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

Histone methyltransferase activity affects metabolism in human cells independently of transcriptional regulation

Thu, 26/10/2023 - 12:00
PLoS Biol. 2023 Oct 26;21(10):e3002354. doi: 10.1371/journal.pbio.3002354. eCollection 2023 Oct.ABSTRACTThe N-terminal tails of eukaryotic histones are frequently posttranslationally modified. The role of these modifications in transcriptional regulation is well-documented. However, the extent to which the enzymatic processes of histone posttranslational modification might affect metabolic regulation is less clear. Here, we investigated how histone methylation might affect metabolism using metabolomics, proteomics, and RNA-seq data from cancer cell lines, primary tumour samples and healthy tissue samples. In cancer, the expression of histone methyltransferases (HMTs) was inversely correlated to the activity of NNMT, an enzyme previously characterised as a methyl sink that disposes of excess methyl groups carried by the universal methyl donor S-adenosyl methionine (SAM or AdoMet). In healthy tissues, histone methylation was inversely correlated to the levels of an alternative methyl sink, PEMT. These associations affected the levels of multiple histone marks on chromatin genome-wide but had no detectable impact on transcriptional regulation. We show that HMTs with a variety of different associations to transcription are co-regulated by the Retinoblastoma (Rb) tumour suppressor in human cells. Rb-mutant cancers show increased total HMT activity and down-regulation of NNMT. Together, our results suggest that the total activity of HMTs affects SAM metabolism, independent of transcriptional regulation.PMID:37883365 | DOI:10.1371/journal.pbio.3002354

Feeding-induced plant metabolite responses to a phoretic gall mite, its carrier psyllid and both, after detachment

Thu, 26/10/2023 - 12:00
Exp Appl Acarol. 2023 Oct 26. doi: 10.1007/s10493-023-00854-8. Online ahead of print.ABSTRACTPhoresy is one of the most distinctive relationships between mites and insects, and the off-host interaction between phoretic mites and their carriers is the most critical factor sustaining the phoretic association. As phoretic associations commonly occur in temporary habitats, little is known about off-host interactions between phoronts and carriers. However, an off-host interaction has been reported, in which the plant-mediated competition between a phoretic gall mite, Aceria pallida, and its psyllid vector, Bactericera gobica, after detachment decreases leaf abscission caused by B. gobica and then directly facilitates their phoretic association. In this obligate phoresy, A. pallida seasonally attaches to B. gobica for overwinter survival and they share the same host plant, Lycium barbarum, during the growing season. It is unknown how the host plant responds to these two herbivores and what plant metabolites are involved in their interspecific interaction. Here, effects of A. pallida and B. gobica on the host plant's transcriptome and metabolome, and on enzymes involved in plant defence, at various infestation stages were studied by inoculating A. pallida and B. gobica either separately or simultaneously on leaves of L. barbarum. Our results showed that (a) A. pallida significantly promoted primary and secondary metabolite accumulation, (b) B. gobica markedly inhibited primary and secondary metabolite accumulation and had little influence on defence enzyme activity, and (c) under simultaneous A. pallida and B. gobica infestation, an intermediate response was predicted. These findings indicate that A. pallida and B. gobica have different effects on host plants, A. pallida inhibits B. gobica mainly by increasing the secondary metabolism of L. barbarum, whereas B. gobica inhibits A. pallida mainly by decreasing the primary metabolism of L. barbarum. In conjunction with our previous research, we speculate that this trade-off in host plant metabolite response between A. pallida and B. gobica after detachment promotes a stable phoretic association.PMID:37882995 | DOI:10.1007/s10493-023-00854-8

Katanin A-subunits KATNA1 and KATNAL1 act co-operatively in mammalian meiosis and spermiogenesis to achieve male fertility

