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

Integrative machine learning approaches for predicting disease risk using multi-omics data from the UK Biobank

Thu, 25/04/2024 - 12:00
bioRxiv [Preprint]. 2024 Apr 20:2024.04.16.589819. doi: 10.1101/2024.04.16.589819.ABSTRACTWe train prediction and survival models using multi-omics data for disease risk identification and stratification. Existing work on disease prediction focuses on risk analysis using datasets of individual data types (metabolomic, genomics, demographic), while our study creates an integrated model for disease risk assessment. We compare machine learning models such as Lasso Regression, Multi-Layer Perceptron, XG Boost, and ADA Boost to analyze multi-omics data, incorporating ROC-AUC score comparisons for various diseases and feature combinations. Additionally, we train Cox proportional hazard models for each disease to perform survival analysis. Although the integration of multi-omics data significantly improves risk prediction for 8 diseases, we find that the contribution of metabolomic data is marginal when compared to standard demographic, genetic, and biomarker features. Nonetheless, we see that metabolomics is a useful replacement for the standard biomarker panel when it is not readily available.PMID:38659731 | PMC:PMC11042345 | DOI:10.1101/2024.04.16.589819

Sodium acetate increases the productivity of HEK293 cells expressing the ECD-Her1 protein in batch cultures: experimental results and metabolic flux analysis

Thu, 25/04/2024 - 12:00
Front Bioeng Biotechnol. 2024 Apr 10;12:1335898. doi: 10.3389/fbioe.2024.1335898. eCollection 2024.ABSTRACTHuman Embryonic Kidney cells (HEK293) are a popular host for recombinant protein expression and production in the biotechnological industry. This has driven within both, the scientific and the engineering communities, the search for strategies to increase their protein productivity. The present work is inserted into this search exploring the impact of adding sodium acetate (NaAc) into a batch culture of HEK293 cells. We monitored, as a function of time, the cell density, many external metabolites, and the supernatant concentration of the heterologous extra-cellular domain ECD-Her1 protein, a protein used to produce a candidate prostate cancer vaccine. We observed that by adding different concentrations of NaAc (0, 4, 6 and 8 mM), the production of ECD-Her1 protein increases consistently with increasing concentration, whereas the carrying capacity of the medium decreases. To understand these results we exploited a combination of experimental and computational techniques. Metabolic Flux Analysis (MFA) was used to infer intracellular metabolic fluxes from the concentration of external metabolites. Moreover, we measured independently the extracellular acidification rate and oxygen consumption rate of the cells. Both approaches support the idea that the addition of NaAc to the culture has a significant impact on the metabolism of the HEK293 cells and that, if properly tuned, enhances the productivity of the heterologous ECD-Her1 protein.PMID:38659646 | PMC:PMC11039900 | DOI:10.3389/fbioe.2024.1335898

Identification of active compounds in Vernonia anthelmintica (L.) willd by targeted metabolome MRM and kaempferol promotes HaCaT cell proliferation and reduces oxidative stress

Thu, 25/04/2024 - 12:00
Front Pharmacol. 2024 Apr 9;15:1343306. doi: 10.3389/fphar.2024.1343306. eCollection 2024.ABSTRACTIntroduction: Vernonia anthelmintica (L.) Willd. is a traditional treatment for vitiligo in Xinjiang. However, its therapeutic mechanism remains unclear owing to its complex composition and limited research on its chemical profile. Methods: We employed a targeted metabolome approach, combining selective reaction monitoring/multiple response monitoring (SRM/MRM) with high-performance liquid chromatography and MRM mass spectrometry to quantitatively analyze the flavonoid constituents of Vernonia anthelmintica. We also used network pharmacology and molecular docking to identify potential vitiligo-linked compounds and targets of V. anthelmintica seeds. Additionally, we assessed HaCaT cell proliferation by AAPH-induced, alongside changes in SOD activity and MDA content, following treatment with V. anthelmintica components. Finally, flow cytometry was used to detect apoptosis and ROS levels. Results and Discussion: We identified 36 flavonoid compounds in V. anthelmintica seeds, with 14 compounds exhibiting druggability. AKT1, VEGFA, ESR1, PTGS2, and IL2 have been identified as key therapeutic target genes, with PI3K/AKT signaling being an important pathway. Notably, kaempferol, one of the identified compounds, exhibited high expression in network pharmacology analysis. Kaempferol exhibited a strong binding affinity to important targets. Further, kaempferol enhanced HaCaT cell viability, inhibited apoptosis, reduced MDA levels, suppressed ROS activity, and upregulated SOD activity, increase the expression of cellular antioxidant genes, including HO-1, GCLC, GCLM, Nrf2, NQO1 and Keap1, providing significant protection against oxidative stress damage in vitro. Here, we present the first comprehensive study integrating SRM/MRM approaches and network analysis to identify active flavonoid compounds within V. anthelmintica (L.) Willd. Moreover, we revealed that its active ingredient, kaempferol, offers protection against AAPH-induced damage in keratinocytes, highlighting its potential as a clinical resource.PMID:38659590 | PMC:PMC11041372 | DOI:10.3389/fphar.2024.1343306

