LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Metabolic Dynamics in Escherichia coli-Based Cell-Free Systems'.
Answer: The field of metabolic engineering has yielded remarkable accomplishments in using cells to produce valuable molecules, and cell-free expression (CFE) systems have the potential to push the field even further. However, CFE systems still face some outstanding challenges, including endogenous metabolic activity that is poorly understood yet has a significant impact on CFE productivity. Here, we use metabolomics to characterize the temporal metabolic changes in CFE systems and their constituent components, including significant metabolic activity in central carbon and amino acid metabolism. We find that while changing the reaction starting state via lysate preincubation impacts protein production, it has a comparatively small impact on metabolic state. We also demonstrate that changes to lysate preparation have a larger effect on protein yield and temporal metabolic profiles, though general metabolic trends are conserved. Finally, while we improve protein production through targeted supplementation of metabolic enzymes, we show that the endogenous metabolic activity is fairly resilient to these enzymatic perturbations. Overall, this work highlights the robust nature of CFE reaction metabolism as well as the importance of understanding the complex interdependence of metabolites and proteins in CFE systems to guide optimization efforts.
Question: Write a study description for the study titled 'Dissection of metabolic reprogramming in polycystic kidney disease reveals coordinated rewiring of bioenergetic pathways'.
Answer: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder caused by loss-of-function mutations in PKD1 or PKD2. Increased glycolysis is a prominent feature of the disease, but how it impacts on other metabolic pathways is unknown. Here, we present an analysis of mouse Pkd1 mutant cells and kidneys to investigate the metabolic reprogramming of this pathology. We show that loss of Pkd1 leads to profound metabolic changes that affect glycolysis, mitochondrial metabolism, and fatty acid synthesis (FAS). We find that Pkd1-mutant cells preferentially use glutamine to fuel the TCA cycle and to sustain FAS. Interfering with either glutamine uptake or FAS retards cell growth and survival. We also find that glutamine is diverted to asparagine via asparagine synthetase (ASNS). Transcriptional profiling of PKD1-mutant human kidneys confirmed these alterations. We find that silencing of Asns is lethal in Pkd1-mutant cells when combined with glucose deprivation, suggesting therapeutic approaches for ADPKD.
Question: Write a study description for the study titled 'Biogeography shaped the metabolome of the genus Espeletia: a phytochemical perspective on an Andean adaptive radiation'.
Answer: The páramo ecosystem has the highest rate of diversification across plant lineages on earth, of which the genus Espeletia (Asteraceae) is a prime example. The current distribution and molecular phylogeny of Espeletia suggest the influence of Andean geography and past climatic fluctuations on the diversification of this genus. However, molecular markers have failed to reveal subtle biogeographical trends in Espeletia diversification, and metabolomic evidence for allopatric segregation in plants has never been reported. Here, we present for the first time a metabolomics approach based on liquid chromatography-mass spectrometry for revealing subtle biogeographical trends in Espeletia diversification. We demonstrate that Espeletia lineages can be distinguished by means of different metabolic fingerprints correlated to the country of origin on a global scale and to the páramo massif on a regional scale. Distinctive patterns in the accumulation of secondary metabolites according to the main diversification centers of Espeletia are also identified and a comprehensive phytochemical characterization is reported. These findings demonstrate that a variation in the metabolic fingerprints of Espeletia lineages followed the biogeography of this genus, suggesting that our untargeted metabolomics approach can be potentially used as a model to understand the biogeographic history of additional plant groups in the páramo ecosystem.
Question: Write a study description for the study titled 'Improving the Screening Analysis of Pesticide Metabolites in Human Biomonitoring by Combining High-Throughput In Vitro Incubation and Automated LC-HRMS Data Processing'.
Answer: There is a current need to monitor human exposure to a large number of pesticides and other chemicals of emerging concern (CECs). This requires screening analysis with high confidence for these compounds and their metabolites in complex matrices, which is hampered by the fact that no reference standards are available for most metabolites. We address this challenge by a high-throughput workflow based on incubation of pesticides (or other CECs) with human liver S9, followed by solid-phase extraction, liquid chromatography-high-resolution mass spectrometry (LC-HRMS) analysis, and automated data processing to generate a database (retention time, precursor m/z, and MS2 spectral library) for the annotation in human samples. The metabolite prioritization consists of statistical comparisons and mass defect and m/z range filtering to obtain a subset of probable phase I metabolites, for which molecular formulas and likely metabolic transformation are retrieved. We tested the workflow on 22 pesticides, for which we could determine 91 metabolite molecular formulas which are only partly covered by the literature and/or predicted by in silico metabolization. Our workflow allows for an efficient generation of metabolite reference information, which can be used directly for annotating LC-HRMS data from human samples. A full structure elucidation of individual metabolites can be limited to those being actually present in human samples.
