Amino Acid Biosynthesis Pathways Research Articles

Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis.

Over the past decade, the role of the gut microbiota in many disease states has gained a great deal of attention. Mounting evidence from case-control and observational studies has linked changes in the gut microbiota to the pathophysiology of osteoporosis (OP). Nonetheless, the results of these studies contain discrepancies, leaving the literature without a consensus on osteoporosis-associated microbial signatures. Here, we conducted a comprehensive meta-analysis combining and reexamining five publicly available 16S rRNA partial sequence data sets to identify gut bacteria consistently associated with osteoporosis across different cohorts. After adjusting for the batch effect associated with technical variation and heterogeneity of studies, we observed a significant shift in the microbiota composition in the osteoporosis group. An increase in the relative abundance of opportunistic pathogens Clostridium sensu stricto, Bacteroides, and Intestinibacter was observed in the OP group. Moreover, short-chain-fatty-acid (SCFA) producers, including members of the genera Collinsella, Megasphaera, Agathobaculum, Mediterraneibacter, Clostridium XIV, and Dorea, were depleted in the OP group relative to the healthy control (HC) group. Lactic acid-producing bacteria, including Limosilactobacillus, were significantly increased in the OP group. The random forest algorithm further confirmed that these bacteria differentiate the two groups. Furthermore, functional prediction revealed depletion of the SCFA biosynthesis pathway (glycolysis, tricarboxylic acid [TCA] cycle, and Wood-Ljungdahl pathway) and amino acid biosynthesis pathway (methionine, histidine, and arginine) in the OP group relative to the HC group. This study uncovered OP-associated compositional and functional microbial alterations, providing robust insight into OP pathogenesis and aiding the possible development of a therapeutic intervention to manage the disease. IMPORTANCE Osteoporosis is the most common metabolic bone disease associated with aging. Mounting evidence has linked changes in the gut microbiota to the pathophysiology of osteoporosis. However, which microbes are associated with dysbiosis and their impact on bone density and inflammation remain largely unknown due to inconsistent results in the literature. Here, we present a meta-analysis with a standard workflow, robust statistical approaches, and machine learning algorithms to identify notable microbial compositional changes influencing osteoporosis.

Milk metabolomics analyses of lactating dairy cows with divergent residual feed intake reveals physiological underpinnings and novel biomarkers.

The opportunity to select for feed efficient cows has been limited by inability to cost-effectively record individual feed efficiency on an appropriate scale. This study investigated the differences in milk metabolite profiles between high- and low residual feed intake (RFI) categories and identified biomarkers of residual feed intake and models that can be used to predict residual feed intake in lactating Holsteins. Milk metabolomics analyses were undertaken at early, mid and late lactation stages and residual feed intake was calculated in 72 lactating dairy cows. Cows were ranked and grouped into high residual feed intake (RFI >0.5 SD above the mean, n = 20) and low residual feed intake (RFI <0.5 SD below the mean, n = 20). Milk metabolite profiles were compared between high residual feed intake (least efficient) and low residual feed intake (most efficient) groups. Results indicated that early lactation was predominantly characterized by significantly elevated levels of medium chain acyl carnitines and glycerophospholipids in high residual feed intake cows. Citrate cycle and glycerophospholipid metabolism were the associated pathways enriched with the significantly different metabolites in early lactation. At mid lactation short and medium chain acyl carnitines, glycerophospholipids and amino acids were the main metabolite groups differing according to residual feed intake category. Late lactation was mainly characterized by increased levels of amino acids in high residual feed intake cows. Amino acid metabolism and biosynthesis pathways were enriched for metabolites that differed between residual feed intake groups at the mid and late lactation stages. Receiver operating characteristic curve analysis identified candidate biomarkers: decanoylcarnitine (area under the curve: AUC = 0.81), dodecenoylcarnitine (AUC = 0.81) and phenylalanine (AUC = 0.85) at early, mid and late stages of lactation, respectively. Furthermore, panels of metabolites predicted residual feed intake with validation coefficient of determination (R 2) of 0.65, 0.37 and 0.60 at early, mid and late lactation stages, respectively. The study sheds light on lactation stage specific metabolic differences between high-residual feed intake and low-residual feed intake lactating dairy cows. Candidate biomarkers that distinguished divergent residual feed intake groups and panels of metabolites that predict individual residual feed intake phenotypes were identified. This result supports the potential of milk metabolites to select for more efficient cows given that traditional residual feed intake phenotyping is costly and difficult to conduct in commercial farms.

