PubMed
Broad Microbial Community Functions in a Conventional Activated Sludge System Exhibit Temporal Stability
Environ Sci Technol. 2024 Dec 4. doi: 10.1021/acs.est.4c09535. Online ahead of print.ABSTRACTWastewater microbial communities within conventional activated sludge (CAS) systems can perform hundreds of biotransformations whose relative importance, frequency, and temporal stability remain largely unexplored. To improve our understanding of biotransformations in CAS systems, we collected 24 h composite samples from the influent and effluent of a CAS system over 14 days, analyzed samples using high-resolution mass spectrometry (HRMS), and conducted a nontarget analysis of our HRMS acquisitions. We found that over 50% of the chemical features in the influent were completely removed, and the daily number of detected features exhibited low variability with a coefficient of variation of 0.07. Additionally, we found 352 Core chemical features present in every sample at both locations. We used chemical features to search for evidence of 19 potential biotransformations and detected 9 of these biotransformations at a frequency of over 80 times per day, where evidence for dehydrogenations, hydroxylations, and acetylations was most frequently detected. The daily number of detections for the 9 biotransformations exhibited coefficients of variation ranging from 0.13-0.20, revealing the broad temporal stability for these wastewater microbial community functions. This stability contrasts with the previously observed temporal variability for micropollutant biotransformations, suggesting that micropollutant biotransformations are linked to specialized microbial community functions.PMID:39628310 | DOI:10.1021/acs.est.4c09535
Effects of seed infection by Fusarium verticillioides on maize performance against Sesamia nonagrioides attack
Physiol Plant. 2024 Nov-Dec;176(6):e14649. doi: 10.1111/ppl.14649.ABSTRACTIn maize (Zea mays L), the fungus Fusarium verticillioides can behave as a pathogen, but it is also able of asymptomatic colonization as an endophyte. Therefore, it would be of great value to identify metabolites and/or metabolic pathways implicated in mutualistic and pathogenic interactions. The objectives of the present study were: (i) to investigate the effect of seed colonization by F. verticillioides on maize growth in a group of inbreds with contrasting resistance to F. verticillioides; (ii) to know if maize priming by Fusarium seed infection affects maize response to other parasites and if these differences could depend on genotype resistance to Fusarium; and (iii) to determine which metabolites could be associated to beneficial/detrimental changes on maize performance. Targeted and untargeted metabolomic approaches were carried out to characterize the response of control and primed plants to the most common maize pest in the Mediterranean area, Sesamia nonagrioides Lefèbvre (Lepidoptera: Noctuidae). The study cannot assume a differential pattern of infection between resistant and susceptible inbreds, but seed inoculation with F. verticillioides upon infestation with S. nonagrioides, significantly altered defense metabolism in resistant inbreds. Meanwhile it also induced a lipid response in susceptible inbreds that could mediate their increased plant susceptibility to insect attack. Although an endophytic interaction between the fungus and specific genotypes cannot be proven, defense pathways were favorably altered by F. verticillioides colonization among resistant inbreds.PMID:39627872 | DOI:10.1111/ppl.14649
Machine learning based metabolomic and genetic profiles for predicting multiple brain phenotypes
