Changes In Metabolite Concentrations Research Articles

Plasma amino acid signatures define types of pediatric diabetes

Metabolic biomarkers with pathophysiological relevance is lacking in pediatric diabetes. We aimed to identify novel metabolic biomarkers in pediatric type 1 (T1D) and type 2 diabetes (T2D). We hypothesized that (1) targeted plasma metabolomics, focused on plasma amino acid concentrations, could identify distinctively altered patterns in children with T1D or T2D, and (2) there are specific changes in concentrations of metabolites related to branch chain amino acids (BCAA) and arginine metabolism in children with T2D. In a pilot study, we enrolled children with T1D (n=15) and T2D (n=13), and healthy controls (n=15). Fasting plasma amino acid concentrations were measured by ultra-performance liquid chromatography, and compared between the groups after adjustment for confounding factors. The mean age (SD) of participants was 16.4 (0.9) years. There were no group differences in age, gender, race/ethnicity, or 24-h protein intake. Mean BMI percentile was higher in the T2D than the T1D group or controls (p<0.001). The T2D group had lower arginine, citrulline, glutamine, glycine, phenylalanine, methionine, threonine, asparagine and symmetric dimethylarginine (SDMA) but higher aspartate than controls, after adjusting for BMI percentiles (all p<0.05). Children with T2D also had lower glycine but higher ornithine, proline, leucine, isoleucine, valine, total BCAA, lysine and tyrosine than those with T1D after adjusting for confounding factors (all p<0.05). Children with T1D had lower phenylalanine, methionine, threonine, glutamine, tyrosine, asymmetric dimethylarginine (ADMA) and SDMA than controls (all p<0.05). Children with T2D and T1D have distinct fasting plasma amino acid signatures that suggest varying pathogenic mechanisms and could serve as biomarkers for these conditions.

Nanobiochar Application in Combination with Mulching Improves Metabolites and Curd Quality Traits in Cauliflower

Sustainable nutrient management approaches could improve production and quality without affecting soil health. We conducted a field experiment to investigate the interactive effects of mulching (no mulch, plastic mulch, and straw mulch) and nanobiochar (NBC) foliar application on biomass, nutrient contents, and metabolites in the leaf and curd of cauliflower (Brassica oleracea var. botrytis). After 20 days of transplantation, NBC (0.1% w/v) was applied as a foliar spray for four consecutive weeks (one spray per week). At the curd initiation stage, changes in chlorophyll, carotenoids, and metabolite concentrations in leaves and curd were determined. The application of nanobiochar significantly enhanced the curd weight and improved curd morphology. Yield traits including curd weight, curd diameter, basal diameter, and stalk length were increased by 30, 13, 16, and 20% by NBC application compared to control. Plastic mulching also increased the aboveground biomass by 32% when compared to no mulching. Moreover, plastic mulching and nanobiochar prominently enhanced root dry weight, curd weight, rough solidity index, total soluble sugar in leaf and curd, calcium in curd, and potassium in leaf and curd of cauliflower. Overall, this study revealed the potential of the foliar application of NBC in promoting the biomass and nutritional properties of cauliflower.

Pre-estrus progesterone does not affect post-estrus luminal metabolome in cross-bred beef cows.

