LuYuxing/MetaBench huggingface dataset:
Question: Write a study description for the study titled 'Emerald ash borer (Agrilus planipennis) infestation bioassays and metabolic profiles of green ash (Fraxinus pennsylvanica) provide evidence for an induced host defensive response to larval infestation'.
Answer: INTRODUCTION: Larvae of the invasive emerald ash borer [EAB, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae)], kill over 99% of green ash (Fraxinus pennsylvanica Marshall) trees they infest, yet a small percentage of green ash (“lingering ash”) survive years of heavy EAB attack. In the face of an ongoing invasion that threatens multiple North American Fraxinus species with extinction, any evidence for reproducible defensive responses in the native species merits investigation.METHODS: We evaluated the capacity of 3 families of green ash F1 progeny to kill EAB larvae when challenged in greenhouse studies by infestation with a uniform density of EAB eggs followed by dissection 8 weeks post-infestation and comparison of the host metabolomic profiles.RESULTS: The mean proportions of host-killed larvae in the 2 families of F1 progeny from lingering ash parents were significantly higher than that of host-killed larvae in the family of F1 progeny from susceptible ash parents (p < 0.001). Untargeted metabolomics comparing F1 progeny in the quartile with the highest percent host-killed larvae (HHK) to F1 progeny in the quartile with the lowest percent host-killed larvae (LHK) and to the uninfested F1 progeny within each family revealed evidence for induced biochemical responses to EAB. Infested trees produced significantly higher levels of select secoiridoids than uninfested trees, and LHK progeny produced significantly higher levels of select secoiridoids than the HHK progeny. HHK progeny produced significantly higher abundances of 3 metabolites annotated as aromatic alkaloids than the LHK and uninfested individuals.DISCUSSION: Based on these results, we hypothesize that green ash responds to EAB infestation. However, only certain trees have the genetic capacity to tailor a response that kills enough EAB larvae to prevent lethal damage to the vascular system. Rigorous tests of this hypothesis will require 15–20 years of additional crossing, phenotyping, and omics analyses. The results of this investigation will encourage the establishment and continuation of breeding programs that, in concert with biocontrol and management, could provide trees that slow, if not halt, the decimation of the Fraxinus gene pool. At the same time, ongoing work on host-insect interaction will contribute to our understanding of how forest trees recognize and defend themselves against phloem-feeding insects.
Question: Write a study description for the study titled 'UPLC-Q-TOF/MS-Based Plasma and Urine Metabolomics Contribute to the Diagnosis of Sepsis'.
Answer: In this study, we aimed to identify potential metabolic biomarkers that can improve the diagnostic accuracy of sepsis. Sixty-six patients including 30 septic and 36 nonsepsis patients from an intensive care unit were recruited. The global plasma and urine metabolomic profiles were determined by ultraperformance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry-based methodology. The risk factors, including both traditional physiological indicators and metabolic biomarkers, were investigated by binary logistic regression analysis and used to build a least absolute shrinkage and selection operator (Lasso) regression model to evaluate the ability of diagnosis. Fifty-five metabolites in plasma and 11 metabolites in urine were identified through orthogonal projections to latent structures discriminant analysis (OPLS-DA). Among them, ten (PE (20:4(5Z, 8Z, 11Z, 14Z)/P-18:0), harderoporphyrinogen, chloropanaxydiol, (Z)-2-octenal, N1,N8-diacetylspermidine, 1-nitroheptane, venoterpine, α-CEHC, LysoPE (20:0/0:0), corticrocin) metabolites were identified as risk factors. The Lasso regression model incorporating these ten metabolic biomarkers and five traditional physiological indicators displayed better differentiation than the traditional model, represented by the elevated area under receiver operating characteristic curve (AUROC) from 96.80 to 100.0%. Furthermore, patients with septic shock presented a significantly lower level of PE-Cer (d16:1(4E)/19:0). This study suggests that metabolomic profiling could be an effective tool for sepsis diagnosis.
Question: Write a study description for the study titled 'Targeting methionine synthase in a fungal pathogen causes a metabolic imbalance that impacts cell energetics, growth and virulence'.