J Transl Med. 2024 Dec 3;22(1):1098. doi: 10.1186/s12967-024-05868-3.ABSTRACTBACKGROUND: It is unclear regarding the association between metabolomic state/genetic risk score(GRS) and brain volumes and how much of variance of brain volumes is attributable to metabolomic state or GRS.METHODS: Our analysis included 8635 participants (52.5% females) aged 40-70 years at baseline from the UK Biobank. Metabolomic profiles were assessed using nuclear magnetic resonance at baseline (between 2006 and 2010). Brain volumes were measured using magnetic resonance imaging between 2014 and 2019. Machine learning was used to generate metabolomic state and GRS for each of 21 brain phenotypes.RESULTS: Individuals in the top 20% of metabolomic state had 2.4-35.7% larger volumes of 21 individual brain phenotypes compared to those in the bottom 20% while the corresponding number for GRS ranged from 1.5 to 32.8%. The proportion of variance of brain volumes (R [2]) explained by the corresponding metabolomic state ranged from 2.2 to 19.4%, and the corresponding number for GRS ranged from 0.8 to 8.7%. Metabolomic state provided no or minimal additional prediction values of brain volumes to age and sex while GRS provided moderate additional prediction values (ranging from 0.8 to 8.8%). No significant interplay between metabolomic state and GRS was observed, but the association between metabolomic state and some regional brain volumes was stronger in men or younger individuals. Individual metabolomic profiles including lipids and fatty acids were strong predictors of brain volumes.CONCLUSIONS: In conclusion, metabolomic state is strongly associated with multiple brain volumes but provides minimal additional prediction value of brain volumes to age + sex. Although GRS is a weaker contributor to brain volumes than metabolomic state, it provides moderate additional prediction value of brain volumes to age + sex. Our findings suggest metabolomic state and GRS are important predictors for multiple brain phenotypes.PMID:39627804 | DOI:10.1186/s12967-024-05868-3
Pre-pregnancy obesity is associated with an altered maternal metabolome and reduced Flt3L expression in preterm birth
Sci Rep. 2024 Dec 3;14(1):30027. doi: 10.1038/s41598-024-81194-4.ABSTRACTMechanisms linking pre-pregnancy obesity to increased preterm birth risk are unclear. Here, we examined the impact of pre-pregnancy obesity on metabolites, Fms-related tyrosine kinase 3 ligand (Flt3L), and proinflammatory cytokine profiles in preterm birth. We used cytokine bead array, ELISA and Gas Chromatography-Mass Spectrometry (GC-MS) to determine cytokine and metabolite profiles in maternal and cord blood samples from 124 pregnant women in Australia, who gave birth at term (n = 86) or preterm (n = 38). Besides the expected variations in birth weight and gestational age, all demographic characteristics, including pre-pregnancy body mass index, were similar between the term and preterm birth groups. Mothers in the preterm birth group had reduced Flt3L (P = 0.002) and elevated IL-6 (P = 0.002) compared with term birthing mothers. Among mothers who gave birth preterm, those with pre-pregnancy obesity had lower Flt3L levels (P = 0.02) compared with lean mothers. Flt3L and IL-6 were similar in cord blood across both groups, but TNFα levels (P = 0.02) were reduced in preterm newborns. Metabolomic analysis revealed significant shifts in essential metabolites in women with pre-pregnancy obesity, some of which were linked to preterm births. Our findings suggest that maternal pre-pregnancy obesity alters the metabolome and reduces Flt3L expression, potentially increasing risk of preterm birth.PMID:39627409 | DOI:10.1038/s41598-024-81194-4
Metabolomic and transcriptomic insights into the mechanisms of renal ischemia-reperfusion injury progression
Sci Rep. 2024 Dec 3;14(1):30101. doi: 10.1038/s41598-024-81600-x.ABSTRACTRenal ischemia-reperfusion injury (IRI) is an important cause of acute kidney injury (AKI). However, the pathophysiological changes and mechanisms during IRI-AKI progression remain unclear. This study aims toinvestigate the potential mechanisms in the progression of IRI-AKI by integrating metabolomics and transcriptomics data, providing a reference for the subsequent identification of biomarkers and therapeutic targets. IRI-AKI rat models with 30 min of ischemia and 24-72 h of reperfusion surgery simulating the progression of AKI were established. Compared to the control group underwent sham surgery (NC group), most of the differentially expressed metabolites (DEMs) in IRI-AKI 24 h and IRI-AKI 72 h decreased, mainly including amino acids, organic acids, and carnitines. Additionally, we found that DEMs were mainly enriched in amino acid-related pathways, among which valine, leucine, and isoleucine biosynthesis were dramatically altered in all comparisons. Transcriptomics revealed that differentially expressed genes (DEGs) were primarily involved in amino acid, lipid, and fatty acid metabolism. By integrating metabolomics and transcriptomics, we found valine, leucine, and isoleucine biosynthesis play key roles in IRI-AKI development. Our findings concluded that valine, leucine, and isoleucine pathways are hubs that potentially connect transcriptomes to metabolomes, providing new insights regarding the pathogenesis of IRI-AKI and its potential biomarkers and therapeutic strategies.PMID:39627404 | DOI:10.1038/s41598-024-81600-x
