Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

An assessment of the impact of traditional rice cooking practice and eating habits on arsenic and iron transfer into the food chain of smallholders of Indo-Gangetic plain of South-Asia: Using AMMI and Monte-Carlo simulation model

Mon, 01/04/2024 - 12:00
Heliyon. 2024 Mar 21;10(7):e28296. doi: 10.1016/j.heliyon.2024.e28296. eCollection 2024 Apr 15.ABSTRACTThe current study was designed to investigate the consequences of rice cooking and soaking of cooked rice (CR) with or without arsenic (As) contaminated water on As and Fe (iron) transfer to the human body along with associated health risk assessment using additive main-effects and multiplicative interaction (AMMI) and Monte Carlo Simulation model. In comparison to raw rice, As content in cooked rice (CR) and soaked cooked rice (SCR) enhanced significantly (at p < 0.05 level), regardless of rice cultivars and locations (at p < 0.05 level) due to the use of As-rich water for cooking and soaking purposes. Whereas As content in CR and SCR was reduced significantly due to the use of As-free water for cooking and soaking purposes. The use of As-free water (AFW) also enhanced the Fe content in CR. The overnight soaking of rice invariably enhanced the Fe content despite the use of As-contaminated water in SCR however, comparatively in lesser amount than As-free rice. In the studied area, due to consumption of As-rich CR and SCR children are more vulnerable to health hazards than adults. Consumption of SCR (prepared with AFW) could be an effective method to minimize As transmission and Fe enrichment among consumers.PMID:38560133 | PMC:PMC10981068 | DOI:10.1016/j.heliyon.2024.e28296

Corrigendum: Integrated analysis of transcriptome and metabolome reveals the mechanism of chlorine dioxide repressed potato (Solanum tuberosum L.) tuber sprouting

Mon, 01/04/2024 - 12:00
Front Plant Sci. 2024 Mar 15;15:1373758. doi: 10.3389/fpls.2024.1373758. eCollection 2024.ABSTRACT[This corrects the article DOI: 10.3389/fpls.2022.887179.].PMID:38559767 | PMC:PMC10978740 | DOI:10.3389/fpls.2024.1373758

Protocol for preliminary, multicenteric validation of "PoCOsteo device": A point of care tool for proteomic and genomic study of osteoporosis

Mon, 01/04/2024 - 12:00
Biol Methods Protoc. 2024 Mar 22;9(1):bpae006. doi: 10.1093/biomethods/bpae006. eCollection 2024.ABSTRACTOne of the goals of the HORIZON 2020 project PoCOsteo was to develop a medical device, which would measure and/or quantify proteomic as well as genomic factors as present in whole blood samples collected through finger prick. After validating the tool in the clinical setting, the next step would be its clinical validation based on the existing guidelines. This article presents the protocol of a validation study to be carried out independently at two different centers (Division of Endocrinology and Diabetology at the Medical University of Graz as a clinic-based cohort, and the Endocrinology and Metabolism Research Institute at the Tehran University of Medical Sciences as a population-based cohort). It aims to assess the tool according to the Clinical & Laboratory Standards Institute guidelines, confirming if the proteomics and genomics measurements provided by the tool are accurate and reproducible compared with the existing state-of-the-art tests. This is the first time that such a detailed protocol for lab validation of a medical tool for proteomics and genomic measurement is designed based on the existing guidelines and thus could be used as a template for clinical validation of future point-of-care tools. Moreover, the multicentric cohort design will allow the study of a large number of diverse individuals, which will improve the validity and generalizability of the results for different settings.PMID:38559752 | PMC:PMC10978377 | DOI:10.1093/biomethods/bpae006

Mulberry and <em>Hippophae</em>-based solid beverage promotes weight loss in rats by antagonizing white adipose tissue PPARγ and FGFR1 signaling