Answer: There is an urgent need to develop novel antifungals to tackle the threat that fungal pathogens pose to human health. In this work, we have performed a thorough characterisation and validation of the promising target methionine synthase. We have uncovered that in Aspergillus fumigatus the absence of its enzymatic activity triggers a metabolic imbalance that causes a reduction in intracellular ATP. This drop in cell energetics prevents fungal growth, even in the presence of methionine. Using a tetOFF genetic model to mimic drug treatment we show that repression of methionine synthase in growing hyphae halts growth in vitro, which translates into a beneficial effect in vivo when targeting established infections. Finally, a structural-based virtual screening of methionine synthases reveals key differences between the human and fungal structures and unravels particularities of the fungal pockets that can direct the design of novel specific and broad-spectrum inhibitors. Therefore, methionine synthase is a valuable target for the development of new antifungals.
Question: Write a study description for the study titled 'Myocardial-intrinsic defects underlie an Rbfox-mediated zebrafish model of hypoplastic left heart syndrome'.
Answer: Hypoplastic left heart syndrome (HLHS) is characterized by underdevelopment of left sided structures including the ventricle, valves, and aorta1. Although the mechanisms of disease pathogenesis remain elusive due to a paucity of candidate genes and animal models, prevailing paradigm suggests that HLHS is a multigenic disease of co-occurring phenotypes2,3. Here, we report that zebrafish lacking two orthologs of the RNA binding protein RBFOX2, a gene previously linked to HLHS in humans4,5, display cardiovascular defects overlapping those in HLHS patients. In contrast to current models, we demonstrate that co-existing ventricular, valve, and aortic deficiencies in rbfox mutant zebrafish arise secondary to impaired myocardial function as all three phenotypes are rescued when Rbfox is expressed specifically in the myocardium. On a molecular and cellular level, we find diminished expression and alternative splicing of sarcomere and mitochondrial components in rbfox-deficient hearts that compromise sarcomere assembly and mitochondrial respiration, respectively. Injection of human RBFOX2 mRNA restores ventricular structure and function in rbfox mutant zebrafish, while HLHS-linked RBFOX2 variants fail to rescue. Taken together, our data suggest that mutations in RBFOX2 are causal for HLHS pathogenesis and provide a complimentary paradigm for HLHS emergence where co-existing ventricular, valve, and aortic deficiencies have a monogenic etiology caused by myocardial dysfunction.
Question: Write a study description for the study titled 'L-Citrulline and L-arginine regulate the reproductive performance of young and adult cows through distinct metabolic pathways and the shared pyrimidine metabolic pathway respectively'.
Answer: (Background)To investigate the impact of L-arginine (L-Arg) and L-citrulline (L-Cit) on cow reproductive performance.(Methods) 90 healthy, age-matched Simmental cows were randomly assigned to three groups: control, L-Arg, and L-Cit, with 30 cows per group. Estrus synchronization was performed, and various parameters were assessed, including estrus rate, conception rate, and early embryo apoptosis, following intraperitoneal administration of L-Arg and L-Cit. Additionally, reproductive hormones, serum antioxidant levels, and plasma metabolites were measured. (Results)Results indicated that both the estrus and conception rates in the L-Arg and L-Cit groups were significantly higher than those in the control group (P < 0.05). Furthermore, serum LH levels and VEGF concentrations on day 1 and day 8 were elevated in the L-Arg and L-Cit groups compared to controls (P < 0.05). Estrus rate and serum NO concentration in the L-Cit group were notably higher than those in the control group (P < 0.05). At day 8 and day 21, estrus rate, conception rate, P levels, and serum VEGF concentrations were significantly greater in both the L-Arg and L-Cit groups compared to controls (P < 0.05). Additionally, serum NO concentration was significantly higher in the L-Cit group than in the control group (P < 0.05). The activities of T-AOC and GSH-Px in serum were significantly increased in both primiparous and multiparous cows in the L-Arg and L-Cit groups relative to the control group (P < 0.05). Metabolomic analysis revealed that in primiparous cows, the protein digestion and absorption, ABC transporters, and AMPK signaling pathways were significantly enriched. In multiparous cows, pyrimidine metabolism was notably enriched. (Conclusions)Under the experimental conditions, L-Arg modulated the production of Dimethyl sulfone, 1,5-pentanediamine, Bassanolide, and Phenylalanine in primiparous cows through the protein digestion and absorption and ABC transporters pathways, while L-Cit influenced the same metabolites via the ABC transporters pathway. Both L-Arg and L-Cit promoted increased NO, GSH-Px, T-AOC, and VEGF levels, enhancing early embryo implantation. Additionally, L-Arg and L-Cit synergistically influenced pyrimidine metabolism, regulating the production of N-myristoylphosphorylcholine, N-oleoyl-d-erythro-sphingosylphosphorylcholine, 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine, and 1-docosahexaenoyl- 2-stearoyl-sn-glycero-3-phosphocholine. This modulation resulted in increased NO, GSH-Px, T-AOC, and VEGF in multiparous cows, ultimately supporting early embryo implantation.
