Search Results (139)

Background/Objectives: Nitrogen (N) is an essential macronutrient that strongly influences maize growth and metabolism. While many studies have focused on nitrogen responses during later developmental stages, early-stage physiological and metabolic responses remain less explored. This study investigated the effect of different nitrogen-deficient levels on maize seedling growth and primary metabolite profiles. Methods: Seedlings were treated with N-modified nutrient solution, which contained 0% to 120% of the standard nitrogen level (8.5 mM). Results: Nitrogen starvation (N0) significantly reduced plant height (by 11–14%), shoot fresh weight (over 30%) compared to the optimal N supply (N100). Total leaf nitrogen content under N0–N20 was less than half of that in N100, whereas moderate N deficiency resulted in moderate reductions in growth and nitrogen content. Metabolite analysis revealed that N deficiency induced the accumulation of soluble sugars and organic acids (up to threefold), while sufficient N promoted the synthesis of amino acids related to nitrogen assimilation and protein biosynthesis. Statistical analyses (PCA and ANOVA) showed that both genotypes (MB and TYC) and tissue type (upper vs. lower leaves) influenced the metabolic response to nitrogen, with MB displaying more consistent shifts and TYC exhibiting greater variability under moderate stress. Conclusions: These findings highlight the sensitivity of maize seedlings to early nitrogen deficiency, with severity influenced by nitrogen level, tissue-specific position, and genotype; thus underscore the close coordination between physiological growth and primary metabolic pathways in response to nitrogen availability. These findings expand current knowledge of nitrogen response mechanisms and offer practical insights for improving nitrogen use efficiency in maize cultivation. Full article

The detection of elevated long-chain acylcarnitine levels, particularly C14:1 and the C14:1/C2 ratio, during neonatal screening may indicate very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), although similar findings can result from postnatal starvation. We investigated the relationship between false-positive results, postnatal weight loss, and subsequent growth. Additionally, we explored potential diagnostic markers of postnatal starvation. The following neonates from Oita Prefecture (April 2014–March 2024) were included in this study: patients identified as false-positive for VLCADD (n = 19), patients with VLCADD (n = 3), and children negative in mass screening who completed their 3-year-old health check-up (n = 30). The false-positive group exhibited significant weight loss at blood sampling for neonatal screening. An acylcarnitine analysis showed significant increases in various short- to long-chain fatty acids in the false-positive group, likely owing to enhanced fatty acid catabolism via β-oxidation. Elevation of a broad range of fatty acids and reduced amino acid levels seemed to be associated with significant weight loss at blood sampling. Full article

For marine bacteria, the phycosphere is attractive as a major source of labile nutrients, but it also presents challenges due to the accumulation of stressors, such as reactive oxygen species (ROS) from algal metabolisms. Therefore, successful colonization of bacteria in the phycosphere requires an efficient mechanism to fight against oxidative stress, which is still a missing piece in studying bacteria–algae interactions. Here, we demonstrate that a common metabolite, indole acetic acid (IAA), enables the Roseobacter clade Sulfitobacter mediterraneus SC1-11, an IAA-producer, to resist hydrogen peroxide (H₂O₂) stress and that IAA biosynthesis can be activated by low concentrations of H₂O₂. Proteomics and metabolomics analyses revealed that bacteria consume high amino acid levels when exposed to H₂O₂ stress, while exogenous supplementation with IAA effectively protects bacteria from ROS damage and alleviates amino acid starvation by upregulating several proteins responsible for replication, recombination, and repair, as well as two proteins involved in amino acid transport and metabolism. Furthermore, the supplementation of some amino acids, such as arginine, also showed a significant protective effect on bacteria under H₂O₂ stress. This study highlights an unprecedented role of IAA in regulating amino acid metabolisms for resisting oxidative stress, which may be a specific strategy for adapting to the phycosphere. Full article

Hemerocallis citrina is an herbaceous perennial plant used in Asian cuisine and Traditional Chinese Medicine. Here, we tested the therapeutic potential of extracts (HCE30%, HCE50%, and HCN) in vivo, using models of two human genetic neurodegenerative diseases—Machado–Joseph Disease/Spinocerebellar Ataxia type 3 (MJD/SCA3) and Frontotemporal Dementia with Parkinsonism associated to chromosome 17 (FTDP-17). Chronic treatment with HCE30% extract ameliorated the motor deficits typically observed in these models. Interestingly, we found that the effect on the motor phenotype of the MJD/SCA3 model was dependent on serotonergic signaling and on the action of the HLH-30/TFEB transcription factor, known to regulate the cellular response to amino acid starvation, the autophagy and mitophagy pathways, lysosome localization and biogenesis, exocytosis, and mitochondrial biogenesis. Altogether, our findings reinforce the idea that phytochemicals act through the modulation of serotonergic neurotransmission and introduce a novel layer to the HLH-30/TFEB regulatory network. Thus, it also strengthens the use of these pathways as therapeutic targets for protein-related neurodegenerative disorders and confirms the utility of medicinal plants as a source of innovation in the quest for new therapeutic agents. Full article

