Search

Super soft kernel texture is associated with superior milling and baking performance in soft wheat. To understand the mechanism underlying super soft kernel texture, we studied proteomic changes between a normal soft and a super soft during kernel development. The cultivar 'Alpowa', a soft white spring wheat, was crossed to a closely related super soft spring wheat line 'BC2SS163' to produce F6 recombinant inbred lines (RILs). Four normal soft RILs and four super soft RILs along with the parents were selected for proteomic analysis. Alpowa and the normal soft RILs showed hardness indices of 20 to 30, whereas BC2SS163 and the super soft RILs showed hardness indices of -2 to -6. Kernels were collected from normal soft and super soft genotypes at 7 days post anthesis (dpa), 14 dpa, 28 dpa, and maturity and were subject to quantitative proteomic analysis. Throughout kernel development, 175 differentially abundant proteins (DAPs) were identified. Most DAPs were observed at 7 dpa, 14 dpa, and 28 dpa. Of the 175 DAPs, 32 had higher abundance in normal soft wheat, whereas 143 DAPs had higher abundance in super soft wheat. A total of 18 DAPs were associated with carbohydrate metabolism and five DAPs were associated with lipids. The gene TraesCS4B02G091100.1 on chromosome arm 4BS, which encodes for sucrose-phosphate synthase, was identified as a candidate gene for super soft kernel texture in BC2SS163. This study enhanced our understanding of the mechanism underlying super soft kernel texture in soft white spring wheat. [ABSTRACT FROM AUTHOR]

Flavin-containing monooxygenase 5 (FMO5) is a member of the FMO family of proteins, best known for their roles in the detoxification of foreign chemicals and, more recently, in endogenous metabolism. We have previously shown that Fmo5-/- mice display an age-related lean phenotype, with much reduced weight gain from 20 weeks of age. The phenotype is characterized by decreased fat deposition, lower plasma concentrations of glucose, insulin and cholesterol, higher glucose tolerance and insulin sensitivity, and resistance to diet-induced obesity. In the present study we report the use of metabolomic and transcriptomic analyses of livers of Fmo5-/- and wild-type mice to identify factors underlying the lean phenotype of Fmo5-/- mice and gain insights into the function of FMO5. Metabolomics was performed by the Metabolon platform, utilising ultrahigh performance liquid chromatography-tandem mass spectroscopy. Transcriptomics was performed by RNA-Seq and results analysed by DESeq2. Disruption of the Fmo5 gene has wide-ranging effects on the abundance of metabolites and expression of genes in the liver. Metabolites whose concentration differed between Fmo5-/- and wild-type mice include several saturated and monounsaturated fatty acids, complex lipids, amino acids, one-carbon intermediates and ADP-ribose. Among the genes most significantly and/or highly differentially expressed are Apoa4, Cd36, Fitm1, Hspa5, Hyou1, Ide, Me1 and Mme. The results reveal that FMO5 is involved in upregulating the NRF2-mediated oxidative stress response, the unfolded protein response and response to hypoxia and cellular stress, indicating a role for the enzyme in adaptation to oxidative and metabolic stress. FMO5 also plays a role in stimulating a wide range of metabolic pathways and processes, particularly ones involved in lipid homeostasis, the uptake and metabolism of glucose, the generation of cytosolic NADPH, and in one-carbon metabolism. The results predict that FMO5 acts by stimulating the NRF2, XBP1, PPARA and PPARG regulatory pathways, while inhibiting STAT1 and IRF7 pathways. [ABSTRACT FROM AUTHOR]

Most of the popular scion varieties of mango possess alternate/irregular bearing. There are many external and internal factors assigned, among them carbohydrate reserves, and nutrient content plays important roles in the floral induction process in many crop species. In addition to that rootstock can alter the carbohydrate reserve and nutrient acquisition of scion varieties in fruit crops. The present investigation was carried out to understand the effect of rootstocks on the physiochemical traits of leaf, and bud and nutrient content in regular and alternate bearing varieties of mango. The rootstock "Kurukkan" promoted starch content in leaves of both alternate bearing varieties 'Dashehari' (5.62 mg/g) and regular 'Amrapali' (5.49 mg/g) and encouraged higher protein content (6.71 mg/g) and C/N ratio (37.94) in buds of alternate bearing 'Dashehari'. While Olour rootstock upregulated the reducing sugar in leaves of 'Amrapali' (43.56 mg/g) and promoted K (1.34%) and B (78.58 ppm) content in reproductive buds of 'Dashehari'. Stomatal density in 'Dashehari' scion variety was found higher on Olour rootstock (700.40/mm 2), while the rootstock fails to modify stomatal density in the scion variety regular bearer 'Amrapali'. Further, a total of 30 carbohydrate metabolism-specific primers were designed and validated in 15 scion/rootstock combinations. A total of 33 alleles were amplified among carbohydrate metabolism-specific markers, which varied from 2 to 3 alleles with a mean of 2.53 per locus. Maximum and minimum PIC value was found for NMSPS10, and NMTPS9 primers (0.58). Cluster analysis revealed that scion grafted on Kurukkan rootstock clustered together except 'Pusa Arunima' on Olour rootstock. Our analysis revealed that Fe is the key component that is commonly expressed in both leaf and bud. Although Stomatal density (SD) and Intercellular CO2 Concentration (Ci) are more specific to leaf and Fe, B, and total sugar (TS) are abundant in buds. Based on the results it can be inferred that the physiochemical and nutrient responses of mango scion varieties are manipulated by the rootstock, hence, the scion-rootstock combination can be an important consideration in mango for selecting suitable rootstock for alternate/irregular bearer varieties. [ABSTRACT FROM AUTHOR]

Background: Monitoring human circulating N-glycome could provide valuable insight into an individual's metabolic status. Therefore, we examined if aberrant carbohydrate metabolism in gestational diabetes mellitus (GDM) associates with alterations in plasma protein, immunoglobulin G (IgG) and immunoglobulin A (IgA) N-glycosylation. Methods: Plasma protein, IgG and IgA N-glycans were enzymatically released, purified and chromatographically profiled in 48 pregnant women with normal glucose tolerance and 41 pregnant women with GDM, all sampled at 24–28 weeks of gestation. Linear mixed models adjusting for age and multiple testing (FDR<0.05) were used to investigate the associations between glycosylation features, metabolic markers and GDM status. Results: Fasting insulin exhibited significant associations to numerous glycan traits, including plasma protein galactosylation, sialylation, branching, core fucosylation and bisection, to IgG core fucosylated, bisected (FA2B) and afucosylated disialylated (A2G2S2) glycan and to IgA trisialylated triantennary (A3G3S3) glycan (padj range: 4.37x10-05–4.94x10-02). Insulin resistance markers HOMA2-IR and HOMA2-%B were mostly associated to the same glycan structures as fasting insulin. Both markers showed positive association with high-branched plasma glycans (padj = 1.12x10-02 and 2.03x10-03) and negative association with low-branched plasma glycans (padj = 1.21x10-02 and 2.05x10-03). Additionally, HOMA2-%B index was significantly correlated with glycosylation features describing IgG sialylation. Multiple plasma protein IgG and IgA glycans showed significant associations with total cholesterol and triglyceride levels. None of the tested glycan traits showed a significant difference between GDM and normoglycemic pregnancies. Conclusion: Markers of glucose homeostasis and lipid metabolism in pregnancy show extensive associations to various N-glycosylation features. However, plasma protein, IgG and IgA N-glycans were not able to differentiate pregnant women with and without GDM, possibly due to numerous physiological changes accompanying pregnancy, which confound the impact of GDM on protein glycosylation. [ABSTRACT FROM AUTHOR]

The increase in the concentration of CO2 in the atmosphere has attracted widespread attention. To explore the effect of elevated CO2 on lettuce growth and better understand the mechanism of elevated CO2 in lettuce cultivation, 3 kinds of lettuce with 4 real leaves were selected and planted in a solar greenhouse. One week later, CO2 was applied from 8:00 a.m. to 10:00 a.m. on sunny days for 30 days. The results showed that the growth potential of lettuce was enhanced under CO2 enrichment. The content of vitamin C and chlorophyll in the three lettuce varieties increased, and the content of nitrate nitrogen decreased. The light saturation point and net photosynthetic rate of leaves increased, and the light compensation point decreased. Transcriptome analysis showed that there were 217 differentially expressed genes (DEGs) shared by the three varieties, among which 166 were upregulated, 44 were downregulated, and 7 DEGs were inconsistent in the three materials. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs involved mainly the ethylene signaling pathway, jasmonic acid signaling pathway, porphyrin and chlorophyll metabolism pathway, starch and sucrose metabolism pathway, etc. Forty-one DEGs in response to CO2 enrichment were screened out by Gene Ontology (GO) analysis, and the biological processes involved were consistent with KEGG analysis. which suggested that the growth and nutritional quality of lettuce could be improved by increasing the enzyme activity and gene expression levels of photosynthesis, hormone signaling and carbohydrate metabolism. The results laid a theoretical foundation for lettuce cultivation in solar greenhouses and the application of CO2 fertilization technology. [ABSTRACT FROM AUTHOR]

OBJECTIVE:The SI gene encodes the sucrase-isomaltase enzyme, a disaccharidase expressed in the intestinal brush border. Hypomorphic SI variants cause recessive congenital sucrase-isomaltase deficiency (CSID) and related gastrointestinal (GI) symptoms. Among children presenting with chronic, idiopathic loose stools, we assessed the prevalence of CSID-associated SI variants relative to the general population and the relative GI symptom burden associated with SI genotype within the study population. METHODS:A prospective study conducted at 18 centers enrolled 308 non-Hispanic white children ≤18 years old who were experiencing chronic, idiopathic, loose stools at least once per week for >4 weeks. Data on demographics, GI symptoms, and genotyping for 37 SI hypomorphic variants were collected. Race/ethnicity-matched SI data from the Exome Aggregation Consortium (ExAC) database was used as the general population reference. RESULTS:Compared with the general population, the cumulative prevalence of hypomorphic SI variants was significantly higher in the study population (4.5% vs. 1.3%, P < .01; OR = 3.5 [95% CI: 6.1, 2.0]). Within the study population, children with a hypomorphic SI variant had a more severe GI symptom burden than those without, including: more frequent episodes of loose stools (P < .01), higher overall stool frequency (P < .01), looser stool form (P = .01) and increased flatulence (P = .02). CONCLUSION:Non-Hispanic white children with chronic idiopathic loose stools have a higher prevalence of CSID-associated hypomorphic SI variants than the general population. The GI symptom burden was greater among the study subjects with a hypomorphic SI variant than those without hypomorphic SI variants.

