Changes In Metabolite Concentrations Research Articles

The MEMIC is an ex vivo system to model the complexity of the tumor microenvironment.

ABSTRACTThere is an urgent need for accurate, scalable and cost-efficient models of the tumor microenvironment. Here, we detail how to fabricate and use the metabolic microenvironment chamber (MEMIC) – a 3D-printed ex vivo model of intratumoral heterogeneity. A major driver of the cellular and molecular diversity in tumors is accessibility to the blood stream. Whereas perivascular tumor cells have direct access to oxygen and nutrients, cells further from the vasculature must survive under progressively more ischemic environments. The MEMIC simulates this differential access to nutrients, allow co-culturing any number of cell types, and it is optimized for live imaging and other microscopy-based analyses. Owing to a modular design and full experimental control, the MEMIC provides insights into the tumor microenvironment that would be difficult to obtain via other methods. As proof of principle, we show that cells sense gradual changes in metabolite concentration leading to predictable molecular and cellular spatial patterns. We propose the MEMIC as a complement to standard in vitro and in vivo experiments, diversifying the tools available to accurately model, perturb and monitor the tumor microenvironment.

Alterations to the urinary metabolome following semi-controlled short exposures to ultrafine particles at a major airport

BackgroundInflammation, oxidative stress and reduced cardiopulmonary function following exposure to ultrafine particles (UFP) from airports has been reported but the biological pathways underlying these toxicological endpoints remain to be explored. Urinary metabolomics offers a robust method by which changes in cellular pathway activity can be characterised following environmental exposures.ObjectiveWe assessed the impact of short-term exposures to UFP from different sources at a major airport on the human urinary metabolome.Methods21 healthy, non-smoking volunteers (aged 19–27 years) were repeatedly (2–5 visits) exposed for 5h to ambient air at Amsterdam Airport Schiphol, while performing intermittent, moderate exercise. Pre- to-post exposure changes in urinary metabolite concentrations were assessed via 1H NMR spectroscopy and related to total and source-specific particle number concentrations (PNC) using linear mixed effects models.ResultsTotal PNC at the exposure site was on average, 53,500 particles/cm3 (range 10,500–173,200) and associated with significant reductions in urinary taurine (−0.262 AU, 95% CI: −0.507 to −0.020) and dimethylamine concentrations (−0.021 AU, 95% CI: −0.040 to −0.067). Aviation UFP exposure accounted for these changes, with the reductions in taurine and dimethylamine associating with UFP produced during both aircraft landing and take-off. Significant reductions in pyroglutamate concentration were also associated with aviation UFP specifically, (−0.005 AU, 95% CI: −0.010 – <0.000) again, with contributions from both landing and take-off UFP exposure. While non-aviation UFPs induced small changes to the urinary metabolome, their effects did not significantly impact the overall response to airport UFP exposure.DiscussionFollowing short-term exposures at a major airport, aviation-related UFP caused the greatest changes to the urinary metabolome. These were consistent with a heightened antioxidant response and altered nitric oxide synthesis. Although some of these responses could be adaptive, they appeared after short-term exposures in healthy adults. Further study is required to determine whether long-term exposures induce injurious effects.

Untargeted metabolomics analysis of Ralstonia eutropha during plant oil cultivations reveals the presence of a fucose salvage pathway

Process engineering of biotechnological productions can benefit greatly from comprehensive analysis of microbial physiology and metabolism. Ralstonia eutropha (syn. Cupriavidus necator) is one of the best studied organisms for the synthesis of biodegradable polyhydroxyalkanoate (PHA). A comprehensive metabolomic study during bioreactor cultivations with the wild-type (H16) and an engineered (Re2058/pCB113) R. eutropha strain for short- and or medium-chain-length PHA synthesis has been carried out. PHA production from plant oil was triggered through nitrogen limitation. Sample quenching allowed to conserve the metabolic states of the cells for subsequent untargeted metabolomic analysis, which consisted of GC–MS and LC–MS analysis. Multivariate data analysis resulted in identification of significant changes in concentrations of oxidative stress-related metabolites and a subsequent accumulation of antioxidative compounds. Moreover, metabolites involved in the de novo synthesis of GDP-l-fucose as well as the fucose salvage pathway were identified. The related formation of fucose-containing exopolysaccharides potentially supports the emulsion-based growth of R. eutropha on plant oils.

