GMP Content Research Articles

The effects of casein glycomacropeptide on general health status in children with PKU: A randomized crossover trial

In PKU, it is suggested that casein glycomacropeptide based protein substitute (GMP) may have physiological advantage when satiety, oxidative stress, renal function and inflammation are considered. Its prebiotic properties may also help gastrointestinal (GI) tolerance.In children with PKU, a randomized/crossover trial comparing phenylalanine-free amino acids (AA) vs GMP as the single source of protein substitute for 12-weeks in each arm was conducted. There was a 4-week wash out period with AA in-between. At baseline and end of each intervention, blood and fecal samples were taken to monitor gut health, oxidative stress, renal function, inflammatory markers and plasma amino acids. Satiety and Pediatric Quality of Life (PedsQL) GI symptoms questionnaires were completed. Usual weekly blood spots for phenylalanine and tyrosine were done.Twelve patients (8 males; aged 4-9y) with PKU participated. GMP improved the following GI symptoms: stomach pain (p = 0.003), heartburn and reflux (p = 0.041) and wind/ bloating (p = 0.018). With GMP, there was also a trend for less constipation (p = 0.068), discomfort with eating (p = 0.065) and nausea and vomiting (p = 0.087). There was no changes on stool gut health markers (IgA, short chain fatty acids and fecal calprotectin). There were no statistically significant differences for renal, oxidative stress, inflammatory and gut health markers or measures of satiety except for adiponectin (p = 0.028) and total antioxidant capacity (p = 0.049), although the latter was possibly without clinical significance. Mean dried blood spot Phe was 114 μmol/L higher with GMP vs AA (p < 0.001). There was no difference in tyrosine levels. In conclusion, GI symptoms significantly improved with GMP versus AA. The phenylalanine content of GMP may present challenges when it is used as the only protein substitute in children with classical PKU with low Phe tolerance.

Effects of Moisture Migration and Changes in Gluten Network Structure during Hot Air Drying on Quality Characteristics of Instant Dough Sheets.

The impact of hot air drying temperature on instant dough sheets' qualities was investigated based on water migration and gluten network structure changes. The results revealed that the drying process redistributed the hydrogen proton, with deeply bound water accounting for more than 90%. The T2 value decreased as the drying temperature increased, effectively restricting moisture mobility. Meanwhile, microstructural analysis indicated that instant dough sheets presented porous structures, which significantly reduced the rehydration time of instant dough sheets (p < 0.05). In addition, elevated drying temperatures contributed to the cross-linking of proteins, as evidenced by increased GMP and disulfide bond content (reaching a maximum at 80 °C), which improved the texture and cooking properties. Hence, the water mobility was effectively reduced by controlling the drying temperature. The temperature had a facilitating impact on promoting the aggregation of the gluten network structure, which improved the quality of the instant dough sheets.

Moderate regulation of wheat B-starch ratio: Improvement of molecular structure, spatial conformation, aggregation behavior of reconstituted fermented doughs and its processing suitability

Aiming to investigate the changes and effects of different particle sizes of wheat A/B starch during dough fermentation, the present study reconstituted A/B starch fractions in ratios of 100:0, 75:25, 50:50, 25:75, and 0:100, further blended with gluten and subjected to slight (20 min), medium (30 min), and high (60 min) fermentation processes by yeasts. Results showed that fermentation gas production promoted gluten network extension, inducing starch granule exposure and dough surface roughness. Also, fermentation fractured protein intermolecular disulfide bonds and decreased α-helix and β-folded structure content, contributing to GMP, LPP, and SPP content decreases. Moreover, moderately increasing the B-starch ratio in the dough can improve gluten network stability, continuity, and air-holding capacity. The 25A-75B steam bread exhibited optimal processing suitability (better morphology, texture, and quality) due to its higher GMP and polymer protein content with lower free sulfhydryl and monomeric protein content. Further, conformational relationships indicated the key indicators influencing dough products' properties were free sulfhydryl content, GMP content, protein molecular weight distribution, and secondary structure. The obtained findings contributed to understanding the effect of wheat starch granule size distribution on dough processing behavior, and future targeted breeding for wheat cultivars with high B-starch content for improved fermentation pasta product qualities.