Mon, 01/04/2024 - 12:00
Front Endocrinol (Lausanne). 2024 Mar 15;15:1344262. doi: 10.3389/fendo.2024.1344262. eCollection 2024.ABSTRACTObesity, a multifactorial disease with many complications, has become a global epidemic. Weight management, including dietary supplementation, has been confirmed to provide relevant health benefits. However, experimental evidence and mechanistic elucidation of dietary supplements in this regard are limited. Here, the weight loss efficacy of MHP, a commercial solid beverage consisting of mulberry leaf aqueous extract and Hippophae protein peptides, was evaluated in a high-fat high-fructose (HFF) diet-induced rat model of obesity. Body component analysis and histopathologic examination confirmed that MHP was effective to facilitate weight loss and adiposity decrease. Pathway enrichment analysis with differential metabolites generated by serum metabolomic profiling suggests that PPAR signal pathway was significantly altered when the rats were challenged by HFF diet but it was rectified after MHP intervention. RNA-Seq based transcriptome data also indicates that MHP intervention rectified the alterations of white adipose tissue mRNA expressions in HFF-induced obese rats. Integrated omics reveals that the efficacy of MHP against obesogenic adipogenesis was potentially associated with its regulation of PPARγ and FGFR1 signaling pathway. Collectively, our findings suggest that MHP could improve obesity, providing an insight into the use of MHP in body weight management.PMID:38559696 | PMC:PMC10978776 | DOI:10.3389/fendo.2024.1344262

The Farm to Table HFpEF Kitchen: Selecting the Right Ingredients for the Discerning Palate

Mon, 01/04/2024 - 12:00
JACC Basic Transl Sci. 2024 Mar 28;9(3):300-302. doi: 10.1016/j.jacbts.2024.01.003. eCollection 2024 Mar.NO ABSTRACTPMID:38559628 | PMC:PMC10978389 | DOI:10.1016/j.jacbts.2024.01.003

Chemical composition and antioxidant activity of <em>Polygonatum kingianum</em> processed by the traditional method of "Nine Cycles of Steaming and Sun-Drying"

Mon, 01/04/2024 - 12:00
Food Chem X. 2024 Mar 15;22:101292. doi: 10.1016/j.fochx.2024.101292. eCollection 2024 Jun 30.ABSTRACTPolygonatum kingianum Coll. et (Hemsl) is a famous Chinese traditional food and medicine analogous plant. The rhizome of P. kingianum showed a decrease in levels of alkaloids, amino acids and derivatives, terpenoids, and an increase in organic acid and saccharides when it was processed by the traditional method of "Nine Cycles of Steaming and Sun-Drying". The relative content of 341 metabolites were increased (fold change, FC > 2; variable importance in projection, VIP > 1 and P-value, P < 0.05); while 456 metabolites were decreased (FC < 0.5, VIP > 1, and P < 0.05). The changes in chemical components result in a decrease in numb taste and an increase in sweetness. The increased antioxidant activity was observed in the processed samples. Together, this work has advanced the mechanism of reducing numb taste and enhancing antioxidant activity in the resource plants, such as P. kingianum, processed by the traditional method.PMID:38559439 | PMC:PMC10978476 | DOI:10.1016/j.fochx.2024.101292

Colonization of root endophytic fungus Serendipita indica improves drought tolerance of Pinus taeda seedlings by regulating metabolome and proteome

Mon, 01/04/2024 - 12:00
Front Microbiol. 2024 Mar 15;15:1294833. doi: 10.3389/fmicb.2024.1294833. eCollection 2024.ABSTRACTPinus taeda is an important forest tree species for plantations because of its rapid growth and high yield of oleoresins. Although P. taeda plantations distribute in warm and wet southern China, drought, sometime serious and long time, often occurs in the region. To explore drought tolerance of P. taeda and usage of beneficial microorganisms, P. taeda seedlings were planted in pots and were inoculated with root endophytic fungus Serendipita indica and finally were treated with drought stress for 53 d. Metabolome and proteome of their needles were analyzed. The results showed that S. indica inoculation of P. taeda seedlings under drought stress caused great changes in levels of some metabolites in their needles, especially some flavonoids and organic acids. Among them, the levels of eriocitrin, trans-aconitic acid, vitamin C, uric acid, alpha-ketoglutaric acid, vitamin A, stachydrine, coumalic acid, itaconic acid, calceolarioside B, 2-oxoglutaric acid, and citric acid were upregulated more than three times in inoculated seedlings under drought stress, compared to those of non-inoculated seedlings under drought stress. KEGG analysis showed that some pathways were enriched in inoculated seedlings under drought stress, such as flavonoid biosynthesis, ascorbate and aldarate metabolism, C5-branched dibasic acid metabolism. Proteome analysis revealed some specific differential proteins. Two proteins, namely, H9X056 and H9VDW5, only appeared in the needles of inoculated seedlings under drought stress. The protein H9VNE7 was upregulated more than 11.0 times as that of non-inoculated seedlings under drought stress. In addition, S. indica inoculation increased enrichment of water deficient-inducible proteins (such as LP3-1, LP3-2, LP3-3, and dehydrins) and those involved in ribosomal structures (such as A0A385JF23). Meanwhile, under drought stress, the inoculation caused great changes in biosynthesis and metabolism pathways, mainly including phenylpropanoid biosynthesis, cutin, suberine and wax biosynthesis, and 2-oxocarboxylic acid metabolism. In addition, there were positive relationships between accumulation of some metabolites and enrichment of proteins in P. taeda under drought stress. Altogether, our results showed great changes in metabolome and proteome in inoculated seedlings under drought stress and provided a guideline to further study functions of metabolites and proteins, especially those related to drought stress.PMID:38559354 | PMC:PMC10978793 | DOI:10.3389/fmicb.2024.1294833

