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Arginine–glycine–glycine motif proteins play a crucial role in determining mRNA fate. Suppressor of clathrin deficiency 6 (Scd6) is a conserved arginine–glycine–glycine motif containing ribonucleoprotein (RNP) condensate–resident, translation repressor, and decapping activator protein in Saccharomyces cerevisiae. Identifying protein factors that can modulate Scd6 function is critical to understanding the regulation of mRNA fate by Scd6. In this study, using an approach that combined mRNA tethering assay with flow cytometry, we screened 50 genes for their role in modulating the translation repression activity of Scd6. We identified 8 conserved modulators with human homologs. Of these, we further characterized in detail guanine nucleotide exchange factor Rho1 multicopy suppressor 2 (Rom2) and glycolytic enzyme triose phosphate dehydrogenase 3 (Tdh3), which, respectively, impede and promote translation repression activity of Scd6. Our study reveals that Rom2 negatively regulates the arginine methylation of Scd6 and antagonizes its localization to P-bodies. Tdh3 , on the other hand, promotes Scd6 interaction with Hmt1 , thereby promoting the arginine methylation of Scd6 and enhanced eIF4G1 interaction, which is known to promote its repression activity. Identifying these novel modulators provides exciting new insights into the role of a metabolic enzyme of the glycolytic pathway and guanine nucleotide exchange factor implicated in the cell wall integrity pathway in regulating Scd6 function and, thereby, cytoplasmic mRNA fate. [ABSTRACT FROM AUTHOR]

ABSTRACT: Chronic heat stress has detrimental effects on the growth performance of broilers, and the potential mechanism is under exploration. In this study, the protein carbonyl modification was introduced to glycolytic enzymes to evaluate its relationship with the growth performance of heat-stressed (HS) broilers. A total of 144 male 28-day-old broilers were assigned to 3 treatments: the normal control group (NC, raised at 22°C with free access to feed and water), the HS group (raised at 32°C with free access to feed and water), and the pair-fed group (PF, raised at 22°C with an amount of feed equal to that consumed by the HS group on a previous day). Results showed that heat stress decreased the average daily growth, increased the feed-to-gain ratio (F/G), decreased breast muscle rate, and increased abdominal fat rate compared with the NC and PF groups (P < 0.05). Higher cloacal temperature and serum creatine kinase activity were found in the HS group than those of the NC and PF groups (P < 0.05). Heat stress increased the contents of carbonyl, advanced glycation end-products, malonaldehyde, and the activities of catalase, glutathione peroxidase, and total antioxidant capacity compared with the NC and PF groups (P < 0.05). Heat stress increased the contents of glucose and lactate, declined the glycogen content, and lowered the relative protein expressions of pyruvate kinase muscle type, lactate dehydrogenase A type (LDHA), and citrate synthase compared to those of the NC group (P < 0.05). In contrast to the NC and PF groups, heat stress intensified the carbonylation levels of phosphoglucomutase 1, triosephosphate isomerase 1, β-enolase, and LDHA, which were positively correlated with the F/G (P < 0.05). These findings demonstrate that heat stress depresses growth performance on account of oxidative stress and glycolysis disorders. It further increases the carbonylation of glycolytic enzymes, which potentially correlates with the F/G by disturbing the mode of energy supply of broilers.