The concentration of progesterone through the estrous cycle modulates uterine function to affect the luminal metabolome. This paper reports that the dynamic changes in the bovine uterine luminal metabolome during diestrus are independent of the concentration of progesterone in the previous cycle. In cattle, the concentration of sex steroids modulates uterine function, which is reflected in the composition of the luminal metabolome. Ultimately, the uterine luminal metabolome influences embryonic growth and development. Our objectives were (i) to compare the luminal metabolome 4, 7, and 14 days after estrus of cows that were exposed to greater (HP4; n = 16) vs lower (LP4; n = 24) concentrations of progesterone before displaying estrus and ovulating spontaneously and (ii) to identify changes in the luminal concentration of metabolites across these time points. Luminal epithelial cells and fluid were collected using a cytology brush, and gene expression and metabolite concentrations were assessed by RNAseq and targeted mass spectrometry, respectively. Metabolome profile was similar between treatments within each of days 4, 7, and 14 (false discovery rate (FDR): ≥ 0.1). Concentrations of 53 metabolites changed, independent of treatment, across the diestrus. Metabolites were mostly lipids (40 out 53) and the greatest concentrations were at day 14 (FDR: ≤ 0.1). On day 7, the concentration of putrescine and the gene expression of ODC1, PAOX, SLC3A2, and SAT1 increased (P ≤ 0.05). On day 14, the concentration of 3 ceramides, 4 glucosylceramides, and 12 sphingomyelins and the expression of SGMS2 were increased, in addition to the concentration of choline and 20 phosphatidylcholines. Collectively, the post-estrus concentration of luminal metabolites changed dynamically, independent of the concentration of sex steroids on the previous cycle, and the greatest magnitude changes were on day 14 when lipid metabolism was the most enriched pathway.

Healthy Nordic diet and associations with plasma concentrations of metabolites in the choline oxidation pathway: a cross-sectional study from Northern Sweden

BackgroundThe choline oxidation pathway and metabolites involved have been linked to diseases including cardiovascular disease, type 2 diabetes and cancer. A healthy Nordic diet is a recently defined dietary pattern associated with decreased risk for these diseases. Our aim was to explore associations between adherence to a healthy Nordic diet and plasma concentrations of metabolites of the choline oxidation pathway.MethodsThe Healthy Nordic Food Index (HNFI) and Baltic Sea Diet Score (BSDS) were applied to cross-sectional data (n = 969) from the Västerbotten Intervention Programme in Northern Sweden to score adherence to a healthy Nordic diet. Data included responses to a dietary questionnaire and blood sample analyses (1991–2008). Associations of diet scores with plasma concentrations of metabolites of the choline oxidation pathway and total homocysteine (tHcy), seven metabolites in total, were evaluated with linear regression, adjusting for age, BMI, education and physical activity.ResultsHNFI scores showed linear relationships with plasma choline (β = 0.11), betaine (β = 0.46), serine (β = 0.98) and tHcy (β = − 0.38), and BSDS scores with betaine (β = 0.13) and tHcy (β = − 0.13); unstandardized beta coefficients, all significant at P < 0.05. The regression models predicted changes in plasma metabolite concentrations (± 1 SD changes in diet score) in the range of 1–5% for choline, betaine, serine and tHcy. No other statistically significant associations were observed.ConclusionsA healthy Nordic diet was associated with plasma concentrations of several metabolites of the choline oxidation pathway. Although relationships were statistically significant, effect sizes were moderate. Further research is warranted to explore the underlying mechanisms and associations with health outcomes.

Adiposity and plasma concentrations of kynurenine pathway metabolites and traditional markers of inflammation

AimThe kynurenine pathway is increasingly recognised to play a role in inflammation and disease. We assessed the cross-sectional and longitudinal associations of adiposity measures (body mass index, waist-hip ratio, waist circumference and fat mass ratio) with plasma concentrations of kynurenine pathway metabolites and traditional markers of inflammation. MethodsWe used data from 970 Melbourne Collaborative Cohort Study participants who had plasma markers measured at baseline (median age 59 years) and follow-up (median age 70 years). Linear regression was used to assess cross-sectional and longitudinal associations between four adiposity measures and concentrations of i) nine kynurenine pathway metabolites; ii) two derived markers; iii) eight traditional inflammatory markers. ResultsCross-sectionally, most kynurenine metabolites were strongly associated with adiposity measures at both time points; associations were generally stronger than for most inflammation markers except CRP (e.g. body mass index at baseline, quinolinic acid (per S.D. β = 0.30, 95%CI: 0.24–0.36, P = 10−21), kynurenine (β = 0.25, 95%CI: 0.19–0.31, P = 10−16) and CRP (β = 0.31, 95%CI: 0.25–0.37, P = 10−24), and remained largely unchanged after adjustment for confounders. Longitudinally, changes in adiposity measures over approximately a decade were positively associated with changes in kynurenine metabolite concentrations (in particular for 3-hydroxyanthranilic acid, kynurenine and quinolinic acid), and more strongly so than for other markers of inflammation, including CRP. ConclusionsIn middle-aged and older adults, plasma concentrations of kynurenine metabolites are strongly associated with adiposity, both cross-sectionally and longitudinally. Our study demonstrates that kynurenine metabolites may be valuable markers to monitor the adverse consequences of obesity.