NMR metabolomics as a complementary tool to brix-acid tests for navel orange quality control of long-term cold storage
Sci Rep. 2024 Dec 3;14(1):30078. doi: 10.1038/s41598-024-77871-z.ABSTRACTQuality control plays a crucial role in maintaining the reputation of agricultural organizations by ensuring that their products meet the expected standards and preventing any loss during the packaging process. A significant responsibility of quality control is conducting periodic product assessments. However, subjective interpretation during physical inspections of fruits can lead to variability in reporting. To counter this, assessing total soluble solids (Brix) and percent acidity (Acid) can provide a more objective approach. Nevertheless, it is essential to note that many fruit metabolites can impact these parameters. Nuclear magnetic resonance (NMR) spectroscopy, particularly 1H-NMR, has become a popular tool for quality control in recent years due to its precision, sample preservation, and high throughput analysis. This manuscript investigates if the standard Brix/Acid tests are directly related to the levels of metabolites during cold storage. Using citrus as the model system, a metabolomics analysis was conducted to identify patterns in the cold storage metabolite profiles of the juice, albedo, and flavedo tissues. The results show that Brix (or total dissolved solids) correlates well with sucrose, glucose, and fructose levels and moderately with choline levels. Acid (percent acidity) levels displayed a negative correlation with both fructose and choline levels. Interestingly, the formate levels were susceptible to storage time and directly related to Acid measurements. This study suggests metabolomics could be a complementary technique to quality control of fruits in cold storage, especially with cost-effective desktop NMR spectrometers.PMID:39627282 | DOI:10.1038/s41598-024-77871-z
Habitual dietary methyl donor's intake and metabolic profile in obese individuals: a cross-sectional study
Sci Rep. 2024 Dec 3;14(1):30046. doi: 10.1038/s41598-024-75388-z.ABSTRACTConsidering the role of dietary methyl donor (DMD) in numerous biochemical processes, we hypothesized that DMD could play an important role in metabolic syndrome such as hyperlipidemia, hypertension, insulin resistance, and appetite in obese individuals. This cross-sectional study was conducted on 335 obese people. We collected dietary data using a valid and reliable 147-question Food Frequency Questionnaire (FFQ). Multivariate multinomial logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between dietary methyl intake and cardio-metabolic risk factors. After adjusting for confounding variables, individuals at the fourth and third quartile of DMD, were more likely to have lower low-density lipoprotein cholesterol (LDL-C) (OR = 0.968, CI = 0.943-0.994, P = 0.015 and OR = 0.978, CI = 0.957-0.998, P = 0.03 respectively) versus first quartile. Also, total cholesterol (TC) showed a significant decrease in forth quartile of DMD in model III (OR = 0.974, CI = 0.951-0.997, P = 0.029). Current results suggested that, high DMDs' consumption, significantly associated with decreased risk of cardiometabolic risk factors.PMID:39627237 | DOI:10.1038/s41598-024-75388-z
Ellagic acid alleviates high-fructose diet-induced non-alcoholic fatty liver disease by modulating liver metabolic profiles and gut microbiota