Multi-omics analyses reveal interactions between the skin microbiota and skin metabolites in atopic dermatitis

Mon, 01/04/2024 - 12:00
Front Microbiol. 2024 Mar 15;15:1349674. doi: 10.3389/fmicb.2024.1349674. eCollection 2024.ABSTRACTINTRODUCTION: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. Skin microecological imbalance is an important factor in the pathogenesis of AD, but the underlying mechanism of its interaction with humans remains unclear.METHODS: 16S rRNA gene sequencing was conducted to reveal the skin microbiota dynamics. Changes in skin metabolites were tracked by LC-MS metabolomics. We then explored the potential mechanism of interaction by analyzing the correlation between skin bacterial communities and metabolites in corresponding skin-associated samples.RESULTS: Samples from 18 AD patients and 18 healthy volunteers (HVs) were subjected to 16S rRNA gene sequencing and LC-MS metabolomics. AD patients had dysbiosis of the skin bacterial community with decreased species richness and evenness. The relative abundance of the genus Staphylococcus increased significantly in AD, while the abundances of the genera Propionibacterium and Brevundimonas decreased significantly. The relative abundance of the genera Staphylococcus in healthy females was significantly higher than those in healthy males, while it showed no difference in AD patients with or without lesions. The effects of AD status, sex and the presence or absence of rashes on the number of differentially abundant metabolites per capita were successively reduced. Multiple metabolites involved in purine metabolism and phenylalanine metabolism pathways (such as xanthosine/xanthine and L-phenylalanine/trans-cinnamate) were increased in AD patients. These trends were much more obvious between female AD patients and female HVs. Spearman correlation analysis revealed that the genus Staphylococcus was positively correlated with various compounds involved in phenylalanine metabolism and purine metabolic pathways. The genera Brevundimonas and Lactobacillus were negatively correlated with various compounds involved in purine metabolism, phenylalanine metabolism and sphingolipid signaling pathways.DISCUSSION: We suggest that purine metabolism and phenylalanine metabolism pathway disorders may play a certain role in the pathogenic mechanism of Staphylococcus aureus in AD. We also found that females are more likely to be colonized by the genus Staphylococcus than males. Differentially abundant metabolites involved in purine metabolism and phenylalanine metabolism pathways were more obvious in female. However, we should notice that the metabolites we detected do not necessarily derived from microbes, they may also origin from the host.PMID:38559353 | PMC:PMC10978668 | DOI:10.3389/fmicb.2024.1349674

A Sample-Centric and Knowledge-Driven Computational Framework for Natural Products Drug Discovery

Mon, 01/04/2024 - 12:00
ACS Cent Sci. 2024 Feb 20;10(3):494-510. doi: 10.1021/acscentsci.3c00800. eCollection 2024 Mar 27.ABSTRACTThe ENPKG framework organizes large heterogeneous metabolomics data sets as a knowledge graph, offering exciting opportunities for drug discovery and chemodiversity characterization.PMID:38559298 | PMC:PMC10979503 | DOI:10.1021/acscentsci.3c00800

A systems-biology approach connects aging mechanisms with Alzheimer's disease pathogenesis

Mon, 01/04/2024 - 12:00
bioRxiv [Preprint]. 2024 Mar 17:2024.03.17.585262. doi: 10.1101/2024.03.17.585262.ABSTRACTAge is the strongest risk factor for developing Alzheimer's disease, the most common neurodegenerative disorder. However, the mechanisms connecting advancing age to neurodegeneration in Alzheimer's disease are incompletely understood. We conducted an unbiased, genome-scale, forward genetic screen for age-associated neurodegeneration in Drosophila to identify the underlying biological processes required for maintenance of aging neurons. To connect genetic screen hits to Alzheimer's disease pathways, we measured proteomics, phosphoproteomics, and metabolomics in Drosophila models of Alzheimer's disease. We further identified Alzheimer's disease human genetic variants that modify expression in disease-vulnerable neurons. Through multi-omic, multi-species network integration of these data, we identified relationships between screen hits and tau-mediated neurotoxicity. Furthermore, we computationally and experimentally identified relationships between screen hits and DNA damage in Drosophila and human iPSC-derived neural progenitor cells. Our work identifies candidate pathways that could be targeted to attenuate the effects of age on neurodegeneration and Alzheimer's disease.PMID:38559190 | PMC:PMC10980014 | DOI:10.1101/2024.03.17.585262