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Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzing the sixth step of glycolysis has been investigated for allosteric features that might be used as potential target for specific inhibition of Staphylococcus aureus (S.aureus). X-ray structure of bacterial enzyme for which a tunnel-like opening passing through the center previously proposed as an allosteric site has been subjected to six independent 500 ns long Molecular Dynamics simulations. Harmonic bond restraints were employed at key residues to underline the allosteric feature of this region. A noticeable reduction was observed in the mobility of NAD+ binding domains when restrictions were applied. Also, a substantial decrease in cross-correlations between distant Cα fluctuations was detected throughout the structure. Mutual information (MI) analysis revealed a similar decrease in the degree of correspondence in positional fluctuations in all directions everywhere in the receptor. MI between backbone and side-chain torsional variations changed its distribution profile and decreased considerably around the catalytic sites when restraints were employed. Principal component analysis clearly showed that the restrained state sampled a narrower range of conformations than apo state, especially in the first principal mode due to restriction in the conformational flexibility of NAD+ binding domain. Clustering the trajectory based on catalytic site residues displayed a smaller repertoire of conformations for restrained state compared to apo. Representative snapshots subjected to k-shortest pathway analysis revealed the impact of bond restraints on the allosteric communication which displayed distinct optimal and suboptimal pathways for two states, where observed frequencies of critical residues Gln51 and Val283 at the proposed site changed considerably. [Display omitted] • Allosteric potential of a proposed site in Sa GAPDH was explored via bond restraints. • Reduced mobility and change in communication pathways upon perturbation. • Significant decrease in mutual correspondence upon perturbation of the allosteric site. • Restricted conformational space when restraints were employed. • Perturbation of the predicted site changed the dynamic feature of the receptor. [ABSTRACT FROM AUTHOR]

Chronic heat stress has detrimental effects on the growth performance of broilers, and the potential mechanism is under exploration. In this study, the protein carbonyl modification was introduced to glycolytic enzymes to evaluate its relationship with the growth performance of heat-stressed (HS) broilers. A total of 144 male 28-day-old broilers were assigned to 3 treatments: the normal control group (NC , raised at 22°C with free access to feed and water), the HS group (raised at 32°C with free access to feed and water), and the pair-fed group (PF , raised at 22°C with an amount of feed equal to that consumed by the HS group on a previous day). Results showed that heat stress decreased the average daily growth, increased the feed-to-gain ratio (F/G), decreased breast muscle rate, and increased abdominal fat rate compared with the NC and PF groups (P < 0.05). Higher cloacal temperature and serum creatine kinase activity were found in the HS group than those of the NC and PF groups (P < 0.05). Heat stress increased the contents of carbonyl, advanced glycation end-products, malonaldehyde, and the activities of catalase, glutathione peroxidase, and total antioxidant capacity compared with the NC and PF groups (P < 0.05). Heat stress increased the contents of glucose and lactate, declined the glycogen content, and lowered the relative protein expressions of pyruvate kinase muscle type, lactate dehydrogenase A type (LDHA), and citrate synthase compared to those of the NC group (P < 0.05). In contrast to the NC and PF groups, heat stress intensified the carbonylation levels of phosphoglucomutase 1, triosephosphate isomerase 1, β-enolase, and LDHA, which were positively correlated with the F/G (P < 0.05). These findings demonstrate that heat stress depresses growth performance on account of oxidative stress and glycolysis disorders. It further increases the carbonylation of glycolytic enzymes, which potentially correlates with the F/G by disturbing the mode of energy supply of broilers. [ABSTRACT FROM AUTHOR]

Identification of cues originating from skeletal muscle that govern bone formation is essential for understanding the crosstalk between muscle and bone and for developing therapies for degenerative bone diseases. Here, we identified that skeletal muscle secreted multiple extracellular vesicles (Mu-EVs). These Mu-EVs traveled through the bloodstream to reach bone, where they were phagocytized by bone marrow mesenchymal stem/stromal cells (BMSCs). Mu-EVs promoted osteogenic differentiation of BMSCs and protected against disuse osteoporosis in mice. The quantity and bioactivity of Mu-EVs were tightly correlated with the function of skeletal muscle. Proteomic analysis revealed numerous proteins in Mu-EVs, some potentially regulating bone metabolism, especially glycolysis. Subsequent investigations indicated that Mu-EVs promoted the glycolysis of BMSCs by delivering lactate dehydrogenase A into these cells. In summary, these findings reveal that Mu-EVs play a vital role in BMSC metabolism regulation and bone formation stimulation, offering a promising approach for treating disuse osteoporosis. [Display omitted] • Skeletal muscle secretes Mu-EVs, which can travel via blood vessels to bone • Supplementation with Mu-EVs alleviates disuse osteoporosis after muscle atrophy • Mu-EVs promote osteogenic differentiation of BMSCs by enhancing glycolysis • Glycolic profiles transported by Mu-EVs function as non-canonical myokines In their study, Ma et al. demonstrate that skeletal muscle secretes abundant extracellular vesicles (Mu-EVs). These Mu-EVs promote glycolysis in BMSCs by delivering glycolic profiles to enhance bone formation. The quantity and bioactivity of Mu-EVs are found to correlate with skeletal muscle function. Importantly, supplementation with Mu-EVs is shown to alleviate disuse osteoporosis following muscle atrophy, suggesting a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