Metabolomic Responses of Lettuce (Lactuca sativa) to Allelopathic Benzoquinones from Iris sanguinea Seeds.

Weed management is important in modern crop protection. Chemical weed control using synthetic herbicides, however, suffers from resistance and ecotoxicity. Metabolomic investigation of allelopathy (or allelochemicals) may provide novel alternatives to synthetic herbicides. This study aimed to investigate the detailed metabolomic responses of plants to allelochemicals in Iris seed extracts. The seed extracts of Iris sanguinea showed the strongest growth inhibitory activity against alfalfa, barnyard grass, lettuce, and mustard. 3-Hydroxyirisquinone (3-[10(Z)-heptadecenyl]-2-hydroxy-5-methoxy-1,4-benzoquinone) was isolated as a major allelochemical from I. sanguinea seeds through bioassay-guided fractionation. The compound inhibited the growth of shoots and roots by browning root tips. Discriminant analysis identified 33 differentially regulated lettuce metabolites after treatment with 3-hydroxyirisquinone (3HIQ). Metabolic pathway analysis revealed that several metabolic pathways, including aromatic amino acid biosynthesis and respiratory pathways, were affected by the compounds. Differential responses of membrane lipids (accumulation of unsaturated fatty acids) and extensive formation of reactive oxygen species were observed in root tissues following treatment with 3HIQ. Overall, alkylbenzoquinone from I. sanguinea induced extensive metabolic modulation, oxidative stress, and growth inhibition. The metabolomic responses to allelochemicals may provide fundamental information for the development of allelochemical-based herbicides.

Crystal Structure of the Commercial Herbicide, Amidosulfuron, in Complex with Arabidopsis thaliana Acetohydroxyacid Synthase

Amidosulfuron (AS) is from the commercial sulfonylurea herbicide family. It is highly effective against dicot broad-leaf weeds. This herbicide targets acetohydroxyacid synthase (AHAS), the first enzyme in the branched chain amino acid biosynthesis pathway. Here, we have determined the crystal structure of AS in complex with wildtype Arabidopsis thaliana AHAS (AtAHAS) and with the resistance mutant, S653T. In both structures, the cofactor, ThDP, is modified to a peracetate adduct, consistent with time-dependent accumulative inhibition. Compared to other AHAS-inhibiting herbicides of the sulfonylurea family, AS lacks a second aromatic ring. The replacement is an aryl sulfonyl group with a reduced number of interactions with the enzyme and relatively low affinity (Ki = 4.2 μM vs low nM when two heteroaromatic rings are present). This study shows that effective herbicides can have a relatively high Ki for plant AHAS but can still be a potent herbicide provided accumulative inhibition also occurs.

A prognostic risk model, tumor immune environment modulation, and drug prediction of ferroptosis and amino acid metabolism-related genes in hepatocellular carcinoma.

The prognosis of hepatocellular carcinoma (HCC) is challenging due to its heterogeneity. Ferroptosis and amino acid metabolism have been shown to be closely related to HCC. We obtained HCC-related expression data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. We then crossed differentially expressed genes (DEGs), amino acid metabolism genes, and ferroptosis-related genes (FRGs) to obtain amino acid metabolism-ferroptosis-related differentially expressed genes (AAM-FR DEGs). Moreover, we developed a prognostic model using Cox analysis, followed by a correlation analysis of risk scores with clinical characteristics. We also performed an immune microenvironment analysis and drug sensitivity analysis. Finally, the expression levels of model genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical assays. We found that the 18 AAM-FR DEGs were mainly enriched to the alpha-amino acid metabolic process and amino acid biosynthesis pathways. Cox analysis identified CBS, GPT2, SUV39H1, and TXNRD1 as prognostic biomarkers for the risk model construction. Our results showed that the risk scores differed between pathology stage, pathology T stage, and HBV, and the number of HCC patients in the two groups. In addition, the expression of PD-L1 and CTLA-4 was high in the high-risk group, and the half-maximal inhibitory concentration (IC50) of sorafenib also differed between the two groups. Finally, the experimental validation demonstrated that the expression of biomarkers was consistent with the study analysis. Therefore, in this study, we constructed and validated a prognostic model (CBS, GPT2, SUV39H1, and TXNRD1) related to ferroptosis and amino acid metabolism and examined their prognostic value for HCC.