Protective Effects of Thymoquinone on Endothelial Cell Dysfunction in Hypercholesterolemia

Background: Increased reactive oxygen species (ROS) have been implicated as important mechanisms that contribute to endothelial dysfunction (ED). The administration of thymoquinone in animal models significantly inhibits ROS production. Purpose: The protective effects of thymoquinone on endothelial cell dysfunction were studied in cholesterol-fed rabbits. Thirty rabbits were randomly divided into five groups. Methods: The negative control group was fed a standard diet, the positive control group was fed the same diet with 2 % cholesterol, the Thymoquinone group was fed the same diet with 2 % cholesterol and Thymoquinone 100 mg/Kg BW/day, 200 mg/Kg BW/day or 400 mg/Kg BW/day. Results: The cholesterol-rich diet significantly increased Malondialdehyde (MDA) in the aortic blood vessels, as reflected by Thiobarbituric Acid-Reactive Substances (TBARS), inhibited endothelium-dependent vascular relaxations to acetylcholine and decrease cyclic GMP were compared with vessels from normal rabbits (negative control). In cholesterol-fed rabbits, Thymoquinone treatment decreased MDA in plasma production, improved endothelium-dependent relaxations to acetylcholine and increase cyclic GMP production. Conclusion: These results suggest that dietary treatment of rabbits with thymoquinone may prevent superoxide anion (O2-) induced inactivation of endothelium-dependent relaxing factor (EDRF), improve the endothelium-dependent relaxation to acetylcholine in the aortic blood vessels, and increase cyclic GMP content in aortic of cholesterol-fed rabbits.

Changes in rheology and components during the processing of Chinese traditional handmade hollow dried noodle

The study of the changes in rheological properties and components during the processing of Chinese traditional handmade hollow dried noodle (HHDN) is essential to explaining the excellent quality of HHDN. The dynamic oscillation frequency sweep, stress relaxation, and uniaxial extension characteristics of the dough after kneading, stretching, and resting were investigated at six sampling points during the processing of HHDN. The result showed that stretching led to an increase in G' and G0, and a significant decrease (P < 0.05) in extensibility from 131.02 mm to 57.99 mm. Confocal laser scanning microscopy (CLSM) was used to observe the microstructure of the gluten network, which was destroyed during stretching and restored during resting. Studies of changes in components showed that the stretching process resulted in a decrease in GMP content from 3.24 (g/100 g) to 3.18 (g/100 g), and the resting process resulted in β-sheets decreasing significantly (P < 0.05). The degree of starch pasting increased significantly (P < 0.05) after stretching. The results of the correlation analysis showed that components changes were highly correlated with the rheological properties during the processing of HHDN.

Synthesis and secretion of Nerve Growth Factor is regulated by Nitric Oxide in bladder cells in vitro under a hyperglycemic environment

Urine samples of female patients with overactive bladder (OAB) are characterized by low levels of nerve growth factor (NGF) and elevated concentrations of nitric oxide (NO) compared to healthy controls. We therefore examined how NO might regulate NGF synthesis using rat bladder smooth muscle (SMCs) and urothelial (UROs) cells in culture. In UROs, incubation in hyperglycemic conditions to mimic insulin insensitivity present in the OAB cohort increased secretion of NO and concomitantly decreased NGF, except when the NO synthase inhibitor, l-NAME (1 mM) was present. Sodium nitroprusside (SNP) (300 μM, 24 h), a NO generator, decreased NGF levels and decreased cyclic GMP (cGMP) content, a process validated by the cGMP synthase inhibitor ODQ (100 μM). Alternatively, SNP increased mRNA of both NGF and matrix metalloproteinase-9 (MMP-9). MMP-9 knockout of UROs by Crispr-Cas9 potently decreased the effect of SNP on NGF, implying a dependent role of NO on MMP-9. On the other hand, matrix metalloproteinase-7 (MMP-7) activity was increased by SNP, which taken together with increase in NGF mRNA, suggests a compensatory mechanism. In SMCs, hyperglycemic conditions had the same effect on extracellular content of NO and NGF than in UROs. SNP also decreased NGF secretion but increased cGMP content. Stable permeable analogs of cGMP 8-(4-Chlorophenylthio)-cGMP (1 mM) and N2,2′-O-Dibutyryl-cGMP (3 mM) inhibited NGF release. NGF and MMP-9 mRNA expression was unchanged by SNP. Deletion of MMP-9 in SMCs by Crispr-Cas9 did not alter the effect of SNP. Finally, SNP decreased MMP-7 activity, diminishing the conversion of proNGF to NGF. These results demonstrate that enhanced NO secretion triggered by high glucose decreases NGF secretion through pathways unique for each cell type that involve cGMP and proteases MMP-7 and MMP-9. These results might help to explain our observations from the urine from patients with OAB associated with metabolic syndrome.