Treponema pallidum (T. pallidum), an obligate extracellular bacterium, is the causative agent of sexually transmitted bacterial diseases. In this study, the glycolytic enzyme enolase (Tp Eno) of T. pallidum were injected intramuscularly into C57BL/6 mice, resulting in higher levels of specific anti -Tp Eno antibodies and Tp Eno-specific splenocyte proliferation than those in the mice immunized with recombinant protein Tp Eno. Cytokine (IL-4, IL-6, IL-10, IFN-γ, and TNF-α) analysis of splenocytes showed that the Tp Eno could slightly trigger the Th1-biased immune response. Furthermore, immunization of mice with Tp Eno elicited a significant production of IFN-γ by CD4+ T-cells in the spleen. Subsequently, mice were inoculated intradermally (between the scapulae), intraperitoneally, intrarectally and via the corpora cavernosa with 2.5 × 106 organisms per site (1 × 107 total organisms). The bacterial organ burden detected in the blood, spleen, liver, testes or brain of immunized mice suggested that Tp Eno enhances protective immunity to inhibit T. pallidum colonization in distal tissues. Therefore, Tp Eno vaccination enhances Tp Eno-specific immunogenicity and provides protection against T. pallidum dissemination. • The C57BL/6 mice was attempted to evaluate immunogenicity and protection of Tp Eno against T. pallidum infection. • Tp Eno represents a promising new vaccine candidate that can stop the spread of T. pallidum. • Spirochetes are present in local sites of inoculation and disseminate to other tissues after 30 days post-inoculation in mice. [ABSTRACT FROM AUTHOR]

The non-starch polysaccharides (NSPs) of two jelly-fig cultivars were extracted to compare their effects on the delay of glucose release and in vitro starch digestion with those of commercial agar. The ability of jelly-fig NSPs to retard glucose diffusion was investigated. The NSPs of both jelly-fig cultivars regulated glucose absorption. The Hongjiu cultivar had the highest rate of α-amylase inhibition (63.17 ± 0.04%). Jelly-fig NSPs reduced amylose leaching by 19–32%. The Hongjiu cultivar showed stronger cholesterol absorption ability compared with other NSPs. In vitro starch digestion indicated that jelly-fig NSPs were beneficial to the retardation of glucose release. The viscosity of jelly-fig NSPs was similar to those in in vitro starch digestion, indicating that the effects of jelly-fig on glucose release were strongly associated with viscosity. Scanning electron microscopy (SEM) indicated that jelly-fig NSP-treated starch granules were densely packed with smooth surfaces. The Hongjiu cultivar starch granules (34.93 μm) were substantially smaller than those of the control group (115 μm), indicating that starch granule gelatinization and swelling were attenuated. The NSPs of Hongjiu cultivar demonstrate potential in retarding glucose release in combination with starch sources to lower their glycemic index. This provides a novel natural source for blood glucose-controlling component in food products. • The jelly fig NSPs possess the potential for retarding glucose release. • The jelly fig NSPs exhibited regulation of starch degradation. • The jelly fig NSPs showed stronger cholesterol absorption ability. • Viscosity was a major contributing factor in retarding glucose release. [ABSTRACT FROM AUTHOR]