Effect of calcium peroxide assisted microwave irradiation pretreatment on humus formation and microbial community in straw and dairy manure composting

In this study, the effects of four pretreatment methods on the crystallinity of maize straw were compared, and the CaO2 assisted microwave pretreatment was selected for straw and dairy manure composting. The humification and microbial community were investigated. Results showed that the pretreatment increased the initial water-soluble carbon, which favored the microbial activity, and the CO2 release increased by 15.71%. Pretreatment promoted the lignocellulose degradation, with total degradation ratio of 37.06%. The final humic acid content was 11.39 g/kg higher than the control. Spearman correlation analysis indicated that polyphenols and amino acids were significantly related to humus formation. In addition, pretreatment rendered the Firmicutes the most dominant phylum, and increased the metabolic intensity of reducing sugar metabolism, aromatic amino acid biosynthesis and carbon fixation pathways. Redundancy analysis revealed that the dominant genus of Firmicutes was significantly positively correlated with humus, while that of Actinobacteriota was correlated with CO2 release.

Application of glutamic acid improved As tolerance in aromatic rice at early growth stage

To alleviate the arsenic (As) toxicity in aromatic rice, a hydroponic experiment of two As concentrations (0 and 100 μM sodium arsenite: A0, A1), three glutamic acid (Glu) concentrations (0, 100, and 500 μM l-glutamic acid: G0, G1, and G2) with Xiangyaxiangzhan and Meixiangzhan 2 was conducted. Results showed that the root As content were increased under A1G2 but reduced under A1G1 for Xiangyaxiangzhan as compared with A1G0. A decrement of As was transported from root to shoot caused by up-regulated OsABCC1 relative expression in Meixiangzhan 2. Likewise, As stress enhanced the H2O2 and malondialdehyde content, resulting in the impaired cell wall observed by transmission electron microscopy. However, compared with A1G0, the superoxide dismutase activity, ascorbic acid, glutathione, proline, and soluble sugar content were increased under A1G1. Additionally, arsenate reductase, monodehydroascorbate reductase activity, Glu, proline, and soluble sugar content were found positively associated with the As accumulation. Further, the metabolome analysis indicated that the pathway of amino acid and arginine biosynthesis were notably enriched after Glu application. Generally, 100 μM Glu application was the better treatment to enhance As tolerance in aromatic rice through up-regulating amino acid biosynthesis with increasing antioxidants and osmolytes to scavenge excessive reactive oxygen species.

Virulence Factors of the Gut Microbiome Are Associated with BMI and Metabolic Blood Parameters in Children with Obesity.