Molecular Characterization and Marker Development of the HMW-GS Gene from Thinopyrum elongatum for Improving Wheat Quality

The quality of wheat primarily depends on its storage protein quality, especially in regards to gluten content and high-molecular-weight glutenin subunits (HMW-GS). The number of HMW-GS alleles is limited in bread wheat (Triticum aestivum L.), whereas it is abundant in wheat relatives. Therefore, HMW-GS alleles from wheat relatives could provide a potential for improving quality in wheat breeding. Thinopyrum elongatum (EE) is one of the relatives of wheat. The E genome is closely related to the ABD genome in wheat; therefore, Th. elongatum is often used as an excellent exogenous gene donor for wheat genetic improvement. In this study, the high-molecular glutenin subunit gene was cloned and sequenced from Th. elongatum. A specific molecular marker for identifying the Glu-1Ey subunit gene was developed and applied to detected wheat-Th. elongatum alien introgression lines. Quality analysis indicated that the substitution and addition lines containing Th. elongatum alleles significantly (p &lt; 0.05) increased grain protein content by 3.76% to 5.11%, wet-gluten content by 6.55% to 8.73%, flour 8-MW by 0.25% to 6.35%, and bread volume value by 33.77 mL to 246.50 mL, in comparing it with Chinese Spring. The GMP content and lactic acid SRC showed significant positive correlations with flour processing quality and might be used as indicators for wheat quality. The results were expected to provide a novel route for improving processing quality in wheat quality breeding.

Genetic dissection of protein and starch during wheat grain development using QTL mapping and GWAS.

Protein, starch, and their components are important for wheat grain yield and end-products, which are affected by wheat grain development. Therefore, QTL mapping and a genome-wide association study (GWAS) of grain protein content (GPC), glutenin macropolymer content (GMP), amylopectin content (GApC), and amylose content (GAsC) were performed on wheat grain development at 7, 14, 21, and 28 days after anthesis (DAA) in two environments using a recombinant inbred line (RIL) population of 256 stable lines and a panel of 205 wheat accessions. A total of 29 unconditional QTLs, 13 conditional QTLs, 99 unconditional marker-trait associations (MTAs), and 14 conditional MTAs significantly associated (p < 10-4) with four quality traits were found to be distributed on 15 chromosomes, with the phenotypic variation explained (PVE) ranging from 5.35% to 39.86%. Among these genomic variations, three major QTLs [QGPC3B, QGPC2A, and QGPC(S3|S2)3B] and SNP clusters on the 3A and 6B chromosomes were detected for GPC, and the SNP TA005876-0602 was stably expressed during the three periods in the natural population. The QGMP3B locus was detected five times in three developmental stages in two environments with 5.89%-33.62% PVE, and SNP clusters for GMP content were found on the 3A and 3B chromosomes. For GApC, the QGApC3B.1 locus had the highest PVE of 25.69%, and SNP clusters were found on chromosomes 4A, 4B, 5B, 6B, and 7B. Four major QTLs of GAsC were detected at 21 and 28 DAA. Most interestingly, both QTL mapping and GWAS analysis indicated that four chromosomes (3B, 4A, 6B, and 7A) were mainly involved in the development of protein, GMP, amylopectin, and amylose synthesis. Of these, the wPt-5870-wPt-3620 marker interval on chromosome 3B seemed to be most important because it played an important role in the synthesis of GMP and amylopectin before 7 DAA, in the synthesis of protein and GMP from 14 to 21 DAA, and in the development of GApC and GAsC from 21 to 28 DAA. Using the annotation information of IWGSC Chinese Spring RefSeq v1.1 genome assembly, we predicted 28 and 69 candidate genes for major loci from QTL mapping and GWAS, respectively. Most of them have multiple effects on protein and starch synthesis during grain development. These results provide new insights and information for the potential regulatory network between grain protein and starch synthesis.

Sports Participation Promotes Beneficial Adaptations in the Erythrocyte Guanylate Nucleotide Pool in Male Athletes Aged 20-90 Years.