Enhanced mucosal mitochondrial function corrects dysbiosis and OXPHOS metabolism in IBD

Mon, 01/04/2024 - 12:00
bioRxiv [Preprint]. 2024 Mar 14:2024.03.14.584471. doi: 10.1101/2024.03.14.584471.ABSTRACTBACKGROUND: Mitochondrial (Mito) dysfunction in IBD reduces mucosal O2 consumption and increases O2 delivery to the microbiome. Increased enteric O2 promotes blooms of facultative anaerobes (eg. Proteobacteria ) and restricts obligate anaerobes (eg. Firmicutes ). Dysbiotic metabolites negatively affect host metabolism and immunity. Our novel compound (AuPhos) upregulates intestinal epithelial cell (IEC) mito function, attenuates colitis and corrects dysbiosis in humanized Il10-/- mice. We posit that AuPhos corrects IBD-associated dysbiotic metabolism.METHODS: Primary effect of AuPhos on mucosal Mito respiration and healing process was studied in ex vivo treated human colonic biopsies and piroxicam-accelerated (Px) Il10-/- mice. Secondary effect on microbiome was tested in DSS-colitis WT B6 and germ-free 129.SvEv WT or Il10-/- mice reconstituted with human IBD stool (Hu- Il10-/- ). Mice were treated orally with AuPhos (10- or 25- mg/kg; q3d) or vehicle, stool samples collected for fecal lipocalin-2 (f-LCN2) assay and microbiome analyses using 16S rRNA sequencing. AuPhos effect on microbial metabolites was determined using untargeted global metabolomics. AuPhos-induced hypoxia in IECs was assessed by Hypoxyprobe-1 staining in sections from pimonidazole HCl-infused DSS-mice. Effect of AuPhos on enteric oxygenation was assessed by E. coli Nissle 1917 WT (aerobic respiration-proficient) and cytochrome oxidase (cydA) mutant (aerobic respiration-deficient).RESULTS: Metagenomic (16S) analysis revealed AuPhos reduced relative abundances of Proteobacteria and increased blooms of Firmicutes in uninflamed B6 WT, DSS-colitis, Hu-WT and Hu- Il10-/- mice. AuPhos also increased hypoxyprobe-1 staining in surface IECs suggesting enhanced O2 utilization. AuPhos-induced anaerobiosis was confirmed by a significant increase in cydA mutant compared to WT (O2-utlizing) E.coli . Ex vivo treatment of human biopsies with AuPhos showed significant increase in Mito mass, and complexes I and IV. Further, gene expression analysis of AuPhos-treated biopsies showed increase in stem cell markers (Lgr4, Lgr5, Lrig1), with concomitant decreases in pro-inflammatory markers (IL1β,MCP1, RankL). Histological investigation of AuPhos-fed Px- Il10-/- mice showed significantly decreased colitis score in AuPhos-treated Px- Il10-/- mice, with decrease in mRNA of pro-inflammatory cytokines and increase in Mito complexes ( ND5 , ATP6 ). AuPhos significantly altered microbial metabolites associated with SCFA synthesis, FAO, TCA cycle, tryptophan and polyamine biosynthesis pathways. AuPhos increased pyruvate, 4-hydroxybutyrate, 2-hydroxyglutarate and succinate, suggesting an upregulation of pyruvate and glutarate pathways of butyrate production. AuPhos reduced IBD-associated primary bile acids (BA) with concomitant increase in secondary BA (SBA). AuPhos treatment significantly decreased acylcarnitines and increased L-carnitine reflective of enhanced FAO. AuPhos increases TCA cycle intermediates and creatine, energy reservoir substrates indicating enhanced OxPHOS. Besides, AuPhos also upregulates tryptophan metabolism, decreases Kynurenine and its derivatives, and increases polyamine biosynthesis pathway (Putresceine and Spermine).CONCLUSION: These findings indicate that AuPhos-enhanced IEC mitochondrial function reduces enteric O2 delivery, which corrects disease-associated metabolomics by restoring short-chain fatty acids, SBA, AA and IEC energy metabolism.PMID:38559035 | PMC:PMC10979996 | DOI:10.1101/2024.03.14.584471