Introduction: One of the stages of reproduction of SARS-CoV-2 is the S-protein glycosylation to facilitate penetration into target cells. It has been suggested that SARS-CoV-2 is able to enter erythrocytes, interact with heme and porphyrin, which could influence HbA1c levels. Assessment of HbA1c levels in individuals with acute COVID-19 and after recovery may show clinical relevance of this hypothesis. Aim: To assess HbA1c levels in patients with COVID-19 in the acute phase and in early (6–8 weeks) and late (52±2 weeks) periods after recovery. Materials and methods: We conducted a multicenter prospective study, which included patients hospitalized in Endocrinology Research Centre and the City Clinical Hospital № 52" diagnosed with COVID-19, virus identified/ not identified. Patients were divided into three groups according to baseline HbA1c level and the presence or absence of previous history of diabetes previous history of diabetes mellitus (DM): HbA1c ≤ 6.0%, HbA1c > 6.0% and patients with DM. Patients were examined during the acute COVID-19 phase and in early (6–8 weeks) and late (52±2 weeks) periods after recovery. Oral glucose tolerance test was performed in the group with initial HbA1c > 6.0% to clarify the diagnosis. Results: We included 194 patients in the study. During the follow-up, 52 patients were examined in 6–8 week period: 7 with HbA1c ≤ 6.0%, 34 with HbA1c > 6.0%, 11—with previously diagnosed DM. Carbohydrate metabolism assessment in the later stages (52±2 weeks) after recovery was performed in 78 patients: 33 patients with HbA1c ≤ 6.0%, 36 patients with HbA1c > 6.0% and 9 patients with previously established diabetes. HbA1c median in patients with HbA1c ≤ 6.0% was 5.7% [5.3;5.8], with HbA1c>6.0% -6.4% [6.2; 6.6], with previously diagnosed DM—7.7% [7.2; 8.9]. Statistically significant decrease in HbA1c over time 6–8 weeks after extracts were obtained in both groups of individuals without a history of DM (Wilcoxon test, p<0.05). After 52±2 weeks we observed HbA1c decrease in all three groups (Fridman test, p<0.05): in patients with HbA1c ≤ 6.0% median HbA1c was 5.5[5.3;5.7], with HbA1c>6.0% - 6.1[6.15;6.54], with previously diagnosed DM—7.8 [5.83; 8.08]. Development of DM after 52±2 weeks was recorded in 7.24% of all examined patients without a history of DM, which is 16.6% of the total number of patients examined in dynamics with HbA1c > 6.0%. Conclusion: HbA1c elevation during the acute phase of COVID-19 may be false due to the effect of SARS-CoV-2 on hemoglobin kinetics and/or detection on the surface of the SARS-CoV-2 virion highly glycosylated S-proteins by high performance liquid chromatography determinations. Upon detection HbA1c > 6.0% in patients with COVID-19 in the active phase of the disease without concomitant hyperglycemia re-determine the level of HbA1c after recovery is recommended. [ABSTRACT FROM AUTHOR]

The multicomponent phosphoenolpyruvate (PEP)-dependent sugar-transporting phosphotransferase system (PTS) in Escherichia coli takes up sugar substrates from the medium and concomitantly phosphorylates them, releasing sugar phosphates into the cytoplasm. We have recently provided evidence that many of the integral membrane PTS permeases interact with the fructose PTS (FruA/FruB) [1]. However, the biochemical and physiological significance of this finding was not known. We have carried out molecular genetic/biochemical/physiological studies that show that interactions of the fructose PTS often enhance, but sometimes inhibit the activities of other PTS transporters many fold, depending on the target PTS system under study. Thus, the glucose (Glc), mannose (Man), mannitol (Mtl) and N-acetylglucosamine (NAG) permeases exhibit enhanced in vivo sugar transport and sometimes in vitro PEP-dependent sugar phosphorylation activities while the galactitol (Gat) and trehalose (Tre) systems show inhibited activities. This is observed when the fructose system is induced to high levels and prevented when the fruA/fruB genes are deleted. Overexpression of the fruA and/or fruB genes in the absence of fructose induction during growth also enhances the rates of uptake of other hexoses. The β-galactosidase activities of man, mtl, and gat-lacZ transcriptional fusions and the sugar-specific transphosphorylation activities of these enzyme transporters were not affected either by frustose induction or by fruAB overexpression, showing that the rates of synthesis of the target PTS permeases were not altered. We thus suggest that specific protein-protein interactions within the cytoplasmic membrane regulate transport in vivo (and sometimes the PEP-dependent phosphorylation activities in vitro) of PTS permeases in a physiologically meaningful way that may help to provide a hierarchy of preferred PTS sugars. These observations appear to be applicable in principle to other types of transport systems as well.

Saccharomyces cerevisiae is known for its outstanding ability to produce ethanol in industry. Underlying the dynamics of gene expression in S. cerevisiae in response to fermentation could provide informative results, required for the establishment of any ethanol production improvement program. Thus, representing a new approach, this study was conducted to identify the discriminative genes between improved and repressed ethanol production as well as clarifying the molecular responses to this process through mining the transcriptomic data. The significant differential expression probe sets were extracted from available microarray datasets related to yeast fermentation performance. To identify the most effective probe sets contributing to discriminate ethanol content, 11 machine learning algorithms from RapidMiner were employed. Further analysis including pathway enrichment and regulatory analysis were performed on discriminative probe sets. Besides, the decision tree models were constructed, the performance of each model was evaluated and the roots were identified. Based on the results, 171 probe sets were identified by at least 5 attribute weighting algorithms (AWAs) and 17 roots were recognized with 100% performance Some of the top ranked presets were found to be involved in carbohydrate metabolism, oxidative phosphorylation, and ethanol fermentation. Principal component analysis (PCA) and heatmap clustering validated the top-ranked selective probe sets. In addition, the top-ranked genes were validated based on GSE78759 and GSE5185 dataset. From all discriminative probe sets, OLI1 and CYC3 were identified as the roots with the best performance, demonstrated by the most weighting algorithms and linked to top two significant enriched pathways including porphyrin biosynthesis and oxidative phosphorylation. ADH5 and PDA1 were also recognized as differential top-ranked genes that contribute to ethanol production. According to the regulatory clustering analysis, Tup1 has a significant effect on the top-ranked target genes CYC3 and ADH5 genes. This study provides a basic understanding of the S. cerevisiae cell molecular mechanism and responses to two different medium conditions (Mg2+ and Cu2+) during the fermentation process. [ABSTRACT FROM AUTHOR]

The effects of compression load to a specific body part, e.g. leg, arm, or trunk, evoke many functions and are applied in various fields including clinical medicine, sports, and general health care. Nevertheless, little is known about the functional mechanism of compression load, especially regarding its effects on metabolic function. We investigated the effects of compression load to the trunk on the metabolism. We designed adjustable compression clothes for mice and attached them to ten-week-old C57BL/6N male mice in a controlled environment. The mice were divided into compression and no-compression groups, the latter only wearing the clothes without added compression. The evoked metabolic changes were evaluated using indirect calorimetry and transcriptomics with liver tissue to investigate the mechanism of the metabolic changes induced by the compression load. The results indicated decreases in body weight gain, food intake, and respiratory exchange ratio in the compression group compared to the no-compression group, but these effects were limited in the "light period" which was an inactive phase for mice. As a result of the transcriptome analysis after eight hours of compression load to the trunk, several DEGs, e.g., Cpt1A, Hmgcr, were classified into functional categories relating to carbohydrate metabolism, lipid metabolism, or immune response. Lipid metabolism impacts included suppression of fatty acid synthesis and activation of lipolysis and cholesterol synthesis in the compression group. Taken together, our results showed that activation of lipid metabolism processes in an inactive phase was induced by the compression load to the trunk. [ABSTRACT FROM AUTHOR]

Tomatoes (Solanum lycopersicum L.) have been bred to exude higher amounts or different types of the specialized plant metabolites, acylsugars, from type IV trichomes. Acylsugars are known to deter several herbivorous insect pests, including the western flower thrips (WFT), Frankliniella occidentalis (Pergande); however, all previous studies investigated the effect of acylsugars on leaves, or acylsugar extracts obtained from leaves. In spite of the WFT predilection for flowers, there is a gap in knowledge about flower defenses against thrips damage. This is especially important in light of their capacity to acquire and inoculate viruses in the genus Orthotospovirus, such as Tomato spotted wilt orthotospovirus (TSWV), in flowers. Therefore, we turned our attention to assessing thrips oviposition differences on flowers of 14 entries, including 8 interspecific hybrids, 5 tomato lines bred for specific acylsugar-related characteristics (type IV trichome densities, acylsugar amount, sugar moiety and fatty acid profile), and a fresh market tomato hybrid, Mt. Spring, which only produces trace amounts of acylsugars. Our results show that the density of the acylsugar droplet bearing type IV trichomes is greatest on sepals, relative to other flower structures, and accordingly, WFT avoids oviposition on sepals in favor of trichome-sparse petals. In concordance with past studies, acylsugar amount was the most important acylsugar-related characteristic suppressing WFT oviposition. Certain acylsugar fatty acids, specifically i-C5, i-C9 and i-C11, were also significantly associated with changes in WFT oviposition. These results support continued breeding efforts to increase acylsugar amounts and explore modifications of fatty acid profile and their roles in deterring thrips oviposition. The finding that acylsugar production occurs and reduces thrips oviposition in tomato flowers will be important in efforts to use acylsugar-mediated resistance to reduce incidence of orthotospoviruses such as TSWV in tomato by deterring virus transmission and development of thrips vector populations in the crop.