Effect of negative energy balance on plasma metabolites, minerals, hormones, cytokines and ovarian follicular growth rate in Holstein dairy cows

IntroductionThe aim of this study was to evaluate the effect of negative energy balance (NEB) on the final growth of the dominant ovarian follicle in Holstein cows.Material and MethodsCows at 14 to 21 d postpartum from an intensive dairy farm were randomly selected and allocated into a positive energy balance group (PEB, with β-hydroxybutyric acid (BHBA) level < 1.2 mmol/L, n = 15) and an NEB group (BHBA > 1.2 mmol/L, n = 15). Plasma samples were collected at 21, 50 and 55 d postpartum to assess the concentrations of energy metabolites, minerals, hormones and cytokines. Ovaries were examined by transrectal ultrasound on days 50 and 55 (120 hours later) to evaluate the diameter of the largest follicle.ResultsCompared with PEB cows, there were a more severe body condition loss and a lower milk yield in NEB cows (P < 0.05) and these had greater concentrations of plasma BHBA, non-esterified fatty acids, triglycerides, urea nitrogen, growth hormone, interleukin 6, and fibroblast growth factor 21 and lesser concentrations of plasma glucose, total cholesterol, insulin, insulin-like growth factor 1, insulin-like growth factor binding protein 3, leptin, brain-derived neurotrophic factor and angiopoietin-like protein 8 on d 21 (P < 0.05), while plasma minerals were not affected by energy status (P > 0.05). These changes persisted until the end of the study period (50–55 days postpartum) resulting in a lower follicular growth rate for cows in the NEB than the PEB group.ConclusionThese observations indicate that follicular growth rate is associated with measurable changes in energy metabolite, hormone and cytokine concentrations caused by early postpartum NEB.

Osteogenic Response of Human Mesenchymal Stem Cells Analysed Using Combined Intracellular and Extracellular Metabolomic Monitoring.

The skeleton is a metabolically active organ undergoing continuous remodelling initiated by mesenchymal progenitors present in bone and bone marrow. Under certain pathological conditions this remodelling balance shifts towards increased resorption resulting in weaker bone microarchitecture, and there is consequently a therapeutic need to identify pathways that could inversely enhance bone formation from stem cells. Metabolomics approaches recently applied to stem cell characterisation could help identify new biochemical markers involved in osteogenic differentiation. Combined intra- and extracellular metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS) on human mesenchymal stem cells (MSCs) undergoing osteogenic differentiation in vitro. Using a combination of univariate and multivariate analyses, changes in metabolite and nutrient concentration were monitored in cultures under osteogenic treatment over 10 days. A subset of differentially detected compounds was identified in differentiating cells, suggesting a direct link to metabolic processes involved in osteogenic response. These results highlight new metabolite candidates as potential biomarkers to monitor stem cell differentiation towards the bone lineage.

Using TD-NMR relaxometry and 1D 1H NMR spectroscopy to evaluate aging of Nellore beef

The aim of this study was to explore the use of TD-NMR relaxometry and 1H NMR spectroscopy-based for detecting differences in meat quality attributes. There was limited association between various TD-NMR signals and any physicochemical parameters of fresh and aged meat differing in tenderness ratings. Samples were then divided into three groups based on statistical changes in metabolite concentration. Group A samples possessed near linear increases in metabolite concentration over aging time; whereas samples assigned to Groups B and C were characterized by increases in metabolites that peaked between 7 and 14 days, and up to 14 days aging, respectively. 1H NMR spectroscopy discriminated meat quality using changes in metabolites reflective of glycolysis, the citric acid cycle, protein degradation, amino acid generation and purine metabolisms. These data suggest segregation of meat quality is possible using both NMR technologies but additional work is necessary to understand fully their utility in a commercial industry setting.

Multivariate approach for longitudinal analysis of brain metabolite levels from ages 5-11 years in children with perinatal HIV infection