As epigenetic regulators, long non‑coding RNAs (lncRNAs) are involved in various important regulatory processes and typically interact with RNA‑binding proteins (RBPs) to exert their core functional effects. An increasing number of studies have demonstrated that lncRNAs can regulate the occurrence and development of cancer through a variety of complex mechanisms and can also participate in tumor glucose metabolism by directly or indirectly regulating the Warburg effect. As one of the metabolic characteristics of tumor cells, the Warburg effect provides a large amount of energy and numerous intermediate products to meet the consumption demands of tumor metabolism, providing advantages for the occurrence and development of tumors. The present review article summarizes the regulatory effects of lncRNAs on the reprogramming of glucose metabolism after interacting with RBPs in tumors. The findings discussed herein may aid in the better understanding of the pathogenesis of malignancies, and may provide novel therapeutic targets, as well as new diagnostic and prognostic markers for human cancers.

Phosphoglucomutase 1 (PGM1) catalyzes the conversion between glucose-1-phosphate and glucose-6-phosphate in the glycolysis/glucogenesis pathway. PGM1s are typically cytosolic enzymes in organisms lacking chloroplasts. However, the protozoan Cryptosporidium parasites possess two tandemly duplicated PGM1 genes evolved by a gene duplication after their split from other apicomplexans. Moreover, the downstream PGM1 isoform contains an N-terminal signal peptide, predicting a non-cytosolic location. Here we expressed recombinant proteins of the two PGM1 isoforms from the zoonotic Cryptosporidium parvum, namely CpPGM1A and CpPGM1B, and confirmed their enzyme activity. Both isoforms followed Michaelis–Menten kinetics towards glucose-1-phosphate (Km = 0.17 and 0.13 mM, Vmax = 7.30 and 2.76 μmol/min/mg, respectively). CpPGM1A and CpPGM1B genes were expressed in oocysts, sporozoites and intracellular parasites at a similar pattern of expression, however CpPGM1A was expressed at much higher levels than CpPGM1B. Immunofluorescence assay showed that CpPGM1A was present in the cytosol of sporozoites, however this was enriched towards the plasma membranes in the intracellular parasites; whereas CpPGM1B was mainly present under sporozoite pellicle, although relocated to the parasitophorous vacuole membrane in the intracellular development. These observations indicated that CpPGM1A played a house-keeping function, while CpPGM1B played a different biological role that remains to be defined by future investigations. [ABSTRACT FROM AUTHOR]

Phosphoglucomutase 1 (PGM1) catalyzes the conversion between glucose-1-phosphate and glucose-6-phosphate in the glycolysis/glucogenesis pathway. PGM1s are typically cytosolic enzymes in organisms lacking chloroplasts. However, the protozoan Cryptosporidium parasites possess two tandemly duplicated PGM1 genes evolved by a gene duplication after their split from other apicomplexans. Moreover, the downstream PGM1 isoform contains an N-terminal signal peptide, predicting a non-cytosolic location. Here we expressed recombinant proteins of the two PGM1 isoforms from the zoonotic Cryptosporidium parvum , namely CpPGM1A and CpPGM1B, and confirmed their enzyme activity. Both isoforms followed Michaelis-Menten kinetics towards glucose-1-phosphate ( K m = 0.17 and 0.13 mM, V max = 7.30 and 2.76 μmol/min/mg, respectively). CpPGM1A and CpPGM1B genes were expressed in oocysts, sporozoites and intracellular parasites at a similar pattern of expression, however CpPGM1A was expressed at much higher levels than CpPGM1B . Immunofluorescence assay showed that CpPGM1A was present in the cytosol of sporozoites, however this was enriched towards the plasma membranes in the intracellular parasites; whereas CpPGM1B was mainly present under sporozoite pellicle, although relocated to the parasitophorous vacuole membrane in the intracellular development. These observations indicated that CpPGM1A played a house-keeping function, while CpPGM1B played a different biological role that remains to be defined by future investigations.