased, whereas salicylic acid and jasmonoyl-isoleucine decreased, with increasing N nutrition. Untargeted metabolome analyses revealed 2179 features in xylem sap, of which 863 were differentially affected by N treatments. We identified 124 metabolites, mainly from specialized metabolism of the groups of salicinoids, phenylpropanoids, phenolics, flavonoids, and benzoates. Their abundances increased with decreasing N, except coumarins. Brennaria salicis growth was reduced in nutrient-supplemented xylem sap of low- and high- NO3 - -fed plants compared to that of NH4 + -fed plants. The drastic changes in xylem sap composition caused massive changes in the transcriptional landscape of leaves and recruited defenses related to systemic acquired and induced systemic resistance. Our study uncovers unexpected complexity and variability of xylem composition with consequences for plant defenses.
Question: Write a study description for the study titled 'Correspondence of coral holobiont metabolome with symbiotic bacteria, archaea and Symbiodinium communities'.
Answer: Microbial symbiotic partners, such as those associated with reef-building corals, mediate biochemical transformations that influence host performance and survival. While evidence suggests microbial community composition partly accounts for differences in coral physiology, how these symbionts affect metabolic pathways remains underexplored. We aimed to assess functional variation between coral-associated microbial partners in hospite. To this end, we characterized and compared microbial community composition and metabolomic profiles from 9 coral species. These data support and expand on previous research by demonstrating microbial communities and metabolite profiles are species-specific and are correlated to one another. Using Porites spp. as a case study, we present evidence that the relative abundance of different sub-clades of Symbiodinium and bacterial/archaeal families influence the composition of functionally important metabolites. Our data suggests that while some microbial partners benefit the union, others are more opportunistic and possibly parasitize the host. Consequently, coral partner choice likely influences cellular metabolic activities and, therefore, holobiont nutrition.
Question: Write a study description for the study titled 'Plasma metabolomic profiling during peri-parturition in healthy Thoroughbred mares'.
Answer: Background: Accurate prediction of the timing of parturition is crucial to ensure the health and well-being of both mares and foals. However, equine pregnancies are characterized by significant variability in gestation length, unique endocrine mechanisms, and subtle physiological changes before parturition. Objectives: This study aimed to investigate the characteristic changes in the peripheral blood metabolome of mares before and after parturition using metabolomic approaches.Study Design: a longitudinal study.Methods: Peripheral blood samples were collected from nine successfully foaling Thoroughbred mares from four days before to five days after parturition, and a non-targeted metabolomic analysis was performed using GC-MS.Results: PLS-DA and hierarchical clustering analysis demonstrated cluster separation between pre-parturition, parturition, and post-parturition. ANOVA revealed significant differences in 49 metabolites across all time points. In those metabolites, glycerol-3-phosphate (G3P) levels increased three days before parturition. Four metabolites that changed significantly before parturition were enriched in six metabolic pathways. After parturition, 22 metabolites exhibited significant differences and were enriched in 20 pathways. Main Limitations: The number of animals and samples included in this study was limited, and factors such as the age and reproductive history of the mares were not considered. In addition, this study did not conduct quantitative research to determine the specific concentrations and ranges of the key metabolites.Conclusions: The results of this study suggest that G3P are potential biomarkers for predicting parturition and provides new insights into mare’s pre- and post-parturition blood metabolic changes.Background: Accurate prediction of the timing of parturition is crucial to ensure the health and well-being of both mares and foals. However, equine pregnancies are characterized by significant variability in gestation length, unique endocrine mechanisms, and subtle physiological changes before parturition.
Question: Write a study description for the study titled 'Wax ester and lipophilic compound profiling of Euglena gracilis by gas chromatography-mass spectrometry: toward understanding of wax ester fermentation under hypoxia'.