Circulating fatty acid-binding protein 4 response to acute aerobic exercise in healthy men.

This study aimed to investigate the association between changes in FABP4 concentration and hormones and metabolites levels during and after acute low- and moderate-intensity aerobic exercise in healthy men. Eleven healthy men (24.4 ± 1.4 years) were administered three trials in random order: 1) low-intensity aerobic exercise trial (LE trial; acute exercise at 40% peak oxygen uptake [Vo2peak] + bed rest), 2) moderate-intensity aerobic exercise trial (ME trial: acute exercise at 60%Vo2peak + bed rest), and 3) bed rest (Con trial). Expired gas and venous blood samples were collected at baseline, and immediately, 30 and 60 min after exercise, and substrate oxidation and hormone, metabolite, and FABP4 concentrations were measured. FABP4 concentration did not increase during aerobic exercise in LE and ME trials (p > 0.05) However, FABP4 concentration significantly increased after the acute aerobic exercise in both the LE and ME trials (p ≤ 0.003). Increased FABP4 concentration after acute exercise was not correlated with adrenaline, noradrenaline, other hormone, and metabolite concentration changes. These findings suggest that FABP4 concentration increases after acute aerobic exercise independently of exercise intensity. Furthermore, increased FABP4 concentration after acute aerobic exercise may not be involved in the magnitude of adrenaline, noradrenaline, and lipolytic response.

Longitudinal Data to Assess Relationships among Plasma Folate, Vitamin B12, Non-esterified Fatty Acid, and β-Hydroxybutyrate Concentrations of Holstein Cows during the Transition Period.

It is well established that the plasma metabolite profile changes during metabolic dysfunction, such as elevated non-esterified fatty acid (NEFA) release when body reserve mobilization is excessive in early lactation cows. Relationships between changes in plasma concentrations of metabolites caused by a metabolic impairment and the status of vitamins, such as folates and vitamin B12, have barely been studied in cattle. This study was undertaken to assess relationships between peripartum plasma concentrations of folates, vitamin B12, NEFA, and beta-hydroxybutyrate (BHB). Longitudinal data of 48 multiparous Holstein cows from 5 studies were taken from days -14 to 21 relative to calving. Blood samples were taken weekly before calving and either twice or thrice per week postpartum, and plasma was analyzed for folate, vitamin B12, NEFA, and BHB concentrations. Postpartum plasma NEFA and BHB concentrations were negatively related to plasma folate concentration at days -14 and -7 relative to parturition, whereas the opposite relationship was noted for the plasma vitamin B12:folate ratio. The plasma folate and NEFA areas under the curve from the whole studied period were negatively associated, and the opposite was observed with the association between the plasma vitamin B12:folate ratio and NEFA as well as the BHB areas under the curve. The results suggest that there is an increased use of folate for metabolic functions during elevated concentrations of plasma NEFA and BHB. Future research should focus on finding an optimal plasma vitamin B12:folate ratio to favor cow health during the challenging period of parturition.

Metabolomics-based Sleepiness Markers for Risk Prevention and Traffic Safety (ME-SMART): a monocentric, controlled, randomized, crossover trial