Int J Food Sci Nutr. 2024 Dec 3:1-15. doi: 10.1080/09637486.2024.2435849. Online ahead of print.ABSTRACTThis study integrated analyses of gut microbiota and metabolomics to investigate the impact of ellagic acid (EA) on non-alcoholic fatty liver disease (NAFLD). Compared to the high-fructose diet (HFruD) group, the EA group exhibited reduced body weight and fat mass, alongside improvements in blood glucose and lipid metabolism. Liver metabolomics analysis revealed that EA increased the abundance of metabolites in pathways related to unsaturated fatty acids, amino acids and bile acids. Furthermore, EA induced alterations in the composition and structure of gut microbiota, notably decreasing bacterial genera enriched by HFruD while promoting beneficial bacteria such as Faecalibaculum. Correlation analysis demonstrated significant associations among NAFLD markers, gut microbiota and liver metabolites influenced by EA. This study provides new insights into the anti-NAFLD effects of EA, suggesting EA as a promising nutraceutical for improving NAFLD.PMID:39627026 | DOI:10.1080/09637486.2024.2435849
The amino acid metabolism pathway of peripheral T lymphocytes and ketamine-induced schizophrenia-like phenotype
J Psychiatry Neurosci. 2024 Dec 3;49(6):E413-E426. doi: 10.1503/jpn-240038. Print 2024 Nov-Dec.ABSTRACTBACKGROUND: The intricate interplay between peripheral adaptive immune cells and the central nervous system (CNS) has garnered increasing recognition. Given that alterations in cell quantities often translate into modifications in metabolite profiles and that these metabolic changes can potentially traverse the bloodstream and enter the CNS, thereby modulating the progression of mental illnesses, we sought to explore the metabolic profiles of peripheral immune cells in a ketamine-treated mouse model of schizophrenia.METHODS: We used flow cytometry to scrutinize the alterations in peripheral adaptive immune cells in a ketamine-induced schizophrenia mouse model. Subsequently, we implemented an untargeted metabolomic approach with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to detect the metabolite profiles of peripheral abnormal lymphocytes and identify differential metabolites present in plasma. We then employed targeted metabolomics using UPLC-MS/MS to quantify the common differential metabolites detected in mouse plasma.RESULTS: Flow cytometry analysis detected a notable increase in the count of peripheral CD3+ T cells in a ketamine-induced schizophrenia mouse model. Subsequent untargeted metabolomics analysis revealed that the amino acid metabolism pathway underwent substantial alterations. A detailed quantification of 22 amino acid profiles in the peripheral plasma indicated significant elevation in the levels of glycine, alanine, asparagine, and aspartic acid.LIMITATIONS: Our ongoing research has yet to conclusively identify the precise amino acid metabolism pathway that serves as the pivotal factor in the manifestation of the schizophrenia-like phenotype induced by ketamine.CONCLUSION: The peripheral amino acid metabolism pathway is involved in the ketamine-induced schizophrenia-like phenotype. The metabolic profile of peripheral immune cells could provide accurate biomarkers for the diagnosis and treatment of psychiatric diseases.PMID:39626901 | DOI:10.1503/jpn-240038
Cellular pathway disturbances elicited by realistic dexamethasone concentrations in gills of mussel Mytilus galloprovincialis as assessed by a multi-biomarker approach
Environ Toxicol Pharmacol. 2024 Dec 1:104598. doi: 10.1016/j.etap.2024.104598. Online ahead of print.ABSTRACTThe growing usage of glucocorticoids for a variety of diseases raises concerns since these drugs, including the anti-inflammatory dexamethasone (DEX), are frequently found in the environment. The impact of DEX was evaluated on mussels Mytilus galloprovincialis (Lamarck, 1819) by exposure to environmental concentrations (C1: 4ng/L; C2: 40ng/L; C3: 400ng/L; C4: 2000 ng/L), and sampling at 3 (T3), 6 (T6), and 12 (T12) days. A multi-biomarker approach was applied on gills, involved in gas exchange, feed filtering, and osmoregulation. A dose- and time-dependent uptake of DEX was recorded, besides haemocyte infiltration, increased neutral and acid mucopolysaccharides, and a general pro-oxidant effect witnessed by lipid peroxidation and altered antioxidant system. Metabolomics revealed rise in protein turnover and energy demand by fluctuations in free amino acids (alanine, glycine) and energy-related metabolites (succinate, ATP/ADP). It is necessary to reduce DEX dosage from the environment by recovery strategies and effective eco-pharmacovigilance programs.PMID:39626850 | DOI:10.1016/j.etap.2024.104598