Thu, 26/10/2023 - 12:00
Development. 2023 Oct 26:dev.201956. doi: 10.1242/dev.201956. Online ahead of print.ABSTRACTKatanin microtubule severing enzymes are potent M-phase regulators in oocytes and somatic cells. How the complex, and evolutionarily critical, male mammalian meiotic spindle is sculpted remains unknown. Here, using multiple single and double gene knockout mice, we reveal that the canonical katanin A-subunit, KATNA1, and its close paralogue, KATNAL1, together execute multiple aspects of meiosis. We show KATNA1 and KATNAL1 collectively regulate the male meiotic spindle, cytokinesis and midbody abscission, in addition to diverse spermatid remodelling events, including Golgi organisation, and acrosome and manchette formation. We also define KATNAL1-specific roles in sperm flagella development, manchette regulation, and sperm-epithelial disengagement. Finally, using proteomic approaches we define the KATNA1, KATNAL1, and KATNB1 mammalian testis interactome, which includes a network of cytoskeletal and vesicle trafficking proteins. Collectively, we reveal the presence of multiple katanin A-subunit paralogs in mammalian spermatogenesis allows for 'customized cutting' via neofunctionalization and protective buffering via gene redundancy.PMID:37882691 | DOI:10.1242/dev.201956

Proteometabolomics of initial and recurrent glioblastoma highlights an increased immune cell signature with altered lipid metabolism

Thu, 26/10/2023 - 12:00
Neuro Oncol. 2023 Oct 26:noad208. doi: 10.1093/neuonc/noad208. Online ahead of print.ABSTRACTBACKGROUND: There is an urgent need to better understand the mechanisms associated with the development, progression, and onset of recurrence after initial surgery in glioblastoma (GBM). The use of integrative phenotype-focused -omics technologies such as proteomics and lipidomics provides an unbiased approach to explore the molecular evolution of the tumor and its associated environment.METHODS: We assembled a cohort of patient-matched initial (iGBM) and recurrent (rGBM) specimens of resected GBM. Proteome and metabolome composition were determined by mass spectrometry-based techniques. We performed neutrophil-GBM cell co-culture experiments to evaluate the behavior of rGBM-enriched proteins in the tumor microenvironment. ELISA-based quantitation of candidate proteins was performed to test the association of their plasma concentrations in iGBM with the onset of recurrence.RESULTS: Proteomic profiles reflect increased immune cell infiltration and extracellular matrix reorganization in rGBM. ASAH1, SYMN, and GPNMB were highly enriched proteins in rGBM. Lipidomics indicates the downregulation of ceramides in rGBM. Cell analyses suggest a role for ASAH1 in neutrophils and its localization in extracellular traps. Plasma concentrations of ASAH1 and SYNM show an association with time-to-recurrence.CONCLUSIONS: We describe the potential importance of ASAH1 in tumor progression and development of rGBM via metabolic rearrangement and showcase the feedback from the tumor microenvironment to plasma proteome profiles. We report the potential of ASAH1 and SYNM as plasma markers of rGBM progression. The published datasets can be considered as a resource for further functional and biomarker studies involving additional -omics technologies.PMID:37882631 | DOI:10.1093/neuonc/noad208

Landscape of gut microbiota and metabolites and their interaction in comorbid heart failure and depressive symptoms: a random forest analysis study

Thu, 26/10/2023 - 12:00
mSystems. 2023 Oct 26:e0051523. doi: 10.1128/msystems.00515-23. Online ahead of print.ABSTRACTDepression is an individual risk factor for poor prognosis in patients with heart failure (HF). Recent studies show that gut microbiota and metabolites play a critical role in comorbid HF and depressive symptoms. We recruited 95 subjects including 35 HF patients with depressive symptoms (HF-DS), 36 HF patients without depressive symptoms (HF-NDS), and 24 healthy controls (HC). The 16S rRNA, metagenome sequencing, and untargeted metabolomic analysis were employed to test fecal samples. Our analysis found a significant difference in composition of gut microbiota in HF-DS, HF-NDS, and HC populations. At the genus level, Mediterranea, Tolumona, and Parabacteroides were significantly increased in HF-DS patients compared with HF-NDS patients, while Pedobacter, Azospirillum, and Ruminiclostridium were significantly decreased. Furthermore, anti-inflammatory mediators (abietic acid, quinic acid, linoleic acid, etc.) and neurotransmitters (catechin, serotonin, tryptamine, phenylethylamine, etc.) were reduced in HF-DS. The enrichment analysis revealed that the gut microbiota highly conformed to the functional pathways of metabolites, and amino acid-related metabolism, fatty acid-related metabolism, and cAMP signaling pathways may be crucial biological mechanisms involved in the development of comorbid depression and HF. Finally, Cloacibacillus and alpha-tocopherol were determined as diagnostic markers for HF-DS patients. IMPORTANCE There is increasing evidence that alterations in gut microbial composition and function are associated with cardiovascular or psychiatric disease. Therefore, it is meaningful to investigate the taxonomic and functional characterization of the microbiota in HF patients who also have depressive symptoms. In this cross-sectional study, Cloacibacillus and alpha-tocopherol were determined as new diagnostic markers. Furthermore, intestinal microecosystem disorders are closely linked to depressive symptoms in HF patients, providing a new reference viewpoint for understanding the gut-heart/brain axis.PMID:37882579 | DOI:10.1128/msystems.00515-23