BackgroundToo little sleep and the consequences thereof are a heavy burden in modern societies. In contrast to alcohol or illicit drug use, there are no quick roadside or workplace tests for objective biomarkers for sleepiness. We hypothesize that changes in physiological functions (such as sleep–wake regulation) are reflected in changes of endogenous metabolism and should therefore be detectable as a change in metabolic profiles. This study will allow for creating a reliable and objective panel of candidate biomarkers being indicative for sleepiness and its behavioral outcomes.MethodsThis is a monocentric, controlled, randomized, crossover, clinical study to detect potential biomarkers. Each of the anticipated 24 participants will be allocated in randomized order to each of the three study arms (control, sleep restriction, and sleep deprivation). These only differ in the amount of hours slept per night. In the control condition, participants will adhere to a 16/8 h wake/sleep regime. In both sleep restriction and sleep deprivation conditions, participants will accumulate a total sleep deficit of 8 h, achieved by different wake/sleep regimes that simulate real-life scenarios. The primary outcome is changes in the metabolic profile (i.e., metabolome) in oral fluid. Secondary outcome measures will include driving performance, psychomotor vigilance test, d2 Test of Attention, visual attention test, subjective (situational) sleepiness, electroencephalographic changes, behavioral markers of sleepiness, changes in metabolite concentrations in exhaled breath and finger sweat, and correlation of metabolic changes among biological matrices.DiscussionThis is the first trial of its kind that investigates complete metabolic profiles combined with performance monitoring in humans over a multi-day period involving different sleep–wake schedules. Hereby, we aim to establish a candidate biomarker panel being indicative for sleepiness and its behavioral outcomes. To date, there are no robust and easily accessible biomarkers for the detection of sleepiness, even though the vast damage on society is well known. Thus, our findings will be of high value for many related disciplines.Trial registrationClinicalTrials.gov Identifier NCT05585515, released on 18.10.2022; Swiss National Clinical Trial Portal SNCTP000005089, registered on 12 August 2022.

NMR Metabolomics and DNA Sequencing of Escherichia coli and Staphylococcus aureus Cultures Treated with Hydrolyzable Tannins

Escherichia coli and Staphylococcus aureus are globally among the most prominent bacterial strains associated with antibacterial resistance-caused deaths. Naturally occurring polyphenols, such as hydrolyzable tannins, have been shown to potently inhibit E. coli and S. aureus. The current study investigated the metabolome changes of E. coli and S. aureus cultures after treatments with different hydrolyzable tannins using an NMR metabolomics approach. Additionally, the effect of these tannin treatments influencing a more complex bacterial system was studied in a biomimetic setting with fecal samples inoculated into the growth medium. Metabolite concentration changes were observed in all three scenarios: E. coli, S. aureus, and fecal batch culture. The metabolome of E. coli was more altered by the tannin treatments than S. aureus when compared to control cultures. A dimeric hydrolyzable tannin, rugosin D, was found to be the most effective of the studied compounds in influencing bacterial metabolome changes and in inhibiting E. coli and S. aureus growth. It was also observed that the tannin structure should have both hydrophobic and hydrophilic regions to efficiently influence E. coli and S. aureus growth.

Change in medial frontal cerebral metabolite concentrations following bariatric surgery.

Obesity is associated with adverse effects on brain health, including an increased risk of neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined changes in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery. Thirty-five patients with obesity (body mass index ≥ 35 kg/m2 ) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel proton magnetic resonance spectroscopy at baseline (presurgery) and within 1 year postsurgery. Spectra were obtained from a large medial frontal brain region using a PRESS sequence on a 3-T Siemens Verio scanner. The acquisition parameters were TR = 3000 ms and TE = 37 ms. Tissue-corrected metabolite concentrations were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycated hemoglobin (HbA1c ), a measure of blood sugar levels. Bariatric surgery was associated with a reduction in cerebral choline-containing compounds (Cho; t [34] = - 3.79, p < 0.001, d = -0.64) and myo-inositol (mI; t [34] = - 2.81, p < 0.01, d = -0.47) concentrations. There were no significant changes in N-acetyl-aspartate, creatine, or glutamate and glutamine concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p < 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p < 0.05). In conclusion, participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

A Systematic Role of Metabolomics, Metabolic Pathways, and Chemical Metabolism in Lung Cancer.