Question: Write a study description for the study titled 'EMP1 safeguards hematopoietic stem cells by suppressing sphingolipid metabolism and alleviating endoplasmic reticulum stress'.
Answer: The long-term maintenance of hematopoietic stem cells (HSCs) relies on the regulation of endoplasmic reticulum (ER) stress at a low level, but the underlying mechanism remains poorly understood. Here, we demonstrate that suppression of ER stress improves the functions of HSCs and protects HSCs against ionizing radiation (IR)-induced injury. We identify epithelial membrane protein 1 (EMP1) as a key regulator that mitigates ER stress in HSCs. Emp1 deficiency leads to the accumulation of protein aggregates and elevated ER stress, ultimately resulting in impaired HSC maintenance and self-renewal. Mechanistically, EMP1 is located within the ER and interacts with ceramide synthase 2 (CERS2) to limit the production of a class of sphingolipids, dihydroceramides (dhCers). DhCers accumulate in Emp1-deficient HSCs and induce protein aggregation. Furthermore, Emp1 deficiency renders HSCs more susceptible to IR, while overexpression of Emp1 or inhibition of CERS2 protects HSCs against IR-induced injury. These findings highlight the critical role played by the EMP1-CERS2-dhCers axis in constraining ER stress and preserving HSC potential.
Question: Write a study description for the study titled 'Fasudil may alleviate alcohol-induced astrocyte damage by modifying lipid metabolism, as determined by metabonomics analysis'.
Answer: Alcohol dependence is a chronic, relapsing encephalopathy characterized by compulsive craving for alcohol, loss of control over alcohol use, and the presence of negative emotions and physical discomfort when alcohol is unavailable. Harmful use of alcohol is one of the greatest risk factors for death, illness and disability. Rho kinase inhibitors have neuroprotective effects. This study used metabonomics analysis to assess untreated astrocytes, astrocytes exposed to 75 mmol/L of alcohol, and astrocytes exposed to 75 mmol/L of alcohol and treated with 15 µg/mL fasudil for 24 h. One of the clearest differences between the alcohol-exposed and fasudil-treated alcohol-exposed groups was the abundance of lipids and lipid-like molecules, although glycerophospholipid metabolism was comparable in both groups. Our findings show that fasudil may alleviate alcohol-induced astrocyte damage by modifying lipid metabolism, providing a new approach for preventing and treating alcohol dependence.
Question: Write a study description for the study titled 'geoRge: A Computational Tool To Detect the Presence of Stable Isotope Labeling in LC/MS-Based Untargeted Metabolomics'.
Answer: Studying the flow of chemical moieties through the complex set of metabolic reactions that happen in the cell is essential to understanding the alterations in homeostasis that occur in disease. Recently, LC/MS-based untargeted metabolomics and isotopically labeled metabolites have been used to facilitate the unbiased mapping of labeled moieties through metabolic pathways. However, due to the complexity of the resulting experimental data sets few computational tools are available for data analysis. Here we introduce geoRge, a novel computational approach capable of analyzing untargeted LC/MS data from stable isotope-labeling experiments. geoRge is written in the open language R and runs on the output structure of the XCMS package, which is in widespread use. As opposed to the few existing tools, which use labeled samples to track stable isotopes by iterating over all MS signals using the theoretical mass difference between the light and heavy isotopes, geoRge uses unlabeled and labeled biologically equivalent samples to compare isotopic distributions in the mass spectra. Isotopically enriched compounds change their isotopic distribution as compared to unlabeled compounds. This is directly reflected in a number of new m/z peaks and higher intensity peaks in the mass spectra of labeled samples relative to the unlabeled equivalents. The automated untargeted isotope annotation and relative quantification capabilities of geoRge are demonstrated by the analysis of LC/MS data from a human retinal pigment epithelium cell line (ARPE-19) grown on normal and high glucose concentrations mimicking diabetic retinopathy conditions in vitro. In addition, we compared the results of geoRge with the outcome of X(13)CMS, since both approaches rely entirely on XCMS parameters for feature selection, namely m/z and retention time values. geoRge is available as an R script at https://github.com/jcapelladesto/geoRge.
Question: Write a study description for the study titled 'Multi-omics Analysis Reveals New Insights into Yak Lung Fibrosis Mechanisms Under High-Altitude Adaptation'.