Question: Write a study description for the study titled 'A Pilot Characterization of the Human Chronobiome'.
Answer: Physiological function, disease expression and drug effects vary by time-of-day. Clock disruption in mice results in cardio-metabolic, immunological and neurological dysfunction; circadian misalignment using forced desynchrony increases cardiovascular risk factors in humans. Here we integrated data from remote sensors, physiological and multi-omics analyses to assess the feasibility of detecting time dependent signals - the chronobiome - despite the noise attributable to the behavioral differences of free-living human volunteers. The majority (62%) of sensor readouts showed time-specific variability including the expected variation in blood pressure, heart rate, and cortisol. While variance in the multi-omics is dominated by inter-individual differences, temporal patterns are evident in the metabolome (5.4% in plasma, 5.6% in saliva) and in several genera of the oral microbiome. This demonstrates, despite a small sample size and limited sampling, the feasibility of characterizing at scale the human chronobiome in the wild. Such reference data at scale are a prerequisite to detect and mechanistically interpret discordant data derived from patients with temporal patterns of disease expression, to develop time-specific therapeutic strategies and to refine existing treatments.
Question: Write a study description for the study titled 'Unexpected similarities between the Schizosaccharomyces and human blood metabolomes, and novel human metabolites (Blood fraction)'.
Answer: Metabolomics, a new branch of chemical biology, provides compositional and quantitative information about the state of organism or cell at the levels of metabolite constituents. We here report non-targeted metabolome of human blood that is made up of plasma and red blood cells (RBCs), using liquid-chromatography and mass spectrometry (LC-MS). Previously, metabolome of a microbe, the fission yeast Schizosaccharomyces pombe, was reported. Two sets of metabolome results are highly similar in their compositions: among 133 compounds identified in human blood, 101 (75%) are also present in S. pombe, and among 57 compounds enriched in RBC, 45 (78%) are also present in S. pombe. Most abundant metabolites are ATP, glutathione and glutamine. Many of other relatively abundant metabolites identified are also implicated in energy, anti-oxidant and amino acid metabolism. We show fourteen newly-identified blood compounds; citramalate, GDP-glucose, trimethyl-histidine, trimethyl-phenylalanine, trimethyl-tryptophan, trimethyl-tyrosine, UDP-acetyl-glucosamine, UDP-glucuronate, dimethyl-lysine, glutamate methyl ester, N-acetyl-(iso)leucine, N-acetyl-glutamate, N2-acetyl-lysine, and N6-acetyl-lysine (the first eight are enriched in RBC). Ten of them are also detected in S. pombe, and ten of them are methylated or acetylated, amino acids. Trimethylated or acetylated free amino acids are also abundant in white blood cell. Their physiologic role may be investigated in the future by yeast genetics.
Question: Write a study description for the study titled 'Untargeted Metabolomics To Ascertain Antibiotic Modes of Action'.