The development of metabolic diseases is linked to the gut microbiota. A cross-sectional study involving 45 children (6 to 12 years old) was conducted to investigate the relationship between gut microbiota and childhood obesity. Anthropometric and metabolic measurements, food-frequency questionnaires (FFQs), and feces samples were obtained. Using the body mass index (BMI) z-score, we categorized each participant as normal weight (NW), or overweight and obese (OWOB). We determined 2 dietary profiles: one with complex carbohydrates and proteins (pattern 1), and the other with saturated fat and simple carbohydrates (pattern 2). The microbial taxonomic diversity and metabolic capacity were determined using shotgun metagenomics. We found differences between both BMI groups diversity. Taxa contributing to this difference, included Eubacterium sp., Faecalibacterium prausnitzii, Dialister, Monoglobus pectinilyticus, Bifidobacterium pseudocatenulatum, Intestinibacter bartlettii, Bacteroides intestinalis, Bacteroides uniformis, and Methanobrevibacter smithii. Metabolic capacity differences found between NW and OWOB, included the amino acid biosynthesis pathway, the cofactor, carrier, and vitamin biosynthesis pathway, the nucleoside and nucleotide biosynthesis and degradation pathways, the carbohydrate-sugar degradation pathway, and the amine and polyamine biosynthesis pathway. We found significant associations between taxa such as Ruminococcus, Mitsuokella multacida, Klebsiella variicola, and Citrobacter spp., metabolic pathways with the anthropometric, metabolic, and dietary data. We also found the microbiome's lipooligosaccharide (LOS) category as differentially abundant between BMI groups. Metabolic variations emerge during childhood as a result of complex nutritional and microbial interactions, which should be explained in order to prevent metabolic illnesses in adolescence and maturity. IMPORTANCE The alteration of gut microbiome composition has been commonly observed in diseases involving inflammation, such as obesity and metabolic impairment. Inflammatory host response in the gut can be a consequence of dietary driven dysbiosis. This response is conducive to blooms of particular bacterial species, adequate to survive in an inflammatory environment by means of genetical capability of utilizing alternative nutrients. Understanding the genomic and metabolic contribution of microbiota to inflammation, including virulence factor prevalence and functional potential, will contribute to identifying modifiable early life exposures and preventive strategies associated with obesity risk in childhood.

Assessing the ecological risk of tritium and Carbon-14 discharge on cyanobacteria through metabolic profiling

The ecological risk posed by tritium (T) and carbon-14 (C-14) discharge from nuclear accidents has gained attention. This study evaluated the toxic impact of T and C-14 (at a concentration of 37 kBq/L for 15 days) on the cyanobacteria (Synechococcus elongatus). The results showed that the assimilation efficiency of cyanobacteria was significantly higher for C-14 than T, and the intracellular C-14 activity reached 30.62–40.58 kBq/kg. T and C-14 exposure had no significant effect on cell proliferation but impacted photosynthesis and respiration. T exposure increased the content of Ca, Mg, Na, P, K, and Mn, while C-14 exposure primarily affected trace element absorption in cyanobacteria. 31, 27, and 58 different metabolites (DEMs) were identified under T, C-14, and combined exposure conditions. These DEMs were enriched in the amino acid biosynthesis pathway, and nitrogen assimilation was one of the crucial pathways affected by T and C-14 exposure. The absorption of mineral elements by cyanobacteria was influenced by the variation in metabolites in the ABC transporter pathway caused by T and C-14 exposure. Our findings provide insights into the metabolic response of cyanobacteria to T and C-14 exposure and will help to guide the ecological risk evaluation of nuclear accidents.

Enzyme Feed Additive with Arazyme Improve Growth Performance, Meat Quality, and Gut Microbiome of Pigs.

The supplementation of pig diets with exogenous enzymes is widely used with the expectation that it will improve the efficiency of nutrient utilization, thereby, improving growth performance. This study aims to evaluate the effects of a 0.1% (v/v) multi-enzyme (a mixture of arazyme (2,500,000 Unit/kg), xylanase (200,000 Unit/kg) and mannanase (200,000 Unit/kg)) supplementation derived from invertebrate symbiotic bacteria on pig performance. Here, 256 growing pigs were assigned to control and treatment groups, respectively. The treatment group exhibited a significantly reduced average slaughter age; the final body weight and average daily gain increased compared with that of the control group. In the treatment group, the longissimus muscle showed a remarkable decrease in cooking loss, shear force, and color values with increased essential and non-essential amino acid concentrations. Furthermore, the concentrations of mono- and polyunsaturated fatty acids in the treatment group increased. Feed additive supplementation increased the family of Ruminococcaceae and genera Lactobacillus, Limosilactobacillus, Turicibacter, and Oscillibacter, which play a positive role in the host physiology and health. Predicted metabolic pathway analysis confirmed that operational taxonomic units and predicted amino acid biosynthesis pathways were strongly associated. The results suggest that applying exogenous enzymes derived from invertebrate symbiotic bacteria enhances animal performance.