The guanine nucleotide pool (GTP, guanosine-5'-triphosphate; GDP, guanosine-5'-diphosphate, and GMP, guanosine-5'-monophosphate) is an essential energy donor in various biological processes (eg protein synthesis and gluconeogenesis) and secures several vital regulatory functions in the human body. The study aimed to predict the trends of age-related changes in erythrocyte guanine nucleotides and examine whether competitive sport and related physical training promote beneficial adaptations in erythrocyte guanylate concentrations. The study included 86 elite endurance runners (EN) aged 20-81 years, 58 sprint-trained athletes (SP) aged 21-90 years, and 62 untrained individuals (CO) aged 20-68 years. The concentration of erythrocyte GTP and total guanine nucleotides (TGN) were highest in the SP group, lower in the EN group, and lowest in the CO group. Both athletic groups had higher guanylate energy charge (GEC) values than the CO group (p = 0.012). Concentrations of GTP, TGN, and GEC value significantly decreased, while GDP and GMP concentrations progressively increased with age. Such a profile of change suggests a deterioration of the GTP-related regulatory function in older individuals. Our study explicitly shows that lifelong sports participation, especially of sprint-oriented nature, allows for maintaining a higher erythrocyte guanylate pool concentration, supporting cells' energy metabolism, regulatory and transcription properties, and thus more efficient overall body functioning.

Rheo-Fermentation Dough Properties, Bread-Making Quality and Aroma Characteristics of Red Bean (Vigna angularis) Sourdough Induced by LAB Weissella confusa QS813 Strain Fermentation.

This study investigated the impact of in situ-formed exopolysaccharides (EPS) in red bean (Vigna angularis) sourdough fermented by Weissella confusa QS813 on dough rheo-fermentation properties, bread-making quality and aroma characteristics of red bean sourdough bread. The EPS formed in red bean sourdough and sourdough-induced acidification improved the maximum dough fermentation height, gas retention coefficient and viscoelastic properties of dough. Doughs had a lower increase rate of total SDS-soluble gluten proteins, a low decline in GMP content and similar free sulfhydryl content to wheat dough. Resultantly, breads showed declines in baking loss and hardness, increase in specific volume and lower moisture loss and staling rate after 7 days of storage. Finally, despite a reduction in the total content of aroma compounds, new aroma compounds such as acetic acid and higher contents of 3-methyl-1-butanol and 2,3-butanediol were enriched in red bean sourdough bread. Sourdough acidification probably promoted interaction of EPS with gluten or red bean proteins through bond interactions to form structures which stabilized gluten in dough and increased water-binding ability in red bean sourdough bread. This study provided a better understanding of the role of EPS in sourdough in improving bread quality and of promising strategies to address consumer demand for nutritious and clean-label products.

Impact of wheat starch granule size on viscoelastic behaviors of noodle dough sheet and the underlying mechanism

The contribution of starch to dough behaviors has been largely overshadowed by the role of gluten, receiving much less attention in comparison. The impact of wheat starch granule size on the viscoelastic behaviors of low-moisture noodle dough and its underlying mechanism were investigated. Dough with a high ratio of B-type starch granules (BS) had higher viscoelastic moduli (G″ and G′), percent stress relaxation (SR%), and smaller creep compliance (J max ), indicating higher viscoelasticity and strength. This might be related to the higher filling ability and water-binding capacity of B-type starch. Compared to large A-type starch granules (AS), small B-type granules would easily embed to form a more closely packed and uniform network structure. In addition, the differences in water distribution and hydration properties could affect the hydrophobicity of starch and the surface environments of the protein, thus influencing the polymer interactions in the doughs. The hydrogen bonds were the main con-covalent bonds in the low-moisture noodle dough. With increasing B-/A-type starch ratios, β-sheet and hydrogen bond contents significantly increased, while the GMP content showed a decrease, suggesting the enhanced hydrogen bond interaction in a high ratio of B-type starch dough could cooperate with intermolecular disulfide bonds to stabilize the network structure of gluten, improving the dough strength. These results demonstrated that the viscoelastic behaviors of dough sheets were related to the granule size distribution of wheat starch. Finally, a schematic model describing the mechanism of the influence of starch granule size on dough behaviors was built. • B-type wheat starch granules promoted uniform and compact gluten network formation. • Small B-type granules led to stronger hydrogen bond interaction in the noodle dough. • The enhanced interaction by hydrogen bonding could improve the dough strength. • Viscoelasticity of dough sheet increased with increasing B- to A-type starch ratios.