Inhibition of hepatitis B virus <em>via</em> selective apoptosis modulation by Chinese patent medicine Liuweiwuling Tablet

Thu, 25/04/2024 - 12:00
World J Gastroenterol. 2024 Apr 7;30(13):1911-1925. doi: 10.3748/wjg.v30.i13.1911.ABSTRACTBACKGROUND: Liuweiwuling Tablet (LWWL) is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus (HBV) infection. Previous studies have indicated an anti-HBV effect of LWWL, specifically in terms of antigen inhibition, but the underlying mechanism remains unclear.AIM: To investigate the potential mechanism of action of LWWL against HBV.METHODS: In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines. The in vivo experiment involved a hydrodynamic injection-mediated mouse model with HBV replication. Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS: In HepG2.1403F cells, LWWL (0.8 mg/mL) exhibited inhibitory effects on HBV DNA, hepatitis B surface antigen and pregenomic RNA (pgRNA) at rates of 51.36%, 24.74% and 50.74%, respectively. The inhibition rates of LWWL (0.8 mg/mL) on pgRNA/covalently closed circular DNA in HepG2.1403F, HepG2.2.15 and HepG2.A64 cells were 47.78%, 39.51% and 46.74%, respectively. Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis (PI3K-AKT, CASP8-CASP3 and P53 pathways). Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group (CG) among HBV-replicating cell lines, including HepG2.2.15 (2.92% ± 1.01% vs 6.68% ± 2.04%, P < 0.05), HepG2.A64 (4.89% ± 1.28% vs 8.52% ± 0.50%, P < 0.05) and HepG2.1403F (3.76% ± 1.40% vs 7.57% ± 1.35%, P < 0.05) (CG vs LWWL-treated group). However, there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells (5.04% ± 0.74% vs 5.51% ± 1.57%, P > 0.05), L02 cells (5.49% ± 0.80% vs 5.48% ± 1.01%, P > 0.05) and LX2 cells (6.29% ± 1.54% vs 6.29% ± 0.88%, P > 0.05). TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBV-replicating mouse model, while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model.CONCLUSION: Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV, potentially involving selective regulation of apoptosis. These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.PMID:38659485 | PMC:PMC11036500 | DOI:10.3748/wjg.v30.i13.1911

The athlete gut microbiota: state of the art and practical guidance

Thu, 25/04/2024 - 12:00
Benef Microbes. 2024 Apr 26:1-30. doi: 10.1163/18762891-bja00007. Online ahead of print.ABSTRACTThe gut microbiota has been proposed to grant the athlete a metabolic advantage that might be key when optimising performance. While a taxonomic core set of microorganisms characterising the athlete's gut microbiota has not been delineated, some compositional features might be associated with improved metabolic efficiency, which appears to be driven by the production of bacterial metabolites, such as short-chain fatty acids. Not only long-term exercise but also dietary patterns associated with high-level sports practice contribute to this microbial environment, yet isolating the impact of individual dietary components is challenging. The present review synthetises the available evidence on the compositional aspects of the athlete's gut microbiota, discusses mechanisms involved in the bidirectional association between exercise and the gut environment, and evaluates the role of athletes' diet in this interplay. Additionally, a practical approach to indicators commonly reported in metagenomic and metabolomic analyses is provided to explore how these insights can translate to support dietary protocols.PMID:38659188 | DOI:10.1163/18762891-bja00007

Subcutaneous injection of adipose stromal cell-secretome improves renal function and reduces inflammation in established acute kidney injury