Chicken is the first sequenced avian that has a crucial role in human life for its meat and egg production. Because of various metabolic disorders, study the metabolism of chicken cell is important. Herein, the first genome-scale metabolic model of a chicken cell named iES1300, consists of 2427 reactions, 2569 metabolites, and 1300 genes, was reconstructed manually based on KEGG, BiGG, CHEBI, UNIPROT, REACTOME, and MetaNetX databases. Interactions of metabolic genes for growth were examined for E. coli, S. cerevisiae, human, and chicken metabolic models. The results indicated robustness to genetic manipulation for iES1300 similar to the results for human. iES1300 was integrated with transcriptomics data using algorithms and Principal Component Analysis was applied to compare context-specific models of the normal, tumor, lean and fat cell lines. It was found that the normal model has notable metabolic flexibility in the utilization of various metabolic pathways, especially in metabolic pathways of the carbohydrate metabolism, compared to the others. It was also concluded that the fat and tumor models have similar growth metabolisms and the lean chicken model has a more active lipid and carbohydrate metabolism. [ABSTRACT FROM AUTHOR]

As the main forms of carbohydrates, starch and sucrose play a vital role in the balance and coordination of various carbohydrates. Lanzhou lily is the most popular edible lily in China, mainly distributed in the central region of Gansu. To clarify the relationship between carbohydrate metabolism and bulb development of Lanzhou lily, so as to provide a basis for the promotion of the growth and development in Lanzhou lily and its important economic value, we studied lily bulbs in the squaring stage, flowering stage, half withering stage and withering stage. The plant height, fresh weight of mother and daughter bulbs continued to increase during the whole growth period and fresh weight of stem and leaf began to decrease in the half withering stage. The content of starch, sucrose and total soluble sugar in the lily mother bulb accumulated mostly in the flowering, withering and half withering stages, respectively. Starch, sucrose and total soluble sugar accumulated in the daughter bulb with the highest concentration during the withering stage. In the transcription level, sucrose synthase (SuSy1) and sucrose invertase (INV2) expressed the highest in squaring stage, and the expression was significantly higher in the mother bulb than in the daughter bulb. In flowering stage, the expression levels of soluble starch synthase (SSS1), starch-branching enzyme (SBE) and adenosine diphosphate-glucose pyrophosphorylase (AGP1) genes were higher in the mother bulb than in the daughter bulb. Altogether, our results indicate that starch and sucrose are important for the bulb growth and development of Lanzhou lily. [ABSTRACT FROM AUTHOR]

The permanent draft genome sequence of Actinotignum schaalii DSM 15541T is presented. The annotated genome includes 2,130,987 bp, with 1777 protein-coding and 58 rRNA-coding genes. Genome sequence analysis revealed absence of genes encoding for: components of the PTS systems, enzymes of the TCA cycle, glyoxylate shunt and gluconeogensis. Genomic data revealed that A. schaalii is able to oxidize carbohydrates via glycolysis, the nonoxidative pentose phosphate and the Entner-Doudoroff pathways. Besides, the genome harbors genes encoding for enzymes involved in the conversion of pyruvate to lactate, acetate and ethanol, which are found to be the end products of carbohydrate fermentation. The genome contained the gene encoding Type I fatty acid synthase required for de novo FAS biosynthesis. The plsY and plsX genes encoding the acyltransferases necessary for phosphatidic acid biosynthesis were absent from the genome. The genome harbors genes encoding enzymes responsible for isoprene biosynthesis via the mevalonate (MVA) pathway. Genes encoding enzymes that confer resistance to reactive oxygen species (ROS) were identified. In addition, A. schaalii harbors genes that protect the genome against viral infections. These include restriction-modification (RM) systems, type II toxin-antitoxin (TA), CRISPR-Cas and abortive infection system. A. schaalii genome also encodes several virulence factors that contribute to adhesion and internalization of this pathogen such as the tad genes encoding proteins required for pili assembly, the nanI gene encoding exo-alpha-sialidase, genes encoding heat shock proteins and genes encoding type VII secretion system. These features are consistent with anaerobic and pathogenic lifestyles. Finally, resistance to ciprofloxacin occurs by mutation in chromosomal genes that encode the subunits of DNA-gyrase (GyrA) and topisomerase IV (ParC) enzymes, while resistant to metronidazole was due to the frxA gene, which encodes NADPH-flavin oxidoreductase.

Lactobacillus paragasseri was identified as a novel sister taxon of L. gasseri in 2018. Since the reclassification of L. paragasseri, there has been hardly any report describing the probiotic properties of this species. In this study, an L. paragasseri strain UBLG-36 was sequenced and analyzed to determine the molecular basis that may confer the bacteria with probiotic potential. UBLG-36 was previously documented as an L. gasseri strain. Average nucleotide identity and phylogenomic analysis allowed accurate taxonomic identification of UBLG-36 as an L. paragasseri strain. Analysis of the draft genome (~1.94 Mb) showed that UBLG-36 contains 5 contigs with an average G+C content of 34.85%. Genes essential for the biosynthesis of bacteriocins, adhesion to host epithelium, stress resistance, host immunomodulation, defense, and carbohydrate metabolism were identified in the genome. Interestingly, L. paragasseri UBLG-36 also harbored genes that code for enzymes involved in oxalate catabolism, such as formyl coenzyme A transferase (frc) and oxalyl coenzyme A decarboxylase (oxc). In vitro oxalate degradation assay showed that UBLG-36 is highly effective in degrading oxalate (averaging more than 45% degradation), a feature that has not been reported before. As a recently identified bacterium, there are limited genomic reports on L. paragasseri, and our draft genome sequence analysis is the first to describe and emphasize the probiotic potential and oxalate degrading ability of this species. With results supporting the probiotic functionalities and oxalate catabolism of UBLG-36, we propose that this strain is likely to have immense biotechnological applications upon appropriate characterization. [ABSTRACT FROM AUTHOR]

Huanglongbing (HLB; citrus greening) is the most devastating disease of citrus worldwide. No cure is yet available for this disease and infected trees generally decline after several months. Disease management depends on early detection of symptoms and chemical control of insect vectors. In this work, different combinations of organic compounds were tested for the ability to modulate citrus molecular responses to HLB disease beneficially. Three small-molecule regulating compounds were tested: 1) L-arginine, 2) 6-benzyl-adenine combined with gibberellins, and 3) sucrose combined with atrazine. Each treatment contained K-phite mineral solution and was tested at two different concentrations. Two trials were conducted: one in the greenhouse and the other in the orchard. In the greenhouse study, responses of 42 key genes involved in sugar and starch metabolism, hormone-related pathways, biotic stress responses, and secondary metabolism in treated and untreated mature leaves were analyzed. TGA5 was significantly induced by arginine. Benzyladenine and gibberellins enhanced two important genes involved in biotic stress responses: WRKY54 and WRKY59. Sucrose combined with atrazine mainly upregulated key genes involved in carbohydrate metabolism such as sucrose-phosphate synthase, sucrose synthase, starch synthase, and α-amylase. Atrazine also affected expression of some key genes involved in systemic acquired resistance such as EDS1, TGA6, WRKY33, and MYC2. Several treatments upregulated HSP82, which might help protect protein folding and integrity. A subset of key genes was chosen as biomarkers for molecular responses to treatments under field conditions. GPT2 was downregulated by all small-molecule treatments. Arginine-induced genes involved in systemic acquired resistance included PR1, WRKY70, and EDS1. These molecular data encourage long-term application of treatments that combine these regulating molecules in field trials.

The rising demand for popcorn necessitates improving the popping quality with higher yield of popcorn cultivars. Towards this direction several Quantitative Traits Loci (QTLs) for popping traits have been identified. However, identification of accurate and consistent QTLs across different genetic backgrounds and environments is necessary to effectively utilize the identified QTLs in marker-assisted breeding. In the current study, 99 QTLs related to popping traits reported in 8 different studies were assembled and projected on the reference map "Genetic 2005" using BioMercator v4.2 to identify metaQTLs with consistent QTLs. Total ten metaQTLs were identified on chromosome 1 (7 metaQTLs) and 6 (3 metaQTLs) with physical distance ranging between 0.43 and 12.75 Mb, respectively. Four identified metaQTLs, viz., mQTL1_1, mQTL1_5, mQTL1_7 and mQTL6_2 harboured 5–8 QTL clusters with moderately high R2 value. The clustered QTLs were from two or more experiments. Based on the expression pattern in endosperm and pericarp tissues, a total of 229 genes were selected. Nineteen of these genes are involved in carbohydrate metabolism. Of the 19 genes specifically involved in carbohydrate metabolism, 11 of them were in these regions, implying the importance of these clustered QTLs. MetaQTL1_1 at bin location 1.01 coincided with the reported QTLs related to various agronomic traits like stalk diameter, tassel length, leaf area and plant height. The identified metaQTLs can be further explored for fine mapping and candidate gene identification, which can be validated by loss or gain of function. Identified metaQTLs can be used for introgression of popping traits towards enhancing the popping ability. [ABSTRACT FROM AUTHOR]

Background: Obesity is the cause of cardiovascular diseases and other diseases, leading to increased medical costs, and causing a great burden to individuals, families and society. The prevalence of obesity is increasing and has become a global health problem. There is growing evidence that gut microbiota plays an important role in obesity. In this article, we revealed the differences in the gut microbiota between 21 people with obesity and 21 control subjects, and predicted the functional potential changes by 16S rRNA sequencing of the fecal bacteria of the subjects. Methods: The raw sequencing data of 21 healthy Beijing volunteers was downloaded from Microbial Genome Database System. Microbial 16S rRNA genes of 21 adults with obesity were sequenced on an Illumina MiSeq instrument and analyzed by using bioinformatics and statistical methods. Results: The diversity of gut microbiota in people with obesity decreased significantly. There were significant differences in gut microbiota between the Obesity and Control group at different levels. At the phylum level, Firmicutes, Bacteroidetes, Actinobacteria and Fusobacteria are significantly different between the Obesity and Control group. In people with obesity, the ratio of Firmicutes/Bacteroidetes decreased significantly. At the genus level, there were significant differences among the 16 major genera, of which four genera Prevotella, Megamonas, Fusobacterium and Blautia increased significantly in people with obesity, while the remaining 12 genera, Faecalibacterium, Lachnospiracea_incertae_sedis, Gemmiger and Clostridium XlVa, etc. decreased significantly. At the species level, nine species including Bacteroides uniformis and Prevotella copri had significant differences. Compared with the control group, subjects with obesity were abnormalities in 57 pathways, mainly in Carbohydrate metabolism and Lipid metabolism. Conclusions: Overall, our study revealed differences in the gut microbiota between people with obesity and control subjects, providing novel target for the treatment of individuals with obesity. [ABSTRACT FROM AUTHOR]