Answer: The lung of yak is an important adaptive organ in the cold and low oxygen environment. Hypoxia can induce the pathological manifestations of pulmonary fibrosis in yak, but there was no study on hypoxia induced pulmonary fibrosis in yak. In this study full target metabolomics were used to conduct studies on normal and fibrotic lung tissues of yaks. The results showed that Palmitoyl-L-carnitine, Decanoyl-L-carnitine and O-Acetylcarnitine were significantly highly expressed in fibrotic lung, Racemethionine and L-Methionine S-oxide were significantly lower expressed in fibrotic lungs. This study revealed the molecular mechanism of anti-fibrosis of yak lung, and these findings provided a scientific basis for formulating effective prevention and control strategies, contributing to safeguarding yak health and the sustainable development of plateau animal husbandry, and providing strong support for animal health management and disease prevention and control in plateau areas.
Question: Write a study description for the study titled 'Sphingolipid-dependent Dscam sorting regulates axon segregation'.
Answer: "Neurons are highly polarized cells with distinct protein compositions in axonal and dendritic compartments. Cellular mechanisms controlling polarized protein sorting have been described for mature nervous system but little is known about the segregation in newly differentiated neurons. In a forward genetic screen for regulators of Drosophila brain circuit development, we identified mutations in Serine Palmitoyltransferase (SPT), an evolutionary conserved enzyme in sphingolipid biosynthesis. Here we show that reduced levels of sphingolipids in SPT mutants cause axonal morphology defects similar to loss of cell recognition molecule Dscam. Loss- and gain-of-function studies show that neuronal sphingolipids are critical to prevent aggregation of axonal and dendritic Dscam isoforms, thereby ensuring precise Dscam localization to support axon branch segregation. Furthermore, SPT mutations causing neurodegenerative HSAN-I disorder in humans also result in formation of stable Dscam aggregates and axonal branch phenotypes in Drosophila neurons, indicating a causal link between developmental protein sorting defects and neuronal dysfunction."
Question: Write a study description for the study titled 'Metabolic Profiling of Escherichia coli-Based Cell-Free Expression Systems for Process Optimization'.
Answer: Biotechnology has transformed the production of various chemicals and pharmaceuticals due to its efficient and selective processes, but it is inherently limited by its use of live cells as 'biocatalysts.' Cell-free expression (CFE) systems, which use a protein lysate isolated from whole cells, have the potential to overcome these challenges and broaden the scope of biomanufacturing. Implementation of CFE systems at scale will require determining clear markers of lysate activity and developing supplementation approaches that compensate for potential variability across batches and experimental protocols. Towards this goal, we use metabolomics to relate lysate preparation and performance to metabolic activity. We show that lysate processing affects the metabolite makeup of lysates, and that lysate metabolite levels change over the course of a CFE reaction regardless of whether a target compound is produced. Finally, we use this information to develop ways to standardize lysate activity and to design an improved CFE system.
Question: Write a study description for the study titled 'Mechanistic study of the effects of salivary components from OSCC patients on tumor growth using a mouse model of oral squamous cell carcinoma'.
Answer: Mechanistic study of the effects of salivary components from OSCC patients on tumor growth using a mouse model of oral squamous cell carcinoma
Question: Write a study description for the study titled 'Global Metabonomic and Proteomic Analysis of Human Conjunctival Epithelial Cells (IOBA-NHC) in Response to Hyperosmotic Stress'.
Answer: “Dry eye” is a multi-factorial inflammatory disease affecting the ocular surface. Tear hyperosmolarity in dry eye contributes to inflammation and cell damage. Recent research efforts on dry eye have been directed towards biomarker discovery for diagnosis, response to treatment and disease mechanisms. This study employed a spontaneously immortalized normal human conjunctival cell line, IOBA-NHC as a model to investigate hyperosmotic stress-induced changes of metabolites and proteins. Global and targeted metabonomic analyses, as well as proteomic analysis were performed on IOBA-NHC cells incubated in serum-free media at 280 mOsm (control), 380 mOsm and 480 mOsm for 24 h. Twenty-one metabolites and seventy-six iTRAQ-identified proteins showed significant changes under at least one hyperosmotic stress treatment as compared to controls. SWATH-based proteomic analysis further confirmed the involvement of inflammatory pathways such as prostaglandin 2 synthesis in IOBA-NHC cells under hyperosmotic stress. This study is the first to identify glycerophosphocholine synthesis and O-linked β-N-acetylglucosamine glycosylation as key activated pathways in ocular surface cells under hyperosmotic stress. These findings extend the current knowledge in metabolite markers of dry eye and provide potential therapeutic targets for its treatment.
Question: Write a study description for the study titled 'Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice'.
Answer: Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt's health effects.
Question: Write a study description for the study titled 'Lipidomics study for investigating the role of the Unfolded Protein Response In Arabidopsis seed filling'.