Integrated plasma metabolomic and cytokine analysis reveals a distinct immunometabolic signature in atopic dermatitis

Mon, 01/04/2024 - 12:00
Front Immunol. 2024 Mar 15;15:1354128. doi: 10.3389/fimmu.2024.1354128. eCollection 2024.ABSTRACTIMPORTANCE: Disease models for atopic dermatitis (AD) have primarily focused on understanding underlying environmental, immunologic, and genetic etiologies. However, the role of metabolic mechanisms in AD remains understudied.OBJECTIVE: To investigate the circulating blood metabolomic and cytokine profile of AD as compared to healthy control patients.DESIGN: This study collected plasma from 20 atopic dermatitis with moderate-to-severe itch (score of ≥5 on the itch Numeric Rating Scale and IGA score ≥3) and 24 healthy control patients. Mass-spectrometry based metabolite data were compared between AD and healthy controls. Unsupervised and supervised machine learning algorithms and univariate analysis analyzed metabolic concentrations. Metabolite enrichment and pathway analyses were performed on metabolites with significant fold change between AD and healthy control patients. To investigate the correlation between metabolites levels and cytokines, Spearman's rank correlation coefficients were calculated between metabolites and cytokines.SETTING: Patients were recruited from the Johns Hopkins Itch Center and dermatology outpatient clinics in the Johns Hopkins Outpatient Center.PARTICIPANTS: The study included 20 atopic dermatitis patients and 24 healthy control patients.MAIN OUTCOMES AND MEASURES: Fold changes of metabolites in AD vs healthy control plasma.RESULTS: In patients with AD, amino acids isoleucine, tyrosine, threonine, tryptophan, valine, methionine, and phenylalanine, the amino acid derivatives creatinine, indole-3-acrylic acid, acetyl-L-carnitine, L-carnitine, 2-hydroxycinnamic acid, N-acetylaspartic acid, and the fatty amide oleamide had greater than 2-fold decrease (all P-values<0.0001) compared to healthy controls. Enriched metabolites were involved in branched-chain amino acid (valine, leucine, and isoleucine) degradation, catecholamine biosynthesis, thyroid hormone synthesis, threonine metabolism, and branched and long-chain fatty acid metabolism. Dysregulated metabolites in AD were positively correlated cytokines TARC and MCP-4 and negatively correlated with IL-1a and CCL20.CONCLUSIONS AND RELEVANCE: Our study characterized novel dysregulated circulating plasma metabolites and metabolic pathways that may be involved in the pathogenesis of AD. These metabolic pathways serve as potential future biomarkers and therapeutic targets in the treatment of AD.PMID:38558806 | PMC:PMC10978712 | DOI:10.3389/fimmu.2024.1354128

Effect of the gut microbiome, plasma metabolome, peripheral cells, and inflammatory cytokines on obesity: a bidirectional two-sample Mendelian randomization study and mediation analysis

Mon, 01/04/2024 - 12:00
Front Immunol. 2024 Mar 15;15:1348347. doi: 10.3389/fimmu.2024.1348347. eCollection 2024.ABSTRACTBACKGROUND: Obesity is a metabolic and chronic inflammatory disease involving genetic and environmental factors. This study aimed to investigate the causal relationship among gut microbiota abundance, plasma metabolomics, peripheral cell (blood and immune cell) counts, inflammatory cytokines, and obesity.METHODS: Summary statistics of 191 gut microbiota traits (N = 18,340), 1,400 plasma metabolite traits (N = 8,299), 128 peripheral cell counts (blood cells, N = 408,112; immune cells, N = 3,757), 41 inflammatory cytokine traits (N = 8,293), and 6 obesity traits were obtained from publicly available genome-wide association studies. Two-sample Mendelian randomization (MR) analysis was applied to infer the causal links using inverse variance-weighted, maximum likelihood, MR-Egger, weighted median, weighted mode, and Wald ratio methods. Several sensitivity analyses were also utilized to ensure reliable MR results. Finally, we used mediation analysis to identify the pathway from gut microbiota to obesity mediated by plasma metabolites, peripheral cells, and inflammatory cytokines.RESULTS: MR revealed a causal effect of 44 gut microbiota taxa, 281 plasma metabolites, 27 peripheral cells, and 8 inflammatory cytokines on obesity. Among them, five shared causal gut microbiota taxa belonged to the phylum Actinobacteria, order Bifidobacteriales, family Bifidobacteriaceae, genus Lachnospiraceae UCG008, and species Eubacterium nodatum group. Furthermore, we screened 42 shared causal metabolites, 7 shared causal peripheral cells, and 1 shared causal inflammatory cytokine. Based on known causal metabolites, we observed that the metabolic pathways of D-arginine, D-ornithine, linoleic acid, and glycerophospholipid metabolism were closely related to obesity. Finally, mediation analysis revealed 20 mediation relationships, including the causal pathway from gut microbiota to obesity, mediated by 17 metabolites, 2 peripheral cells, and 1 inflammatory cytokine. Sensitivity analysis represented no heterogeneity or pleiotropy in this study.CONCLUSION: Our findings support a causal relationship among gut microbiota, plasma metabolites, peripheral cells, inflammatory cytokines, and obesity. These biomarkers provide new insights into the mechanisms underlying obesity and contribute to its prevention, diagnosis, and treatment.PMID:38558794 | PMC:PMC10981273 | DOI:10.3389/fimmu.2024.1348347