Wed, 24/04/2024 - 12:00
Stem Cell Res Ther. 2024 Apr 24;15(1):119. doi: 10.1186/s13287-024-03736-x.ABSTRACTBACKGROUND: Adipose stromal cells (ASC) are a form of mesenchymal stromal cells that elicit effects primarily via secreted factors, which may have advantages for the treatment of injury or disease. Several previous studies have demonstrated a protective role for MSC/ASC on mitigating acute kidney injury but whether ASC derived factors could hasten recovery from established injury has not been evaluated.METHODS: We generated a concentrated secretome (CS) of human ASC under well-defined conditions and evaluated its ability to improve the recovery of renal function in a preclinical model of acute kidney injury (AKI) in rats. 24 h following bilateral ischemia/reperfusion (I/R), rats were randomized following determination of plasma creatinine into groups receiving vehicle -control or ASC-CS treatment by subcutaneous injection (2 mg protein/kg) and monitored for evaluation of renal function, structure and inflammation.RESULTS: Renal function, assessed by plasma creatinine levels, recovered faster in ASC-CS treated rats vs vehicle. The most prominent difference between the ASC-CS treated vs vehicle was observed in rats with the most severe degree of initial injury (Pcr > 3.0 mg/dl 24 h post I/R), whereas rats with less severe injury (Pcr < 2.9 mg/dl) recovered quickly regardless of treatment. The quicker recovery of ASC-treated rats with severe injury was associated with less tissue damage, inflammation, and lower plasma angiopoietin 2. In vitro, ASC-CS attenuated the activation of the Th17 phenotype in lymphocytes isolated from injured kidneys.CONCLUSIONS: Taken together, these data suggest that ASC-CS represents a potent therapeutic option to improve established AKI.PMID:38659070 | DOI:10.1186/s13287-024-03736-x

Conditioned medium-enriched umbilical cord mesenchymal stem cells: a potential therapeutic strategy for spinal cord injury, unveiling transcriptomic and secretomic insights

Wed, 24/04/2024 - 12:00
Mol Biol Rep. 2024 Apr 24;51(1):570. doi: 10.1007/s11033-024-09503-8.ABSTRACTINTRODUCTION: Spinal cord injury (SCI) leads to significant destruction of nerve tissue, causing the degeneration of axons and the formation of cystic cavities. This study aimed to examine the characteristics of human umbilical cord-derived mesenchymal stem cells (HUCMSCs) cultured in a serum-free conditioned medium (CM) and assess their effectiveness in a well-established hemitransection SCI model.MATERIALS AND METHODS: In this study, HUCMSCs cultured medium was collected and characterized by measuring IL-10 and identifying proteomics using mass spectroscopy. This collected serum-free CM was further used in the experiments to culture and characterize the HUMSCs. Later, neuronal cells derived from CM-enriched HUCMSC were tested sequentially using an injectable caffeic acid-bioconjugated gelatin (CBG), which was further transplanted in a hemitransection SCI model. In vitro, characterization of CM-enriched HUCMSCs and differentiated neuronal cells was performed using flow cytometry, immunofluorescence, electron microscopy, and post-transplant analysis using immunohistology analysis, qPCR, in vivo bioluminescence imaging, and behavioral analysis using an infrared actimeter.RESULTS: The cells that were cultured in the conditioned media produced a pro-inflammatory cytokine called IL-10. Upon examining the secretome of the conditioned media, the Kruppel-like family of KRAB and zinc-finger proteins (C2H2 and C4) were found to be activated. Transcriptome analysis also revealed an increased expression of ELK-1, HOXD8, OTX2, YY1, STAT1, ETV7, and PATZ1 in the conditioned media. Furthermore, the expression of Human Stem-101 confirmed proliferation during the first 3 weeks after transplantation, along with the migration of CBG-UCNSC cells within the transplanted area. The gene analysis showed increased expression of Nestin, NeuN, Calb-2, Msi1, and Msi2. The group that received CBG-UCNSC therapy showed a smooth recovery by the end of week 2, with most rats regaining their walking abilities similar to those before the spinal cord injury by week 5.CONCLUSIONS: In conclusion, the CBG-UCNSC method effectively preserved the integrity of the transplanted neuronal-like cells and improved locomotor function. Thus, CM-enriched cells can potentially reduce biosafety risks associated with animal content, making them a promising option for clinical applications in treating spinal cord injuries.PMID:38658405 | DOI:10.1007/s11033-024-09503-8