Spiders being one of the most diverse group in phylum arthropod are of great importance due to their role as predators, silk producer, and in medicinal applications. Spiders in prey–predator relationships play a crucial role in balancing the food-chain of any ecosystem; therefore it is essential to characterize the gut microbiota of spiders collected from natural environments. In the present work, the largest effort so far has been made to characterize the gut microbiota of 35 spider species belonging to four different families using 16S amplicon targeting sequencing. Further, we compared the gut microbiota composition including endosymbiont abundance in spider species collected from different geographical locations. The results obtained revealed the presence of genera like Acinetobacter (15%), V7clade (9%), Wolbachia (8%), Pseudomonas (5%), Bacillus (6%). Although comparative analysis revealed that the gut bacterial composition in all the spider families has a similar pattern, in terms of community richness and evenness. The bacterial diversity in the spider family, Lycosidae are more diverse than in Salticidae, Tetragnathidae and Araneidae. Furthermore, it was observed that the abundance of endosymbiont genera, i.e. Wolbachia and Rickettsia, leads to shift in the abundance of other bacterial taxa and may cause sexual alterations in spider species. Moreover, predicted functional analysis based on PICRUSt2 reveals that gut microbiota of spider species were involved in functions like metabolism of carbohydrates, cofactors and vitamins, amino acids; biosynthesis of organic compounds, fatty acids, lipids etc. Based on the results obtained, it can be said that different locations do not correlate with community composition of gut microbiota in spider species collected from natural environments. [ABSTRACT FROM AUTHOR]

Insects hold considerable ecological and agricultural importance making it vital to understand the factors impacting their reproductive output. Environmental stressors are examples of such factors which have a substantial and significant influence on insect reproductive fitness. Insects are also ectothermic and small in size which makes them even more susceptible to environmental stresses. The present study assesses the consequence of desiccation on the mating latency and copulations duration in tropical Drosophila melanogaster. We tested flies for these reproductive behavioral parameters at varying body water levels and with whole metabolome analysis in order to gain a further understanding of the physiological response to desiccation. Our results showed that the duration of desiccation is positively correlated with mating latency and mating failure, while having no influence on the copulation duration. The metabolomic analysis revealed three biological pathways highly affected by desiccation: starch and sucrose metabolism, galactose metabolism, and phenylalanine, tyrosine and tryptophan biosynthesis. These results are consistent with carbohydrate metabolism providing an energy source in desiccated flies and also suggests that the phenylalanine biosynthesis pathway plays a role in the reproductive fitness of the flies. Desiccation is a common issue with smaller insects, like Drosophila and other tropical insects, and our findings indicate that this lack of ambient water can immediately and drastically affect the insect reproductive behaviour, which becomes more crucial because of unpredictable and dynamic weather conditions. [ABSTRACT FROM AUTHOR]

The unique properties of carbon-based nanomaterials, including fullerenol, have attracted great interest in agricultural and environmental applications. Iron (Fe) is an essential micronutrient for major metabolic processes, for which a shortage causes chlorosis and reduces the yield of many crops cultivated worldwide. In the current study, the metabolic responses of Cucumis sativus (a Strategy I plant) to fullerenol treatments were investigated depending on the Fe status of plants. Cucumber plants were grown hydroponically, either with [+FeII (ferrous) and +FeIII (ferric)] or in Fe-free (−FeII and −FeIII) nutrient solution, with (+F) or without (−F) a fullerenol supply. Iron species-dependent effects were observed in either Fe-fed or Fe-starved plants, with alteration of metabolites involved in the metabolism of carbohydrates, amino acids, organic acids, lipophilic compounds. Metabolic perturbations triggered by fullerenol in the FeIII-treated plants were in the opposite kind from those in the FeII-treated plants. Whereas in the FeIII-fed plants, fullerenol activated the metabolisation of carbohydrates and amino acids, in the FeII-fed plants, fullerenol activated the metabolisation of lipophilic compounds and repressed the metabolisation of carbohydrates and amino acids. In FeIII-deficient plants, fullerenol stimulated the metabolism of C3 carboxylates and lipophilic compounds while repressing the metabolism of amino acids, hexoses and dicarboxylates, while in FeII-deficient plants, activations of the metabolism of amino acids and dicarboxylates and repression of sterol metabolism by fullerenol were observed. The results indicated that the valence state of Fe sources is of importance for re-programming metabolome responses in cucumber to fullerenol either in Fe-sufficient or Fe-deficient conditions. These investigations are significant for understanding fullerenol interactions and risk assessment in plants with different Fe statuses. [ABSTRACT FROM AUTHOR]

The specific genes regulating the quantitative variation in macronutrient preference and food intake are virtually unknown. We fine mapped a previously identified mouse chromosome 17 region harboring quantitative trait loci (QTL) with large effects on preferential macronutrient intake-carbohydrate (Mnic1), total kilcalories (Kcal2), and total food volume (Tfv1) using interval-specific strains. These loci were isolated in the [C57BL/6J.CAST/EiJ-17.1-(D17Mit19-D17Mit50); B6.CAST-17.1] strain, possessing a ∼ 40.1 Mb region of CAST DNA on the B6 genome. In a macronutrient selection paradigm, the B6.CAST-17.1 subcongenic mice eat 30% more calories from the carbohydrate-rich diet, ∼ 10% more total calories, and ∼ 9% more total food volume per body weight. In the current study, a cross between carbohydrate-preferring B6.CAST-17.1 and fat-preferring, inbred B6 mice was used to generate a subcongenic-derived F2 mapping population; genotypes were determined using a high-density, custom SNP panel. Genetic linkage analysis substantially reduced the 95% confidence interval for Mnic1 (encompassing Kcal2 and Tfv1) from 40.1 to 29.5 Mb and more precisely established its boundaries. Notably, no genetic linkage for self-selected fat intake was detected, underscoring the carbohydrate-specific effect of this locus. A second key finding was the separation of two energy balance QTLs: Mnic1/Kcal2/Tfv1 for food intake and a newly discovered locus regulating short term body weight gain. The Mnic1/Kcal2/Tfv1 QTL was further de-limited to 19.0 Mb, based on the absence of nutrient intake phenotypes in subcongenic HQ17IIa mice. Analyses of available sequence data and gene ontologies, along with comprehensive expression profiling in the hypothalamus of non-recombinant, cast/cast and b6/b6 F2 controls, focused our attention on candidates within the QTL interval. Zfp811, Zfp870, and Btnl6 showed differential expression and also contain stop codons, but have no known biology related to food intake regulation. The genes Decr2, Ppard and Agapt1 are more appealing candidates because of their involvement in lipid metabolism and down-regulation in carbohydrate-preferring animals.

Evolutionary interactions between parasitoid wasps and insect hosts have been well studied at the organismal level, but little is known about the molecular mechanisms that insects use to resist wasp parasitism. Here we study the interaction between a braconid wasp (Aphidius ervi) and its pea aphid host (Acyrthosiphon pisum). We first identify variation in resistance to wasp parasitism that can be attributed to aphid genotype. We then use transcriptome sequencing to identify genes in the aphid genome that are differentially expressed at an early stage of parasitism, and we compare these patterns in highly resistant and susceptible aphid host lines. We find that resistant genotypes are upregulating genes involved in carbohydrate metabolism and several key innate immune system genes in response to parasitism, but that this response seems to be weaker in susceptible aphid genotypes. Together, our results provide a first look into the complex molecular mechanisms that underlie aphid resistance to wasp parasitism and contribute to a broader understanding of how resistance mechanisms evolve in natural populations. [ABSTRACT FROM AUTHOR]

Trichosanthes kirilowii Maxim. (TK) is a dioecious plant in the Cucurbitaceae for which different sexes have separate medicinal uses. In order to study the genes related to sex determination, transcriptome sequencing was performed on flower buds of male and female plants using the high-throughput sequencing technology. A total of 145,975 unigenes and 7110 DEGs were obtained. There were 6776 DEGs annotated to 1234 GO terms and enriched to 18 functional groups, including five biological processes related to sugar metabolism. KEGG pathway analysis indicated genes involved in hormone transduction, hormone synthesis and carbohydrate metabolism. Many DEGs of TK are involved in reproductive organ formation, hormone signal transduction and regulatory networks. Combining the results of GO, KEGG and qRT-PCR, 11 sex determining candidate genes of TK were selected, including MYB80, MYB108, CER1, CBL9, ABCB19, SERK1, HSP81-3, ACS9, SEP3, AUX1 and YUC6. The results provide a foundation for the study of sex differentiation in TK. [ABSTRACT FROM AUTHOR]

Bifidobacterium longum subsp. infantis is a common member of the intestinal microbiota in breast-fed infants and capable of metabolizing human milk oligosaccharides (HMO). To investigate the bacterial response to different prebiotics, we analyzed both cell wall associated and whole cell proteins in B. infantis. Proteins were identified by LC-MS/MS followed by comparative proteomics to deduce the protein localization within the cell. Enzymes involved in the metabolism of lactose, glucose, galactooligosaccharides, fructooligosaccharides and HMO were constitutively expressed exhibiting less than two-fold change regardless of the sugar used. In contrast, enzymes in N-Acetylglucosamine and sucrose catabolism were induced by HMO and fructans, respectively. Galactose-metabolizing enzymes phosphoglucomutase, UDP-glucose 4-epimerase and UTP glucose-1-P uridylytransferase were expressed constitutively, while galactokinase and galactose-1-phosphate uridylyltransferase, increased their expression three fold when HMO and lactose were used as substrates for cell growth. Cell wall-associated proteomics also revealed ATP-dependent sugar transport systems associated with consumption of different prebiotics. In addition, the expression of 16 glycosyl hydrolases revealed the complete metabolic route for each substrate. Mucin, which possesses O-glycans that are structurally similar to HMO did not induced the expression of transport proteins, hydrolysis or sugar metabolic pathway indicating B. infantis do not utilize these glycoconjugates.