Integrated Metabolomic and Transcriptomic Analysis Reveals That Amino Acid Biosynthesis May Determine Differences in Cold-Tolerant and Cold-Sensitive Tea Cultivars.

Cold stress is one of the major abiotic stresses limiting tea production. The planting of cold-resistant tea cultivars is one of the most effective measures to prevent chilling injury. However, the differences in cold resistance between tea cultivars remain unclear. In the present study, we perform a transcriptomic and metabolomic profiling of Camellia sinensis var. "Shuchazao" (cold-tolerant, SCZ) and C. sinensis var. assamica "Yinghong 9" (cold-sensitive, YH9) during cold acclimation and analyze the correlation between gene expression and metabolite biosynthesis. Our results show that there were 51 differentially accumulated metabolites only up-regulated in SCZ in cold-acclimation (CA) and de-acclimation (DA) stages, of which amino acids accounted for 18%. The accumulation of L-arginine and lysine in SCZ in the CA stage was higher than that in YH9. A comparative transcriptomic analysis showed an enrichment of the amino acid biosynthesis pathway in SCZ in the CA stage, especially "arginine biosynthesis" pathways. In combining transcriptomic and metabolomic analyses, it was found that genes and metabolites associated with amino acid biosynthesis were significantly enriched in the CA stage of SCZ compared to CA stage of YH9. Under cold stress, arginine may improve the cold resistance of tea plants by activating the polyamine synthesis pathway and CBF (C-repeat-binding factor)-COR (cold-regulated genes) regulation pathway. Our results show that amino acid biosynthesis may play a positive regulatory role in the cold resistance of tea plants and assist in understanding the cold resistance mechanism differences among tea varieties.

A systems level approach to study metabolic networks in prokaryotes with the aromatic amino acid biosynthesis pathway.

Metabolism of an organism underlies its phenotype, which depends on many factors, such as the genetic makeup, habitat, and stresses to which it is exposed. This is particularly important for the prokaryotes, which undergo significant vertical and horizontal gene transfers. In this study we have used the energy-intensive Aromatic Amino Acid (Tryptophan, Tyrosine and Phenylalanine, TTP) biosynthesis pathway, in a large number of prokaryotes, as a model system to query the different levels of organization of metabolism in the whole intracellular biochemical network, and to understand how perturbations, such as mutations, affects the metabolic flux through the pathway - in isolation and in the context of other pathways connected to it. Using an agglomerative approach involving complex network analysis and Flux Balance Analyses (FBA), of the Tryptophan, Tyrosine and Phenylalanine and other pathways connected to it, we identify several novel results. Using the reaction network analysis and Flux Balance Analyses of the Tryptophan, Tyrosine and Phenylalanine and the genome-scale reconstructed metabolic pathways, many common hubs between the connected networks and the whole genome network are identified. The results show that the connected pathway network can act as a proxy for the whole genome network in Prokaryotes. This systems level analysis also points towards designing functional smaller synthetic pathways based on the reaction network and Flux Balance Analyses analysis.

Insights into the core bacterial consortia of root endophytes in two cultivated varieties of rice in West Bengal