Prioritization of therapeutic targets for cancers using integrative multi-omics analysis

Wed, 24/04/2024 - 12:00
Hum Genomics. 2024 Apr 24;18(1):42. doi: 10.1186/s40246-024-00571-2.ABSTRACTBACKGROUND: The integration of transcriptomic, proteomic, druggable genetic and metabolomic association studies facilitated a comprehensive investigation of molecular features and shared pathways for cancers' development and progression.METHODS: Comprehensive approaches consisting of transcriptome-wide association studies (TWAS), proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) and MR were performed to identify genes significantly associated with cancers. The results identified in above analyzes were subsequently involved in phenotype scanning and enrichment analyzes to explore the possible health effects and shared pathways. Additionally, we also conducted MR analysis to investigate metabolic pathways related to cancers.RESULTS: Totally 24 genes (18 transcriptomic, 1 proteomic and 5 druggable genetic) showed significant associations with cancers risk. All genes identified in multiple methods were mainly enriched in nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Additionally, biosynthesis of ubiquinol and urate were found to play an important role in gastrointestinal tumors.CONCLUSIONS: A set of putatively causal genes and pathways relevant to cancers were identified in this study, shedding light on the shared biological processes for tumorigenesis and providing compelling genetic evidence to prioritize anti-cancer drugs development.PMID:38659038 | DOI:10.1186/s40246-024-00571-2

Gut microbiota composition and metabolic characteristics in patients with Craniopharyngioma

Wed, 24/04/2024 - 12:00
BMC Cancer. 2024 Apr 25;24(1):521. doi: 10.1186/s12885-024-12283-w.ABSTRACTBACKGROUND: Emerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches.METHODS: We enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients.RESULTS: The composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly.CONCLUSIONS: The gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.PMID:38658858 | DOI:10.1186/s12885-024-12283-w

OmicNavigator: open-source software for the exploration, visualization, and archival of omic studies

Wed, 24/04/2024 - 12:00
BMC Bioinformatics. 2024 Apr 24;25(1):162. doi: 10.1186/s12859-024-05743-4.ABSTRACTBACKGROUND: The results of high-throughput biology ('omic') experiments provide insight into biological mechanisms but can be challenging to explore, archive and share. The scale of these challenges continues to grow as omic research volume expands and multiple analytical technologies, bioinformatic pipelines, and visualization preferences have emerged. Multiple software applications exist that support omic study exploration and/or archival. However, an opportunity remains for open-source software that can archive and present the results of omic analyses with broad accommodation of study-specific analytical approaches and visualizations with useful exploration features.RESULTS: We present OmicNavigator, an R package for the archival, visualization and interactive exploration of omic studies. OmicNavigator enables bioinformaticians to create web applications that interactively display their custom visualizations and analysis results linked with app-derived analytical tools, graphics, and tables. Studies created with OmicNavigator can be viewed within an interactive R session or hosted on a server for shared access.CONCLUSIONS: OmicNavigator can be found at https://github.com/abbvie-external/OmicNavigator.PMID:38658834 | DOI:10.1186/s12859-024-05743-4

Study of cabbage antioxidant system response on early infection stage of Xanthomonas campestris pv. campestris

Wed, 24/04/2024 - 12:00
BMC Plant Biol. 2024 Apr 24;24(1):324. doi: 10.1186/s12870-024-04994-w.ABSTRACTBlack rot, caused by Xanthomonas campestris pv. campestris (Xcc) significantly affects the production of cabbage and other cruciferous vegetables. Plant antioxidant system plays an important role in pathogen invasion and is one of the main mechanisms underlying resistance to biological stress. Therefore, it is important to study the resistance mechanisms of the cabbage antioxidant system during the early stages of Xcc. In this study, 108 CFU/mL (OD600 = 0.1) Xcc race1 was inoculated on "zhonggan 11" cabbage using the spraying method. The effects of Xcc infection on the antioxidant system before and after Xcc inoculation (0, 1, 3, and 5 d) were studied by physiological indexes determination, transcriptome and metabolome analyses. We concluded that early Xcc infection can destroy the balance of the active oxygen metabolism system, increase the generation of free radicals, and decrease the scavenging ability, leading to membrane lipid peroxidation, resulting in the destruction of the biofilm system and metabolic disorders. In response to Xcc infection, cabbage clears a series of reactive oxygen species (ROS) produced during Xcc infection via various antioxidant pathways. The activities of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) increased after Xcc infection, and the ROS scavenging rate increased. The biosynthesis of non-obligate antioxidants, such as ascorbic acid (AsA) and glutathione (GSH), is also enhanced after Xcc infection. Moreover, the alkaloid and vitamin contents increased significantly after Xcc infection. We concluded that cabbage could resist Xcc invasion by maintaining the stability of the cell membrane system and improving the biosynthesis of antioxidant substances and enzymes after infection by Xcc. Our results provide theoretical basis and data support for subsequent research on the cruciferous vegetables resistance mechanism and breeding to Xcc.PMID:38658831 | DOI:10.1186/s12870-024-04994-w

