LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs (T. brucei assay)'.
Answer: Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.T. brucei assay is reported in the current study MTBLS1474.T. congolense assay is reported in MTBLS1309.Linked cross omic data sets:Genome data associated with this study are available in the European Nucleotide Archive (ENA): accession number PRJEB34627.
Question: Write a study description for the study titled 'Lipid biomarkers for algal resistance to viral infection in the ocean'.
Answer: Marine viruses play a key role in regulating phytoplankton populations, greatly affecting the biogeochemical cycling of major nutrients in the ocean. Resistance to viral infection has been reported for various phytoplankton species under laboratory conditions. Nevertheless, the occurrence of resistant cells in natural populations is underexplored due to the lack of sensitive tools to detect these rare phenotypes. Consequently, our current understanding of the ecological importance of resistance and its underlying mechanisms is limited. Here, we sought to identify lipid biomarkers for the resistance of the bloom-forming alga Emiliania huxleyi to its specific virus, E. huxleyi virus (EhV). By applying an untargeted lipidomics approach, we identified a group of glycosphingolipid (GSL) biomarkers that characterize resistant E. huxleyi strains and were thus termed resistance-specific GSLs (resGSLs). Further, we detected these lipid biomarkers in E. huxleyi isolates collected from induced E. huxleyi blooms and in samples collected during an open-ocean E. huxleyi bloom, indicating that resistant cells predominantly occur during the demise phase of the bloom. Last, we show that the GSL composition of E. huxleyi cultures that recover following infection and gain resistance to the virus resembles that of resistant strains. These findings highlight the metabolic plasticity and coevolution of the GSL biosynthetic pathway and underscore its central part in this host-virus arms race.
Question: Write a study description for the study titled 'Protein lactylation of citrate synthase promotes the AKI–CKD transition by activating the NLRP3 inflammasome.'.
Answer: Interstitial renal inflammation contributes to the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). Recently, protein lactylation modification has emerged as a novel mechanism for mediating chronic organ damage. We investigated lactylated protein profiles and the role of protein lactylation during AKI progression. Severe and moderate AKI mouse models were constructed by bilateral renal ischemia for 35 and 25 min, respectively. Lactylation enhancers and inhibitors were used to verify the effect of protein lactylation. Lactylated proteomics was used to detect lactylated protein changes in kidneys, and the lactylated proteins related to kidney injury were screened for verification. We observed significantly higher lactate and protein lactylation levels in the severe AKI model than in the moderate AKI model 1-28 days post-injury. Inhibition of protein lactylation protects against renal interstitial fibrosis. In vitro and in vivo experiments demonstrated that protein lactylation activated Nod-like receptor protein 3 (NLRP3) inflammasomes, promoting the AKI-CKD transition. Comprehensive lactylome profiling of severe AKI models revealed a role for lactylated proteins in metabolic pathways, primarily the tricarboxylic acid (TCA) cycle, where the rate-limiting enzyme, citrate synthase (CS), exhibited significantly elevated lactylation levels 3-7 days post-AKI induction; K370 was the most significant lysine residue. In vitro, following hypoxia/reoxygenation, the modified/lactylated K370T group significantly decreased CS activity and mitochondrial function. Furthermore, CS-K370 lactylation activated the NLRP3 inflammasomes. Thus, lactylation of CS promotes the AKI-CKD transition through NLRP3 inflammasome activation. Inhibition of CS lactylation shows therapeutic potential for preventing this transition.
Question: Write a study description for the study titled 'Metabolomic fingerprint of severe obesity is dynamically affected by bariatric surgery in a procedure-dependent manner'.
Answer: Obesity is associated with multiple diseases. Bariatric surgery is the most effective therapy for severe obesity that can reduce body weight and obesity-associated morbidity. The metabolic alterations associated with obesity and respective changes after bariatric surgery are incompletely understood.We comprehensively assessed metabolic alterations associated with severe obesity and distinct bariatric procedures. In our longitudinal observational study, we applied a (1)H-nuclear magnetic resonance-based global, untargeted metabolomics strategy on human serum samples that were collected before and repeatedly <=1 y after distinct bariatric procedures [i.e., a sleeve gastrectomy, proximal Roux-en Y gastric bypass (RYGB), and distal RYGB]. For comparison, we also analyzed serum samples from normal-weight and less-obese subjects who were matched for 1-y postoperative body mass index (BMI) values of the surgical groups. We identified a metabolomic fingerprint in obese subjects that was clearly discriminated from that of normal-weight subjects. Furthermore, we showed that bariatric surgery (sleeve gastrectomy and proximal and distal RYGB) dynamically affected this fingerprint in a procedure-dependent manner, thereby establishing new fingerprints that could be discriminated from those of BMI-matched and normal-weight control subjects. Metabolites that largely contributed to the metabolomic fingerprints of severe obesity were aromatic and branched-chain amino acids (elevated), metabolites related to energy metabolism (pyruvate and citrate; elevated), and metabolites suggested to be derived from gut microbiota (formate, methanol, and isopropanol; all elevated). Our data indicate that bariatric surgery, irrespective of the specific kind of procedure used, reverses most of the metabolic alterations associated with obesity and suggest profound changes in gut microbiome-host interactions after the surgery. This trial was registered at clinicaltrials.gov as NCT02480322.