Answer: Lipids are being increasingly used as biodiesel feedstock, and several saturated wax esters from Euglena gracilis are candidates for outdoor bulk production. Wax ester fermentation in Euglena is strongly increased by hypoxia, but key events underlying the metabolic shift toward wax ester biosynthesis are poorly understood. Profiling of wax esters and other lipophilic compounds is the first step for research toward the clarification of wax ester fermentation molecular mechanisms, and thus, a simple and comprehensive platform for their profiling is required. In this study, we established a profiling method for wax esters and lipophilic compounds in Euglena using gas chromatography-mass spectrometry (GC–MS). Using this method, we compared accumulation profiles of wax esters and lipophilic compounds between a wild-type Euglena Z strain and a bleached SM-ZK strain. Both the wild-type and the bleached strains contained C14:0 fatty acid-C14:0 fatty alcohol as a dominant wax ester. Wax ester fermentation initiated 4 h after the cessation of oxygen supply by halting the culture agitation resulting in linear increase and proportional changes of wax ester amounts during 24 h. However, complete anoxia by nitrogen gas aeration inhibited wax ester production and the addition of bicarbonates reversed the inhibition, suggesting that there is a need for an additional carbon source for wax ester fermentation under anoxia. Our simple method enables the investigation of metabolic responses leading to wax ester fermentation in Euglena.
Question: Write a study description for the study titled 'Clovamide, a hydroxycinnamic acid amide, is a resistance factor against Phytophthora spp. in Theobroma cacao'.
Answer: The hydroxycinnamic acid amides (HCAAs) are a diverse group of plant specialized phenylpropanoid metabolites distributed widely in the plant kingdom and are known to be involved in tolerance to abiotic and biotic stress. The HCAA clovamide is reported in a small number of distantly related species. To explore the contribution of specialized metabolites to disease resistance in cacao (Theobroma cacao L., chocolate tree), we performed untargeted metabolomics using liquid chromatography – tandem mass spectrometry (LC-MS/MS) and compared the basal metabolite profiles in leaves of two cacao genotypes with contrasting levels of susceptibility to Phytophthora spp. Leaves of the tolerant genotype ‘Scavina 6’ were found to accumulate dramatically higher levels of clovamide and several other HCAAs compared to the susceptible ‘Imperial College Selection 1’ (‘ICS1’). Clovamide was the most abundant metabolite in ‘Scavina 6’ leaf extracts based on MS signal, and was up to 58-fold higher in ‘Scavina 6’ than in ‘ICS1’. In vitro assays demonstrated that clovamide inhibits growth of three pathogens of cacao in the genus Phytophthora, is a substrate for cacao polyphenol oxidase, and is a contributor to enzymatic browning. Furthermore, clovamide inhibited proteinase and pectinase in vitro, activities associated with defense in plant-pathogen interactions. Fruit epidermal peels from both genotypes contained substantial amounts of clovamide, but two sulfated HCAAs were present at high abundance exclusively in ‘Scavina 6’ suggesting a potential functional role of these compounds. The potential to breed cacao with increased HCAAs for improved agricultural performance is discussed.
Question: Write a study description for the study titled 'eRah: A computational tool integrating spectral deconvolution and alignment with quantification and identification of metabolites in GCMS- based metabolomics'.
Answer: Gas chromatography coupled to mass spectrometry (GC-MS) has been a long- standing approach used for identifying small molecules due to the highly reproducible ionization process of electron impact ionization (EI). However, the use of GC-EI MS in untargeted metabolomics produces large and complex datasets characterized by coeluting compounds and extensive fragmentation of molecular ions caused by the hard electron ionization. In order to identify and extract quantitative information of metabolites across multiple biological samples, integrated computational workflows for data processing are needed. Here we introduce eRah, a free computational tool written in the open language R composed of five core functions: (i) noise filtering and baseline removal of GC-MS chromatograms, (ii) an innovative compound deconvolution process using multivariate analysis techniques based on compound match by local covariance (CMLC) and orthogonal signal deconvolution (OSD), (iii) alignment of mass spectra across samples, (iv) missing compound recovery, and (v) identification of metabolites by spectral library matching using publicly available mass spectra. eRah outputs a table with compound names, matching scores and the integrated area of compounds for each sample. The automated capabilities of eRah are demonstrated by the analysis of GC-TOF MS data from plasma samples of adolescents with hyperinsulinaemic androgen excess and healthy controls. The quantitative results of eRah are compared to centWave, the peak-picking algorithm implemented in the widely used XCMS package, MetAlign and ChromaTOF software. Significantly dysregulated metabolites are further validated using pure standards and targeted analysis by GC-QqQ MS, LC-QqQ and NMR.