Multimodal joint deconvolution and integrative signature selection in proteomics

Wed, 24/04/2024 - 12:00
Commun Biol. 2024 Apr 24;7(1):493. doi: 10.1038/s42003-024-06155-z.ABSTRACTDeconvolution is an efficient approach for detecting cell-type-specific (cs) transcriptomic signals without cellular segmentation. However, this type of methods may require a reference profile from the same molecular source and tissue type. Here, we present a method to dissect bulk proteome by leveraging tissue-matched transcriptome and proteome without using a proteomics reference panel. Our method also selects the proteins contributing to the cellular heterogeneity shared between bulk transcriptome and proteome. The deconvoluted result enables downstream analyses such as cs-protein Quantitative Trait Loci (cspQTL) mapping. We benchmarked the performance of this multimodal deconvolution approach through CITE-seq pseudo bulk data, a simulation study, and the bulk multi-omics data from human brain normal tissues and breast cancer tumors, individually, showing robust and accurate cell abundance quantification across different datasets. This algorithm is implemented in a tool MICSQTL that also provides cspQTL and multi-omics integrative visualization, available at https://bioconductor.org/packages/MICSQTL .PMID:38658803 | DOI:10.1038/s42003-024-06155-z

Tackling new psychoactive substances through metabolomics: UHPLC-HRMS study on natural and synthetic opioids in male and female murine models

Wed, 24/04/2024 - 12:00
Sci Rep. 2024 Apr 24;14(1):9432. doi: 10.1038/s41598-024-60045-2.ABSTRACTNovel psychoactive substances (NPS) represent a broad class of drugs new to the illicit market that often allow passing drug-screening tests. They are characterized by a variety of structures, rapid transience on the drug scene and mostly unknown metabolic profiles, thus creating an ever-changing scenario with evolving analytical targets. The present study aims at developing an indirect screening strategy for NPS monitoring, and specifically for new synthetic opioids (NSOs), based on assessing changes in endogenous urinary metabolite levels as a consequence of the systemic response following their intake. The experimental design involved in-vivo mice models: 16 animals of both sex received a single administration of morphine or fentanyl. Urine was collected before and after administration at different time points; the samples were then analysed with an untargeted metabolomics LC-HRMS workflow. According to our results, the intake of opioids resulted in an elevated energy demand, that was more pronounced on male animals, as evidenced by the increase in medium and long chain acylcarnitines levels. It was also shown that opioid administration disrupted the pathways related to catecholamines biosynthesis. The observed alterations were common to both morphine and fentanyl: this evidence indicate that they are not related to the chemical structure of the drug, but rather on the drug class. The proposed strategy may reinforce existing NPS screening approaches, by identifying indirect markers of drug assumption.PMID:38658766 | DOI:10.1038/s41598-024-60045-2

Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development

Wed, 24/04/2024 - 12:00
Nat Commun. 2024 Apr 24;15(1):3468. doi: 10.1038/s41467-024-47437-8.ABSTRACTMetabolism has recently emerged as a major target of genes implicated in the evolutionary expansion of human neocortex. One such gene is the human-specific gene ARHGAP11B. During human neocortex development, ARHGAP11B increases the abundance of basal radial glia, key progenitors for neocortex expansion, by stimulating glutaminolysis (glutamine-to-glutamate-to-alpha-ketoglutarate) in mitochondria. Here we show that the ape-specific protein GLUD2 (glutamate dehydrogenase 2), which also operates in mitochondria and converts glutamate-to-αKG, enhances ARHGAP11B's ability to increase basal radial glia abundance. ARHGAP11B + GLUD2 double-transgenic bRG show increased production of aspartate, a metabolite essential for cell proliferation, from glutamate via alpha-ketoglutarate and the TCA cycle. Hence, during human evolution, a human-specific gene exploited the existence of another gene that emerged during ape evolution, to increase, via concerted changes in metabolism, progenitor abundance and neocortex size.PMID:38658571 | DOI:10.1038/s41467-024-47437-8