Answer: Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also collect data on off-target effects and drug modifications. Here, we present data from an untargeted liquid chromatography-mass spectrometry approach to identify the modes of action of eight compounds: 1-[3-fluoro-4-(5-methyl-2,4-dioxo-pyrimidin-1-yl)phenyl]-3-[2-(trifluoromethyl)phenyl]urea (AZ1), 2-(cyclobutylmethoxy)-5'-deoxyadenosine, triclosan, fosmidomycin, CHIR-090, carbonyl cyanidem-chlorophenylhydrazone (CCCP), 5-chloro-2-(methylsulfonyl)-N-(1,3-thiazol-2-yl)-4-pyrimidinecarboxamide (AZ7), and ceftazidime. Data analysts were blind to the compound identities but managed to identify the target as thymidylate kinase for AZ1, isoprenoid biosynthesis for fosmidomycin, acyl-transferase for CHIR-090, and DNA metabolism for 2-(cyclobutylmethoxy)-5'-deoxyadenosine. Changes to cell wall metabolites were seen in ceftazidime treatments, although other changes, presumably relating to off-target effects, dominated spectral outputs in the untargeted approach. Drugs which do not work through metabolic pathways, such as the proton carrier CCCP, have no discernible impact on the metabolome. The untargeted metabolomics approach also revealed modifications to two compounds, namely, fosmidomycin and AZ7. An untreated control was also analyzed, and changes to the metabolome were seen over 4 h, highlighting the necessity for careful controls in these types of studies. Metabolomics is a useful tool in the analysis of drug modes of action and can complement other technologies already in use.
Question: Write a study description for the study titled 'Critical shifts in lipid metabolism promote megakaryocyte differentiation and proplatelet formation (Shotgun lipidomics assays after inhibition with FSG67 and Triacsin C)'.
Answer: During megakaryopoiesis, megakaryocytes (MK) undergo cellular morphological changes with strong modification of membrane composition and lipid signaling. Here we adopt a lipid-centric multi-omics approach to create a quantitative map of the MK lipidome during maturation and proplatelet formation. Data reveal that MK differentiation is driven by an increased fatty acyl import and de novo lipid synthesis, resulting in an anionic membrane phenotype. Pharmacological perturbation of fatty acid import and phospholipid synthesis blocked membrane remodeling and directly reduced MK polyploidization and proplatelet formation resulting in thrombocytopenia. The anionic lipid shift during megakaryopoiesis was paralleled by lipid-dependent relocalization of the scaffold protein CKIP-1 and recruitment of the kinase CK2α to the plasma membrane, which seems to be essential for sufficient platelet biogenesis. Overall, this study provides a framework to understand how the MK lipidome is altered during maturation and the impact of MK membrane lipid remodeling on MK kinase signaling involved in thrombopoiesis.Shotgun lipidomics assays after inhibition with FSG67 and Triacsin C are reported in the current assay MTBLS6083Shotgun lipidomics assays without inhibition are reported in MTBLS6082Targeted lipidomics assay without inhibition are reported in MTBLS6084
Question: Write a study description for the study titled 'SMN deficiency perturbs monoamine neurotransmitter metabolism in spinal muscular atrophy'.
Answer: Beyond motor neuron degeneration, homozygous mutations in the survival motor neuron 1 (SMN1) gene cause multiorgan and metabolic defects in patients with spinal muscular atrophy (SMA). However, the precise biochemical features of these alterations and the age of onset in the brain and peripheral organs remain unclear. Using untargeted NMR-based metabolomics in SMA mice, we identify cerebral and hepatic abnormalities related to energy homeostasis pathways and amino acid metabolism, emerging already at postnatal day 3 (P3) in the liver. Through HPLC, we find that SMN deficiency induces a drop in cerebral norepinephrine levels in overt symptomatic SMA mice at P11, affecting the mRNA and protein expression of key genes regulating monoamine metabolism, including aromatic L-amino acid decarboxylase (AADC), dopamine beta-hydroxylase (DβH) and monoamine oxidase A (MAO-A). In support of the translational value of our preclinical observations, we also discovered that SMN upregulation increases cerebrospinal fluid norepinephrine concentration in Nusinersen-treated SMA1 patients. Our findings highlight a previously unrecognized harmful influence of low SMN levels on the expression of critical enzymes involved in monoamine metabolism, suggesting that SMN-inducing therapies may modulate catecholamine neurotransmission. These results may also be relevant for setting therapeutic approaches to counteract peripheral metabolic defects in SMA.
Question: Write a study description for the study titled 'Organotypic microfluidic breast cancer model reveals starvation-induced spatial-temporal metabolic adaptations'.