Lung cancer (LC) is considered as one of the leading causes of cancer-associated mortalities. Cancer cells' reprogrammed metabolism results in changes in metabolite concentrations, which can be utilized to identify a distinct metabolic pattern or fingerprint for cancer detection or diagnosis. By detecting different metabolic variations in the expression levels of LC patients, this will help and enhance early diagnosis methods as well as new treatment strategies. The majority of patients are identified at advanced stages after undergoing a number of surgical procedures or diagnostic testing, including the invasive procedures. This could be overcome by understanding the mechanism and function of differently regulated metabolites. Significant variations in the metabolites present in the different samples can be analyzed and used as early biomarkers. They could also be used to analyze the specific progression and type as well as stages of cancer type making it easier for the treatment process. The main aim of this review article is to focus on rewired metabolic pathways and the associated metabolite alterations that can be used as diagnostic and therapeutic targets in lung cancer diagnosis as well as treatment strategies.

Metabolic models of human gut microbiota: Advances and challenges.

The human gut is a complex ecosystem consisting of hundreds of microbial species interacting with each other and with the human host. Mathematical models of the gut microbiome integrate our knowledge of this system and help to formulate hypotheses to explain observations. The generalized Lotka-Volterra model has been widely used for this purpose, but it does not describe interaction mechanisms and thus does not account for metabolic flexibility. Recently, models that explicitly describe gut microbial metabolite production and consumption have become popular. These models have been used to investigate the factors that shape gut microbial composition and to link specific gut microorganisms to changes in metabolite concentrations found in diseases. Here, we review how such models are built and what we have learned so far from their application to human gut microbiome data. In addition, we discuss current challenges of these models and how these can be addressed in the future.

Several Metabolite Families Display Inflexibility during Glucose Challenge in Patients with Type 2 Diabetes: An Untargeted Metabolomics Study.

Metabolic inflexibility is a hallmark of insulin resistance and can be extensively explored with high-throughput metabolomics techniques. However, the dynamic regulation of the metabolome during an oral glucose tolerance test (OGTT) in subjects with type 2 diabetes (T2D) is largely unknown. We aimed to identify alterations in metabolite responses to OGTT in subjects with T2D using untargeted metabolomics of both plasma and subcutaneous adipose tissue (SAT) samples. Twenty subjects with T2D and twenty healthy controls matched for sex, age, and body mass index (BMI) were profiled with untargeted metabolomics both in plasma (755 metabolites) and in the SAT (588) during an OGTT. We assessed metabolite concentration changes 90 min after the glucose load, and those responses were compared between patients with T2D and controls. Post-hoc analyses were performed to explore the associations between glucose-induced metabolite responses and markers of obesity and glucose metabolism, sex, and age. During the OGTT, T2D subjects had an impaired reduction in plasma levels of several metabolite families, including acylcarnitines, amino acids, acyl ethanolamines, and fatty acid derivates (p &lt; 0.05), compared to controls. Additionally, patients with T2D had a greater increase in plasma glucose and fructose levels during the OGTT compared to controls (p &lt; 0.05). The plasma concentration change of most metabolites after the glucose load was mainly associated with indices of hyperglycemia rather than insulin resistance, insulin secretion, or BMI. In multiple linear regression analyses, hyperglycemia indices (glucose area under the curve (AUC) during OGTT and glycosylated hemoglobin (HbA1c)) were the strongest predictors of plasma metabolite changes during the OGTT. No differences were found in the adipose tissue metabolome in response to the glucose challenge between T2D and controls. Using a metabolomics approach, we show that T2D patients display attenuated responses in several circulating metabolite families during an OGTT. Besides the well-known increase in monosaccharides, the glucose-induced lowering of amino acids, acylcarnitines, and fatty acid derivatives was attenuated in T2D subjects compared to controls. These data support the hypothesis of inflexibility in several metabolic pathways, which may contribute to dysregulated substrate partitioning and turnover in T2D. These findings are not directly associated with changes in adipose tissue metabolism; therefore, other tissues, such as muscle and liver, are probably of greater importance.

Associations of parity with health disorders and blood metabolite concentrations in Holstein cows in different production systems.