Phosphorus is a key nutrient for all organisms. The study of phosphate metabolism and its regulation is important for understanding the evolutionary processes of regulatory systems in eukaryotic cells. The methylotrophic yeast Komagataella phaffii is an efficient producer organism, and it is actively used in biotechnological production. The high practical importance of K. phaffii has stimulated active research to find new tools to work with this yeast and optimize its cultivation conditions. In this work, we observed the effect of phosphate starvation on gene expression in K. phaffii at the transcriptome level. Phosphate starvation had a significant effect on general cell metabolism. K. phaffii cells demonstrated a response to this macronutrient deficiency through an altered gene expression of carbon and amino acid metabolism. We observed the activation of phosphate and polyphosphate metabolism gene expression. In this case, there was a suppression of ribosome biogenesis genes and genes involved in fatty acid beta-oxidation and translation processes. Full article

The effects of starvation and refeeding on the gut condition of juvenile largemouth bass (Micropterus salmoides) remain unclear. Therefore, our research aimed to explore these effects. Amylase and lipase activities were remarkably decreased in the starvation (ST) group, yet prominently increased in the refeeding (RE) group (p < 0.05). In addition to the malondialdehyde (MDA) level, catalase (CAT) and superoxide dismutase (SOD) activities were significantly upregulated in the ST group (p < 0.05) in marked contrast to those in the controls; however, the RE group showed no substantial variations in CAT and SOD activities or the MDA level (p > 0.05). During starvation, the expression of Nrf2-Keap1 pathway-associated genes was significantly upregulated (p < 0.05). The comparative levels of TNF-α, IL-1β, and IL-15 were highly increased, with the levels of TGF-β1 and IL-10 apparently downregulated in the ST group; in contrast, these levels were restored to their original values in the RE group (p < 0.05). In contrast to the controls, the ST group showed significantly lower height and width of the villi, muscle thickness, and crypt depth and a higher goblet cell number; however, these values were recovered to some extent in the RE group (p < 0.05). The dominant bacterial phyla in the intestines of both groups were Proteobacteria, Firmicutes, Bacteroidetes, Acidobacteria, and Actinobacteria, with marked inter-group differences in the genera Serratia and Lactobacillus. Metabolomics analysis showed that amino acid metabolism is disrupted during starvation and is restored after refeeding. In summary, this study expands our comprehension of the interaction between oxidative stress and antioxidant defenses among juvenile largemouth bass subjected to starvation and refeeding. Full article

Perlucin is a shell matrix protein that plays a significant role in regulating shell biomineralization. This study aimed to isolate and characterize the perlucin gene and analyze its expression to explore its role in shell formation, regeneration, and responses to thermal stress and starvation in Pacific abalone. The isolated full-length cDNA sequence of Hdh-Perlucin is 1002 bp long, encoding a 163-amino-acid polypeptide with a signal peptide. The mature peptide of Hdh-Perlucin contains a C-type lectin domain with signature motif and six conserved cysteine residues. Gene Ontology analysis suggests that Hdh-Perlucin exhibits carbohydrate-binding activity. Significantly higher expression of Hdh-Perlucin was observed during the juvenile, veliger, and trochophore stages, compared with cell division stage during early development. Upregulated expression was recorded from slow to rapid growth phases and during shell biomineralization, while downregulated expression was noted during starvation. Under thermal stress, expression peaked at 30 °C and 25 °C for 6 and 12 h, respectively, while consistently higher levels were observed at 15 °C throughout the experiment. This study provides the first comprehensive structural and expression analysis of Hdh-Perlucin, highlighting its roles in metamorphosis, shell formation and regeneration, and responses to heat stress and starvation in abalone. Full article

