LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled '4-Octyl itaconate as a metabolite derivative inhibits inflammation via alkylation of STING'.
Answer: The Krebs cycle-derived metabolite itaconate, whose production is catalyzed by immune response gene 1 (IRG1), has excellent potential to link immunity and metabolism in activated macrophages through alkylation or competitive inhibition of target proteins. In support of this, our previous study demonstrated that the stimulator of interferon genes (STING) signaling platform functions as a hub in macrophage immunity and has a profound impact on the prognosis of sepsis. Interestingly, we found that itaconate, an endogenous immunomodulator, can significantly inhibit the activation of STING signaling. Moreover, 4-octyl itaconate (4-OI), which is a permeable itaconate derivative, could alkylate cysteine sites 65, 71, 88, and 147 of STING, thereby inhibiting its phosphorylation and downregulating the production of related inflammatory factors. Furthermore, itaconate and 4-OI inhibited the production of inflammatory factors in sepsis models. Our results have broadened the role of the IRG1-Itaconate axis in immunomodulation and highlighted itaconate and its derivatives as potential therapeutic agents in sepsis.
Question: Write a study description for the study titled 'Untargeted extraction of metabolites 13C labeling profiles from time course labeling switch experiment'.
Answer: Dynamic isotope labeling data provide crucial information about the operation of metabolic pathways, and are commonly generated via liquid chromatography mass spectrometry (LC-MS). Metabolome-wide analysis is challenging as it requires grouping of metabolite features over different samples. We developed DynaMet for fully automated investigations of isotope labeling experiments from LC-high resolution MS raw data. DynaMet enables untargeted extraction of metabolite labeling profiles and provides integrated tools for expressive data visualization. For this study we generated labeling data of the model strain Escherichia coli from 13C glucose labeling switch experiments. Analysis of two biological replicates revealed high robustness and reproducibility of the pipeline. DynaMet analysis of two data sets each comprising 19 samples resulted in 286 and 293 features, respectively, with detection in at least 80% of all samples analyzed. Of these, 222 and 230, respectively, could be fitted with the implemented model. After removing false positives and merging both data sets DynaMet revealed a total number of 291 features with labeling profiles whereof 285 could be generated with implemented fitting function. Comparison with KEGG database resulted in 125 matches corresponding to 98 metabolites covering multiple pathways of core metabolism and major biosynthetic routes. The study results reported here are only a summary. To reproduce the complete results i.e. labeling profiles and corresponding kinetic fits including plots, DynaMet software is required.
Question: Write a study description for the study titled 'Enhancement of oxidative and drought tolerance in Arabidopsis by overaccumulation of antioxidant flavonoids'.
Answer: The notion that plants use specialized metabolism to protect against environmental stresses needs to be experimentally proven by addressing the question of whether stress tolerance by specialized metabolism is directly due to metabolites such as flavonoids. We report that flavonoids with radical scavenging activity mitigate against oxidative and drought stress in Arabidopsis thaliana. Metabolome and transcriptome profiling and experiments with oxidative and drought stress in wild-type, single overexpressors of MYB12/PFG1 (PRODUCTION OF FLAVONOL GLYCOSIDES1) or MYB75/PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT1), double overexpressors of MYB12 and PAP1, transparent testa4 (tt4) as a flavonoid-deficient mutant, and flavonoid-deficient MYB12 or PAP1 overexpressing lines (obtained by crossing tt4 and the individual MYB overexpressor) demonstrated that flavonoid overaccumulation was key to enhanced tolerance to such stresses. Antioxidative activity assays using 2,2-diphenyl-1-picrylhydrazyl, methyl viologen, and 3,3'-diaminobenzidine clearly showed that anthocyanin overaccumulation with strong in vitro antioxidative activity mitigated the accumulation of reactive oxygen species in vivo under oxidative and drought stress. These data confirm the usefulness of flavonoids for enhancing both biotic and abiotic stress tolerance in crops.