Question: Write a study description for the study titled 'Epistasis-driven identification of SLC25A51 as a regulator of human mitochondrial NAD import'.
Answer: About a thousand genes in the human genome encode for membrane transporters. Among these, several solute carrier proteins (SLCs), representing the largest group of transporters, are still orphan and lack functional characterization. We reasoned that assessing genetic interactions among SLCs may be an efficient way to obtain functional information allowing their deorphanization. Here we describe a network of strong genetic interactions indicating a contribution to mitochondrial respiration and redox metabolism for SLC25A51/MCART1, an uncharacterized member of the SLC25 family of transporters. Through a combination of metabolomics, genomics and genetics approaches, we demonstrate a role for SLC25A51 as enabler of mitochondrial import of NAD, showcasing the potential of genetic interaction-driven functional gene deorphanization.
Question: Write a study description for the study titled 'Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the Myc-dependent metabolic reprogramming of stromal cells'.
Answer: Cancer and other cells residing in the same niche engage various modes of interactions to synchronize and to buffer the negative effects of environmental changes. Extracellular miRNAs have been recently implicated in the intercellular crosstalk. Here we show a mechanistic model involving breast-cancer-secreted, extracellular-vesicle-encapsulated miR-105, which is induced by the oncoprotein MYC in cancer cells and in turn activates MYC signaling in cancer-associated fibroblasts (CAFs) to induce a metabolic program. This results in CAFs metabolic plasticity toenhance glycolysis and glutaminolysis to fuel adjacent cancer cells when nutrients are sufficient (the symbiosis mode), and detoxify metabolic wastes (lactic acid and ammonium) by converting them into energy-rich metabolites, when nutrients are deprived whereas metabolic byproducts are accumulated. This commensalism of cancer stroma emphasizes the functional flexibility of non-cancer cell populations contributing to cancer fitness during sustained growth of tumour.
Question: Write a study description for the study titled 'Gut microbiota carcinogen metabolism causes distal tissue tumours'.
Answer: Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development. Similar to drug molecules, pollutants are typically metabolised in the body, which can change their carcinogenic potential and impact tissue distribution through altered toxicokinetics. Although recent studies demonstrated that human-associated microbes can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites, the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota dramatically reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice, which affects the toxicokinetics of nitrosamines. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine-carcinogens. Altogether, these results suggest gut microbiota carcinogen metabolism as a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer.
Question: Write a study description for the study titled 'Untargetted lipidomics dataset: LC-MS analysis in two postmortem brain areas of healthy individuals and schizophrenia patients.'.
Answer: Schizophrenia is a common mental illness. It is a complex disorder with many symptoms and cognitive impairments. Despite extensive study, the molecular mechanisms of this disease are still unknown. Present time studies on the lipid composition of the human brain are extremely fragmented. Of the possible levels of molecular analysis involving gene expression at the RNA or protein level, and the representation of polar metabolites and lipids, the latter seem to us to be the most promising now. We chose lipids as representative data of the pathogenic mechanism because they are the main structural components of brain cell tissue. The dataset provided unique samples of lipid LC-MS profiles of post-mortem human brains. Samples include not only healthy individuals but also patients with schizophrenia.
Question: Write a study description for the study titled 'Untargeted Metabolomics Reveals a Mild Impact of Remote Ischemic Conditioning on the Plasma Metabolome and α-Hydroxybutyrate as a Possible Cardioprotective Factor and Biomarker of Tissue Ischemia'.