Sulfur is a critical element for plant growth and development, serving as a component of amino acids (cysteine and methionine), iron–sulfur clusters, proteins, glutathione, coenzymes, and auxin precursors. Deficiency or low concentrations of sulfur in the soil can lead to significant growth retardation in plants. The objective of our study was to examine the effects of sulfur (S) deficiency and excess on morphological symptoms, sulfur and nitrogen (N) metabolism, as well as antioxidant activity in soybean. We found that S starvation decreased the fine root length, biomass, and activity, and the chlorophyll content was reduced, while excess sulfur promotes lateral root growth. In contrast to sulfur excess, sulfur deficiency inhibits N and S metabolism levels in both subsurface and above-ground parts, and induced the expression of some sulfur transporters (SULTRs). In this study, we created soybean hairy root lines overexpressing the SULTR gene (GmSULTR2;1a) to observe metabolic changes following sulfur deficiency treatment. The results showed that GmSULTR2;1a saved the sulfur-deficient phenotype, and the antioxidant enzyme activity was much higher than that of the wildtype in the absence of sulfur. Our study revealed the important role of sulfur element in soybean growth and development and the regulation of sulfur deficiency by GmSULTR2;1a. Full article

Nitrogen serves as a pivotal nutrient for the proliferation, maturation, and pathogenicity of fungi. Despite its importance, nitrogen starvation is a common challenge encountered during fungal development and host invasion. A key regulatory transcription factor, known as general control non-derepressible 4 (GCN4), has been characterized in various fungal groups, including model fungal, pathogens, and basidiomycetes. This factor is triggered by nitrogen limitation and subsequently stimulates the expression of a multitude of genes involved in amino acid synthesis, thereby countering the effects of nitrogen deficiency. This paper provides a comprehensive review on the activation mechanisms, the structural characteristics and stability of GCN4, and how GCN4 activates its downstream target genes to regulate the physiological processes of fungi. This study lays the theoretical groundwork for future research endeavors that seek to enhance nitrogen utilization, preserve the delicate balance of carbon–nitrogen metabolism, and stimulate growth, development, and secondary metabolism in fungi, especially under nitrogen-limited conditions. Full article

Lipid nanoparticles (LNPs), widely used in disease diagnosis and drug delivery, face the challenge of being surrounded by biological macromolecules such as proteins upon entering the human body. These molecules compete for binding sites on the nanoparticle surfaces, forming a protein corona. The impact of different types of protein coronas on LNP delivery remains unclear. In this study, we employed a newly developed, highly sensitive LNP labeling platform and analyzed the endocytosis of HeLa cells under different nutritional conditions using proteomics to address this critical issue. Our research found that under conditions of complete medium and amino acid starvation, most DNA-FITC vesicles in HeLa cells were located in the perinuclear region 4 h after transfection. In contrast, under serum starvation conditions, only a small portion of DNA-FITC vesicles were in the perinuclear region. On the other hand, through proteomics, we discovered that cells that were enriched in amino acids and complete medium contained more proteins, whereas those under serum starvation had relatively fewer enriched proteins. Through KEGG pathway enrichment analysis, we identified the phagosome and endocytosis pathways as particularly important. Lastly, differential analysis of proteins in these pathways revealed that proteins such as F-actin, Coronin, vATPase, TUBA, TUBB, MHCII, and TSP may have significant impacts on cellular endocytosis. Our research findings indicate that it is necessary to regulate cellular endocytosis based on different protein coronas to achieve optimal cytoplasmic release. Full article

Alanine and glutamine are the principal glucogenic amino acids. Most originate from muscles, where branched-chain amino acids (valine, leucine, and isoleucine) are nitrogen donors and, under exceptional circumstances, a source of carbons for glutamate synthesis. Glutamate is a nitrogen source for alanine synthesis from pyruvate and a substrate for glutamine synthesis by glutamine synthetase. The following differences between alanine and glutamine, which can play a role in their use in gluconeogenesis, are shown: (i) glutamine appearance in circulation is higher than that of alanine; (ii) the conversion to oxaloacetate, the starting substance for glucose synthesis, is an ATP-consuming reaction for alanine, which is energetically beneficial for glutamine; (iii) most alanine carbons, but not glutamine carbons, originate from glucose; and (iv) glutamine acts a substrate for gluconeogenesis in the liver, kidneys, and intestine, whereas alanine does so only in the liver. Alanine plays a significant role during early starvation, exposure to high-fat and high-protein diets, and diabetes. Glutamine plays a dominant role in gluconeogenesis in prolonged starvation, acidosis, liver cirrhosis, and severe illnesses like sepsis and acts as a substrate for alanine synthesis in the small intestine. Interactions among muscles and the liver, kidneys, and intestine ensuring optimal alanine and glutamine supply for gluconeogenesis are suggested. Full article