Answer: The Unfolded Protein Response (UPR) is a retrograde, ER-to-nucleus, signalling pathway which is conserved across kingdoms. In plants, it contributes to development, reproduction, immunity and tolerance to abiotic stress. This lipidomic dataset was produced from Arabidopsis thaliana mature seeds. Wild-type (WT) and mutant deficient for UPR actors (bzip60, ire1a and ire1b single mutants, as well as double ire1 mutants) were used as genetic backgrounds to investigate whether UPR controls lipid seed filling in Arabidopsis thaliana. Our experimental setup also allows to distinguish among differentially-overaccumulated lipids which ones are dependent on IRE1s and/or bZIP60.
Question: Write a study description for the study titled 'New plasma preparation approach to enrich metabolome coverage in untargeted metabolomics: plasma protein bound hydrophobic metabolite release with proteinase K'.
Answer: Plasma untargeted metabolomics is a common method for evaluation of the mechanisms underlying human pathologies and identification of novel biomarkers. The plasma proteins provide the environment for transport of hydrophobic metabolites. The current sample preparation protocol relies on the immediate precipitation of proteins and thus leads to co-precipitation of a significant fraction of hydrophobic metabolites. Here we present a new simple procedure that overcomes the co-precipitation problem and improves metabolome coverage. Introducing an additional step preceding the protein precipitation, namely limited digestion with proteinase K, allows release of associated metabolites through the relaxation of the native proteins tertiary structure. The modified protocol allows clear detection of hydrophobic metabolites including fatty acids and phospholipids. Considering the potential involvement of the hydrophobic metabolites in human cardiovascular and cancer diseases, the method may constitute a novel approach in plasma untargeted metabolomics.
Question: Write a study description for the study titled 'MTBLS11445: Integrative omics reveals distinct metabolic and microbial signatures in broilers under gut health interventions'.
Answer: Maintaining a well-balanced gut microbiota is crucial for ensuring optimal health and performance in poultry production. Common strategies supporting gut health include control methods for coccidiosis which is a common and economically important enteric disease in poultry. These interventions not only affect the gut microbial community but are also expected to influence metabolite levels, reflecting the dynamic relationship between gut microorganisms and metabolic processes. In this study, we compared the caecal content metabolite levels between birds given ionophores (T1) and vaccination against Eimeria species (T2), using liquid chromatography-mass spectrometry based untargeted metabolomic analysis. All statistical methods were on performed on R v4.4.1. Data was normalised using the probabilistic quotient method and subjected through Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) and Data Integration Analysis for Biomarker discovery using Latent Components (DIABLO) analyses using the mixomics package. Pathway analysis was also performed using MetaboAnalystR package. Our analysis revealed that metabolites classified as prenol lipids as robust markers for T1, while indole derivatives were identified for T2. KEGG pathways involving amino acids (Tryptophan, Phenylalanine) were also enriched in both groups. We identified Bacillus fragilis to have the greatest impact on the metabolome, positively correlated to >240 metabolites, while UBA3818 spp. (Ruminococcaceae) was shown to have a significant negative relationship with 22 metabolites. Overall, the results indicated that differences in coccidiosis control elicit diverse metabolic events in broilers through its influences on nutrient breakdown, affecting the performance and health of broilers and may provide novel avenues for gut health interventions against Eimeria.
Question: Write a study description for the study titled 'Organic Acids Modulate Systemic Metabolic Perturbation Caused by Salmonella Pullorum Challenge in Early-Stage Broilers'.
Answer: The objectives of this study were to determine the protective effects of organic acids (OA) in broilers exposed to Salmonella Pullorum challenge at early stage and to explore the potential benefits of OA by metabolomics analysis. The treatment groups included non-challenged, S. Pullorum-challenged, challenged group supplemented with virginiamycin, challenged group supplemented with OA in drinking water, challenged group supplemented with OA in feed, and challenged group supplemented with OA in combination in drinking water and feed. Results showed that early Salmonella challenge induced an acute systemic infection of broilers in the starter phase, followed by the grower phase without triggering clinical signs. OA supplementation promoted growth during the grower phase, and while OA in water contributed more, the positive effects of OA in combination were comparable to those of virginiamycin supplementation in challenged birds. Furthermore, OA could modulate the systemic metabolic perturbation caused by challenge as it alleviated stress responses mediated by steroid hormone, potentially attenuated antioxidant or immune defense, and modified intestinal microbiota metabolism. These results show a metabolic mechanism that may partly explain the potential benefits of OA in Salmonella challenged birds, and may contribute to the use of OA to control or reduce S. Pullorum infection in farm animals.