Responding to Good Medical Practice Consultation 2022

Responding to Good Medical Practice Consultation 2022

Role of Hydrogen Sulfide and Polysulfides in the Regulation of Lipolysis in the Adipose Tissue: Possible Implications for the Pathogenesis of Metabolic Syndrome.

Hydrogen sulfide (H2S) and inorganic polysulfides are important signaling molecules; however, little is known about their role in the adipose tissue. We examined the effect of H2S and polysulfides on adipose tissue lipolysis. H2S and polysulfide production by mesenteric adipose tissue explants in rats was measured. The effect of Na2S and Na2S4, the H2S and polysulfide donors, respectively, on lipolysis markers, plasma non-esterified fatty acids (NEFA) and glycerol, was examined. Na2S but not Na2S4 increased plasma NEFA and glycerol in a time- and dose-dependent manner. Na2S increased cyclic AMP but not cyclic GMP concentration in the adipose tissue. The effect of Na2S on NEFA and glycerol was abolished by the specific inhibitor of protein kinase A, KT5720. The effect of Na2S on lipolysis was not abolished by propranolol, suggesting no involvement of β-adrenergic receptors. In addition, Na2S had no effect on phosphodiesterase activity in the adipose tissue. Obesity induced by feeding rats a highly palatable diet for 1 month was associated with increased plasma NEFA and glycerol concentrations, as well as greater H2S production in the adipose tissue. In conclusion, H2S stimulates lipolysis and may contribute to the enhanced lipolysis associated with obesity.

Selectively hydrolyzed soy protein as an efficient quality improver for steamed bread and its influence on dough components

Selectively hydrolyzed soy protein (SHSP) has the potential to improve the quality of steamed bread. To clarify its underlying mechanism, the influence of SHSP on dough properties and components was investigated and compared with that of soy protein isolate (SPI). The results showed that SHSP addition resulted in steamed bread with higher loaf volume, lower hardness, and higher viscoelasticity. In contrast, SPI addition had the opposite effect. Nevertheless, both soy proteins decreased melting enthalpy and increased starch particle exposure due to competition for water. By analyzing molecular weight distribution and the secondary structure, we determined that the GMP content of fermented dough decreased by 10.04% following 1% SPI addition; however, it was enhanced by 7.90% following 1% SHSP addition. Moreover, the content of β-turns decreased with SHSP addition. The present study provides a theoretical basis for the exploitation of soy proteins as a nutritious and technofunctional dough improver.

FSMP-01. ID1 MEDIATES ONE-CARBON MEDIATED PURINE SYNTHESIS IN GLIOBLASTOMA

Inhibitor of DNA-binding-1 (ID1) is a transcriptional regulatory protein involved in maintenance of self-renewal and inhibition of differentiation, and acts as a key regulator of tumorigenesis in glioblastoma. Studies suggest that de novo purine synthesis is essential for the maintenance of rapid proliferation rates in glioma initiating cells. We hypothesise that ID1 plays a role in reprogramming one-carbon mediated de novo purine synthesis, thereby metabolically contributing to the tumorigenic advantage seen in ID1-high glioblastoma cells. The effect of ID1 regulation on metabolic reprogramming of glioblastoma was studied using ID1-knockout U251 glioblastoma cell lines. Protein expression analysis and liquid chromatography mass-spectrometry were respectively used to assess expression and concentration of metabolic enzymes and intermediates of one-carbon and de novo purine synthesis pathways. CD44 expression was analyzed as a marker of cancer stem cells. The expression of DHFR and MTHFD2 was significantly decreased after ID1 knockout. Furthermore, PAICS expression, and overall concentration of IMP, AMP, GMP, and ATP were reduced after ID1 knockout. ID1 expression in glioblastoma tumor xenografts was associated with positive expression of one-carbon metabolism and purine synthesis enzymes, while ID1-/- cells within the same xenograft had significantly reduced expression of these enzymes. The expression of CD44 was reduced after ID1 knockout. This data suggests that ID1 mediates an increase in one-carbon mediated de novo purine synthesis, thereby regulating metabolic reprogramming in glioblastoma cells. The correlation between CD44 and ID1 expression provides further support that ID1 maintains a less differentiated phenotype in a subset of glioblastoma cells, and metabolic reprogramming is one of the mechanisms through which this phenotype, and the capacity for self-renewal are maintained. Further elucidation of the mechanisms through which ID1 mediates metabolic reprograming of glioblastoma cells can lead to developing effective combination therapies coupling chemotherapeutic strategies with targeting of metabolic programs used by cancer initiating cells.