Metabolic coupling between soil aerobic methanotrophs and denitrifiers in rice paddy fields

Wed, 24/04/2024 - 12:00
Nat Commun. 2024 Apr 24;15(1):3471. doi: 10.1038/s41467-024-47827-y.ABSTRACTPaddy fields are hotspots of microbial denitrification, which is typically linked to the oxidation of electron donors such as methane (CH4) under anoxic and hypoxic conditions. While several anaerobic methanotrophs can facilitate denitrification intracellularly, whether and how aerobic CH4 oxidation couples with denitrification in hypoxic paddy fields remains virtually unknown. Here we combine a ~3300 km field study across main rice-producing areas of China and 13CH4-DNA-stable isotope probing (SIP) experiments to investigate the role of soil aerobic CH4 oxidation in supporting denitrification. Our results reveal positive relationships between CH4 oxidation and denitrification activities and genes across various climatic regions. Microcosm experiments confirm that CH4 and methanotroph addition promote gene expression involved in denitrification and increase nitrous oxide emissions. Moreover, 13CH4-DNA-SIP analyses identify over 70 phylotypes harboring genes associated with denitrification and assimilating 13C, which are mostly belonged to Rubrivivax, Magnetospirillum, and Bradyrhizobium. Combined analyses of 13C-metagenome-assembled genomes and 13C-metabolomics highlight the importance of intermediates such as acetate, propionate and lactate, released during aerobic CH4 oxidation, for the coupling of CH4 oxidation with denitrification. Our work identifies key microbial taxa and pathways driving coupled aerobic CH4 oxidation and denitrification, with important implications for nitrogen management and greenhouse gas regulation in agroecosystems.PMID:38658559 | DOI:10.1038/s41467-024-47827-y

Exercise mitigates a gut microbiota-mediated reduction in adult hippocampal neurogenesis and associated behaviours in rats

Wed, 24/04/2024 - 12:00
Transl Psychiatry. 2024 Apr 24;14(1):195. doi: 10.1038/s41398-024-02904-0.ABSTRACTLifestyle factors, especially exercise, impact the manifestation and progression of psychiatric and neurodegenerative disorders such as depression and Alzheimer's disease, mediated by changes in hippocampal neuroplasticity. The beneficial effects of exercise may be due to its promotion of adult hippocampal neurogenesis (AHN). Gut microbiota has also been showed to be altered in a variety of brain disorders, and disturbances of the microbiota have resulted in alterations in brain and behaviour. However, whether exercise can counteract the negative effects of altered gut microbiota on brain function remains under explored. To this end, chronic disruption of the gut microbiota was achieved using an antibiotic cocktail in rats that were sedentary or allowed voluntary access to running wheels. Sedentary rats with disrupted microbiota displayed impaired performance in hippocampal neurogenesis-dependent tasks: the modified spontaneous location recognition task and the novelty suppressed feeding test. Performance in the elevated plus maze was also impaired due to antibiotics treatment. These behaviours, and an antibiotics-induced reduction in AHN were attenuated by voluntary exercise. The effects were independent of changes in the hippocampal metabolome but were paralleled by caecal metabolomic changes. Taken together these data highlight the importance of the gut microbiota in AHN-dependent behaviours and demonstrate the power of lifestyle factors such as voluntary exercise to attenuate these changes.PMID:38658547 | DOI:10.1038/s41398-024-02904-0

The era of panomics-driven gene discovery in plants

Wed, 24/04/2024 - 12:00
Trends Plant Sci. 2024 Apr 23:S1360-1385(24)00063-3. doi: 10.1016/j.tplants.2024.03.007. Online ahead of print.ABSTRACTPanomics is an approach to integrate multiple 'omics' datasets, generated using different individuals or natural variations. Considering their diverse phenotypic spectrum, the phenome is inherently associated with panomics-based science, which is further combined with genomics, transcriptomics, metabolomics, and other omics techniques, either independently or collectively. Panomics has been accelerated through recent technological advancements in the field of genomics that enable the detection of population-wide structural variations (SVs) and hence offer unprecedented insights into the genetic variations contributing to important agronomic traits. The present review provides the recent trends of panomics-driven gene discovery toward various traits related to plant development, stress tolerance, accumulation of specialized metabolites, and domestication/dedomestication. In addition, the success stories are highlighted in the broader context of enhancing crop productivity.PMID:38658292 | DOI:10.1016/j.tplants.2024.03.007