Stepwise processing of Chlorella sorokiniana confers plant biostimulant that reduces mineral fertilizer requirements
Bioresour Technol. 2024 Dec 1:131923. doi: 10.1016/j.biortech.2024.131923. Online ahead of print.ABSTRACTWe developed a stepwise method to transform Chlorella sorokiniana microalgal biomass into a potent biostimulant. The method, including maceration, high-pressure homogenization, and enzymatic hydrolysis, preserves the bioactive properties of the biomass as a biostimulant while minimizing plant inhibitory effects. Fractions were characterized individually, and optimal concentrations were determined using a rapid Arabidopsis root assay. A blend of optimal concentrations of fractions was identified as the most stimulating extract, increasing the root elongation by 25%. When applied to tomato plants and monitored using high-throughput plant phenotyping, the blend displayed a 25 % reduction in mineral fertilizer use. Metabolomic analysis of the tomato plants showed significantly enhanced carbon and nitrogen metabolism in the leaves. Our findings indicate that the stepwise processing not only produces an effective biostimulant but also generates substantial residual biomass for a potential multiproduct biorefinery approach that can improve the overall techno-economic outlook.PMID:39626806 | DOI:10.1016/j.biortech.2024.131923
Metabolite-level regulation of enzymatic activity controls awakening of cyanobacteria from metabolic dormancy
Curr Biol. 2024 Nov 26:S0960-9822(24)01518-5. doi: 10.1016/j.cub.2024.11.011. Online ahead of print.ABSTRACTTransitioning into and out of dormancy is a crucial survival strategy for many organisms. In unicellular cyanobacteria, surviving nitrogen-starved conditions involves tuning down their metabolism and reactivating it once nitrogen becomes available. Glucose-6-phosphate dehydrogenase (G6PDH), the enzyme that catalyzes the first step of the oxidative pentose phosphate (OPP) pathway, plays a key role in this process. G6PDH is produced at the onset of nitrogen starvation but remains inactive in dormant cells, only to be rapidly reactivated when nitrogen is restored. In this study, we investigated the mechanisms underlying this enzymatic regulation and found that G6PDH inactivation is primarily due to the accumulation of inhibitory metabolites. Moreover, our findings demonstrate that metabolite-level regulation is the driving force behind the resuscitation program. This study highlights the critical importance of metabolite-level regulation in ensuring rapid and precise enzymatic control, enabling microorganisms to swiftly adapt to environmental changes and undergo developmental transitions.PMID:39626669 | DOI:10.1016/j.cub.2024.11.011
The revelation of high-yield amino acids and probiotic characteristics of an intestinal Lacticaseibacillus rhamnosus X9C17
Food Chem. 2024 Nov 26;467:142245. doi: 10.1016/j.foodchem.2024.142245. Online ahead of print.ABSTRACTWith the popularization of probiotic products, tapping high-quality probiotics is crucial. Therefore, in this study, Lacticaseibacillus rhamnosus (X9C17) was selected from a pool of 54 isolates for its remarkable ability to survive in simulated gastrointestinal fluid (Gastric juice: 81.08 %, intestinal juice: 48 %), after which its probiotic characteristics were evaluated. Strain X9C17 exhibits strong antibacterial properties, hydrophobicity, self-aggregation ability and significant antioxidant capacity, and it can produce essential amino acids, including glycine and proline. Therefore, the experimental results show that X9C17 has potential probiotic function. Metabolomics methods were used to study the changes in metabolites in X9C17 fermented milk. The hydroxycinnamic acid, L-3-phenyllactic acid, amino acids and multiple vitamins accumulated in the fermented milk, played a positive role in the probiotic function and unique flavour of the product. In summary, This study offers new insights and data supporting the physiological mechanisms of probiotics and their application in functional fermented foods.PMID:39626560 | DOI:10.1016/j.foodchem.2024.142245