Answer: Remote ischemic conditioning (RIC) is a maneuver by which short non-lethal ischemic events are applied on distant organs or limbs to reduce ischemia and reperfusion injuries caused by e.g. heart attacks. As RIC can be induced using a simple blood pressure cuff e.g. prior to revascularization, it constitutes an easily applicable, safe and low-cost intervention to limit these injuries. Although intensively investigated, the specific mechanism of this protective phenomenon remains incompletely understood. Likewise, the identity of circulating factors, presumed to be involved in the initiation of protection, is unknown. In this study, we aimed to study perturbations in the plasma metabolome following RIC and gain insight into metabolic changes by the intervention as well as to identify potential novel cardio-protective metabolites. Blood plasma samples from 10 healthy males were collected prior to and after RIC and analyzed using untargeted LC-qTOF-MS. The analysis revealed a moderate impact on the plasma metabolome following RIC. However, one metabolite, α-hydroxybutyrate (AHB), stood out as highly significantly upregulated after RIC. AHB might be a novel and more sensitive plasma-biomarker of transient tissue ischemia than lactate. Importantly, it was also found that a cell permeable AHB precursor protects cardiomyocytes from ischemia-reperfusion damage.
Question: Write a study description for the study titled 'Analysis of colorectal adenocarcinoma tissue samples by DESI mass spectrometry imaging'.
Answer: Ex vivo colorectal adenocarcinoma samples were analysed by desorption electrospray ionisation using an Orbitrap mass spectrometer. The samples were analysed in negative mode over the m/z range 600-1000. Some of the samples presented in this dataset were analysed as part of [1]. The study makes available imzML files of profile and centroid mode data, as well as low- and high- resolution optical image files of H&E-stained sections. These files can be found in the zip file named after each tissue section.  Ref: [1] Gerbig S, Golf O, Balog J, Denes J, Baranyai Z, Zarand A, Raso E, Timar J, Takats Z. Analysis of colorectal adenocarcinoma tissue by desorption electrospray ionization mass spectrometric imaging. Anal Bioanal Chem. 2012 Jun;403(8):2315-25. doi:10.1007/s00216-012-5841-x. PMID:22447214
Question: Write a study description for the study titled 'Contribution of fungal microbiome to intestinal physiology, early-life immune development and mucosal inflammation in mice'.
Answer: The gut microbiome consists of a multi-kingdom microbial community. Whilst the role of bacteria as causal contributors governing host physiological development is well established, the role of fungi remains to be determined. Here, we use germ-free mice colonized with defined species of bacteria, fungi, or both to differentiate the causal role of fungi on microbiome assembly, immune development, susceptibility to colitis, and airway inflammation. Fungal colonization promotes major shifts in bacterial microbiome ecology, and has an independent effect on innate and adaptive immune development in young mice. While exclusive fungal colonization is insufficient to elicit overt dextran sulfate sodium-induced colitis, bacterial and fungal co-colonization increase colonic inflammation. Ovalbumin-induced airway inflammation reveals that bacterial, but not fungal colonization is necessary to decrease airway inflammation, yet fungi selectively promotes macrophage infiltration in the airway. Together, our findings demonstrate a causal role for fungi in microbial ecology and host immune functionality, and therefore prompt the inclusion of fungi in therapeutic approaches aimed at modulating early life microbiomes.
Question: Write a study description for the study titled 'Serum organic acid metabolites can be used as potential biomarkers to identify prostatitis, benign prostatic hyperplasia, and prostate cancer (Targeted organic acid assay)'.
Answer: BACKGROUND: Noninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are current clinical challenges.METHODS: The serum metabolites of 20 healthy individuals and patients with prostatitis, BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS).RESULTS: Organic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort. Three diagnostic models identified patients with PROSTATITIS: phenyllactic acid (area under the curve [AUC]=0.773), pyroglutamic acid (AUC=0.725), and pantothenic acid (AUC=0.721). Three diagnostic models identified BPH: citric acid (AUC=0.859), malic acid (AUC=0.820), and D[1]glucuronic acid (AUC=0.810). Four diagnostic models identified PCa: 3-hydroxy-3-methylglutaric acid (AUC=0.804), citric acid (AUC=0.918), malic acid (AUC=0.862), and phenyllactic acid (AUC=0.713). Two diagnostic models distinguished BPH from PCa: phenyllactic acid (AUC=0.769) and pyroglutamic acid (AUC=0.761). Three diagnostic models distinguished benign BPH from PROSTATITIS: citric acid (AUC=0.842), ethylmalonic acid (AUC=0.814), and hippuric acid (AUC=0.733). Six diagnostic models distinguished BPH from prostatitis: citric acid (AUC=0.926), pyroglutamic acid (AUC=0.864), phenyllactic acid (AUC=0.850), ethylmalonic acid (AUC=0.843), 3-hydroxy- 3-methylglutaric acid (AUC=0.817), and hippuric acid (AUC=0.791). Three diagnostic models distinguished PCa patients with PROSTATITISA < 4.0 ng/mL from those with PSA > 4.0 ng/mL: 5-hydromethyl-2-furoic acid (AUC=0.749), ethylmalonic acid (A UC=0.750), and pyroglutamic acid (AUC=0.929).CONCLUSIONS: These results suggest that serum organic acid metabolites can be used as biomarkers to differentiate prostatitis, BPH, and PCa.Targeted organic acid assay is reported in the current study MTBLS6038.Untargeted assay is reported in MTBLS6039.