Question: Write a study description for the study titled 'Chaihu Shugan prevents cholesterol gallstone formation by ameliorating the microbiota dysbiosis and metabolic disturbance in mice'.
Answer: INTRODUCTION: Cholesterol gallstone (CGS) is a biliary tract disorder requiring treatment in approximately 20% of patients. The efficacy of Chaihu Shugan in preventing CGS recurrence after successful treatment remains uncertain.METHODS: We examined the in vivo preventive efficacy of Chaihu Shugan using a CGS mouse model and used multi-omics to study the interplay between gut microbiota, metabolism and gene expression.RESULTS: The intestinal microbiota was severely dysregulated during the formation of CGS, showing a marked decrease in the abundance of beneficial microbiota, especially Lactobacillus and Akkermansia. Chaihu Shugan prevented CGS formation by restoring the composition of the gut microbiota and reversing the metabolic disturbances caused by dysbiosis. This preventive effect of Chaihu Shugan was paralleled by changes in the expression of metabolism-related genes in the liver. A network pharmacology analysis of Chaihu Shugan revealed that obacunone may be the key active metabolite in regulating bile acid metabolism. Multi-omics and correlation analyses elucidated the interplay between gut microbiota, metabolism and gene alterations in the dosedependent effect of Chaihu Shugan.CONCLUSION: Our data show that Chaihu Shugan can prevent CGS and indicate its mechanisms of action.
Question: Write a study description for the study titled 'Croquemort elicits activation of the immune deficiency pathway in ticks'.
Answer: The immune deficiency (IMD) pathway directs host defense in arthropods upon bacterial infection. In Pancrustacea, peptidoglycan recognition proteins sense microbial moieties and initiate nuclear factor-κB-driven immune responses. Proteins that elicit the IMD pathway in non-insect arthropods remain elusive. Here, we show that an Ixodes scapularis homolog of croquemort (Crq), a CD36-like protein, promotes activation of the tick IMD pathway. Crq exhibits plasma membrane localization and binds the lipid agonist 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol. Crq regulates the IMD and jun N-terminal kinase signaling cascades and limits the acquisition of the Lyme disease spirochete B. burgdorferi. Additionally, nymphs silenced for crq display impaired feeding and delayed molting to adulthood due to a deficiency in ecdysteroid synthesis. Collectively, we establish a distinct mechanism for arthropod immunity outside of insects and crustaceans.
Question: Write a study description for the study titled 'Systematic identification of metabolites controlling gene expression in E. coli'.
Answer: Metabolism controls gene expression through allosteric interactions between metabolites and transcription factors. These interactions are usually measured with in vitro assays, but there are no methods to identify them at a genome-scale in vivo. Here we show that dynamic transcriptome and metabolome data identify metabolites that control transcription factors in E. coli. By switching an E. coli culture between starvation and growth, we induce strong metabolite concentration changes and gene expression changes. Using Network Component Analysis we calculate the activities of 209 transcriptional regulators and correlate them with metabolites. This approach captures, for instance, the in vivo kinetics of CRP regulation by cyclic-AMP. By testing correlations between all pairs of transcription factors and metabolites, we predict putative effectors of 71 transcription factors, and validate five interactions in vitro. These results show that combining transcriptomics and metabolomics generates hypotheses about metabolism-transcription interactions that drive transitions between physiological states.
Question: Write a study description for the study titled 'Impact of reproductive activity on physiological metabolism and molecular regulation in the Genus scallopus(Mizuhopecten yessoensis)'.