Comprehensive multi-omics analysis of fermented Chinese artichoke: Insights from Flavoromics, metagenomics, and untargeted metabolomics
Food Chem. 2024 Nov 28;467:142278. doi: 10.1016/j.foodchem.2024.142278. Online ahead of print.ABSTRACTFermented Chinese Artichoke, a traditional Chinese fermented vegetable, has a distinctive flavor profile shaped by its fermentation process. This study applied flavoromics, metagenomics, and untargeted metabolomics to comprehensively analyze flavor compounds, microbial communities, and metabolic transformations during fermentation. We identified 43 volatile organic compounds (VOCs), with Terpineol, 1-Hexanol, and Linalool as the predominant components. Metagenomic analysis highlighted Lactiplantibacillus plantarum, Priestia megaterium, and Pediococcus pentosaceus as the dominant species, while Lactiplantibacillus, Pediococcus, and Bacillus were key in flavor development. Untargeted metabolomics further revealed increases in organic acids, amino acids, and umami compounds, contributing to flavor enhancement. These findings offer valuable insights into flavor formation mechanisms in Fermented Chinese Artichoke and provide guidance for improving its industrial fermentation quality.PMID:39626557 | DOI:10.1016/j.foodchem.2024.142278
Combined metabolomic and transcriptomic analysis to reveal the response of rice to Mn toxicity stress
Ecotoxicol Environ Saf. 2024 Dec 2;289:117454. doi: 10.1016/j.ecoenv.2024.117454. Online ahead of print.ABSTRACTExcessive manganese (Mn) concentrations affect plant gene expression, alter metabolite content, and impede plant growth. Rice plants are particularly susceptible to Mn toxicity stress in acidic soil; however, the underlying molecular mechanisms are so far unclear. This study used transcriptomic and metabolomic sequencing to examine roots and leaves of rice plants subjected to Mn toxicity stress. The findings showed that high Mn stress increased the content of malondialdehyde, proline, and soluble sugar in rice roots by 262.28 %, 803.37 %, and 167.25 %, respectively. In rice roots, the enzymatic activities of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) elevated by 119.69 %, 408.44 %, 151.97 %, and 27.19 %, respectively. In rice leaves, the proline content increased by 632.45 %, whereas the enzymatic activities of POD, SOD, CAT, and APX were elevated by 167.17 %, 14.08 %, 103.60 %, and 146.74 %, respectively. Mn toxicity stress decreased soluble protein content in rice roots, and in the leaves, it reduced the soluble protein, soluble sugar, and chlorophyll contents. In addition, Mn toxicity led to reduced biomass accumulation, plant height, stem diameter, and root growth. The contents of salicylic acid (increased by 118.40 % in roots and 66.38 % in leaves) and jasmonic acid (decreased by 50.18 % in roots and increased by 143.97 % in leaves) were also affected. Transcriptome analysis identified differentially expressed genes associated with transcription factors, antioxidant enzymes, and metal transporters. Metabolomics revealed 176 and 214 different metabolites in the roots and leaves, respectively, that under Mn toxicity stress affected major metabolic pathways associated with fatty and amino acids. The phenylalanine metabolism pathway was significantly enriched in both the roots and leaves. Combined transcriptomic and metabolomic analyses revealed three key pathways: lysine degradation and phenylpropanoid biosynthesis in roots and alpha-linolenic acid metabolism in leaves. Metabolic substances and genes associated with metabolic enzymes were identified. These results enhance our understanding of the molecular processes underlying the responses of rice to Mn toxicity stress and provide a basis for breeding Mn-tolerant rice varieties.PMID:39626483 | DOI:10.1016/j.ecoenv.2024.117454
Inhibitory effect of Zhujing Pill on myopia progression: Mechanistic insights based on metabonomics and network pharmacology