A single dietary factor, daily consumption of a fermented beverage, can modulate the gut bacteria and fecal metabolites within the same ethnic community

Thu, 26/10/2023 - 12:00
mSystems. 2023 Oct 26:e0074523. doi: 10.1128/msystems.00745-23. Online ahead of print.ABSTRACTIn this study, the impact of traditional rice-based fermented alcoholic beverages (two types of Apong drink: Poro and Nogin) on the gut microbiome and health of the Mishing community in India was examined. Two groups (n = 71 in each group, 58 females and 84 males) that consumed one of these beverages were compared to a control group (n = 24, all males) that did not consume either beverage. Gut microbial composition was analyzed by sequencing 16S rRNA of fecal metagenomes and analyzing untargeted fecal metabolites, and short-chain fatty acids (SCFAs). We also collected data on anthropometric measures and serum biochemical markers. Our results showed that Apong drinkers had higher blood pressure, but lower blood glucose and total protein levels than other non-drinkers. Also, gut microbiome composition was found to be affected by the choice of Apong, with Apong drinkers having a more diverse and distinct microbiome compared to non-drinkers. Apong drink type or being a drinker or not explained even a higher variation of fecal metabolome composition than microbiome composition and Apong drinkers had lower levels of the SCFA isovaleric acid than non-drinkers. Overall, this study shows that a single dietary factor can significantly impact the gut microbiome of a community and highlights the potential role of traditional fermented beverages in modulating gut bacteria. Our study investigated how a traditional drink called Apong, made from fermented rice, affects the gut and health of the Mishing community in India. We compared two groups of people who drink Apong to a group of people who do not drink it. To accomplish this, we studied the gut bacteria, fecal metabolites, and blood samples of the participants. It was found that the people who drank Apong had higher blood pressure but lower blood sugar and protein levels than people who did not drink it. We also found that the gut microbiome composition of people who drank Apong was different from those who did not drink it. Moreover, people who drank Apong had lower levels of isovaleric acid in their feces. Overall, this study shows that a traditional drink like Apong can affect the gut bacteria of a community.PMID:37882544 | DOI:10.1128/msystems.00745-23

Branched-chain amino acid modulation of lipid metabolism, gluconeogenesis, and inflammation in a finishing pig model: targeting leucine and valine

Thu, 26/10/2023 - 12:00
Food Funct. 2023 Oct 26. doi: 10.1039/d3fo03899h. Online ahead of print.ABSTRACTBranched-chain amino acids (BCAAs) play a regulatory role in adipogenesis and energy balance. Therefore, this study aimed to investigate the impact of BCAA supplements, especially leucine (Leu) and valine (Val) supplementation, on lipid metabolism and related disorders in a finishing pig model. The results demonstrated that Leu (1%) and Val decreased serum as well as hepatic lipid accumulation. Moreover, metabolomics and lipidomics analyses revealed that Leu and Val markedly downregulated the level of various lipid species in the liver. This outcome may be explained by Leu and Val promoting cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/hormone-sensitive triglyceride lipase (HSL) signaling pathways. Leu and Val altered the fatty acid composition in distinct adipose tissues and decreased the levels of inflammatory factors. Additionally, they significantly decreased back fat thickness, and the results of the fatty acid profiles demonstrated that Leu and Val significantly increased the levels of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) while decreasing those of saturated fatty acids (SFAs), especially in back fat and abdominal fat. Besides, Leu and Val restored glucose homeostasis by suppressing gluconeogenesis through the serine/threonine protein kinase (AKT)/transcription factor forkhead box O1 (FOXO1) signaling pathway in the liver and back fat. In summary, these results suggest that Leu and Val may serve as key regulators for modulating lipid metabolism and steatosis.PMID:37882496 | DOI:10.1039/d3fo03899h

Combining multi-omics analysis to identify host-targeted targets for the control of Brucella infection