Question: Write a study description for the study titled 'Aroma and quality of breads baked from old and modern wheat varieties and their prediction from genomic and flour-based metabolite profiles'.
Answer: Bread aroma is the principal characteristic perceived by the consumer yet it is mostly disregarded in the product chain. The main aim of this study was to evaluate the potential to include bread aroma as a new target criterion into the wheat product chain. The objectives of our study were to (i) quantify the influence of genetic versus environmental factors on the bread aroma and quality characteristics, (ii) evaluate whether bread baked from modern wheat varieties differ in terms of aroma from those baked from old varieties and (iii) compare genomic and metabolomic approaches for their efficiency to predict bread aroma and quality characteristics in a wheat breeding program. Agronomic characters as well as bread aroma and quality traits were assessed for 18 old and 22 modern winter wheat varieties evaluated at up to three locations in Germany. Metabolite profiles of all 120 flour samples were collected using a 7200 GC-QTOF. Considerable differences in the adjusted entry means for all examined bread aroma and quality characters were observed. For aroma, which was rated on a scale from 1 to 9, the adjusted entry means varied for the 40 wheat varieties between 3 and 8. In contrast, the aroma of bread prepared from old and modern wheat varieties did not differ significantly (P<0.05). Bread aroma was not significantly (P<0.05) correlated with grain yield, which suggested that it is possible to select for the former character in wheat breeding programs without reducing the gain of selection for the latter. Finally, we have shown that bread aroma can be better predicted using a combination of metabolite and SNP genotyping profiles instead of the SNP genotyping profile only. In conclusion, we have illustrated possibilities to increase the quality of wheat for consumers in the product chain.
Question: Write a study description for the study titled 'Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction'.
Answer: Defective arginine synthesis, due to the silencing of argininosuccinate synthase 1 (ASS1), is a common metabolic vulnerability in cancer, known as arginine auxotrophy. Understanding how arginine depletion kills arginine-auxotrophic cancer cells will facilitate the development of anti-cancer therapeutic strategies. Here we show that depletion of extracellular arginine in arginine-auxotrophic cancer cells causes mitochondrial distress and transcriptional reprogramming. Mechanistically, arginine starvation induces asparagine synthetase (ASNS), depleting these cancer cells of aspartate, and disrupting their malate-aspartate shuttle. Supplementation of aspartate, depletion of mitochondria, and knockdown of ASNS all protect the arginine-starved cells, establishing the causal effects of aspartate depletion and mitochondrial dysfunction on the arginine starvation-induced cell death. Furthermore, dietary arginine restriction reduced tumor growth in a xenograft model of ASS1-deficient breast cancer. Our data challenge the view that ASNS promotes homeostasis, arguing instead that ASNS-induced aspartate depletion promotes cytotoxicity, which can be exploited for anti-cancer therapies.
Question: Write a study description for the study titled 'P53 dependent hypusination of eIF5A affect mitochondrial translation and senescence immune surveillance'.
Answer: Cellular senescence is characterized by a permanent growth arrest and is associated with tissue aging and cancer. Senescent cells secrete a number of different cytokines referred to as the senescence-associated secretory phenotype (SASP), which impacts the surrounding tissue and immune response. Here, we found that senescent cells exhibit higher rates of protein synthesis compared to proliferating cells and identified eIF5A as a crucial regulator of this process. Polyamine metabolism and hypusination of eIF5A play a pivotal role in sustaining elevated levels of protein synthesis in senescent cells. Mechanistically, we identified a p53-dependent program in senescent cells that maintains hypusination levels of eIF5A. Finally, we demonstrate that functional eIF5A is required for synthesizing mitochondrial ribosomal proteins and monitoring the immune clearance of premalignant senescent cells in vivo. Our findings establish an important role of protein synthesis during cellular senescence and suggest a link between eIF5A, polyamine metabolism and senescence immune surveillance.