Treatment guidelines recommend that children with perinatal HIV infection (PHIV) initiate antiretroviral therapy (ART) early in life and remain on it lifelong. As part of a longitudinal study examining the long-term consequences of PHIV and early ART on the developing brain, 89 PHIV children and a control group of 85 HIV uninfected children (HIV-) received neuroimaging at ages 5, 7, 9 and 11 years, including single voxel magnetic resonance spectroscopy (MRS) in three brain regions, namely the basal ganglia (BG), midfrontal gray matter (MFGM) and peritrigonal white matter (PWM). We analysed age-related changes in absolute metabolite concentrations using a multivariate approach traditionally applied to ecological data, the Correlated Response Model (CRM) and compared these to results obtained from a multilevel mixed effect modelling (MMEM) approach. Both approaches produce similar outcomes in relation to HIV status and age effects on longitudinal trajectories. Both methods found similar age-related increases in both PHIV and HIV- children in almost all metabolites across regions. We found significantly elevated GPC+PCh across regions (95% CI=[0.033; 0.105] in BG; 95% CI=[0.021; 0.099] in PWM; 95% CI=[0.059; 0.137] in MFGM) and elevated mI in MFGM (95% CI=[0.131; 0.407]) among children living with PHIV compared to HIV- children; additionally the CRM model also indicated elevated mI in BG (95% CI=[0.008; 0.248]). These findings suggest persistent inflammation across the brain in young children living with HIV despite early ART initiation.

Plant silicon application alters leaf alkaloid concentrations and impacts parasitoids more adversely than their aphid hosts.

Grasses accumulate large amounts of silicon (Si) which acts as a highly effective physical defence against insect herbivory, however recent evidence shows that Si supplementation also modifies plant secondary metabolite concetrations. Changes in plant secondary metabolites concentrations can have cascading effects on higher trophic levels, such as parasitoids, as they are dependent on the host herbivore for growth and development. However, relatively little is known about how Si application affects higher trophic levels. We examined the effects of Si addition on alkaloid content in leaves of Phalaris aquatica (Poaceae) and the effect on interactions between an aphid (Rhopalosiphum padi) and its parasitoid (Aphidius colemani). Si supplementation had no effect on aphid abundance or parasitism rate. Adult aphids, aphid mummies (parasitised aphids) and the emergent parasitoids were, however, significantly smaller on Si+ plants. Parasitoid traits (size and emergence) were correlated with aphid mummy size. Si addition reduced parasitoid emergence rate and size due to reduced host mummy size, in addition, significantly fewer females emerged from mummies on Si+ plants. Aphid infestation significantly altered alkaloids concentrations, reducing gramine by 80% while increasing tryptamine by 91% in Si- plants. Si addition reduced aphid-induced tryptamine concentrations by 64% and increased 5-MeO-tryptamine by over 800% in control and 142% in aphid infested plants. Our results show that while Si addition has modest impacts on the herbivore, it significantly alters secondary metabolites and has stronger effects on the higher trophic level through changes in the quality of the parasitised host.

Quantification of magnetic resonance spectroscopy data using a combined reference: Application in typically developing infants.

Quantification of proton magnetic resonance spectroscopy (1 H-MRS) data is commonly performed by referencing the ratio of the signal from one metabolite, or metabolite group, to that of another, or to the water signal. Both approaches have drawbacks: ratios of two metabolites can be difficult to interpret because study effects may be driven by either metabolite, and water-referenced data must be corrected for partial volume and relaxation effects in the water signal. Here, we introduce combined reference (CRef) analysis, which compensates for both limitations. In this approach, metabolites are referenced to the combined signal of several reference metabolites or metabolite groups. The approach does not require the corrections necessary for water scaling and produces results that are less sensitive to the variation of any single reference signal, thereby aiding the interpretation of results. We demonstrate CRef analysis using 202 1 H-MRS acquisitions from the brains of 140 infants, scanned at approximately 1 and 3 months of age. We show that the combined signal of seven reference metabolites or metabolite groups is highly correlated with the water signal, corrected for partial volume and relaxation effects associated with cerebral spinal fluid. We also show that the combined reference signal is equally or more uniform across subjects than the reference signals from single metabolites or metabolite groups. We use CRef analysis to quantify metabolite concentration changes during the first several months of life in typically developing infants.

Application of Nitrate, Ammonium, or Urea Changes the Concentrations of Ureides, Urea, Amino Acids and Other Metabolites in Xylem Sap and in the Organs of Soybean Plants (Glycine max (L.) Merr.).

Soybean (Glycine max (L.) Merr.) plants form root nodules and fix atmospheric dinitrogen, while also utilizing the combined nitrogen absorbed from roots. In this study, nodulated soybean plants were supplied with 5 mM N nitrate, ammonium, or urea for 3 days, and the changes in metabolite concentrations in the xylem sap and each organ were analyzed. The ureide concentration in the xylem sap was the highest in the control plants that were supplied with an N-free nutrient solution, but nitrate and asparagine were the principal compounds in the xylem sap with nitrate treatment. The metabolite concentrations in both the xylem sap and each organ were similar between the ammonium and urea treatments. Considerable amounts of urea were present in the xylem sap and all the organs among all the treatments. Positive correlations were observed between the ureides and urea concentrations in the xylem sap as well as in the roots and leaves, although no correlations were observed between the urea and arginine concentrations, suggesting that urea may have originated from ureide degradation in soybean plants, possibly in the roots. This is the first finding of the possibility of ureide degradation to urea in the underground organs of soybean plants.