PLoS One. 2024 Dec 3;19(12):e0312379. doi: 10.1371/journal.pone.0312379. eCollection 2024.ABSTRACTOBJECTIVES: This study endeavored to uncover the mechanisms by which Zhujing pill (ZJP) slows myopia progression.METHODS: We employed biometric analyses to track diopter and axial length changes in guinea pigs with negative lens-induced myopia (LIM). Through integrating metabonomics and network pharmacology, we aimed to predict the anti-myopic targets and active ingredients of ZJP. Subsequent analysis, including real-time fluorescent quantitative PCR (qPCR) and Western blotting (WB), assessed the expression levels of CHRNA7, LPCAT1, and NOS2 in retinal tissues.KEY FINDINGS: Our findings demonstrate that ZJP significantly mitigates diopter increase and axial elongation in LIM guinea pigs. Metabonomic analysis revealed significant changes in 13 serum metabolites, with ZJP reversing the expression of 5 key metabolites. By integrating metabonomics with network pharmacology, we identified core targets of ZJP against myopia and constructed a compound-gene-disease-metabolite network. The expressions of LPCAT1 and CHRNA7 were found to decrease in the LIM group but increase with ZJP treatment, whereas NOS2 expression showed the opposite pattern.CONCLUSIONS: This investigation provides the first evidence of ZJP's multifaceted effectiveness in managing myopia, highlighting its impact on multiple components, targets, and pathways, including the novel involvement of LPCAT1 and CHRNA7 in myopia pathogenesis.PMID:39625993 | DOI:10.1371/journal.pone.0312379
Disentangling the consequences of type 2 diabetes on targeted metabolite profiles using causal inference and interaction QTL analyses
PLoS Genet. 2024 Dec 3;20(12):e1011346. doi: 10.1371/journal.pgen.1011346. Online ahead of print.ABSTRACTCirculating metabolite levels have been associated with type 2 diabetes (T2D), but the extent to which T2D affects metabolite levels and their genetic regulation remains to be elucidated. In this study, we investigate the interplay between genetics, metabolomics, and T2D risk in the UK Biobank dataset using the Nightingale panel composed of 249 metabolites, 92% of which correspond to lipids (HDL, IDL, LDL, VLDL) and lipoproteins. By integrating these data with large-scale T2D GWAS from the DIAMANTE meta-analysis through Mendelian randomization analyses, we find 79 metabolites with a causal association to T2D, all spanning lipid-related classes except for Glucose and Tyrosine. Twice as many metabolites are causally affected by T2D liability, spanning almost all tested classes, including branched-chain amino acids. Secondly, using an interaction quantitative trait locus (QTL) analysis, we describe four metabolites consistently replicated in an independent dataset from the Estonian Biobank, for which genetic loci in two different genomic regions show attenuated regulation in T2D cases compared to controls. The significant variants from the interaction QTL analysis are significant QTLs for the corresponding metabolites in the general population but are not associated with T2D risk, pointing towards consequences of T2D on the genetic regulation of metabolite levels. Finally, through differential level analyses, we find 165 metabolites associated with microvascular, macrovascular, or both types of T2D complications, with only a few discriminating between complication classes. Of the 165 metabolites, 40 are not causally linked to T2D in either direction, suggesting biological mechanisms specific to the occurrence of complications. Overall, this work provides a map of the consequences of T2D on Nightingale targeted metabolite levels and on their genetic regulation, enabling a better understanding of the T2D trajectory leading to complications.PMID:39625957 | DOI:10.1371/journal.pgen.1011346
WHIRLY1 regulates aliphatic glucosinolate biosynthesis in early seedling development of Arabidopsis