Alkaline pH Increases Swimming Speed and Facilitates Mucus Penetration for Vibrio cholerae.

Intestinal mucus is the first line of defense against intestinal pathogens. It acts as a physical barrier between epithelial tissues and the lumen that enteropathogens must overcome to establish a successful infection. We investigated the motile behavior of two Vibrio cholerae strains (El Tor C6706 and Classical O395) in mucus using single-cell tracking in unprocessed porcine intestinal mucus. We determined that V. cholerae can penetrate mucus using flagellar motility and that alkaline pH increases swimming speed and, consequently, improves mucus penetration. Microrheological measurements indicate that changes in pH between 6 and 8 (the physiological range for the human small intestine) had little effect on the viscoelastic properties of mucus. Finally, we determined that acidic pH promotes surface attachment by activating the mannose-sensitive hemagglutinin (MshA) pilus in V. cholerae El Tor C6706 without a measurable change in the total cellular concentration of the secondary messenger cyclic dimeric GMP (c-di-GMP). Overall, our results support the hypothesis that pH is an important factor affecting the motile behavior of V. cholerae and its ability to penetrate mucus. Therefore, changes in pH along the human small intestine may play a role in determining the preferred site for V. cholerae during infection.IMPORTANCE The diarrheal disease cholera is still a burden for populations in developing countries with poor sanitation. To develop effective vaccines and prevention strategies against Vibrio cholerae, we must understand the initial steps of infection leading to the colonization of the small intestine. To infect the host and deliver the cholera toxin, V. cholerae has to penetrate the mucus layer protecting the intestinal tissues. However, the interaction of V. cholerae with intestinal mucus has not been extensively investigated. In this report, we demonstrated using single-cell tracking that V. cholerae can penetrate intestinal mucus using flagellar motility. In addition, we observed that alkaline pH improves the ability of V. cholerae to penetrate mucus. This finding has important implications for understanding the dynamics of infection, because pH varies significantly along the small intestine, between individuals, and between species. Blocking mucus penetration by interfering with flagellar motility in V. cholerae, reinforcing the mucosa, controlling intestinal pH, or manipulating the intestinal microbiome will offer new strategies to fight cholera.

Cell cycle control and environmental response by second messengers in Caulobacter crescentus

BackgroundSecond messengers, c-di-GMP and (p)ppGpp, are vital regulatory molecules in bacteria, influencing cellular processes such as biofilm formation, transcription, virulence, quorum sensing, and proliferation. While c-di-GMP and (p)ppGpp are both synthesized from GTP molecules, they play antagonistic roles in regulating the cell cycle. In C. crescentus, c-di-GMP works as a major regulator of pole morphogenesis and cell development. It inhibits cell motility and promotes S-phase entry by inhibiting the activity of the master regulator, CtrA. Intracellular (p)ppGpp accumulates under starvation, which helps bacteria to survive under stressful conditions through regulating nucleotide levels and halting proliferation. (p)ppGpp responds to nitrogen levels through RelA-SpoT homolog enzymes, detecting glutamine concentration using a nitrogen phosphotransferase system (PTS Ntr). This work relates the guanine nucleotide-based second messenger regulatory network with the bacterial PTS Ntr system and investigates how bacteria respond to nutrient availability.ResultsWe propose a mathematical model for the dynamics of c-di-GMP and (p)ppGpp in C. crescentus and analyze how the guanine nucleotide-based second messenger system responds to certain environmental changes communicated through the PTS Ntr system. Our mathematical model consists of seven ODEs describing the dynamics of nucleotides and PTS Ntr enzymes. Our simulations are consistent with experimental observations and suggest, among other predictions, that SpoT can effectively decrease c-di-GMP levels in response to nitrogen starvation just as well as it increases (p)ppGpp levels. Thus, the activity of SpoT (or its homologues in other bacterial species) can likely influence the cell cycle by influencing both c-di-GMP and (p)ppGpp.ConclusionsIn this work, we integrate current knowledge and experimental observations from the literature to formulate a novel mathematical model. We analyze the model and demonstrate how the PTS Ntr system influences (p)ppGpp, c-di-GMP, GMP and GTP concentrations. While this model does not consider all aspects of PTS Ntr signaling, such as cross-talk with the carbon PTS system, here we present our first effort to develop a model of nutrient signaling in C. crescentus.