Integrative multi-omics analysis reveals the crucial biological pathways involved in the adaptive response to NaCl stress in peanut seedlings

Mon, 01/04/2024 - 12:00
Physiol Plant. 2024 Mar-Apr;176(2):e14266. doi: 10.1111/ppl.14266.ABSTRACTPlant growth is restricted by salt stress, which is a significant abiotic factor, particularly during the seedling stage. The aim of this study was to investigate the mechanisms underlying peanut adaptation to salt stress by transcriptomic and metabolomic analysis during the seedling stage. In this study, phenotypic variations of FH23 and NH5, two peanut varieties with contrasting tolerance to salt, changed obviously, with the strongest differences observed at 24 h. FH23 leaves wilted and the membrane system was seriously damaged. A total of 1470 metabolites were identified, with flavonoids being the most common (21.22%). Multi-omics analyses demonstrated that flavonoid biosynthesis (ko00941), isoflavones biosynthesis (ko00943), and plant hormone signal transduction (ko04075) were key metabolic pathways. The comparison of metabolites in isoflavone biosynthesis pathways of peanut varieties with different salt tolerant levels demonstrated that the accumulation of naringenin and formononetin may be the key metabolite leading to their different tolerance. Using our transcriptomic data, we identified three possible reasons for the difference in salt tolerance between the two varieties: (1) differential expression of LOC112715558 (HIDH) and LOC112709716 (HCT), (2) differential expression of LOC112719763 (PYR/PYL) and LOC112764051 (ABF) in the abscisic acid (ABA) signal transduction pathway, then (3) differential expression of genes encoding JAZ proteins (LOC112696383 and LOC112790545). Key metabolites and candidate genes related to improving the salt tolerance in peanuts were screened to promote the study of the responses of peanuts to NaCl stress and guide their genetic improvement.PMID:38558467 | DOI:10.1111/ppl.14266

Metabolomics approach for predicting stomach and colon contents in dead Arctocephalus pusillus pusillus, Arctocephalus tropicalis, Lobodon carcinophaga and Ommatophoca rossii from sub-Antarctic region

Mon, 01/04/2024 - 12:00
PLoS One. 2024 Apr 1;19(4):e0300319. doi: 10.1371/journal.pone.0300319. eCollection 2024.ABSTRACTThe dietary habits of seals play a pivotal role in shaping management and administration policies, especially in regions with potential interactions with fisheries. Previous studies have utilized various methods, including traditional approaches, to predict seal diets by retrieving indigestible prey parts, such as calcified structures, from intestines, feces, and stomach contents. Additionally, methods evaluating nitrogen and stable isotopes of carbon have been employed. The metabolomics approach, capable of quantifying small-scale molecules in biofluids, holds promise for specifying dietary exposures and estimating disease risk. This study aimed to assess the diet composition of five seal species-Arctocephalus pusillus pusillus, Lobodon carcinophaga, Ommatophoca rossii, and Arctocephalus tropicalis 1 and 2-by analyzing stomach and colon contents collected from stranded dead seals at various locations. Metabolite concentrations in the seal stomach and colon contents were determined using Nuclear Magnetic Resonance Spectroscopy. Among the colon and stomach contents, 29 known and 8 unknown metabolites were identified. Four metabolites (alanine, fumarate, lactate, and proline) from stomach contents and one metabolite (alanine) from colon contents showed no significant differences between seal species (p>0.05). This suggests that traces of these metabolites in the stomach and colon contents may be produced by the seals' gut microbiome or derived from other animals, possibly indicating reliance on fish caught at sea. Despite this insight, the cause of death for stranded seals remains unclear. The study highlights the need for specific and reliable biomarkers to precisely indicate dietary exposures across seal populations. Additionally, there is a call for the development of relevant metabolite and disease interaction networks to explore disease-related metabolites in seals. Ultimately, the metabolomic method employed in this study reveals potential metabolites in the stomach and colon contents of these seal species.PMID:38557648 | DOI:10.1371/journal.pone.0300319