Thu, 26/10/2023 - 12:00
Microb Biotechnol. 2023 Oct 26. doi: 10.1111/1751-7915.14307. Online ahead of print.ABSTRACTHuman infections caused by Brucella (called brucellosis) are among the most common zoonoses worldwide with an estimated 500,000 cases each year. Since chronic Brucella infections are extremely difficult to treat, there is an urgent need for more effective therapeutics. As a facultative intracellular bacterium, Brucella is strictly parasitic in the host cell. Here, we performed proteomic and transcriptomic and metabolomic analyses on Brucella infected patients, mice and cells that provided an extensive "map" of physiological changes in brucellosis patients and characterized the metabolic pathways essential to the response to infection, as well as the associated cellular response and molecular mechanisms. This is the first report utilizing multi-omics analysis to investigate the global response of proteins and metabolites associated with Brucella infection, and the data can provide a comprehensive insight to understand the mechanism of Brucella infection. We demonstrated that Brucella increased nucleotide synthesis in the host, consistent with increased biomass requirement. We also identified IMPDH2, a key regulatory complex that controls nucleotide synthesis during Brucella infection. Pharmacological targeting of IMPDH2, the rate-limiting enzyme in guanine nucleotide biosynthesis, efficiently inhibits B. abortus growth both in vitro and in vivo. Through screening a library of natural products, we identified oxymatrine, an alkaloid obtained primarily from Sophora roots, is a novel and selective IMPDH2 inhibitor. In further in vitro bacterial inhibition assays, oxymatrine effectively inhibited the growth of B. abortus, which was impaired by exogenous supplementation of guanosine, a salvage pathway of purine nucleotides. This moderately potent, structurally novel compound may provide clues for further design and development of efficient IMPDH2 inhibitors and also demonstrates the potential of natural compounds from plants against Brucella.PMID:37882474 | DOI:10.1111/1751-7915.14307

Deep learning and targeted metabolomics-based monitoring of chewing insects in tea plants and screening defense compounds

Thu, 26/10/2023 - 12:00
Plant Cell Environ. 2023 Oct 26. doi: 10.1111/pce.14749. Online ahead of print.ABSTRACTTea is an important cash crop that is often consumed by chewing pests, resulting in reduced yields and economic losses. It is important to establish a method to quickly identify the degree of damage to tea plants caused by leaf-eating insects and screen green control compounds. This study was performed through the combination of deep learning and targeted metabolomics, in vitro feeding experiment, enzymic analysis and transient genetic transformation. A small target damage detection model based on YOLOv5 with Transformer Prediction Head (TPH-YOLOv5) algorithm for the tea canopy level was established. Orthogonal partial least squares (OPLS) was used to analyze the correlation between the degree of damage and the phenolic metabolites. A potential defensive compound, (-)-epicatechin-3-O-caffeoate (EC-CA), was screened. In vitro feeding experiments showed that compared with EC and epicatechin gallate, Ectropis grisescens exhibited more significant antifeeding against EC-CA. In vitro enzymatic experiments showed that the hydroxycinnamoyl transferase (CsHCTs) recombinant protein has substrate promiscuity and can catalyze the synthesis of EC-CA. Transient overexpression of CsHCTs in tea leaves effectively reduced the degree of damage to tea leaves. This study provides important reference values and application prospects for the effective monitoring of pests in tea gardens and screening of green chemical control substances.PMID:37882465 | DOI:10.1111/pce.14749

Germination of aged oat seeds associated with changes in antioxidant enzyme activity and storage compounds mobilization

Thu, 26/10/2023 - 12:00
Physiol Plant. 2023 Sep-Oct;175(5):e14020. doi: 10.1111/ppl.14020.ABSTRACTGermination of aged seeds may be associated with specific metabolic changes. The objective of this study was to examine physiological and metabolic alterations before and after germination of control and aged oat (Avena sativa) seeds. The activity of antioxidant enzymes and the level of storage compounds were measured in the embryo and endosperm at 0, 4, 16, and 32 h of imbibition for control seeds and 0, 4, 16, 32, and 60 h of imbibition for medium vigor seeds after artificially accelerated aging; metabolomic changes were determined in embryos at 16 and 32 h of seed imbibition. In aged oat seeds, superoxide dismutase activity and catalase activity increased in the late imbibition stage. The content of soluble sugars decreased significantly in the later stages of imbibition, while the content of proteins increased in 32 h of seed imbibition eventually producing mannitol and proline. The mobilization of fat in deteriorated seeds was mainly through the sphingolipid metabolic pathway generated by cell growth-promoting dihydrosphingosine-1-phosphate. Ascorbic acid, avenanthramide and proline levels increased significantly at 60 h of imbibition, playing an important role in the germination of aged oat seeds.PMID:37882312 | DOI:10.1111/ppl.14020