Our group has developed two transplantation models for the engraftment of Human Intestinal Organoids (HIOs): the renal subcapsular space (RSS) and the mesentery each with specific benefits for study. While engraftment at both sites generates laminated intestinal structures, a direct comparison between models has not yet been performed. Embryonic stem cells were differentiated into HIOs, as previously described. HIOs from the same batch were transplanted on the same day into either the RSS or mesentery. 10 weeks were allowed for engraftment and differentiation, at which time they were harvested and assessed. Metrics for comparison included: mortality, engraftment rate, gross size, number and grade of lumens, and expression of markers specific to epithelial differentiation, mesenchymal differentiation, and carbohydrate metabolism. Mortality was significantly increased when undergoing mesentery transplantation, however engraftment was significantly higher. Graft sizes were similar between groups. Morphometric parameters were similar between groups, however m-tHIOs presented with significantly fewer lumens than k-tHIO. Transcript and protein level expression of markers specific to epithelial differentiation, mesenchymal differentiation, and carbohydrate metabolism were similar between groups. Transplantation into both sites yields viable tissue of similar quality based on our assessments with enhanced engraftment and a dominant lumen for uniform study benefiting the mesenteric site and survival benefiting RSS. [ABSTRACT FROM AUTHOR]

Aluminum (Al3+) toxicity is one of the most important limitations to agricultural production worldwide. The overall response of plants to Al3+ stress has been documented, but the contribution of protein phosphorylation to Al3+ detoxicity and tolerance in plants is unclear. Using a combination of tandem mass tag (TMT) labeling, immobilized metal affinity chromatography (IMAC) enrichment and liquid chromatography-tandem mass spectrometry (LC-MS/MS), Al3+-induced phosphoproteomic changes in roots of Tamba black soybean (TBS) were investigated in this study. The Data collected in this study are available via ProteomeXchange with the identifier PXD019807. After the Al3+ treatment, 189 proteins harboring 278 phosphosites were significantly changed (fold change > 1.2 or < 0.83, p < 0.05), with 88 upregulated, 96 downregulated and 5 up-/downregulated. Enrichment and protein interaction analyses revealed that differentially phosphorylated proteins (DPPs) under the Al3+ treatment were mainly related to G-protein-mediated signaling, transcription and translation, transporters and carbohydrate metabolism. Particularly, DPPs associated with root growth inhibition or citric acid synthesis were identified. The results of this study provide novel insights into the molecular mechanisms of TBS post-translational modifications in response to Al3+ stress. [ABSTRACT FROM AUTHOR]

Grapevines, although adapted to occasional drought or salt stress, are relatively sensitive to growth- and yield-limiting salinity stress. To understand the molecular mechanisms of salt tolerance and endoplasmic reticulum (ER) stress and identify genes commonly regulated by both stresses in grapevine, we investigated transcript profiles in leaves of the salt-tolerant grapevine rootstock 1616C under salt- and ER-stress. Among 1643 differentially expressed transcripts at 6 h post-treatment in leaves, 29 were unique to ER stress, 378 were unique to salt stress, and 16 were common to both stresses. At 24 h post-treatment, 243 transcripts were unique to ER stress, 1150 were unique to salt stress, and 168 were common to both stresses. GO term analysis identified genes in categories including 'oxidative stress', 'protein folding', 'transmembrane transport', 'protein phosphorylation', 'lipid transport', 'proteolysis', 'photosynthesis', and 'regulation of transcription'. The expression of genes encoding transporters, transcription factors, and proteins involved in hormone biosynthesis increased in response to both ER and salt stresses. KEGG pathway analysis of differentially expressed genes for both ER and salt stress were divided into four main categories including; carbohydrate metabolism, amino acid metabolism, signal transduction and lipid metabolism. Differential expression of several genes was confirmed by qRT-PCR analysis, which validated our microarray results. We identified transcripts for genes that might be involved in salt tolerance and also many genes differentially expressed under both ER and salt stresses. Our results could provide new insights into the mechanisms of salt tolerance and ER stress in plants and should be useful for genetic improvement of salt tolerance in grapevine. [ABSTRACT FROM AUTHOR]

Manila grass (Zoysia matrella), a warm-season turfgrass, usually wilts and browns by late autumn because of low temperature. To elucidate the molecular mechanisms regarding Manila grass responses to cold stress, we performed transcriptome sequencing of leaves exposed to 4°C for 0 (CK), 2h (2h_CT) and 72h (72h_CT) by Illumina technology. Approximately 250 million paired-end reads were obtained and de novo assembled into 82,605 unigenes. A total of 34,879 unigenes were annotated by comparing their sequence to public protein databases. At the 2h- and 72h-cold time points, 324 and 5,851 differentially expressed genes (DEGs) were identified, respectively. Gene ontology (GO) and metabolism pathway (KEGG) enrichment analyses of DEGs indicated that auxin, gibberellins, ethylene and calcium took part in the cold signal transduction in the early period. And in the late cold period, electron transport activities, photosynthetic machinery and activity, carbohydrate and nitrogen metabolism, redox equilibrium and hormone metabolism were disturbed. Low temperature stress triggered high light, drought and oxidative stress. At the physiological level, cold stress induced a decrease in water content, an increase in levels of total soluble sugar, free proline and MDA, and changes in bioactive gibberellins levels, which supported the changes in gene expression. The results provided a large set of sequence data of Manila grass as well as molecular mechanisms of the grass in response to cold stress. This information will be helpful for future study of molecular breeding and turf management. [ABSTRACT FROM AUTHOR]

To evaluated the effects melatonin (MT) on the sugar and acid metabolism of early-ripening peach fruits, the concentration of 150 μmol/L MT was sprayed on the leaves of peach trees. MT increased the contents of total soluble sugar and sucrose in peach fruits during the whole ripening period, and increased the contents of glucose and sorbitol at the mature stage. During the whole ripening period, MT also increased the activities of sucrose synthase, sucrose phosphate synthase, neutral invertase, and acidic invertase and the relative expression levels of sucrose synthase, sucrose phosphate synthase, neutral invertase, and acidic invertase genes, while decreased the activity of sorbitol oxidase and the relative expression level of sorbitol dehydrogenase to some extent. Moreover, MT decreased the contents of total organic acid, malic acid, and citric acid at mature stage. At mature stage, MT decreased the activities of citrate synthetase and phosphoenolpyruvate carboxylase and the relative expression levels of citrate synthetase and phosphoenolpyruvate carboxylase genes, while increased the relative expression levels of Nicotinamide adenine dinucleotide phosphate (NADP+)-malic enzyme, malate dehydrogenase, and aconitase genes. Therefore, MT promotes the sugar accumulation and organic acid degradation in early-ripening peach fruits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Glycerol kinase plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP dependent reaction. In humans, glycerol kinase deficiency results in a wide range of phenotypic variability; patients can have severe metabolic and CNS abnormalities, while others possess hyperglycerolemia and glyceroluria with no other apparent phenotype. In an effort to help understand the pathogenic mechanisms underlying the phenotypic variation, we have created a Drosophila model for glycerol kinase deficiency by RNAi targeting of dGyk (CG18374) and dGK (CG7995). As expected, RNAi flies have reduced glycerol kinase RNA expression, reduced phosphorylation activity and elevated glycerol levels. Further investigation revealed these flies to be hypersensitive to fly food supplemented with glycerol. Due to the hygroscopic nature of glycerol, we predict glycerol hypersensitivity is a result of greater susceptibility to desiccation, suggesting glycerol kinase to play an important role in desiccation resistance in insects. To evaluate a role for genetic modifier loci in determining severity of the glycerol hypersensitivity observed in knockdown flies, we performed a preliminary screen of lethal transposon insertion mutant flies using a glycerol hypersensitive survivorship assay. We demonstrate that this type of screen can identify both enhancer and suppressor genetic loci of glycerol hypersensitivity. Furthermore, we found that the glycerol hypersensitivity phenotype can be enhanced or suppressed by null mutations in eye pigmentation genes. Taken together, our data suggest proteins encoded by eye pigmentation genes play an important role in desiccation resistance and that eye pigmentation genes are strong modifiers of the glycerol hypersensitive phenotype identified in our Drosophila model for glycerol kinase deficiency.

Huanglongbing (HLB) or "citrus greening" is the most destructive citrus disease worldwide. In this work, we studied host responses of citrus to infection with Candidatus Liberibacter asiaticus (CaLas) using next-generation sequencing technologies. A deep mRNA profile was obtained from peel of healthy and HLB-affected fruit. It was followed by pathway and protein-protein network analysis and quantitative real time PCR analysis of highly regulated genes. We identified differentially regulated pathways and constructed networks that provide a deep insight into the metabolism of affected fruit. Data mining revealed that HLB enhanced transcription of genes involved in the light reactions of photosynthesis and in ATP synthesis. Activation of protein degradation and misfolding processes were observed at the transcriptomic level. Transcripts for heat shock proteins were down-regulated at all disease stages, resulting in further protein misfolding. HLB strongly affected pathways involved in source-sink communication, including sucrose and starch metabolism and hormone synthesis and signaling. Transcription of several genes involved in the synthesis and signal transduction of cytokinins and gibberellins was repressed while that of genes involved in ethylene pathways was induced. CaLas infection triggered a response via both the salicylic acid and jasmonic acid pathways and increased the transcript abundance of several members of the WRKY family of transcription factors. Findings focused on the fruit provide valuable insight to understanding the mechanisms of the HLB-induced fruit disorder and eventually developing methods based on small molecule applications to mitigate its devastating effects on fruit production.