Specific changes in gut microbiota and short-chain fatty acid levels in infants with cow's milk protein allergy

Mon, 01/04/2024 - 12:00
Zhongguo Dang Dai Er Ke Za Zhi. 2024 Mar 15;26(3):236-243. doi: 10.7499/j.issn.1008-8830.2308007.ABSTRACTOBJECTIVES: To explore the changes in gut microbiota and levels of short-chain fatty acids (SCFA) in infants with cow's milk protein allergy (CMPA), and to clarify their role in CMPA.METHODS: A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group, and 25 healthy infants were selected as the control group. Fecal samples (200 mg) were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites. Microbial diversity was analyzed in conjunction with metabolites.RESULTS: Compared to the control group, the CMPA group showed altered gut microbial structure and significantly increased α-diversity (P<0.001). The abundance of Firmicutes, Clostridiales and Bacteroidetes was significantly decreased, while the abundance of Sphingomonadaceae, Clostridiaceae_1 and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group (P<0.001). Metabolomic analysis revealed reduced levels of acetic acid, butyric acid, and isovaleric acid in the CMPA group compared to the control group, and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia (P<0.05).CONCLUSIONS: CMPA infants have alterations in gut microbial structure, increased microbial diversity, and decreased levels of SCFA, which may contribute to increased intestinal inflammation.PMID:38557374 | DOI:10.7499/j.issn.1008-8830.2308007

CslA and GlxA from <em>Streptomyces lividans</em> form a functional cellulose synthase complex

Mon, 01/04/2024 - 12:00
Appl Environ Microbiol. 2024 Apr 1:e0208723. doi: 10.1128/aem.02087-23. Online ahead of print.ABSTRACTFilamentous growth of streptomycetes coincides with the synthesis and deposition of an uncharacterized protective glucan at hyphal tips. Synthesis of this glucan depends on the integral membrane protein CslA and the radical copper oxidase GlxA, which are part of a presumably large multiprotein complex operating at growing tips. Here, we show that CslA and GlxA interact by forming a protein complex that is sufficient to synthesize cellulose in vitro. Mass spectrometry analysis revealed that the purified complex produces cellulose chains with a degree of polymerization of at least 80 residues. Truncation analyses demonstrated that the removal of a significant extracellular segment of GlxA had no impact on complex formation, but significantly diminished activity of CslA. Altogether, our work demonstrates that CslA and GlxA form the active core of the cellulose synthase complex and provide molecular insights into a unique cellulose biosynthesis system that is conserved in streptomycetes.IMPORTANCE: Cellulose stands out as the most abundant polysaccharide on Earth. While the synthesis of this polysaccharide has been extensively studied in plants and Gram-negative bacteria, the mechanisms in Gram-positive bacteria have remained largely unknown. Our research unveils a novel cellulose synthase complex formed by the interaction between the cellulose synthase-like protein CslA and the radical copper oxidase GlxA from Streptomyces lividans, a soil-dwelling Gram-positive bacterium. This discovery provides molecular insights into the distinctive cellulose biosynthesis machinery. Beyond expanding our understanding of cellulose biosynthesis, this study also opens avenues for exploring biotechnological applications and ecological roles of cellulose in Gram-positive bacteria, thereby contributing to the broader field of microbial cellulose biosynthesis and biofilm research.PMID:38557137 | DOI:10.1128/aem.02087-23

Integrated Full-Length Transcriptomics and Metabolomics Reveal Glycosyltransferase Involved in the Biosynthesis of Flavonol Glycosides in Laportea bulbifera