Metabolite profiling and screening of callus browning-related genes in lotus (Nelumbo nucifera)

Thu, 26/10/2023 - 12:00
Physiol Plant. 2023 Sep-Oct;175(5):e14027. doi: 10.1111/ppl.14027.ABSTRACTCallus browning is a major drawback to lotus callus proliferation and regeneration. However, the underlying mechanism of its formation remains largely unknown. Herein, we aimed to explore the metabolic and molecular basis of lotus callus browning by combining histological staining, high-throughput metabolomics, and transcriptomic assays for lotus callus at three browning stages. Histological stained brown callus cross sections displayed severe cell death symptoms, accompanied by an obvious accumulation of polyphenols and lignified materials. Widely targeted metabolomics revealed extensively decreased accumulation of most detected flavonoids and benzylisoquinoline alkaloids (BIAs), as well as a few phenolic acids, amino acids and their derivatives in callus with browning symptoms. Conversely, the contents of most detected tannins were significantly increased. Subsequent comparative transcriptomics identified a set of differentially expressed genes (DEGs) associated with the biosynthesis and regulation of flavonoids and BIAs in lotus. Notably, callus browning was coupled with significantly up-regulated expression of two polyphenol oxidase (PPO) and 17 peroxidase (POD) encoding genes, while the expression of ethylene associated genes remained at marginal levels. These results suggest that lotus callus browning is primarily controlled at the level of metabolism, wherein the oxidation of flavonoids and BIAs is crucially decisive.PMID:37882309 | DOI:10.1111/ppl.14027

Transcriptomics integrated with metabolomics to characterize key pigment compounds and genes related to anthocyanin biosynthesis in Zanthoxylum bungeanum peel

Thu, 26/10/2023 - 12:00
Physiol Plant. 2023 Sep-Oct;175(5):e14031. doi: 10.1111/ppl.14031.ABSTRACTZanthoxylum bungeanum is an important condiment with high economic value and its peel color is one of the main quality indexes. However, the key pigment compounds and related genes are still unclear affecting the quality control of the plants. In this study, the contents of four types of pigments were measured in Z. bungeanum and flavonoids were identified as the most important pigments. Based on the targeted flavonoid metabolomics of Z. bungeanum peels, 14 key pigment compounds were screened out from 152 flavonoids, among which cyanidin-3-O-rutinoside and cyanidin-3-O-glucoside were the most critical compounds for peel color. They were further verified to be present in nine varieties of Z. bungeanum by HPLC fingerprints. The 14 compounds were all associated with flavonoid and anthocyanin biosynthesis pathways and the 39 differentially expressed genes related to these pathways were annotated and screened based on transcriptomics. The genes ZbDFR, ZbANS, and ZbUFGT were identified as three key genes for anthocyanin synthesis in Z. bungeanum peels. Further qRT-PCR results confirmed the reliability of transcriptomics and the accuracy of gene screening. Subsequent protein induced expression demonstrated that ZbANS and ZbUFGT were expressed after 12 h induced by IPTG while ZbDFR was expressed after 15 h. Further transient and stable transformation analysis confirmed that both anthocyanin content and the expression of ZbDFR were significantly increased in overexpression Z. bungeanum leaves and Nicotiana benthamiana. The functional effect of stable transformation of ZbDFR was more significant than that of transient transformation with a 7.67-fold/1.49-fold difference in total anthocyanin content and a 42.37-fold/12.32-fold difference in the expression of ZbDFR. This study provides new insights into the chemical composition and the molecular mechanisms of Z. bungeanum peel color and lays an effective foundation for the color quality control, multi-purpose utilization of Z. bungeanum and the creation of new germplasm.PMID:37882301 | DOI:10.1111/ppl.14031

Phenotyping and metabolome analysis reveal the role of AdoMetDC and Di19 genes in determining acquired tolerance to drought in rice