Question: Write a study description for the study titled 'Association between altered tryptophan metabolism, plasma aryl hydrocarbon receptor agonists, and inflammatory Chagas disease'.
Answer: Chagas disease causes a cardiac illness characterized by immunoinflammatory reactions leading to myocardial fibrosis and remodeling. The development of Chronic Chagas Cardiomyopathy (CCC) in some patients while others remain asymptomatic is not fully understood, but dysregulated inflammatory responses are implicated. The Aryl hydrocarbon receptor (AhR) plays a crucial role in regulating inflammation. Certain tryptophan (Trp) metabolites have been identified as AhR ligands with regulatory functions. We investigated AhR expression, agonist response, ligand production and AhR-dependent responses, such as IDO activation and regulatory T (Treg) cells induction, in two T. cruzi-infected mouse strains (B6 and Balb/c) showing different polymorphisms in AhR. Furthermore, we assessed the metabolic profile of Trp catabolites and AhR agonistic activity levels in plasma samples from patients with chronic Chagas disease (CCD) and healthy donors (HD) using a luciferase reporter assay and liquid chromatography-mass spectrophotometry (LC-MS) analysis. T. cruzi-infected B6 mice showed impaired AhR-dependent responses compared to Balb/c mice, including reduced IDO activity, kynurenine levels, Treg cell induction, CYP1A1 up-regulation and AhR expression following agonist activation. Additionally, B6 mice exhibited no detectable AhR agonist activity in plasma and displayed lower CYP1A1 up-regulation and AhR expression upon agonist activation. Similarly, CCC patients had decreased AhR agonistic activity in plasma compared to HD patients and exhibited dysregulation in Trp metabolic pathways, resulting in altered plasma metabolite profiles. Notably, patients with severe CCC specifically showed increased N-acetylserotonin levels in their plasma. The methods and findings presented here contribute to a better understanding of CCC development mechanisms and may identify potential specific biomarkers for T. cruzi infection and the severity of associated heart disease. These insights could be valuable in designing new therapeutic strategies. Ultimately, this research aims to establish the AhR agonistic activity and Trp metabolic profile in plasma as an innovative, non-invasive predictor of prognosis for chronic Chagas disease.
Question: Write a study description for the study titled 'Response to dietary carbohydrates in European seabass (Dicentrarchus labrax) muscle tissue as revealed by NMR-based metabolomics'.
Answer: INTRODUCTION: Feed optimization is a key step to the environmental and economic sustainability of aquaculture, especially for carnivorous species. Plant-derived ingredients can contribute to reduce costs and nitrogenous effluents while sparing wild fish stocks. However, the metabolic use of carbohydrates from vegetable sources by carnivorous fish is still not completely understood.OBJECTIVES: We aimed to study the effects of diets with carbohydrates of different digestibilities, gelatinized starch (DS) and raw starch (RS), in the muscle metabolome of European seabass (Dicentrarchus labrax).METHODS: We followed an NMR-metabolomics approach, using two sample preparation procedures, the intact muscle (HRMAS) and the aqueous muscle extracts (1H NMR), to compare the variations in muscle metabolome between the two diets.RESULTS: In muscle, multivariate analysis revealed similar metabolome shifts for DS and RS diets, when compared with the control diet. HRMAS of intact muscle, which included both hydrophobic and hydrophilic metabolites, showed increased lipid in DS-fed fish by univariate analysis. Regardless of the nature of the starch, increased glycine and phenylalanine, and decreased proline were observed when compared to the Ctr diet. Combined univariate analysis of intact muscle and aqueous extracts indicated specific diet related changes in lipid and amino acid metabolism, consistent with increased dietary carbohydrate supplementation.CONCLUSIONS: Due to differential sample processing, outputs differ in detail but provide complementary information. After tracing nutritional alterations by profiling fillet components, DS seems to be the most promising alternative to fishmeal-based diets in aquaculture. This approach should be reproducible for other farmed fish species and provide valuable information on nutritional and organoleptic properties of the final product.