Plant J. 2024 Dec 3. doi: 10.1111/tpj.17181. Online ahead of print.ABSTRACTWHIRLY1 belongs to a family of plant-specific transcription factors capable of binding DNA or RNA in all three plant cell compartments that contain genetic materials. In Arabidopsis thaliana, WHIRLY1 has been studied at the later stages of plant development, including flowering and leaf senescence, as well as in biotic and abiotic stress responses. In this study, WHIRLY1 knockout mutants of A. thaliana were prepared by CRISPR/Cas9-mediated genome editing to investigate the role of WHIRLY1 during early seedling development. The loss-of-function of WHIRLY1 in 5-day-old seedlings did not cause differences in the phenotype and the photosynthetic performance of the emerging cotyledons compared with the wild type. Nevertheless, comparative RNA sequencing analysis revealed that the knockout of WHIRLY1 affected the expression of a small but specific set of genes during this critical phase of development. About 110 genes were found to be significantly deregulated in the knockout mutant, wherein several genes involved in the early steps of aliphatic glucosinolate (GSL) biosynthesis were suppressed compared with wild-type plants. The downregulation of these genes in WHIRLY1 knockout lines led to decreased GSL contents in seedlings and in seeds. Since GSL catabolism mediated by myrosinases was not altered during seed-to-seedling transition, the results suggest that AtWHIRLY1 plays a major role in modulation of aliphatic GSL biosynthesis during early seedling development. In addition, phylogenetic analysis revealed a coincidence between the evolution of methionine-derived aliphatic GSLs and the addition of a new WHIRLY in core families of the plant order Brassicales.PMID:39625871 | DOI:10.1111/tpj.17181
<em>Sanguibacter biliveldensis</em> sp. nov., a Gram-positive mesophilic bacterium isolated from plant lesions
Int J Syst Evol Microbiol. 2024 Dec;74(12). doi: 10.1099/ijsem.0.006560.ABSTRACTA bacterial strain was isolated from pathogenic lesions of Acer campestre tree leaves from the Teutoburg Forest in North Rhine-Westphalia, Germany, by culture on non-selective agar plates. 16S rRNA sequencing revealed 100% similarity to Sanguibacter keddieii and Sanguibacter inulinus, as well as 99% similarity to Sanguibacter gelidistatuariae and Sanguibacter antarcticus. Here, we used genome-based taxonomy with the Type (Strain) Genome Server (TYGS), which suggests the isolation of a novel prokaryotic strain. According to TYGS-analysis, using whole genome digital DNA-DNA hybridization, only 65.5% similarity to the closest relative S. inulinus was revealed, suggesting a novel species. Growth was observed at both aerobic and anaerobic conditions. Bacterial cells depicted coryneform motile rods, with a length of 1.1-3.3 µm and a constant diameter of 0.5 µm. Cells did not form spores under the tested conditions and stain Gram-positive. Growth occurred between 0.5 and 4% NaCl (optimal: 1%), at pH 5.5-9.5 (optimal: 8.0-9.0). The strain was mesophilic with an optimal growth at 25 °C. Major cellular fatty acids of the novel strain were anteiso-C15 : 0 and C16 : 0.PMID:39625746 | DOI:10.1099/ijsem.0.006560
MASS SPECTROMETRY-BASED MOLECULAR NETWORKS APPLIED TO STUDY THE MOLECULAR INTERACTION BETWEEN TWO ENDOPHYTIC FUNGI ISOLATED FROM Tibouchina granulosa (VELL.) COGN (MELASTOMATACEAE)
Chem Biodivers. 2024 Dec 3:e202402334. doi: 10.1002/cbdv.202402334. Online ahead of print.ABSTRACTEstablishing a microorganism as an endophyte involves complex molecular interactions with its host plant and a broader microbial community. Precise detection methods and comprehensive metabolite annotation are essential to study these interactions. This study focused on characterizing the chemical composition of metabolites produced by two endophytic fungi, Colletotrichum siamense and Xylaria berteroi, isolated from Tibouchina granulosa leaves in axenic conditions and co-culture. We examined the fungal metabolites using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS/ MS) and analysis tools like Cytoscape and GNPS. Co-cultivation revealed unique compounds not produced in isolation, including N-acetyltriptamide. 31 compounds were identified, many with biotechnological potential due to their bioactivities. The untargeted metabolomics approach demonstrated that interactions among these T. granulosa endophytes can activate inactive metabolic pathways under axenic conditions, potentially producing novel bioactive molecules. This is the first study of the chemical profile and interaction between endophytes isolated from T. granulosa.PMID:39625367 | DOI:10.1002/cbdv.202402334