Root endophytes are considered to be one of the potent environment-friendly substitutes for chemical fertilizers, as they possess an ability to induce crosstalk inside the hosts for growth promotion, nitrogen fixation, phosphate solubilization and iron sequestration. This study aimed to explore and evaluate the key root endophytic bacterial consortia of two widely cultivated varieties of rice (Oryza sativa L.), cv. ‘Saraswati’ (OS01) and cv. ‘Kunti’ (OS04). Detailed comparative metagenome data were generated for endophytes of OS01 and OS04 and the species richness was calculated. OS01 showed higher endophyte species richness than OS04, with alpha diversity values of 3.10 and 2.40, respectively. Bacillus, Magnetospirillum, Methanocystis, Desulfomicrobium and Pantoea were identified as common endophyte members for both cultivars. Solibacillus, Paenibacillus, Candidatus, and Melospira were unique members of OS01, and Herbaspirillum, Pandoraea, Anabaenopsis for OS04. Considerable occurrence of nitrogen fixing bacteria and methanogenic bacteria in the cultivars confirmed biological nitrogen fixation, which can contribute to plant development. Core homeotic pathways of amino acid biosynthesis and carbon metabolism were also reflected in endophytes from both cultivars, indicating a supportive environment for microorganisms. Sulfur metabolism pathways were likewise predicted to be active in the niche under study, which may be attributed as a response to arsenic stress. Furthermore, the most abundant genera identified may potentially serve as crucial consortium candidates for host plant development and contribute to better yield in a sustainable manner.

Effects of maternal exposure to procymidone on hepatic metabolism in the offspring of mice.

As an effective fungicide widely used in agricultural production, the excessive procymidone (PRO) residue has been detected in the environment and food. Our previous study demonstrated that PRO could destroy the intestinal barrier in mice and has a joint toxic effect. To explore the cross-generational impact of maternal exposure, 10-week-old C57BL/6 female mice were orally administrated to 10 and 100 mg/kg body weight/day of PRO during pregnancy and lactation. The offspring obtained nutrients from the maternal through the placenta and breast milk, and PRO residues were detected in the liver, intestine, and feces of F1 generation. Fecal examination found that the residual PRO had been completely metabolized when the offspring mice grew to 35 days. The drug residue of F1 generation male mice was higher than that of female mice. We attributed this result to the difference in cytochrome P450 (CYP450) enzyme expression between male and female mice. The transcriptional levels of CYP1A1, CYP1A2, CYP2D9, and CYP3A4, and CYP450 protein expression levels, were higher in female mice. Furthermore, targeted MS of plasma revealed abnormal amino acid levels. In addition, PRO-induced hepatic metabolite changes in F0 and F1-7w mice. KEGG pathway analysis further showed that PRO jointly changed the amino acid biosynthesis pathway of the maternal and offspring. In summary, these results indicated that maternal exposure to PRO during a special period would interfere with self metabolism, and offspring will also have metabolic disorders.

Characterization and Analysis of the Full-Length Transcriptome Provide Insights into Fruit Quality Formation in Kiwifruit Cultivar Actinidia arguta cv. Qinziyu

Kiwifruit is an economically important horticultural crop with extremely high values in nutrition and health care. However, the molecular mechanisms underlying fruit quality formation remain largely limited for most kiwifruit varieties. Recently, a new kiwifruit cultivar with a high level of soluble solids, Actinidia arguta cv. Qinziyu (full-red flesh) was discovered through the introduction and propagation test. To provide new insights into fruit quality formation in a typical kiwifruit cultivar, we integrated full-length transcriptome surveys based on PacBio single-molecule real-time (SMRT) sequencing, key enzyme genes expression involved in carbohydrate and amino acids metabolism pathways, and bHLH gene family analysis to enhance the understanding of soluble sugar, organic acid, and anthocyanin biosynthesis in A. arguta cv. Qinziyu. A total of 175,913 CCSs were generated, of which 124,789 were identified as FLNC transcripts. In total, 45,923 (86.99%) transcripts were successfully annotated, and more than 76.05% of the transcripts were longer than 1 Kb. KEGG pathway analysis showed that 630 candidate genes encoding 55 enzymes were mainly involved in carbohydrate and amino acid biosynthesis pathways. Further analysis verified the expression of 12 key enzyme genes (e.g., pyruvate kinase (PK), enolase (ENO), hexokinase (HK), and phosphoglycerate kinase (PGK)) in flowers using quantitative real-time PCR. Furthermore, we also screened 10 AabHLH proteins’ function in anthocyanin biosynthesis and characterized the AabHLH gene family in A. arguta cv. Qinziyu. Overall, our research data generated by SMRT technology provide the first set of gene isoforms from a full-length transcriptome in A. arguta cv. Qinziyu and more comprehensive insights into the molecular mechanism of fruit quality formation.