Measurement of Disodium 5'‐Inosinate and Disodium 5'‐Guanylate in Aqueous Ethanol by Attenuated Total Reflection Ultraviolet Method

AbstractAn online concentration monitoring method was established by using attenuated total reflection ultraviolet (ATR‐UV) coupled with a suitable partial least squares regression for a multi‐solute crystallization system, namely, disodium 5'‐inosinate (IMP) and disodium 5'‐guanylate (GMP) in aqueous ethanol. The results indicated that the established method accurately predicted the concentration of IMP and GMP in the solution. The solubility data was measured at various temperatures and ethanol/water mass ratios, and the experimental data was well correlated by applying the modified Apelblat equation and modified Jouyban‐Acree model. The implementation of cooling crystallization demonstrates that the developed calibration model is suitable for online concentration monitoring with reasonable accuracy and precision.

A high-throughput and ultrasensitive identification methodology for unauthorized GMP component based on suspension array and logical calculator

To solve the problem of the unauthorized GMP components within import and export goods, the LI-US (Logic Identification of unauthorized GMP content by Universal-primer Suspension-array) system, which takes advantage of suspension array and logic calculator, was developed in the present study. Seventeen signal input channels have been optimized and validated in our research to ensure the multiplex practicality of the LI-US system. Three LI-US logic gates, including a YES gate, an OR gate and an AND gate, were designed as different detection strategies for GMP identification. The feasibility and specificity of the LI-US system were validated in the present study. Combining the optimization and evaluation of the signal input procedure, the sensitivity of this LI-US system reached 0.05% of the GMP mass concentration. The practicability evaluation of LI-US demonstrated its application within different substrates and varieties. In conclusion, the LI-US system was developed with extremely high specificity, sensitivity and practicability among different substrates and varieties, which could meet the demands of unauthorized GMP contents for both import and export goods.

Plasma cyclic guanosine 3′,5′-monophosphate levels: A marker of glutamate-nitric oxide-guanyl cyclase activity?

Remifentanil-based anesthesia can lead to acute opioid tolerance and/or hyperalgesia. A low-dose intraoperative infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine did not result in reduced postoperative morphine consumption after remifentanil-based anesthesia in adolescents. This study investigates the potential role of the glutamate-nitric oxide-cyclic guanosine 3'5'-monophosphate (cyclic GMP) pathway in the failure of low-dose ketamine to prevent remifentanil-induced acute opioid tolerance and/or hyperalgesia. Prospective, double-blind, placebo-controlled randomized clinical trial at a university teaching hospital. PATIENTS, PARTICIPANTS, AND INTERVENTIONS: Thirty-four adolescents receiving remifentanil-based anesthesia for surgical correction of idiopathic scoliosis were randomly assigned to receive either intraoperative ketamine administered as a bolus dose of 0.5 mg/kg in 10 mL of normal saline and a continuous intravenous infusion of 4.0 microg/kg/min or an equal volume of saline. Blood samples were collected before and after the administration of ketamine for analyzing the concentrations of cyclic GMP, ketamine, and norketamine. Blood samples were analyzed using high-performance liquid chromatography and an enzyme immunoassay. The median (interquartile range) value of the concentration of plasma cyclic GMP decreased from 23.7 (17.4-26.7) to 14.8 (14.0-17.3) nmol/L after ketamine infusion (p < 0.005) and from 23.9 (16.3-29.2) to 163 (14.5-18.6) nmol/L after saline infusion (p < 0.005). The median value of the concentration of plasma cyclic GMP at the end of ketamine infusion did not differ significantly when compared with that after saline infusion (p = 0.07). The concentration of plasma cyclic GMP was inversely correlated with the concentration of plasma ketamine (r = -0.61). This study suggests that the low dose of intraoperative ketamine infused was insufficient to suppress the NMDA receptor pathway. The concentrations of plasma cyclic GMP may serve as an indirect biological marker of ketamine-induced NMDA receptor antagonism.