Answer: BACKGROUND: Ductal carcinoma in situ (DCIS) is the earliest stage of breast cancer. During DCIS, tumor cells remain inside the mammary duct, growing under a microenvironment characterized by hypoxia, nutrient starvation, and waste product accumulation; this harsh microenvironment promotes genomic instability and eventually cell invasion. However, there is a lack of biomarkers to predict what patients will transition to a more invasive tumor or how DCIS cells manage to survive in this harsh microenvironment.  METHODS: In this work, we have developed a microfluidic model that recapitulates the DCIS microenvironment. In the microdevice, a DCIS model cell line was grown inside a luminal mammary duct model, embedded in a 3D hydrogel with mammary fibroblasts. Cell behavior was monitored by confocal microscopy and optical metabolic imaging. Additionally, metabolite profile was studied by NMR whereas gene expression was analyzed by RT-qPCR.  FINDINGS: DCIS cell metabolism led to hypoxia and nutrient starvation; revealing an altered metabolism focused on glycolysis and other hypoxia-associated pathways. In response to this starvation and hypoxia, DCIS cells modified the expression of multiple genes, and a gradient of different metabolic phenotypes was observed across the mammary duct model. These genetic changes observed in the model were in good agreement with patient genomic profiles; identifying multiple compounds targeting the affected pathways. In this context, the hypoxia-activated prodrug tirapazamine selectively destroyed hypoxic DCIS cells.  INTERPRETATION: The results showed the capacity of the microfluidic model to mimic the DCIS structure, identifying multiple cellular adaptations to endure the hypoxia and nutrient starvation generated within the mammary duct. These findings may suggest new potential therapeutic directions to treat DCIS. In summary, given the lack of in vitro models to study DCIS, this microfluidic device holds great potential to find new DCIS predictors and therapies and translate them to the clinic.
Question: Write a study description for the study titled 'Haplotype-resolved female and male genomes reveal sex-specific genomic regions and provide insights into thermal stress in Scapharca subcrenata'.
Answer: Integrated analyses of transcriptomic, proteomic and metabolomic data sets consistently highlights the crucial involvement of protein function and retinol metabolism pathways in the heat-resistant strain of S. subcrenata. These findings underscore the significance of these pathways in enabling the strain's ability to withstand high temperatures and adapt to heat stress. The haplotype-resolved female and male genomes and multiomics data presented in this study provide a solid foundation for investigating the molecular mechanisms of sex in S. subcrenata.
Question: Write a study description for the study titled 'The unique composition of Indian gut microbiome, gene catalogue and associated faecal metabolome deciphered using multi-omics approaches'.
Answer: BACKGROUND: Metagenomic studies carried out in the past decade have led to an enhanced understanding of the gut microbiome in human health, however, the Indian gut microbiome is not well explored yet. We analysed the gut microbiome of 110 healthy individuals from two distinct locations (North-Central and Southern) in India using multi-omics approaches, including 16S rRNA gene amplicon sequencing, whole genome shotgun metagenomic sequencing, and metabolomic profiling of faecal and serum samples.  RESULTS: The gene catalogue established in this study emphasizes the uniqueness of the Indian gut microbiome in comparison to other populations. The gut microbiome of the cohort from North-Central India, which was primarily consuming a plant-based diet, was found to be associated with Prevotella, and also showed an enrichment of Branched Chain Amino Acid (BCAA) and lipopolysaccharide (LPS) biosynthesis pathways. In contrast, the gut microbiome of the cohort from Southern India, which was consuming an omnivorous diet, showed associations with Bacteroides, Ruminococcus and Faecalibacterium, and had an enrichment of Short Chain Fatty Acid (SCFA) biosynthesis pathway and BCAA transporters. This corroborated well with the metabolomics results, which showed higher concentration of BCAAs in the serum metabolome of the North-Central cohort and an association with Prevotella. In contrast, the concentration of BCAAs were found higher in the faecal metabolome of the Southern-India cohort, and showed a positive correlation with the higher abundance of BCAA transporters.  CONCLUSIONS: The study reveals the unique composition of Indian gut microbiome, establishes the Indian gut microbial gene catalogue, and compares it with the gut microbiome of other populations. The functional associations revealed using metagenomic and metabolomic approaches provide novel insights on the gut-microbe-metabolic axis, which will be useful for future epidemiological and translational researches.