Altered metabolic pathways in a transgenic mouse model suggest mechanistic role of amyloid precursor protein overexpression in Alzheimer's disease.

The mechanistic role of amyloid precursor protein (APP) in Alzheimer's disease (AD) remains unclear. Here, we aimed to identify alterations in cerebral metabolites and metabolic pathways in cortex, hippocampus and serum samples from Tg2576 mice, a widely used mouse model of AD. Metabolomic profilings using liquid chromatography-mass spectrometry were performed and analysed with MetaboAnalyst and weighted correlation network analysis (WGCNA). Expressions of 11 metabolites in cortex, including hydroxyphenyllactate-linked to oxidative stress-and phosphatidylserine-lipid metabolism-were significantly different between Tg2576 and WT mice (false discovery rate < 0.05). Four metabolic pathways from cortex, including glycerophospholipid metabolism and pyrimidine metabolism, and one pathway (sulphur metabolism) from hippocampus, were significantly enriched in Tg2576 mice. Network analysis identified five pathways, including alanine, aspartate and glutamate metabolism, and mitochondria electron transport chain, that were significantly correlated with AD genotype. Changes in metabolite concentrations and metabolic pathways are present in the early stage of APP pathology, and may be important for AD development and progression.

Changes in metabolite concentrations in the abdominal muscle of the kuruma shrimp Marsupenaeus japonicus in response to different salinities

Invertebrates change the metabolite concentrations in their bodies to adapt to environmental salinity. The kuruma shrimp Marsupenaeus japonicus is one such invertebrate. It lives in coastal areas and is also known to change free amino acid concentrations depending on environmental salinity. To examine the relationship between the concentrations of metabolites, including amino acids, in the kuruma shrimp with environmental salinity, metabolome analysis was performed on the abdominal muscle of shrimps acclimated at 17, 34 and 40‰ salinity for 24 h. Principal component analysis revealed that the accumulation patterns of metabolites using the 111 metabolites detected in the shrimps exposed to different salinities were depicted in a salinity-dependent manner. The concentrations of alanine and glutamine were increased following exposure to increasing levels of salinity, suggesting that these free amino acids function in intracellular osmoregulation of the kuruma shrimp. Furthermore, the concentration of glycolytic metabolites was significantly decreased at high salinity. The concentrations of most of the metabolites related to the tricarboxylic acid (TCA) cycle also tended to decrease at high salinity. Considering the levels of expression of the genes related to various metabolic pathways, it seems that glycolysis is accelerated at high salinity.

Global coordination of metabolic pathways in Escherichia coli by active and passive regulation

Microorganisms adjust metabolic activity to cope with diverse environments. While many studies have provided insights into how individual pathways are regulated, the mechanisms that give rise to coordinated metabolic responses are poorly understood. Here, we identify the regulatory mechanisms that coordinate catabolism and anabolism in Escherichia coli. Integrating protein, metabolite, and flux changes in genetically implemented catabolic or anabolic limitations, we show that combined global and local mechanisms coordinate the response to metabolic limitations. To allocate proteomic resources between catabolism and anabolism, E. coli uses a simple global gene regulatory program. Surprisingly, this program is largely implemented by a single transcription factor, Crp, which directly activates the expression of catabolic enzymes and indirectly reduces the expression of anabolic enzymes by passively sequestering cellular resources needed for their synthesis. However, metabolic fluxes are not controlled by this regulatory program alone; instead, fluxes are adjusted mostly through passive changes in the local metabolite concentrations. These mechanisms constitute a simple but effective global regulatory program that coarsely partitions resources between different parts of metabolism while ensuring robust coordination of individual metabolic reactions.

Simultaneous Biochemical and Physiological Responses of the Roots and Leaves of Pancratium maritimum (Amaryllidaceae) to Mild Salt Stress.