The endophytic bacterial diversity of rose was analyzed by high-throughput sequencing of 16S rDNA and functional prediction of the bacterial community. The number of bacterial sequence reads obtained from 18 rose samples ranged from 63,951 to 114,833, and reads were allocated to 1982 OTUs based on sequences of the V3-V4 region. The highest Shannon Index was found in Luogang rose (1.93), while the lowest was found in Grasse rose (0.35). The bacterial sequence reads were grouped into three different phyla: Firmicutes, Proteobacteria, and Actinobacteria. At the genus level, Bacillus and Staphylococcus had the highest abundance across all 18 samples; Bacillus was particularly abundant in Daguo rose (99.09%), Rosa damascena (99.65%), and Fenghua rose (99.58%). Unclassified OTUs were also found in all samples. PICRUSt gene prediction revealed that each endophyte sample contained multiple KEGG functional modules related to human metabolism and health. A high abundance of functional genes were involved in (1) Amino Acid Metabolism, (2) Carbohydrate Metabolism, (3) Cellular Processes and Signaling, (4) Energy Metabolism, and (5) Membrane Transport, indicating that the endophytic community comprised a wide variety of microorganisms and genes that could be used for further studies. The rose endophytic bacterial community is rich in diversity; community composition varies among roses and contains functional information related to human health. [ABSTRACT FROM AUTHOR]

Exogenously hypercholesterolemic (ExHC) rats develop diet-induced hypercholesterolemia (DIHC) when fed with dietary cholesterol. Previously, we reported that, under the high-sucrose-diet-feeding condition, a loss-of-function mutation in Smek2 results in low activity of fatty acid synthase (FAS) followed by the shortage of hepatic triacylglycerol content in ExHC rats and the onset of DIHC. However, the relationship between the Smek2 mutation and FAS dysfunction is still unclear. Here, we focused on carbohydrate metabolism, which provides substrates for FAS, and analyzed carbohydrate and lipid metabolisms in ExHC rats to clarify how the deficit of Smek2 causes DIHC. Male ExHC and SD rats were fed high-sucrose or high-starch diets containing 1% cholesterol for 2 weeks. Serum cholesterol levels of the ExHC rats were higher, regardless of the dietary carbohydrate. Hepatic triacylglycerol levels were higher in only the SD rats fed the high-sucrose diet. Moreover, the ExHC rats exhibited a diabetes-like status and accumulation of hepatic glycogen and low hepatic mRNA levels of liver-type phosphofructokinase (Pfkl), which encodes a rate-limiting enzyme for glycolysis. These results suggest that the glucose utilization, particularly glycolysis, is impaired in the liver of ExHC rats. To evaluate how the diet with extremely low glucose affect to DIHC, ExHC.BN-Dihc2BN, a congenic strain that does not develop DIHC, and ExHC rats were fed a high-fructose diet containing 1% cholesterol for 2 weeks. The serum cholesterol and hepatic triacylglycerol levels were similar in the strains. Results of water-soluble metabolite analysis with primary hepatocytes, an increase in fructose-6-phosphate and decreases in succinate, malate and aspartate in ExHC rats, support impaired glycolysis in the ExHC rats. Thus, the Smek2 mutation causes abnormal hepatic glucose utilization via downregulation of Pfkl expression. This abnormal glucose metabolism disrupts hepatic fatty acid synthesis and causes DIHC in the ExHC rats. [ABSTRACT FROM AUTHOR]

This paper describes CarbMetSim, a discrete-event simulator that tracks the blood glucose level of a person in response to a timed sequence of diet and exercise activities. CarbMetSim implements broader aspects of carbohydrate metabolism in human beings with the objective of capturing the average impact of various diet/exercise activities on the blood glucose level. Key organs (stomach, intestine, portal vein, liver, kidney, muscles, adipose tissue, brain and heart) are implemented to the extent necessary to capture their impact on the production and consumption of glucose. Key metabolic pathways (glucose oxidation, glycolysis and gluconeogenesis) are accounted for in the operation of different organs. The impact of insulin and insulin resistance on the operation of various organs and pathways is captured in accordance with published research. CarbMetSim provides broad flexibility to configure the insulin production ability, the average flux along various metabolic pathways and the impact of insulin resistance on different aspects of carbohydrate metabolism. The simulator does not yet have a detailed implementation of protein and lipid metabolism. This paper contains a preliminary validation of the simulator's behavior. Significant additional validation is required before the simulator can be considered ready for use by people with Diabetes. [ABSTRACT FROM AUTHOR]

Polybrominated diphenyl ethers (PBDEs) were formally used as flame-retardants and are chemically stable, lipophlic persistent organic pollutants which are known to bioaccumulate in humans. Although its toxicities are well characterized, little is known about the changes in transcriptional regulation caused by PBDE exposure. Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of transcriptional and translational processes. It is hypothesized that lncRNAs can regulate nearby protein-coding genes (PCGs) and changes in the transcription of lncRNAs may act in cis to perturb gene expression of its neighboring PCGs. The goals of this study were to 1) characterize PCGs and lncRNAs that are differentially regulated from exposure to PBDEs; 2) identify PCG-lncRNA pairs through genome annotation and predictive binding tools; and 3) determine enriched canonical pathways caused by differentially expressed lncRNA-PCGs pairs. HepaRG cells, which are human-derived hepatic cells that accurately represent gene expression profiles of human liver tissue, were exposed to BDE-47 and BDE-99 at a dose of 25 μM for 24 hours. Differentially expressed lncRNA-PCG pairs were identified through DESeq2 and HOMER; significant canonical pathways were determined through Ingenuity Pathway Analysis (IPA). LncTar was used to predict the binding of 19 lncRNA-PCG pairs with known roles in drug-processing pathways. Genome annotation revealed that the majority of the differentially expressed lncRNAs map to PCG introns. PBDEs regulated overlapping pathways with PXR and CAR such as protein ubiqutination pathway and peroxisome proliferator-activated receptor alpha-retinoid X receptor alpha (PPARα-RXRα) activation but also regulate distinctive pathways involved in intermediary metabolism. PBDEs uniquely down-regulated GDP-L-fucose biosynthesis, suggesting its role in modifying important pathways involved in intermediary metabolism such as carbohydrate and lipid metabolism. In conclusion, we provide strong evidence that PBDEs regulate both PCGs and lncRNAs in a PXR/CAR ligand-dependent and independent manner. [ABSTRACT FROM AUTHOR]

Intestinal microbiota performed numerous important functions during digestion. The first filial generation (F1) hybrids of Hainan black goats and Saanen goats had different traits, black goats (BG) and white goats (WG), which also brought different production performance. We explored the difference of gut microbiota between black goats and white goats that both belonged to the first filial generation (F1) hybrids. In general, the alpha diversity of the black goat group was significantly higher than the white goat group. The species richness had no significant difference, while the species evenness of BG was higher than WG. Bacteroides, Oscillospira, Alistipes, Ruminococcus, Clostridium and Oscillibacter, as the core gut microbial genera, all had high abundance in BG and WG group. Only the Bacteroides and Bacteroidaceae 5-7N15 were the different genera between the BG and WG group, of which Bacteroides overlapped with the core genera and enriched in the WG group. Besides, PICRUSt analysis showed that there was a high abundance in the secondary metabolic pathways including membrane transport, replication and repair, carbohydrate metabolism and amino acid metabolism. We found the intestinal microbial species of black goats and white goats were very similar for living in the identical growing environment and feeding conditions, but there was still a slight difference in the content. On the one hand, it was proved that the small effect of genotype and the great effect of diet affected the intestinal microbiota together. On the other hand, it was also proved that these different traits of first filial generation (F1) hybrids may not related to gut microbiota and only because of different genotype. Moreover, characterization of the gut microbiota in BG and WG will be useful in goats gut microbiota research. [ABSTRACT FROM AUTHOR]

Background: Microbial communities of the mouse gut have been extensively studied; however, their functional roles and regulation are yet to be elucidated. Metagenomic and metatranscriptomic analyses may allow us a comprehensive profiling of bacterial composition and functions of the complex gut microbiota. The present study aimed to investigate the active functions of the microbial communities in the murine cecum by analyzing both metagenomic and metatranscriptomic data on specific bacterial species within the microbial communities, in addition to the whole microbiome. Results: Bacterial composition of the healthy mouse gut microbiome was profiled using the following three different approaches: 16S rRNA-based profiling based on amplicon and shotgun sequencing data, and genome-based profiling based on shotgun sequencing data. Consistently, Bacteroidetes, Firmicutes, and Deferribacteres emerged as the major phyla. Based on NCBI taxonomy, Muribaculaceae, Lachnospiraceae, and Deferribacteraceae were the predominant families identified in each phylum. The genes for carbohydrate metabolism were upregulated in Muribaculaceae, while genes for cofactors and vitamin metabolism and amino acid metabolism were upregulated in Deferribacteraceae. The genes for translation were commonly enhanced in all three families. Notably, combined analysis of metagenomic and metatranscriptomic sequencing data revealed that the functions of translation and metabolism were largely upregulated in all three families in the mouse gut environment. The ratio of the genes in the metagenome and their expression in the metatranscriptome indicated higher expression of carbohydrate metabolism in Muribaculum, Duncaniella, and Mucispirillum. Conclusions: We demonstrated a fundamental methodology for linking genomic and transcriptomic datasets to examine functional activities of specific bacterial species in a complicated microbial environment. We investigated the normal flora of the mouse gut using three different approaches and identified Muribaculaceae, Lachnospiraceae, and Deferribacteraceae as the predominant families. The functional distribution of these families was reflected in the entire microbiome. By comparing the metagenomic and metatranscriptomic data, we found that the expression rates differed for different functional categories in the mouse gut environment. Application of these methods to track microbial transcription in individuals over time, or before and after administration of a specific stimulus will significantly facilitate future development of diagnostics and treatments. [ABSTRACT FROM AUTHOR]