Answer: Genus scallopus(Mizuhopecten yessoensis), a commercially important shellfish species in China, suffers a persistently high post-spawning mortality rate, severely constraining industry development. Thus, this study investigated the physiological and molecular impact of reproductive activity on M. yessoensis. There were significant decreases (P <0.05) in nutritional components (crude protein, crude lipid, and glycogen content) within the gonads before and after spawning, with a particularly pronounced reduction in crude lipids. Histological examination showed that, post spawning, lumens formed within the gonadal follicles of both sexes following gamete release, accompanied by decreased germ cell numbers. Enzyme activity assays indicated significant changes in enzyme activities post spawning. Superoxide dismutase and lactate dehydrogenase exhibited significant differences (P <0.01) in the female mantle. ATPase content displayed a decreasing trend in all tissues of both male and female scallops. Alanine aminotransferase showed significant differences (P <0.01) in the gonads and adductor muscles, and aspartate aminotransferase activity increased significantly (P <0.05) in the adductor muscles, of both male and female scallops. Gonadal metabolomics analysis identified 1,644 differential metabolites between pre- and post-spawning periods, primarily enriched in lipid and amino acid metabolic pathways. Female metabolic changes were concentrated in lipid and amino acid metabolism, whereas males showed alterations in sulfur-containing compound metabolism. In summary, the reproductive process significantly impacts the physiological status and metabolic patterns of M. yessoensis, with distinct variations between sexes. This study provides fundamental data for in-depth analysis of energy allocation during bivalve reproduction and lays a theoretical foundation for exploring the regulatory networks of reproductive metabolism in M. yessoensis at the molecular level.
Question: Write a study description for the study titled 'Four layer multi-omics reveals molecular responses to aneuploidy in Leishmania'.
Answer: Aneuploidy causes system-wide disruptions in the stochiometric balances of transcripts, proteins, and metabolites, often resulting in detrimental effects for the organism. The protozoan parasite Leishmania has an unusually high tolerance for aneuploidy, but the molecular and functional consequences for the pathogen remain poorly understood. Here, we addressed this question in vitro and present the first integrated analysis of the genome, transcriptome, proteome, and metabolome of highly aneuploid Leishmania donovani strains. Our analyses unambiguously establish that aneuploidy in Leishmania proportionally impacts the average transcript- and protein abundance levels of affected chromosomes, ultimately correlating with the degree of metabolic differences between strains. This proportionality was present in both proliferative and non-proliferative in vitro promastigotes. However, protein complex subunits and non-cytoplasmic proteins, showed dosage compensation, responding less or even not at all to aneuploidy-induced dosage changes. In contrast to other Eukaryotes, we did not observe the widespread regulation at the transcript level that typically modulates some of the negative effects of aneuploidy. Further, the majority of differentially expressed proteins between aneuploid strains were encoded by non-aneuploid chromosomes and were not driven by a significant underlying transcript change, suggesting that aneuploidy is accompanied by extensive post-transcriptional protein-level modulation. This makes Leishmania a unique Eukaryotic model for elucidating post-transcriptional protein-abundance modulation in the context of aneuploidy.Data availability:Proteomic data associated with this study are available in the PRIDE repository: accession number PXD028521.
Question: Write a study description for the study titled 'Metabolomic Profiling of Mice Serum during Toxoplasmosis Progression Using Liquid Chromatography-Mass Spectrometry'.
Answer: Better understanding of the molecular changes associated with disease is essential for identifying new routes to improved therapeutics and diagnostic tests. The aim of this study was to investigate the dynamic changes in the metabolic profile of mouse sera during T. gondii infection. We carried out untargeted metabolomic analysis of sera collected from female BALB/c mice experimentally infected with the T. gondii Pru strain (Genotype II). Serum samples were collected at 7, 14 and 21 day post infection (DPI) from infected and control mice and were subjected to liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS)-based global metabolomics analysis. Multivariate statistical analysis identified 79 differentially expressed metabolites in ESI+ mode and 74 in ESI− mode in sera of T. gondii-infected mice compared to the control mice. Further principal component analysis (PCA) and partial least squares-discrimination analysis (PLS-DA) identified 19 dysregulated metabolites (5 in ESI+ mode and 14 in ESI− mode) related to the metabolism of amino acids and energy metabolism. The potential utility of these metabolites as diagnostic biomarkers was validated through receiver operating characteristic (ROC) curve analysis. These findings provide putative metabolite biomarkers for future study and allow for hypothesis generation about the pathophysiology of toxoplasmosis.