Thu, 26/10/2023 - 12:00
Physiol Plant. 2023 Sep-Oct;175(5):e13992. doi: 10.1111/ppl.13992.ABSTRACTWater-saving attempts for rice cultivation often reduce yields. Maintaining productivity under drought is possible when rice genotypes are bred with improved metabolism and spikelet fertility. Although attempts have been made to introgress water mining and water use efficiency traits, combining acquired tolerance traits (ATTs), that is, specific traits induced or upregulated to better tolerate severe stress, appears equally important. In our study, we screened 90 rice germplasm accessions that represented the molecular and phenotypic variations of 851 lines of the 3 K rice panel. Utilising phenomics, we identified markers linked to ATTs through association analysis of over 0.2 million SNPs derived from whole-genome sequences. Propensity to respond to 'induction' stress varied significantly among genotypes, reflecting differences in cellular protection against oxidative stress. Among the ATTs, the hydroxyl radical and proline contents exhibited the highest variability. Furthermore, these significant variations in ATTs were strongly correlated with spikelet fertility. The 43 significant markers associated with ATTs were further validated using a different subset of contrasting genotypes. Gene expression studies and metabolomic profiling of two well-known contrasting genotypes, APO (tolerant) and IR64 (sensitive), identified two ATT genes: AdoMetDC and Di19. Our study highlights the relevance of polyamine biosynthesis in modulating ATTs in rice. Genotypes with superior ATTs and the associated markers can be effectively employed in breeding rice varieties with sustained spikelet fertility and grain yield under drought.PMID:37882292 | DOI:10.1111/ppl.13992

Rhizobacteria-enhanced drought tolerance and post-drought recovery of creeping bentgrass involving differential modulation of leaf and root metabolism

Thu, 26/10/2023 - 12:00
Physiol Plant. 2023 Sep-Oct;175(5):e14004. doi: 10.1111/ppl.14004.ABSTRACTRhizobacteria that produce 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase (ACCd) that inhibits ethylene production may mitigate stress damages. The objectives of this study were to examine whether a novel strain of ACCd-producing bacteria, Paraburkholderia aspalathi "WSF23," promotes plant tolerance to drought stress and post-stress recovery and determine changes in metabolic profiles in leaves and roots associated with the positive ACCd-bacteria effects in cool-season perennial grass species. Creeping bentgrass (Agrostis Stolonifera L. cv. "Penncross") plants were inoculated with P. aspalathi "WSF23" and exposed to drought by withholding irrigation for 35 days, followed by re-watering for 15 days in growth chambers. Inoculated plants demonstrated increased turf quality, canopy density, and root growth during drought stress and more rapid re-growth upon re-watering. Metabolomic analysis demonstrated that inoculation with P. aspalathi "WSF 23" increased the content of metabolites in the metabolic pathways related to stress defense, including osmoregulation, cell wall stability, and antioxidant protection in both leaves and roots, as well as nitrogen metabolism in roots of creeping bentgrass exposed to drought stress. The promotion of post-stress recovery by P. aspalathi "WSF 23" was mainly associated with enhanced carbohydrate and pyrimidine metabolism and zeatin biosynthesis pathways in leaves and increased carbohydrates, biosynthesis of DNA and proteins, cellular metabolism, and TCA cycle activity in roots. These results provide insights into the metabolic pathways regulated by "WSF23," with the PGPR conferring improvements in drought stress tolerance and post-drought recovery in a perennial grass species.PMID:37882287 | DOI:10.1111/ppl.14004

Regulatory roles of microRNA163 in responses to stresses in Arabidopsis

Thu, 26/10/2023 - 12:00
Physiol Plant. 2023 Sep-Oct;175(5):e14053. doi: 10.1111/ppl.14053.ABSTRACTMicroRNAs (miRNAs) are small regulatory RNAs that participate in various biological processes by silencing target genes. In Arabidopsis, microRNA163 (miR163) was found to be involved in seed germination, root development, and biotic resistance. However, the regulatory roles of miR163 remain unclear. In the current study, the mir163 mutant was investigated to comprehensively understand and characterize its functions in Arabidopsis. RNA-sequencing and Gene Ontology enrichment analyses revealed that miR163 might be involved in "response to stimulus" and "metabolic process". Interestingly, "response to stress", including heat, cold, and oxidative stress, was enriched under the subcategory of "response to stimulus". We observed that miR163 and PXMT were repressed and induced under heat stress, respectively. Furthermore, the study detected significant differences in seed germination rate, hypocotyl length, and survival rate, indicating a variation in the thermotolerance between WT and mir163 mutant. The results revealed that the mir163 mutant had a lesser degree of germination inhibition by heat treatment than WT. In addition, the mir163 mutant showed a better survival rate and longer hypocotyl length under heat treatment than the WT. The metabolomes of WT and mir163 mutant were further analyzed. The contents of benzene derivatives and flavonoids were affected by miR163, which could enhance plants' defense abilities. In conclusion, miR163/targets regulated the expression of stress-responsive genes and the accumulation of defense-related metabolites to alter stress tolerance.PMID:37882263 | DOI:10.1111/ppl.14053