Data were obtained from studies in Australia, Canada, and the United States using individual cow data from 28,230 Holstein cows to evaluate associations between parity and disease. Our goal was to develop understanding of disease risks for cows of differing parity. We hypothesized that there would be increased risks of disease and changes in metabolite concentrations with increased parity. Parity ≥5 represented 2,533 cows or 9.0%, parity 4 was 9.8% (2,778), parity 3 as 19.0% (5,355), parity 2 as 28.1% (7,925), and parity 1 was 34.1% (9,639) of the sample. Of these cows, 15.5% were in Australia, 14.7% in Canada, and 69.8% in the United States. Lactational incidence (LI) risk of clinical hypocalcemia increased with parity from 0.1% for parity 1 to 13% for parity ≥5 cows. The marked increase suggests profound differences in metabolism with increased parity. The LI of clinical mastitis was 17.4%. The odds of mastitis increased with parity to 2.5 times greater in parity ≥5 than in parity 1. The LI of lameness increased with parity; specifically, the odds of lameness was 5.6 times greater for parity ≥5 than parity 1. Dystocia incidence was 8.7% and greatest for parity 1 cows. The LI of retained placenta was 7.4% and increased with parity, with the odds for parity ≥5 2.3 times greater than for parity 1. The LI of metritis was 10% and of endometritis 14%, with the greatest odds in parity 1. The LI of clinical ketosis was 3.3% with a marked increase in odds with parity. The prevalence of subclinical ketosis was 26.8% with only cows in parity 1 having lower odds than other parities. Parity ≥5 cows had greater odds (odds ratio = 1.7) of respiratory disease than parity 1 cows, which were lesser than other parities. Metabolite concentrations were evaluated in 5,154 Holstein cows in the precalving, calving, and immediate postcalving data sets. Metabolic measures near peak lactation provided 1,906 observations. Concentrations of β-hydroxybutyrate (BHB) and nonesterified fatty acids increased with parity on d 1 to 3 of lactation and at peak lactation. On d 1 to 3 after calving differences in glucose, nonesterified fatty acids, and BHB indicated a greater reliance on mobilized lipid to export energy to peripheral tissues as BHB for greater parity cows. Differences in concentrations among parity groups were marked at times, for example >0.20 mM in Ca for parity 1 and 2 to parity ≥5 and >0.33 mM for all older parities compared with parity 1 for P on the day of calving. The marked increase suggests profound differences in metabolism with increased parity are probably influenced, in part, by increased production. We found marked differences in concentrations of metabolites with parity that are consistent with reduced reproduction, health, and body condition for higher parity cows. These unfavorable differences in metabolism in Ca, P, glucose, and cholesterol concentrations for higher parity cows also complement the often-substantial differences in disease risk with parity and suggest a need to carefully consider the parity structure in study design. Managers and advisors will need to consider methods to reduce risk of health disorders tailored to cows of different ages.

Project-Oriented RF Coil Comparison and Optimization for Preclinical, Single-Voxel MR Spectroscopy of the Rat Visual Cortex at 9.4 T

As one of the most important cortical structures in the brain, the visual cortex plays a primary role in processing visual data. Observing the metabolic changes in this region using single-voxel MR spectroscopy (MRS) can provide a plethora of information on the disease stage and progress in vivo. For single-voxel MRS experiments, a target voxel is always chosen and specifically investigated. The volume of the voxel must be sufficiently small to avoid any interference from adjacent areas but large enough to maximise its signal-to-noise ratio (SNR). Of the factors used to improve SNR, e.g. enlarging voxel size or increasing the number of signal averaging, the optimisation of the RF coil can contribute significantly to the SNR improvement. In this work, we compared and optimised RF coils which include a circularly-polarised (CP) high-pass birdcage coil and two CP surface coils with different dimensions. The coils were particularly designed for the entire rat head, brain and the target region (visual cortex), respectively. The performance of these coils was evaluated based on the project-specific purpose of investigating metabolite concentration changes in the visual cortex of the in vivo rat brain, assessed by means of single-voxel MRS at 9.4 T. In the SNR comparison, the values obtained using the optimised small loop coil were found to be approximately 5 and 1.35 times higher than those using the birdcage volume head coil and the medium-sized loop coil, respectively. In other words, using the optimised coil rather than, for example, the birdcage coil allows the acquisition to be completed more quickly by a factor of 25 times. In conclusion, by using the optimised setup, we can i) benefit either from reduced measurement time or in the acquisition of high-quality MR images or ii) obtain spectra with a minimum quantification error.