Metabolite Changes during the Transition from Hyperthyroidism to Euthyroidism in Patients with Graves' Disease.

An excess of thyroid hormones in Graves' disease (GD) has profound effects on systemic energy metabolism that are currently partially understood. In this study, we aimed to provide a comprehensive understanding of the metabolite changes that occur when patients with GD transition from hyperthyroidism to euthyroidism with methimazole treatment. Eighteen patients (mean age, 38.6±14.7 years; 66.7% female) with newly diagnosed or relapsed GD attending the endocrinology outpatient clinics in a single institution were recruited between January 2019 and July 2020. All subjects were treated with methimazole to achieve euthyroidism. We explored metabolomics by performing liquid chromatography-mass spectrometry analysis of plasma samples of these patients and then performed multivariate statistical analysis of the metabolomics data. Two hundred metabolites were measured before and after 12 weeks of methimazole treatment in patients with GD. The levels of 61 metabolites, including palmitic acid (C16:0) and oleic acid (C18:1), were elevated in methimazole-naïve patients with GD, and these levels were decreased by methimazole treatment. The levels of another 15 metabolites, including glycine and creatinine, were increased after recovery of euthyroidism upon methimazole treatment in patients with GD. Pathway analysis of metabolomics data showed that hyperthyroidism was closely related to aminoacyl-transfer ribonucleic acid biosynthesis and branched-chain amino acid biosynthesis pathways. In this study, significant variations of plasma metabolomic patterns that occur during the transition from hyperthyroidism to euthyroidism were detected in patients with GD via untargeted metabolomics analysis.

Heritability of Protein and Metabolite Biomarkers Associated with COVID-19 Severity: A Metabolomics and Proteomics Analysis.

Prior studies have characterized protein and metabolite changes associated with SARS-CoV-2 infection; we hypothesized that these biomarkers may be part of heritable metabolic pathways in erythrocytes. Using a twin study of erythrocyte protein and metabolite levels, we describe the heritability of, and correlations among, previously identified biomarkers that correlate with COVID-19 severity. We used gene ontology and pathway enrichment analysis tools to identify pathways and biological processes enriched among these biomarkers. Many COVID-19 biomarkers are highly heritable in erythrocytes. Among heritable metabolites downregulated in COVID-19, metabolites involved in amino acid metabolism and biosynthesis are enriched. Specific amino acid metabolism pathways (valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and arginine biosynthesis) are heritable in erythrocytes. Metabolic pathways downregulated in COVID-19, particularly amino acid biosynthesis and metabolism pathways, are heritable in erythrocytes. This finding suggests that a component of the variation in COVID-19 severity may be the result of phenotypic variation in heritable metabolic pathways; future studies will be necessary to determine whether individual variation in amino acid metabolism pathways correlates with heritable outcomes of COVID-19.

Molecular evolution and signatures of selective pressures on Bos, focusing on the Nelore breed (Bos indicus).

Evolutionary history leads to genome changes over time, especially for species that have experienced intense selective pressures over a short period. Here, we investigated the genomic evolution of Bos species by searching for potential selection signatures, focusing on Nelore, an economically relevant cattle breed in Brazil. We assessed the genomic processes determining the molecular evolution across Nelore and thirteen other related taxa by evaluating (i) amino acid sequence conservation, (ii) the dN/dS ratio, and (iii) gene families' turnover rate (λ). Low conserved regions potentially associated with fatty acid metabolism seem to reflect differences in meat fat content in taxa with different evolutionary histories. All Bos species presented genes under positive selection, especially B. indicus and Nelore, which include transport protein cobalamin, glycolipid metabolism, and hormone signaling. These findings could be explained by constant selective pressures to obtain higher immune resistance and efficient metabolism. The gene contraction rate across the Nelore + B. indicus branch was almost nine times higher than that in other lineages (λ = 0.01043 vs. 0.00121), indicating gene losses during the domestication process. Amino acid biosynthesis, reproductive and innate immune system-related pathways were associated with genes recognized within the most frequent rapidly evolving gene families and in genes under positive selection, supporting the substantial relevance of such traits from a domestication perspective. Our data provide new insights into how the genome may respond to intense artificial selection in distinct taxa, and reinforces the presence of selective pressures on traits potentially relevant for future animal breeding investments.