Pancratium maritimum (Amaryllidaceae) is a bulbous geophyte growing on coastal sands. In this study, we investigated changes in concentrations of metabolites in the root and leaf tissue of P. maritimum in response to mild salt stress. Changes in concentrations of osmolytes, glutathione, sodium, mineral nutrients, enzymes, and other compounds in the leaves and roots were measured at 0, 3, and 10 days during a 10-day exposure to two levels of mild salt stress, 50 mM NaCl or 100 mM NaCl in sandy soil from where the plants were collected in dunes near Cuma, Italy. Sodium accumulated in the roots, and relatively little was translocated to the leaves. At both concentrations of NaCl, higher values of the concentrations of oxidized glutathione disulfide (GSSG), compared to reduced glutathione (GSH), in roots and leaves were associated with salt tolerance. The concentration of proline increased more in the leaves than in the roots, and glycine betaine increased in both roots and leaves. Differences in the accumulation of organic osmolytes and electron donors synthesized in both leaves and roots demonstrate that osmoregulatory and electrical responses occur in these organs of P. maritimum under mild salt stress.

Effects of feeding bulls dried corn distiller’s grains plus solubles or CaSO4 on mineral and metabolite concentrations in serum and seminal plasma

Yearling Angus bulls (n = 36) were assigned one of three diets: 1) 60 % concentrate as corn (CON, 0.2 % S, 13.4 % CP; n = 12); 2) 60 % dried corn distiller’s grains plus solubles (60DDGS 0.5 % S, 22.0 % CP; n = 12); 3) CON diet + equivalent sulfur of 60DDGS as CaSO4 (SULF, 0.5 % S, 13.9 % CP; n = 12) to evaluate effects of feeding 60 % DDGS or sulfur as CaSO4 on mineral and metabolite concentrations in serum and seminal plasma. Treatment × day interactions (P < 0.03) were observed for serum Cu, Se, and Mo. For Cu at d 112, lesser (P < 0.01) concentrations were observed in bulls fed the 60DDGS compared to SULF and CON diets. There were greater (P < 0.01) concentrations of Se at d 112 in bulls fed 60DDGS than CON and SULF diets. Concentrations of Mo were greater at d 56 and 112 (P < 0.01) in bulls fed CON compared to SULF and 60DDGS diets. In seminal plasma, there were treatment × day interactions (P < 0.02) for Cu and Mo. For Cu, at d 112, there was a lesser (P < 0.01) concentration in the bulls fed SULF compared to CON and 60DDGS diets. For Mo, there was a greater (P < 0.01) concentration in bulls fed the CON than 60DDGS and SULF diets at d 56 and 112. Changes in mineral and metabolite concentrations may have effects on bull reproductive performance when there is a relatively greater dietary sulfur content.

Riboswitch-Mediated Detection of Metabolite Fluctuations During Live Cell Imaging of Bacteria.

Riboswitches are a class of noncoding RNAs that regulate gene expression in response to changes in intracellular metabolite concentrations. When riboswitches are placed upstream of genetic reporters, the degree of reporter activity reflects the relative abundance of the metabolite that is sensed by the riboswitch. This method describes how reporters for live cell imaging, such as yellow fluorescent protein (YFP), can be placed under genetic control by metabolite-sensing riboswitches in the bacterium Bacillus subtilis. Specifically, a protocol for generating a fluorescent YFP reporter, based on a c-di-GMP responsive riboswitch, is outlined below.

A report on the housing vervet monkeys adjacent to domestic cats as a means of environmental enrichment.

In current research guidelines, much focus is placed on ethical management of animals and the application of principles of reduction, refinement and replacement. Of these refinements through environmental enrichment is an important aspect when housing primate to prevent behavioural problems. In this study, we investigated the co-housing of domestic cats and vervet monkeys as a novel method of enrichment based on the cohabitation and stress alleviation effect of horses housed with goats and from seeing cats cohabitating with vervet monkeys in an animal sanctuary. The study used a habituation method whereby the cats were stepwise introduced to the monkeys by sight and smell but with physical separation. Assessment included changes in behaviour, weight and faecal glucocorticoid metabolite (fGCM) concentrations over time. On the first day of housing, the vervets whilst inquisitive kept their distance. The vervets housed in cages that were closest to the cats were the most active and during the first minute of introduction made more alarm calls, which stopped a few days later. The fGCMs were non-significantly different. The results of this study provide evidence that vervet monkeys and domestic cats could potentially be housed together without overt aggression. We thus suggest further observations to ascertain if the co-housing could have long-term benefits for vervet monkeys, from the companionship that would be offered by the cats.

Changes in the brain directly following alcohol consumption-a study of healthy male individuals, with the use of proton magnetic resonance spectroscopy (1HMRS) and diffusion (DWI).