Question: Write a study description for the study titled 'Untargeted metabolomic analysis in cats with naturally occurring inflammatory bowel disease and alimentary small cell lymphoma'.
Answer: Feline chronic enteropathy (CE) is a common gastrointestinal disorder in cats and mainly comprises inflammatory bowel disease (IBD) and small cell lymphoma (SCL). Differentiation between IBD and SCL can be diagnostically challenging. We characterized the fecal metabolome of 14 healthy cats and 22 cats with naturally occurring CE (11 cats with IBD and 11 cats with SCL). Principal component analysis and heat map analysis showed distinct clustering between cats with CE and healthy controls. Random forest classification revealed good group prediction for healthy cats and cats with CE, with an overall out-of-bag error rate of 16.7%. Univariate analysis indicated that levels of 84 compounds in cats with CE differed from those in healthy cats. Polyunsaturated fatty acids held discriminatory power in differentiating IBD from SCL. Metabolomic profiles of cats with CE resembled those in people with CE with significant alterations of metabolites related to tryptophan, arachidonic acid, and glutathione pathways.
Question: Write a study description for the study titled 'Metabolic balancing by miR-276 shapes the mosquito reproductive cycle and Plasmodium falciparum development'.
Answer: The blood-feeding behavior of Anopheles females delivers essential nutrients for egg development and drives parasite transmission between humans. Plasmodium growth is adapted to the vector reproductive cycle, but how changes in the reproductive cycle impact parasite development remains unclear. Here, we show that the bloodmeal-induced miR-276-5p fine-tunes the expression of branched-chain amino acid transferase to terminate the reproductive cycle. Silencing of miR-276 prolongs high rates of amino acid (AA) catabolism and increases female fertility, suggesting that timely termination of AA catabolism restricts mosquito investment into reproduction. Prolongation of AA catabolism in P. falciparum-infected females also compromises the development of the transmissible sporozoite forms. Our results suggest that Plasmodium sporogony exploits the surplus mosquito resources available after reproductive investment and demonstrate the crucial role of the mosquito AA metabolism in within-vector parasite proliferation and malaria transmission.
Question: Write a study description for the study titled 'Hif1α-Dependent Uncoupling Of Glycolysis Suppresses Tumor Cell Proliferation'.
Answer: Hypoxia-inducible factor-1α (HIF1α) attenuates mitochondrial activity while promoting glycolysis. Paradoxically, it remains unknown why lower glycolysis is compromised in human clear cell renal cell carcinomas (ccRCC), in which HIF1α acts a tumor suppressor by inhibiting cell autonomous proliferation. Here we found that unexpectedly, HIF1α suppresses lower glycolysis after the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) step, leading to reduced lactate secretion in different tumor cell types when cells encounter a limited pyruvate supply such as that typically found in the tumor microenvironment in vivo. This is because HIF1α-dependent attenuation of mitochondrial oxygen consumption increases the NADH/NAD+ ratio that suppresses the activity of NADH-sensitive GAPDH glycolytic enzyme. This is manifested when pyruvate supply is limited since pyruvate acts as an electron acceptor that prevents the increment of the NADH/NAD+ ratio. Furthermore, this anti-glycolytic function provides a molecular basis to explain how HIF1α can suppress tumor cell proliferation by increasing the NADH/NAD+ ratio.
Question: Write a study description for the study titled 'Co-occurrence of direct and indirect extracellular electron transfer mechanisms during electroactive respiration in a dissimilatory sulfate reducing bacterium'.