Periovulatory changes in behavior and fecal hormone metabolite concentrations but not vaginal cytology or vaginoscopy are indicative for the fertile period in female African wild dogs (Lycaon pictus)

Artificial insemination (AI) can aid conservation of African wild dogs (AWD), but methods to determine the appropriate timing of AI in females are not feasible without immobilization. This study determined whether certain behaviors coupled with fecal estrogen (fEM) and progestogen (fPM) metabolite concentrations, could be used as non-invasive parameters to predict the fertile period in female AWDs. Behavior was observed in three alpha females before, during and after the mating period, and feces analyzed for hormone metabolites. During the periovulatory period, females were immobilized 2–3 times to evaluate vulvar condition, blood hormone concentrations and vaginal cytology, and to conduct vaginoscopy. Late estrus (fertile period) could be distinguished from pro-estrus, early estrus, and diestrus using behavior; with a 2- to 5-fold higher rate of male-female affiliative behavior, sexual and non-sexual follow, alpha male initiating behavior, ride-up and copulation (P ≤ 0.05). Sexual behaviors, and male-female resting patterns declined significantly or ceased the day after last mating. Two females showed a 2.5- to 3-fold increase in fPM concentrations during late estrus compared to the pro-estrus period (P ≤ 0.05) and elevated fEM levels that rose in pro-estrus, declined to baseline by late estrus. The one anovulatory female showed no distinct pattern in fPM or fEM concentrations. Vaginal cytology and vaginoscopy could not discriminate between different phases. In summary, behavioral observations coupled with rising fPM and declining fEM can determine the fertile period in African wild dog females, whereas infrequent measurement of blood hormone concentrations, vaginal cytology and vaginoscopy are unreliable.

Dark accumulation of downstream glycolytic intermediates initiates robust photosynthesis in cyanobacteria.

Photosynthesis must maintain stability and robustness throughout fluctuating natural environments. In cyanobacteria, dark-to-light transition leads to drastic metabolic changes from dark respiratory metabolism to CO2 fixation through the Calvin-Benson-Bassham (CBB) cycle using energy and redox equivalents provided by photosynthetic electron transfer. Previous studies have shown that catabolic metabolism supports the smooth transition into CBB cycle metabolism. However, metabolic mechanisms for robust initiation of photosynthesis are poorly understood due to lack of dynamic metabolic characterizations of dark-to-light transitions. Here, we show rapid dynamic changes (on a time scale of seconds) in absolute metabolite concentrations and 13C tracer incorporation after strong or weak light irradiation in the cyanobacterium Synechocystis sp. PCC 6803. Integration of this data enabled estimation of time-resolved nonstationary metabolic flux underlying CBB cycle activation. This dynamic metabolic analysis indicated that downstream glycolytic intermediates, including phosphoglycerate and phosphoenolpyruvate, accumulate under dark conditions as major substrates for initial CO2 fixation. Compared with wild-type Synechocystis, significant decreases in the initial oxygen evolution rate were observed in 12 h dark preincubated mutants deficient in glycogen degradation or oxidative pentose phosphate pathways. Accordingly, the degree of decrease in the initial oxygen evolution rate was proportional to the accumulated pool size of glycolytic intermediates. These observations indicate that the accumulation of glycolytic intermediates is essential for efficient metabolism switching under fluctuating light environments.

Population regulation and adaptive dynamics of cross-feeding.