Pharyngeal gonorrhoea is a common sexually transmitted infection among 'men having sex with other men' (MSM). Neisseria gonorrhoeae (NG) pharyngeal infections are usually characterized by the absence of symptoms, acting as an important reservoir for their further spread. To the best of our knowledge, no information about the composition of the pharyngeal microbiome during an ongoing NG infection is currently available. Therefore, in this study, we characterized the pharyngeal bacterial community profiles associated with NG infection in a well-selected cohort of HIV-negative MSM reporting unsafe oral intercourse. A total of 70 pharyngeal swabs were considered, comparing non-infected subjects (n = 45) versus patients with pharyngeal gonorrhoea (n = 25) whose microbiota composition was analyzed from pharyngeal swabs through sequencing of hypervariable V3-V4 regions of the 16S rRNA gene. The pharyngeal microbiome of all subjects was dominated by Prevotellaceae, Veillonellaceae and Streptococcaceae families. Patients with pharyngeal gonorrhoea harboured a pharyngeal microbiome quite similar to negative subjects. Nevertheless, when looking to less-represented bacterial species (relative abundance approximately 1% or less), an imbalance between aerobe and anaerobe microorganisms was observed in NG-infected patients. In particular, the pharyngeal microbiome of NG-positive individuals was richer in several anaerobes (e.g. Treponema, Parvimonas, Peptococcus, Catonella, Filifactor) and poorer in various aerobe genera (i.e. Pseudomonas, Escherichia), compared to non-infected controls. No significant differences were noticed in the distribution of commensal Neisseria species of the oropharynx between NG-positive and negative subjects. Metabolic variations induced by changes in the microbiome abundance were assessed by a functional prediction of the bacterial metabolic pathways: a more abundant involvement of D-glutamine and D-glutamate metabolism, carbohydrate metabolism, as well as a greater activation of the energy metabolism was observed in patients with pharyngeal gonorrhoea compared to non-infected individuals. Information about the bacterial composition of the pharyngeal microbiome in case of gonorrhoea could shed light on the pathogenesis of the infection and open new perspectives for the prevention and control of this condition. [ABSTRACT FROM AUTHOR]

Diffusing fluid at a deep-sea hydrothermal vent creates rapid, acute physico-chemical gradients that correlate strongly with the distribution of the vent fauna. Two alvinocaridid shrimps, Alvinocaris longirostris and Shinkaicaris leurokolos occupy distinct microhabitats around these vents and exhibit different thermal preferences. S. leurokolos inhabits the central area closer to the active chimney, while A. longirostris inhabits the peripheral area. In this study, we screened candidate genes that might be involved in niche separation and microhabitat adaptation through comparative transcriptomics. The results showed that among the top 20% of overexpressed genes, gene families related to protein synthesis and structural components were much more abundant in S. leurokolos compared to A. longirostris. Moreover, 15 out of 25 genes involved in cellular carbohydrate metabolism were related to trehalose biosynthesis, versus 1 out of 5 in A. longirostris. Trehalose, a non-reducing disaccharide, is a multifunctional molecule and has been proven to act as a protectant responsible for thermotolerance in Saccharomyces cerevisiae. Putative positively selected genes involved in chitin metabolism and the immune system (lectin, serine protease and antimicrobial peptide) were enriched in S. leurokolos. In particular, one collagen and two serine proteases were found to have experienced strong positive selection. In addition, sulfotransferase-related genes were both overexpressed and positively selected in S. leurokolos. Finally, genes related to structural proteins, immune proteins and protectants were overexpressed or positively selected. These characteristics could represent adaptations of S. leurokolos to its microhabitat, which need to be confirmed by more evidence, such as data from large samples and different development stages of these alvinocaridid shrimps. [ABSTRACT FROM AUTHOR]

Glucose is an important nutrient that dictates the development, fertility and lifespan of all organisms. In humans, a deficit in its homeostatic control might lead to hyperglucemia and the development of obesity and type 2 diabetes, which show a decreased ability to respond to and metabolize glucose. Previously, we have reported that high-glucose diets (HGD) induce alterations in triglyceride content, body size, progeny, and the mRNA accumulation of key regulators of carbohydrate and lipid metabolism, and longevity in Caenorhabditis elegans (PLoS ONE 13(7): e0199888). Herein, we show that increasing amounts of glucose in the diet induce the swelling of both mitochondria in germ and muscle cells. Additionally, HGD alter the enzymatic activities of the different respiratory complexes in an intricate pattern. Finally, we observed a downregulation of ceramide synthases (hyl-1 and hyl-2) and antioxidant genes (gcs-1 and gst-4), while mitophagy genes (pink-1 and dct-1) were upregulated, probably as part of a mitohormetic mechanism in response to glucose toxicity. [ABSTRACT FROM AUTHOR]

Background: Pancreatic islets are heavily vascularized in vivo yet lose this vasculature after only a few days in culture. Determining how to maintain islet vascularity in culture could lead to better outcomes in transplanting this tissue for the treatment of type 1 diabetes as well as provide insight into the complex communication between beta-cells and endothelial cells (ECs). We previously showed that islet ECs die in part due to limited diffusion of serum albumin into the tissue. We now aim to determine the impact of hypoxia on islet vascularization. Methods: We induced hypoxia in cultured mouse islets using the hypoxia mimetic cobalt chloride (100 μM CoCl2). We measured the impact on islet metabolism (two-photon NAD(P)H and Rh123 imaging) and function (insulin secretion and survival). We also measured the impact on hypoxia related transcripts (HIF-1α, VEGF-A, PDK-1, LDHA, COX4) and confirmed increased VEGF-A expression and secretion. Finally, we measured the vascularization of islets in static and flowing culture using PECAM-1 immunofluorescence. Results: CoCl2 did not induce significant changes in beta cell metabolism (NAD(P)H and Rh123), insulin secretion, and survival. Consistent with hypoxia induction, CoCl2 stimulated HIF-1α, PDK-1, and LDHA transcripts and also stimulated VEGF expression and secretion. We observed a modest switch to the less oxidative isoform of COX4 (isoform 1 to 2) and this switch was noted in the glucose-stimulated cytoplasmic NAD(P)H responses. EC morphology and survival were greater in CoCl2 treated islets compared to exogenous VEGF-A in both static (dish) and microfluidic flow culture. Conclusions: Hypoxia induction using CoCl2 had a positive effect on islet EC morphology and survival with limited impact on beta-cell metabolism, function, and survival. The EC response appears to be due to endogenous production and secretion of angiogenic factors (e.g. VEGF-A), and mechanistically independent from survival induced by serum albumin. [ABSTRACT FROM AUTHOR]

Aims: Alcohol use is associated with both positive and negative effects on individual cardiovascular risk factors, depending upon which risk factor is assessed. The present analysis uses a summative multisystem index of biologic risk, known as allostatic load (AL), to evaluate whether the overall balance of alcohol-associated positive and negative cardiovascular risk factors may be favorable or unfavorable. Methods: This analysis included 1255 adults from the Midlife in the United States (MIDUS) biomarker substudy. Participants, average age 54.5 (±11) years, were divided into 6 alcohol-use categories based on self-reported drinking habits. Current non-drinkers were classified as lifelong abstainers and former light drinkers, former moderate drinkers, or former heavy drinkers. Current alcohol users were classified as light, moderate, or heavy drinkers. A total AL score was calculated using 24 biomarkers grouped into 7 physiologic systems including cardiovascular, inflammation, glucose metabolism, lipid metabolism, sympathetic and parasympathetic nervous systems, and the hypothalamic-pituitary-adrenal axis. Mixed-effects regression models were fit to determine the relationship between alcohol use categories and AL with controls for covariates that may influence the relationship between alcohol use and AL. Results: 468 (37.6%) individuals were current non-drinkers while 776 (62.4%) were current drinkers. In adjusted mixed-effects regression models, all 3 groups of current drinkers had significantly lower average AL scores than the lifelong abstainer/former light drinker group (light: -0.23, 95% CI -0.40, -0.07, p < 0.01; moderate: -0.20, 95% CI -0.38, -0.02, p < 0.05; heavy: -0.30, 95% CI -0.57, -0.04, p < 0.05), while the average AL scores of former moderate and former heavy drinkers did not differ from the lifelong abstainer/former light drinker group. Conclusions: Current alcohol use is associated cross-sectionally with a favorable multisystem physiologic score known to be associated with better long-term health outcomes, providing evidence in support of long-term health benefits related to alcohol consumption. [ABSTRACT FROM AUTHOR]

A fatty acid analogue, 2-(tridec-12-yn-1-ylthio)acetic acid (1-triple TTA), was previously shown to have hypolipidemic effects in rats by targeting mitochondrial activity predominantly in liver. This study aimed to determine if 1-triple TTA could influence carbohydrate metabolism. Male Wistar rats were treated for three weeks with oral supplementation of 100 mg/kg body weight 1-triple TTA. Blood glucose and insulin levels, and liver carbohydrate metabolism gene expression and enzyme activities were determined. In addition, human myotubes and Huh7 liver cells were treated with 1-triple TTA, and glucose and fatty acid oxidation were determined. The level of plasma insulin was significantly reduced in 1-triple TTA-treated rats, resulting in a 32% reduction in the insulin/glucose ratio. The hepatic glucose and glycogen levels were lowered by 22% and 49%, respectively, compared to control. This was accompanied by lower hepatic gene expression of phosphenolpyruvate carboxykinase, the rate-limiting enzyme in gluconeogenesis, and Hnf4A, a regulator of gluconeogenesis. Gene expression of pyruvate kinase, catalysing the final step of glycolysis, was also reduced by 1-triple TTA. In addition, pyruvate dehydrogenase activity was reduced, accompanied by 10-15-fold increased gene expression of its regulator pyruvate dehydrogenase kinase 4 compared to control, suggesting reduced entry of pyruvate into the TCA cycle. Indeed, the NADPH-generating enzyme malic enzyme 1 (ME1) catalysing production of pyruvate from malate, was increased 13-fold at the gene expression level. Despite the decreased glycogen level, genes involved in glycogen synthesis were not affected in livers of 1-triple TTA treated rats. In contrast, the pentose phosphate pathway seemed to be increased as the hepatic gene expression of glucose-6-phosphate dehydrogenase (G6PD) was higher in 1-triple TTA treated rats compared to controls. In human Huh7 liver cells, but not in myotubes, 1-triple-TTA reduced glucose oxidation and induced fatty acid oxidation, in line with previous observations of increased hepatic mitochondrial palmitoyl-CoA oxidation in rats. Importantly, this work recognizes the liver as an important organ in glucose homeostasis. The mitochondrially targeted fatty acid analogue 1-triple TTA seemed to lower hepatic glucose and glycogen levels by inhibition of gluconeogenesis. This was also linked to a reduction in glucose oxidation accompanied by reduced PHD activity and stimulation of ME1 and G6PD, favouring a shift from glucose- to fatty acid oxidation. The reduced plasma insulin/glucose ratio indicate that 1-triple TTA may improve glucose tolerance in rats. [ABSTRACT FROM AUTHOR]