Answer: Understanding the extracellular electron transfer mechanisms of electroactive bacteria could help determine their potential in microbial fuel cells (MFCs) and their microbial syntrophy with redox-active minerals in natural environments. However, the mechanisms of extracellular electron transfer to electrodes by sulfate-reducing bacteria (SRB) remain underexplored. Here, we utilized double-chamber MFCs with carbon cloth electrodes to investigate the extracellular electron transfer mechanisms of Desulfovibrio vulgaris Hildenborough (DvH), a model SRB, under varying lactate and sulfate concentrations using different DvH mutants. Our MFC setup indicated that DvH can harvest electrons from lactate at the anode and transfer them to cathode, where DvH could further utilize these electrons. Patterns in current production compared to variations of electron donor/acceptor ratios in the anode and cathode suggested that attachment of DvH to the electrode and biofilm density were critical for effective electricity generation. Electron microscopy analysis of DvH biofilms indicated DvH utilized filaments that resemble pili to attach on electrodes and facilitate extracellular electron transfer from cell-to-cell and to the electrode. Proteomics profiling indicated that DvH adapted to electroactive respiration by presenting more pili- and flagellar- related proteins. The mutant with a deletion of the major pilus-producing gene yielded less voltage and far less attachment to both anodic and cathodic electrodes, suggesting the importance of pili in extracellular electron transfer. The mutant with a deficiency in biofilm formation, however, did not eliminate current production indicating the existence of indirect extracellular electron transfer. Untargeted metabolomics profiling showed flavin-based metabolites, potential electron shuttles.
Question: Write a study description for the study titled 'The murine lung microbiome is dysbalanced by the human pathogenic fungus Aspergillus fumigatus resulting in enrichment of anaerobic bacteria'.
Answer: Here, we report significant changes in the composition of the lung microbiome and metabolome of mice under immune suppression, infection of immunosuppressed mice with virulent and avirulent strains of the clinically important human-pathogenic fungus Aspergillus fumigatus, and treatment with the clinically used antifungal drug voriconazole. Our data also indicate the important role of the gut microbiome for the lung homeostasis mediated by the plasma metabolome. In the lung microbiome, infection by A. fumigatus led to a significant increase of anaerobic bacteria, most prominently of Ligilactobacillus murinus. We also isolated live bacteria including L. murinus from the murine lower respiratory tract. In vitro, L. murinus is tolerated and even internalized by alveolar epithelial cells. Co-cultivation of L. murinus and A. fumigatus led to a reduction in oxygen concentration accompanied by an increase of L. murinus cells suggesting that A. fumigatus establishes a microaerophilic niche, thereby promoting growth of anaerobic bacteria.
Question: Write a study description for the study titled 'A Cross-Platform Metabolomics Comparison Identifies Serum Metabolite Signatures of Liver Fibrosis Progression in Chronic Hepatitis C Patients'.
Answer: Metabolomics offers new insights into disease mechanisms that is enhanced when adopting orthogonal instrumental platforms to expand metabolome coverage, while also reducing false discoveries by independent replication. Herein, we report the first inter-method comparison when using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) and nuclear magnetic resonance (NMR) spectroscopy for characterizing the serum metabolome of patients with liver fibrosis in chronic hepatitis C virus (HCV) infection (n = 20) and non-HCV controls (n = 14). In this study, 60 and 30 serum metabolites were detected frequently (>75%) with good technical precision (median CV n = 34) when using standardized protocols for MSI-CE-MS and NMR, respectively. Also, 20 serum metabolite concentrations were consistently measured by both methods over a 500-fold concentration range with an overall mean bias of 9.5% (n = 660). Multivariate and univariate statistical analyses independently confirmed that serum choline and histidine were consistently elevated (p AUC = 0.848, p = 0.00766) using a receiver operating characteristic curve, which was positively correlated with liver stiffness measurements by ultrasound imaging (r = 0.606, p = 0.0047). Moreover, serum 5-oxo-proline concentrations were higher in HCV patients as compared to non-HCV controls (F = 4.29, p = 0.0240) after adjustment for covariates (age, sex, BMI), indicative of elevated oxidative stress from glutathione depletion with the onset and progression of liver fibrosis. Both instrumental techniques enable rapid yet reliable quantification of serum metabolites in large-scale metabolomic studies with good overlap for biomarker replication. Advantages of MSI-CE-MS include greater metabolome coverage, lower operating costs, and smaller sample volume requirements, whereas NMR offers a robust platform supported by automated spectral and data processing software.