The particular importance of evolutionary studies in microbial experimental systems is that starting from the level of the metabolism of individual cells, the adaptive dynamics can be followed step by step by biochemical, genetic, and population dynamical tools. Moreover, the coincidence of evolutionary and ecological time scales helps to clarify the mutual role of ecological and evolutionary principles in predicting adaptive dynamics in general. Ecological principles define the ecological conditions under which adaptive branching can occur. This paper overviews and interprets the results of empirical and modeling studies of the evolution of metabolic cross-feeding in glucose-limited E.coli chemostats and batch cultures in the context of theories of robust coexistence and adaptive dynamics. Empirical results consistently demonstrate that the interactions between cells are mediated by the changing metabolite concentrations in the cultures and modeling confirms that these changes may control the adaptive dynamics of the clones. In consequence, the potential results of evolution can be predicted at the functional level by evolutionary flux balance analysis (evoFBA), while the genetic changes are more contingent. evoFBA follows the scheme of adaptive dynamics theory by calculating the feedback environment that changes during the evolutionary process and provides a promising tool to further investigate adaptive divergence in small microbial communities. Three general conclusions close the paper.

Effects of Heavy Metals on the Metabolome of Pinus sylvestris (Pinaceae)

The effects of Cu, Ni, and Cd on the Pinus sylvestris metabolome was studied in experimental conditions by gas chromatography-mass spectrometry (GC-MS). Structural changes in plant metabolite network became detectable on day 6 of exposure to the metals, 3-6 days earlier than visual signs of toxicity developed. Differences at the metabolome level arose earlier in a control group of plants, and specific effects of particular metals on the plant metabolome became distinct on day 9. Both nature and concentration of a metal equally contributed to the plant metabolome clustering. Plant responses (changes in concentrations of individual metabolites) to metal exposure substantially differed depending on the metal concentration (1 or 5 mM) and nature. The effects of Cd and Cu were generally similar, while the effect of Ni was often different. Dynamic changes visualized in plant metabolite matrix reflected the changes in its correlation structure, rather than depending on the set of particular compounds.

Changes in plasma and milk choline metabolite concentrations in response to the provision of various rumen-protected choline prototypes in lactating dairy cows.

Choline feeding in the form of rumen-protected choline (RPC) has been shown to increase milk production and improve measures of metabolic health (e.g., liver triglyceride) in dairy cows. The objective was to characterize changes in plasma and milk choline and choline metabolite concentrations, including microbial-derived trimethylamine N-oxide (TMAO), in response to increasing ruminal spot-doses, different types of RPC, and ruminal stability of RPC in lactating cows. For experiment 1, 12 mid-lactation (121 ± 16.3 d in milk) Holstein cows were balanced by total plasma choline concentrations and milk yields. Cows were assigned to 1 of 3 lipid-encapsulated RPC products (main plots): prototypes P1, P2, and P3 (containing 59, 56, and 30% choline chloride, respectively). Within each main plot, cows were assigned to a sequence of doses in a 4 × 4 Latin square design: 0, 18, 36, or 54 g of choline chloride. Treatments were preconditioned with ground corn and administered as a single ruminal bolus once per experimental period 1 h postfeeding of a total mixed ration. For experiment 2, we compared a control (0 g of choline chloride) versus P2, and P4 and P5 (60 and 62% choline chloride, respectively) in a repeated 4 × 4 Latin square design. Experiment 2 followed a similar design as experiment 1 with modifications: 12 late-lactation (228 ± 7.10 d in milk) Holstein cows were used; treatments were administered as part of a premeal; and cows received a daily allowance of a total mixed ration as equal provisions every 4 h within 24 h before and after treatment. For both experiments, plasma and milk samples were collected for choline and choline metabolite quantification. Data were analyzed using a mixed model including fixed effects of treatment, period, and time. Contrast statements were used to test for linearity of dose and differences between prototypes for experiment 1 and 2, respectively. Plasma and milk TMAO concentrations increased with RPC dose (peak by h). Milk choline and betaine yields increased with RPC dose in a quadratic manner; albeit, dependent upon RPC type. Milk phosphocholine (PCho) and glycerophosphorylcholine (GPC) yields changed by select RPC dose (experiment 1), however Met, PCho, GPC, phosphatidylcholine, and total choline concentrations in milk, and plasma Met and sphingomyelin concentrations were not responsive. We conclude that plasma or milk choline, betaine, and TMAO concentrations are responsive to RPC type, dose, and stage of lactation evaluated.