Introducing the South African Rare Diseases Access Initiative

Thu, 26/10/2023 - 12:00
S Afr Med J. 2023 Aug 3;113(8):8. doi: 10.7196/SAMJ.2023.v113i8.1142.NO ABSTRACTPMID:37882112 | DOI:10.7196/SAMJ.2023.v113i8.1142

<em>Lactobacillus rhamnosus</em> Sex-Specifically Attenuates Depressive-like Behavior and Mitigates Metabolic Consequences in Obesity

Thu, 26/10/2023 - 12:00
Biol Psychiatry Glob Open Sci. 2023 Mar 15;3(4):651-662. doi: 10.1016/j.bpsgos.2023.02.011. eCollection 2023 Oct.ABSTRACTBACKGROUND: Patients with diabetes exhibit an increased prevalence for emotional disorders compared with healthy humans, partially due to a shared pathogenesis including hormone resistance and inflammation, which is also linked to intestinal dysbiosis. The preventive intake of probiotic lactobacilli has been shown to improve dysbiosis along with mood and metabolism. Yet, a potential role of Lactobacillus rhamnosus (Lacticaseibacillus rhamnosus 0030) (LR) in improving emotional behavior in established obesity and the underlying mechanisms are unknown.METHODS: Female and male C57BL/6N mice were fed a low-fat diet (10% kcal from fat) or high-fat diet (HFD) (45% kcal from fat) for 6 weeks, followed by daily oral gavage of vehicle or 1 × 108 colony-forming units of LR, and assessment of anxiety- and depressive-like behavior. Cecal microbiota composition was analyzed using 16S ribosomal RNA sequencing, plasma and cerebrospinal fluid were collected for metabolomic analysis, and gene expression of different brain areas was assessed using reverse transcriptase quantitative polymerase chain reaction.RESULTS: We observed that 12 weeks of HFD feeding induced hyperinsulinemia, which was attenuated by LR application only in female mice. On the contrary, HFD-fed male mice exhibited increased anxiety- and depressive-like behavior, where the latter was specifically attenuated by LR application, which was independent of metabolic changes. Furthermore, LR application restored the HFD-induced decrease of tyrosine hydroxylase, along with normalizing cholecystokinin gene expression in dopaminergic brain regions; both tyrosine hydroxylase and cholecystokinin are involved in signaling pathways impacting emotional disorders.CONCLUSIONS: Our data show that LR attenuates depressive-like behavior after established obesity, with changes in the dopaminergic system in male mice, and mitigates hyperinsulinemia in obese female mice.PMID:37881580 | PMC:PMC10593880 | DOI:10.1016/j.bpsgos.2023.02.011

Comprehensive metabolomic variations of hawthorn before and after insect infestation based on the combination analysis of <sup>1</sup>H NMR and UPLC-MS