Breast cancers that express epidermal growth factor (EGF) receptors (EGFRs) are associated with poor prognosis. Our group recently showed in breast cancer patients that EGFR expression is strongly correlated with high tumor uptake of the glucose analogue, 18F-fluorodeoxyglucose (FDG). Here, we explored the cellular mechanism and signaling pathways that can explain the relation between EGFR and breast cancer cell glucose metabolism. FDG uptake, lactate production and hexokinase (HK) activity were measured, and proliferation assays and western blots were performed. EGF stimulated an increase of FDG uptake in EGFR-positive T47D and MDA-MB-468 cells, but not in MCF-7 cells. In T47D cells, the effect was dose-dependent and was accompanied by increased lactate production, indicating a shift toward glycolytic flux. This metabolic response occurred through enhanced HK activity and upregulated glucose transporter 1 (GLUT1) expression. EGFR stimulation also increased T47D cell proliferation. Blocking EGFR activation with BIBX1382 or gefitinib completely abolished both FDG uptake and proliferation effects. EGFR stimulation induced MAP kinase (MAPK) and PI3 kinase (PI3K) activation. Increased cell proliferation by EGFR stimulation was completely abolished by MAPK inhibition with PD98059 or by PI3K inhibition with LY294002. Increased FDG uptake was also completely abrogated by PI3K inhibition but was uninfluenced by MAPK inhibition. These findings suggest that the association between breast tumor EGFR expression and high FDG uptake might be contributed by stimulation of the PI3K pathway downstream of EGFR activation. This was in contrast to EGFR-mediated cell proliferation that required MAPK as well as PI3K signaling. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate which clinical and metabolic tests offer optimal accuracy and acceptability to help diagnose diabetes among a large sample of people with serious mental illness in receipt of antipsychotic medication. Methods: A prospective observational study design of biochemical and clinical factors was used. Biochemical measures were fasting glucose, insulin and lipids, oral glucose tolerance testing (OGTT), hemoglobin A1c, and insulin resistance assessed with the homeostatic model (HOMA-IR) were determined in a consecutive cohort of 798 adult psychiatric inpatients receiving antipsychotics. Clinical variables were gender, age, global assessment of functioning (GAF), mental health clinicians’ global impression (CGI), duration of severe mental illness, height, weight, BMI and waist/hip ratio. In addition, we calculated the risk using combined clinical predictors using the Leicester Practice Risk Score (LPRS) and the Topics Diabetes Risk Score (TDRS). Diabetes was defined by older criteria (impaired fasting glucose (IFG) or OGTT) as well as2010 criteria (IFG or OGTT or Glycated haemoglobin (HBA1c)) at conventional cut-offs. Results: Using the older criteria, 7.8% had diabetes (men: 6.3%; women: 10.3%). Using the new criteria, 10.2% had diabetes (men: 8.2%, women: 13.2%), representing a 30.7% increase (p = 0.02) in the prevalence of diabetes. Regarding biochemical predictors, conventional OGTT, IFG, and HbA1c thresholds used to identify newly defined diabetes missed 25%, 50% and 75% of people with diabetes, respectively. The conventional HBA1c cut-point of ≥6.5% (48 mmol/mol) missed 7 of 10 newly defined cases of diabetes while a cut-point of ≥5.7% improved sensitivity from 44.4% to up to 85%. Specific algorithm approaches offered reasonable accuracy. Unfortunately no single clinical factor was able to accurately rule-in a diagnosis of diabetes. Three clinical factors were able to rule-out diabetes with good accuracy namely: BMI, waist/hip ratio and height. A BMI < 30 had a 92% negative predictive value in ruling-out diabetes. Of those not diabetic, 20% had a BMI ≥ 30. However, for complete diagnosis a specific biochemical protocol is still necessary. Conclusions: Patients with SMI maintained on antipsychotic medication cannot be reliably screened for diabetes using clinical variables alone. Accurate assessment requires a two-step algorithm consisting of HBA1c ≥5.7% followed by both FG and OGTT which does not require all patients to have OGTT and FG. [ABSTRACT FROM AUTHOR]

Multi-marker tests hold promise for identifying symptomatic women at risk of imminent preterm delivery (PTD, <37 week’s gestation). This study sought to determine the relationship of inflammatory mediators and metabolites in cervicovaginal fluid (CVF) with spontaneous PTD (sPTD) and delivery within 14 days of presentation with symptoms of preterm labour (PTL). CVF samples from 94 (preterm = 19, term = 75) singleton women with symptoms of PTL studied between 19+0–36+6 weeks’ gestation were analysed for cytokines/chemokines by multiplexed bead-based immunoassay, while metabolites were quantified by enzyme-based spectrophotometry in a subset of 61 women (preterm = 16, term = 45). Prevalence of targeted vaginal bacterial species was determined for 70 women (preterm = 14, term = 66) by PCR. Overall, 10 women delivered within 14 days of sampling. Predictive capacities of individual biomarkers and cytokine-metabolite combinations for sPTD and delivery within 14 days of sampling were analysed by logistic regression models and area under the receiver operating characteristic curve. Fusobacterium sp., Mubiluncus mulieris and Mycoplasma hominis were detected in more preterm-delivered than term women (P<0.0001), while, M. curtisii was found in more term-delivered than preterm women (P<0.0001). RANTES (0.91, 0.65–1.0), IL-6 (0.79, 0.67–0.88), and Acetate/Glutamate ratio (0.74, 0.61–0.85) were associated with delivery within 14 days of sampling (AUC, 95% CI). There were significant correlations between cytokines and metabolites, and several cytokine-metabolite combinations were associated with sPTD or delivery within 14 days of sampling (e.g. L/D-lactate ratio+Acetate/Glutamate ratio+IL-6: 0.84, 0.67–0.94). Symptomatic women destined to deliver preterm and within 14 days of sampling express significantly higher pro-inflammatory mediators at mid to late gestation. In this cohort, IL-6, Acetate/Glutamate ratio and RANTES were associated with delivery within 14 days of sampling, consistent with their roles in modulating infection-inflammation-associated preterm labour in women presenting with symptoms of preterm birth. Replication of these observations in larger cohorts of women could show potential clinical utility. [ABSTRACT FROM AUTHOR]

Background: Obesity and metabolic syndrome (MetS) are associated with high risk of cardiac dysfunction and heart failure. We assessed the effect of obesity and metabolic health status on left ventricular (LV) structure and function in subjects without overt heart disease. Methods: In 789 subjects (58.8±13.0 years, 50.7% males) without overt heart disease, LV morphology and function were compared among 6 groups stratified by body mass index (BMI) (normal weight, overweight and obese) and metabolic health status (meeting ≤1 criterion of MetS excluding waist circumference defined as metabolically healthy; otherwise, metabolically unhealthy). Results: LV ejection fraction (LVEF) was not different among the 6 groups (P>0.05). However, high BMI and poor metabolic health were associated with poorer global longitudinal strain (GLS), higher LV mass index (LVMI) and higher E/e′ (P<0.001). Poor metabolic health status was associated with greater adverse changes in LV structure and function than obesity, and among MetS components, high systolic blood pressure (SBP) showed the greatest impact. Higher SBP, BMI and triglycerides were independently associated with worse GLS, and higher SBP was also associated with worse LVMI and E/e´. GLS, LVMI and E/e´ worsened in proportion to the number of MetS criteria or continuous MetS scores. Adverse myocardial changes associated with obesity were significant in the metabolically healthy group, but not in the metabolically unhealthy group. Conclusions: Obesity and poor metabolic health status were associated with subclinical decrement in LV systolic and diastolic function, and higher LV mass, but not with LVEF, in subjects without overt heart disease. [ABSTRACT FROM AUTHOR]

Our previous single-cell based gene expression analysis pointed out significant variations of LDHA level during erythroid differentiation. Deeper investigations highlighted that a metabolic switch occurred along differentiation of erythroid cells. More precisely we showed that self-renewing progenitors relied mostly upon lactate-productive glycolysis, and required LDHA activity, whereas differentiating cells, mainly involved mitochondrial oxidative phosphorylation (OXPHOS). These metabolic rearrangements were coming along with a particular temporary event, occurring within the first 24h of erythroid differentiation. The activity of glycolytic metabolism and OXPHOS rose jointly with oxgene consumption dedicated to ATP production at 12-24h of the differentiation process before lactate-productive glycolysis sharply fall down and energy needs decline. Finally, we demonstrated that the metabolic switch mediated through LDHA drop and OXPHOS upkeep might be necessary for erythroid differentiation. We also discuss the possibility that metabolism, gene expression and epigenetics could act together in a circular manner as a driving force for differentiation. [ABSTRACT FROM AUTHOR]

The apolipoprotein ε4 allele (APOE4) is the strongest genetic risk factor for Alzheimer’s disease (AD). APOE4 carriers develop systemic metabolic dysfunction decades before showing AD symptoms. Accumulating evidence shows that the metabolic dysfunction accelerates AD development, including exacerbated amyloid-beta (Aβ) retention, neuroinflammation and cognitive decline. Therefore, preserving metabolic function early on may be critical to reducing the risk for AD. Here, we show that inulin increases beneficial microbiota and decreases harmful microbiota in the feces of young, asymptomatic APOE4 transgenic (E4FAD) mice and enhances metabolism in the cecum, periphery and brain, as demonstrated by increases in the levels of SCFAs, tryptophan-derived metabolites, bile acids, glycolytic metabolites and scyllo-inositol. We show that inulin also reduces inflammatory gene expression in the hippocampus. This knowledge can be utilized to design early precision nutrition intervention strategies that use a prebiotic diet to enhance systemic metabolism and may be useful for reducing AD risk in asymptomatic APOE4 carriers. [ABSTRACT FROM AUTHOR]