Mon, 01/04/2024 - 12:00
J Agric Food Chem. 2024 Apr 1. doi: 10.1021/acs.jafc.4c00488. Online ahead of print.ABSTRACTMany species of the Urticaceae family are important cultivated fiber plants that are known for their economic and industrial values. However, their secondary metabolite profiles and associated biosynthetic mechanisms have not been well-studied. Using Laportea bulbifera as a model, we conducted widely targeted metabolomics, which revealed 523 secondary metabolites, including a unique accumulation of flavonol glycosides in bulblet. Through full-length transcriptomic and RNA-seq analyses, the related genes in the flavonoid biosynthesis pathway were identified. Finally, weighted gene correlation network analysis and functional characterization revealed four LbUGTs, including LbUGT78AE1, LbUGT72CT1, LbUGT71BX1, and LbUGT71BX2, can catalyze the glycosylation of flavonol aglycones (kaempferol, myricetin, gossypetin, and quercetagetin) using UDP-Gal and UDP-Glu as the sugar donors. LbUGT78AE1 and LbUGT72CT1 showed substrate promiscuity, whereas LbUGT71BX1 and LbUGT71BX2 exhibited different substrate and sugar donor selectivity. These results provide a genetic resource for studying Laportea in the Urticaceae family, as well as key enzymes responsible for the metabolism of valuable flavonoid glycosides.PMID:38557049 | DOI:10.1021/acs.jafc.4c00488

Energy Resolved Mass Spectrometry for Interoperable Non-resonant Collisional Spectra in Metabolomics

Mon, 01/04/2024 - 12:00
J Am Soc Mass Spectrom. 2024 Apr 1. doi: 10.1021/jasms.3c00410. Online ahead of print.ABSTRACTIn untargeted metabolomics, the unambiguous identification of metabolites remains a major challenge. This requires high-quality spectral libraries for reliable metabolite identification, which is essential for translating metabolomics data into meaningful biological information. Several attempts have been made to generate reproducible product ion spectra (PIS) under a low collision energy (ELab) regime and nonresonant collisional conditions but have not fully succeeded. We examined the ERMS (energy-resolved mass spectrometry) breakdown curves of two lipo-amino acids and showed the possibility to highlight "singular points", called descriptors hereafter (linked to respective ELab depending on the instrument), for each of the monomodal product ion profiles. Using several instruments based on different technologies, the PIS recorded at these specific ELab sites shows remarkable similarities. The descriptors appeared as being independent of the fragmentation mechanisms and can be used to overcome the main instrumental effects that limit the interoperability of spectral libraries. This proof-of-concept study, performed on two particular lipo-amino acids, demonstrates the high potential of ERMS-derived information to determine the instrument-specific ELab at which PIS recorded in nonresonant conditions become highly similar and instrument-independent, thus comparable across platforms. This innovative but straightforward approach could help remove some of the obstacles to metabolite identification in nontargeted metabolomics, putting an end to a challenging chimera.PMID:38557041 | DOI:10.1021/jasms.3c00410

Dose-Dependent Effect on Plant Growth of Exposure to Metal-Organic Framework MIL-101(Cr)

Mon, 01/04/2024 - 12:00
Environ Sci Technol. 2024 Apr 1. doi: 10.1021/acs.est.3c09086. Online ahead of print.ABSTRACTWith the increasing use of metal-organic frameworks (MOFs), they will inevitably enter the environment intentionally or unintentionally. However, the effects of MOFs on plant growth are poorly understood. Here, we investigated the effects of exposure of the rhizosphere to MOFs on plant growth. MIL-101(Cr) was selected as a research model due to its commercial availability and wide use. Soybean plants at the two-leaf stage were subjected to various durations (1-7 days) and concentrations (0-1000 mg/L) of exposure in hydroculture with a control group treated with ultrapure water. We found that MIL-101(Cr) had a positive effect on soybean growth at a lower dose (i.e., 200 mg/L); however, at higher doses (i.e., 500 and 1000 mg/L), it exhibited significant toxicity to plant growth, which is evidenced by leaf damage. To investigate the mechanism of this effect, we used Cr as an indicator to quantify, track, and image MIL-101(Cr) in the plant with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Results indicated that MIL-101(Cr) primarily accumulated in the cortex of roots (up to 40 times higher than that in stems), with limited translocation to stems and negligible presence in leaves and cotyledons. In addition, metabolomic analysis of soybeans indicated that low-dose MIL-101(Cr) could increase the sucrose content of soybean roots to promote plant growth, while a high dose could induce lipid oxidation in roots. This study provides valuable insights into the ecological toxicology of MOFs and underscores the importance of assessing their environmental impact for sustainable agricultural practices.PMID:38557036 | DOI:10.1021/acs.est.3c09086

Pages