Identification of exhaled volatile organic compounds that characterize asthma phenotypes: A J-VOCSA study

Wed, 24/04/2024 - 12:00
Allergol Int. 2024 Apr 23:S1323-8930(24)00047-9. doi: 10.1016/j.alit.2024.04.003. Online ahead of print.ABSTRACTBACKGROUND: Asthma is characterized by phenotypes of different clinical, demographic, and pathological characteristics. Identifying the profile of exhaled volatile organic compounds (VOCs) in asthma phenotypes may facilitate establishing biomarkers and understanding asthma background pathogenesis. This study aimed to identify exhaled VOCs that characterize severe asthma phenotypes among patients with asthma.METHODS: This was a multicenter cross-sectional study of patients with severe asthma in Japan. Clinical data were obtained from medical records, and questionnaires were collected. Exhaled breath was sampled and subjected to thermal desorption gas chromatography-mass spectrometry (GC/MS).RESULTS: Using the decision tree established in the previous nationwide asthma cohort study, 245 patients with asthma were divided into five phenotypes and subjected to exhaled VOC analysis with 50 healthy controls (HCs). GC/MS detected 243 VOCs in exhaled breath samples, and 142 frequently detected VOCs (50% of all samples) were used for statistical analyses. Cluster analysis assigning the groups with similar VOC profile patterns showed the highest similarities between phenotypes 3 and 4 (early-onset asthma phenotypes), followed by the similarities between phenotypes 1 and 2 (late-onset asthma phenotypes). Comparisons between phenotypes 1-5 and HC revealed 19 VOCs, in which only methanesulfonic anhydride showed p < 0.05 adjusted by false discovery rate (FDR). Comparison of these phenotypes yielded several VOCs showing different trends (p < 0.05); however, no VOCs showed p < 0.05 adjusted by FDR.CONCLUSIONS: Exhaled VOC profiles may be useful for distinguishing asthma and asthma phenotypes; however, these findings need to be validated, and their pathological roles should be clarified.PMID:38658257 | DOI:10.1016/j.alit.2024.04.003

Rapid characterization of non-volatile phenolic compounds reveals the reliable chemical markers for authentication of traditional Chinese medicine Xiang-ru among confusing Elsholtzia species

Wed, 24/04/2024 - 12:00
Chin J Nat Med. 2024 Apr;22(4):375-384. doi: 10.1016/S1875-5364(24)60614-X.ABSTRACTThe aerial parts of Mosla chinensis Maxim. and Mosla chinensis cv. 'Jiangxiangru' (MCJ) are widely utilized in traditional Chinese medicine (TCM), known collectively as Xiang-ru. However, due to clinical effectiveness concerns and frequent misidentification, the original plants have increasingly been substituted by various species within the genera Elsholtzia and Mosla. The challenge in distinguishing between these genera arises from their similar morphological and metabolic profiles. To address this issue, our study introduced a rapid method for metabolic characterization, employing high-resolution mass spectrometry-based metabolomics. Through detailed biosynthetic and chemometric analyses, we pinpointed five phenolic compounds-salviaflaside, cynaroside, scutellarein-7-O-D-glucoside, rutin, and vicenin-2-among 203 identified compounds, as reliable chemical markers for distinguishing Xiang-ru from closely related Elsholtzia species. This methodology holds promise for broad application in the analysis of plant aerial parts, especially in verifying the authenticity of aromatic traditional medicinal plants. Our findings underscore the importance of non-volatile compounds as dependable chemical markers in the authentication process of aromatic traditional medicinal plants.PMID:38658100 | DOI:10.1016/S1875-5364(24)60614-X

Reverse metabolomics as a novel strategy to annotate the human metabolome

Wed, 24/04/2024 - 12:00
Chin J Nat Med. 2024 Apr;22(4):289-290. doi: 10.1016/S1875-5364(24)60589-3.NO ABSTRACTPMID:38658091 | DOI:10.1016/S1875-5364(24)60589-3

Pages