Physiological changes and gene responses during Ganoderma lucidum growth with selenium supplementation.

Ganoderma lucidum basidiomycota is highly appreciated for its health and nutrition value. In the present study, Ganoderma lucidum was cultivated as selenium transformation carrier, and the physiological changes and gene responses by selenium supplementation were revealed through high-throughput RNA-Seq technology. As a result, selenium supplementation increased the stipe length and the cap size, but decreased the cap thickness of G. lucidum. Mineral salt supplementation could greatly promote the formation of triterpene acids and selenium in G. lucidum. The highest yield was gained in the treatment with selenium content of 200 µg/g. Subsequently, the tissues of G. lucidum at budding and mature stages in this treatment group were sampled for transcriptome analysis and compared to those of a control group without selenium supplementation. A total of 16,113 expressed genes were obtained from the transcriptome of G. lucidum, and GO-annotated unigenes were mainly involved in molecular functions and KEGG-annotated ones were highly expressed in ribosomal pathway. Furthermore, genes involved in carbon metabolism pathway were most promoted by selenium at budding stage of G. lucidum, while gene expression was the highest in the pathway of amino acid biosynthesis at mature stage of G. lucidum. Specially, selenium-related genes in G. lucidum, such as GL23172-G, GL29881-G and GL28298-G, played a regulatory role in oxidoreductase, antioxidant activity and tryptophan synthesis. The results provide a theoretical basis for further study of selenium-enriched mushrooms and aid to development of Se-enriched foodstuff and health products made from fungi.

Role of miRNAs in regulation of SA-mediated upregulation of genes involved in folate and methionine metabolism in foxtail millet.

The effect of exogenous salicylic acid (SA) on folate metabolism and the related gene regulatory mechanisms is still unclear. In this study, the panicle of foxtail millet treated with different SA concentrations showed that 6 mM SA doubled the 5-methyltetrahydrofolate content compared to that of the control. An untargeted metabolomic analysis revealed that 275 metabolites were enriched in amino acid metabolic pathways. Significantly, the relative content of methionine (Met) after 6 mM SA treatment was 3.14 times higher than the control. Transcriptome analysis revealed that differentially expressed genes were mainly enriched in the folate and amino acid biosynthesis pathways (including Met, Cys, Pro, Ser etal.). The miRNA-mRNA interactions related to the folate and Met metabolic pathways were analyzed and several likely structural gene targets for miRNAs were identified, miRNA-seq analysis revealed that 33 and 51 miRNAs targeted 11 and 15 genes related to the folate and Met pathways, respectively. Eight key genes in the folate metabolism pathway were likely to be up-regulated by 14 new miRNAs and 20 new miRNAs up-regulated the 9 key genes in the Met metabolism pathway. The 6 miRNA-mRNA interactions related to the folate and Met metabolism pathways were verified by qRT-PCR, and consistent with the prediction. The results showed that DHFR1 gene expression level related to folate synthesis was directly up-regulated by Nov-m0139-3p with 3.8 times, but DHFR2 was down-regulated by Nov-m0731-5p with 0.62 times. The expression level of CYSC1 and APIP related to Met synthesis were up-regulated by Nov-m0461-5p and Nov-m0664-3p with 4.27 and 1.32 times, respectively. Our results suggested that exogenous SA could induce the folate and Met accumulated in the panicle of foxtail millet. The higher expression level of DHFR1, FTHFD, CYSC1 and APIP in the folate and Met metabolism pathway and their regulators, including Nov-m0139-3p, Nov-m0717-5p, Nov-m0461-5p and Nov-m0664-3p, could be responsible for these metabolites accumulation. This study lays the theoretical foundation for elucidating the post-transcription regulatory mechanisms of folate and Met metabolism.