Thu, 26/10/2023 - 12:00
Curr Res Food Sci. 2023 Oct 11;7:100616. doi: 10.1016/j.crfs.2023.100616. eCollection 2023.ABSTRACTHawthorn, the sliced and dried ripe fruits of Crataegus pinnatifida Bge. Var. Major N. E. Br. (Rosaceae), is an edible and medicinal substance with a variety of health-promoting benefits. Hawthorn needs to be stored in warehouses after harvesting to meet people's perennial demand. However, it is easily infested by insects of Plodia interpunctella and Tribolium castaneum during storage, which inevitably leads to poor quality and causes adverse effects on people's health. So far, there has been no report on insect-infested hawthorn. In this study, we analyzed the changes of metabolites in hawthorn before and after insect infestation and screened out potential biomarkers to effectively and quickly detect the occurrence of insect infestation. A combination analysis of 1H nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to identify the primary and secondary metabolites. By the comparison of hawthorn and insect-infested hawthorn samples, it was found that the differences were mainly manifested in the content of metabolites. The metabolites of 32 and 1463 were identified by 1H NMR and UPLC-MS analysis, respectively. According to the parameters of VIP >1 and P < 0.05, 10 differential metabolites were screened from 1H NMR analysis. Based on the parameters of VIP >1.0, P < 0.05, and (FC) > 1 or < 1, 47 differential metabolites were screened from UPLC-MS analysis. Therefore, a total of 57 differential metabolites were considered as differential biomarkers. The heat map analysis showed that the content of some differential biomarkers with significant pharmacological activities decreased after insect infestation. Through receiver operating characteristic (ROC) curve assessment, 52 differential biomarkers (6 of 1H NMR analysis and 46 of UPLC-MS analysis) were screened to distinguish whether insect infestation occurred in hawthorn. This is the first report on the changes of metabolites between hawthorn and insect-infested hawthorn and on the screening of differential biomarkers for monitoring insects. These results contributed to evaluate quality of hawthorn and ensure food safety for consumers. It also laid a foundation for further research on the infestation mechanism and safe storage monitoring in hawthorn.PMID:37881336 | PMC:PMC10594559 | DOI:10.1016/j.crfs.2023.100616

Shoot-to-root communication via GmUVR8-GmSTF3 photosignaling and flavonoid biosynthesis fine-tunes soybean nodulation under UV-B light

Thu, 26/10/2023 - 12:00
New Phytol. 2023 Oct 25. doi: 10.1111/nph.19353. Online ahead of print.ABSTRACTLegume nodulation requires light perception by plant shoots and precise long-distance communication between shoot and root. Recent studies have revealed that TGACG-motif binding factors (GmSTFs) integrate light signals to promote root nodulation; however, the regulatory mechanisms underlying nodule formation in changing light conditions remain elusive. Here, we applied genetic engineering, metabolite measurement, and transcriptional analysis to study soybean (Glycine max) nodules. We clarify a fine-tuning mechanism in response to ultraviolet B (UV-B) irradiation and rhizobia infection, involving GmUVR8-dependent UV-B perception and GmSTF3/4-GmMYB12-GmCHS-mediated (iso)flavonoid biosynthesis for soybean nodule formation. GmUVR8 receptor-perceived UV-B signal triggered R2R3-MYB transcription factors GmMYB12-dependent flavonoid biosynthesis separately in shoot and root. In shoot, UV-B-triggered flavonoid biosynthesis relied on GmUVR8a, b, c receptor-dependent activation of GmMYB12L-GmCHS8 (chalcone synthase) module. In root, UV-B signaling distinctly promotes the accumulation of the isoflavones, daidzein, and its derivative coumestrol, via GmMYB12B2-GmCHS9 module, resulting in hypernodulation. The mobile transcription factors, GmSTF3/4, bind to cis-regulatory elements in the GmMYB12L, GmMYB12B2, and GmCHS9 promoters, to coordinate UV-B light perception in shoot and (iso)flavonoid biosynthesis in root. Our findings establish a novel shoot-to-root communication module involved in soybean nodulation and reveal an adaptive strategy employed by soybean roots in response to UV-B light.PMID:37881032 | DOI:10.1111/nph.19353

Systematic Metabolic Profiling of Mice with Sleep-Deprivation

Thu, 26/10/2023 - 12:00
Adv Biol (Weinh). 2023 Oct 25:e2300413. doi: 10.1002/adbi.202300413. Online ahead of print.ABSTRACTAdequate sleep is essential for the biological maintenance of physical energy. Lack of sleep can affect thinking, lead to emotional anxiety, reduce immunity, and interfere with endocrine and metabolic processes, leading to disease. Previous studies have focused on long-term sleep deprivation and the risk of cancer, heart disease, diabetes, and obesity. However, systematic metabolomics analyses of blood, heart, liver, spleen, kidney, brown adipose tissue, and fecal granules have not been performed. This study aims to systematically assess the metabolic changes in the target organs caused by sleep deprivation in vivo, to search for differential metabolites and the involved metabolic pathways, to further understand the impact of sleep deprivation on health, and to provide strong evidence for the need for early intervention.PMID:37880935 | DOI:10.1002/adbi.202300413

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