To use proton magnetic resonance spectroscopy (1HMRS) and diffusion weighted imaging (DWI) to identify ethanol in the brain directly after consumption, and examine changes in brain metabolite levels and brain microstructure relative to the duration of time following exposure to alcohol. The study involved 44 male volunteers (18-55years). All brain changes were assessed in the frontal lobes, occipital lobes, basal ganglia and cerebellum, however the detailed analyses focused on the frontal lobes. All participants were examined four times, i.e. before and 0.5-hour, 1hour and 2hours after consumption of 150mL pure vodka (60g of ethanol). The highest ethanol levels were identified between 0.5 and 1hour following alcohol intake. There were significant increases in the concentrations of lipids and lactates approximately one hour after alcohol consumption, and the concentration levels were found to normalise during the following two hours. Some statistically insignificant trends of changes were found for tCr, tCho, mI, GABA, Glc, Glx and tNAA. For the DWI and ADC (Apparent Diffusion Coefficient of water) values, the findings showed statistically insignificant decrease and increase, followed by a tendency towards normalisation. Similar associations in changes of metabolite concentrations and DWI and ADC values were found in the other locations investigated in the study. A single dose of alcohol as used in this experiment produces increases in lipids and lactates in brain tissues that appear reversible.

Multimodal Magnetic Resonance Imaging and Therapeutic Intervention With Yi-nao-jie-yu Decoction in a Rat Model of Post-stroke Depression.

Post-stroke depression (PSD) is the most common neuropsychiatric complication after a stroke, though its neuropathological characteristics have not been fully elucidated. Comprehensive and non-invasive magnetic resonance (MR) assessment techniques are urgently needed for current research, as diffusion tensor imaging (DTI), arterial spin labeling (ASL), and magnetic resonance spectroscopy (MRS) can allow for a comprehensive assessment of neuropathological changes in the brain. These techniques can provide information about microscopic tissue integrity, cerebral perfusion, and cerebral metabolism, and can serve as powerful tools for investigating neurophysiological changes associated with PSD. Yi-nao-jie-yu decoction (YNJYD) is a Chinese herbal formulation based on the theory of traditional Chinese medicine, with demonstrated clinical efficacy in the treatment of PSD. The aim of this study was to use these MR techniques to evaluate changes in PSD and YNJYD-treated rats. This is the first experimental study in animals to investigate neuropathological changes associated with PSD using a combination of multiple MR techniques, including DTI, ASL, and MRS. In addition, we investigated the effect of YNJYD in a rat model of PSD by assessing changes in brain tissue microstructure, brain metabolism, and cerebral perfusion. First, depressive-like behaviors of PSD rats were assessed by the open field test (OFT), sucrose preference test (SPT), and Morris water maze (MWM) test, and then the integrity of the rats' microstructure was assessed by DTI, the levels of regional cerebral perfusion were assessed by ASL, and changes in the relative concentrations of brain metabolites were determined by MRS. The results showed that OFT and SPT scores were significantly reduced in PSD rats, as was performance in the MWM; these PSD-associated changes were attenuated in rats administered YNJYD, with improved depressive-like behaviors evidenced by increased OFT and SPT scores and improved performance in the MWM task. Furthermore, we found that PSD rats had lower perfusion levels in the prefrontal cortex (PFC) and hippocampus (HP), microstructural damage, and abnormal changes in the concentrations of brain metabolites; YNJYD exerted therapeutic effects on PSD rats by improving microcirculation in the PFC and HP, regulating glutamatergic systems and membrane phospholipid metabolism, and repairing microstructural damage.

Stem lodging resistance in hulless barley: Transcriptome and metabolome analysis of lignin biosynthesis pathways in contrasting genotypes

Hulless barley is an important economic and food crop for local population in the Qinghai-Tibet plateau. However, due to extreme weather conditions, its production suffers from stem lodging stress, inflicting significant yield losses. Herein, we selected five lodging resistant and five non-resistant genotypes to investigate changes in concentration of lignin related metabolites and expression levels of related genes in node samples. The lodging resistant genotypes displayed high content of lignin intermediate metabolites. 57% of the expressed genes were differentially expressed (DEG) between the two groups. 31 DEGs participate in the lignin pathways and we found that 65% of these DEGs were strongly up-regulated in the lodging resistant group, indicating a mechanism towards high lignin synthesis within said group. The candidate structural genes as well as the co-expressed TFs identified in this study represent important molecular tools for functional characterization and exploitation in molecular breeding programmes.