Food deprivation can occur for different reasons. Fasting (<24 h duration) occurs to meet religious or well-being goals. Starvation (>1-day duration) occurs when there is intentional (hunger strike or treatment of a medical condition) or unintentional (anorexia nervosa, drought, epidemic famine, war, or natural disaster) food deprivation. A scoping review was undertaken using the PubMed database to explore 1805 abstracts and review 88 eligible full-text articles to explore the adaptive relationships that emerge between cortisol, insulin, glucagon, and thyroid hormones on the metabolic pathways of macronutrients in humans during fasting and starvation. The collected data indicate that fasting and starvation prime the human body to increase cortisol levels and decrease the insulin/glucagon ratio and triiodothyronine (T₃) levels. During fasting, increased levels of cortisol and a decreased insulin/glucagon ratio enhance glycogenolysis and reduce the peripheral uptake of glucose and glycogenesis, whereas decreased T₃ levels potentially reduce glycogenolysis. During starvation, increased levels of cortisol and a decreased insulin/glucagon ratio enhance lipolysis, proteolysis, fatty acid and amino acid oxidation, ketogenesis, and ureagenesis, and decreased T₃ levels reduce thermogenesis. We present a potential crosstalk between T₃ and the above hormones, including between T₃ and leptin, to extend their adaptive roles in the metabolism of endogenous macronutrients during food deprivation. Full article

According to the latest World Health Organization (WHO) report, an estimated 10.6 million people were diagnosed with tuberculosis (TB) in 2022, and 1.30 million died. A major concern is the emergence of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains, fueled by the length of anti-TB treatment and HIV comorbidity. Innovative anti-TB agents acting with new modes of action are the only solution to counteract the spread of resistant infections. To escape starvation and survive inside macrophages, Mtb has evolved to become independent of the host by synthesizing its own amino acids. Therefore, targeting amino acid biosynthesis could subvert the ability of the mycobacterium to evade the host immune system, providing innovative avenues for drug discovery. The aim of this review is to give an overview of the most recent progress in the discovery of amino acid biosynthesis inhibitors. Among the hits discovered over the past five years, tryptophan (Trp) inhibitors stand out as the most advanced and have significantly contributed to demonstrating the feasibility of this approach for future TB drug discovery. Future efforts should be directed at prioritizing the chemical optimization of these hits to enrich the TB drug pipeline with high-quality leads. Full article

The ubiquitin–proteasome system (UPS) is an essential mechanism responsible for the selective degradation of substrate proteins via their conjugation with ubiquitin. Since cardiomyocytes have very limited self-renewal capacity, as they are prone to protein damage due to constant mechanical and metabolic stress, the UPS has a key role in cardiac physiology and pathophysiology. While altered proteasomal activity contributes to a variety of cardiac pathologies, such as heart failure and ischemia/reperfusion injury (IRI), the environmental cues affecting its activity are still unknown, and they are the focus of this work. Following a recent study by Ciechanover’s group showing that amino acid (AA) starvation in cultured cancer cell lines modulates proteasome intracellular localization and activity, we tested two hypotheses in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs, CMs): (i) AA starvation causes proteasome translocation in CMs, similarly to the observation in cultured cancer cell lines; (ii) manipulation of subcellular proteasomal compartmentalization is associated with electrophysiological abnormalities in the form of arrhythmias, mediated via altered intracellular Ca²⁺ handling. The major findings are: (i) starving CMs to AAs results in proteasome translocation from the nucleus to the cytoplasm, while supplementation with the aromatic amino acids tyrosine (Y), tryptophan (W) and phenylalanine (F) (YWF) inhibits the proteasome recruitment; (ii) AA-deficient treatments cause arrhythmias; (iii) the arrhythmias observed upon nuclear proteasome sequestration(-AA+YWF) are blocked by KB-R7943, an inhibitor of the reverse mode of the sodium–calcium exchanger NCX; (iv) the retrograde perfusion of isolated rat hearts with AA starvation media is associated with arrhythmias. Collectively, our novel findings describe a newly identified mechanism linking the UPS to arrhythmia generation in CMs and whole hearts. Full article

Growing evidence points to the presence of differentially culturable tubercle bacteria (DCTB) in clinical specimens from individuals with active tuberculosis (TB) disease. These bacteria are unable to grow on solid media but can resuscitate in liquid media. Given the epidemiological success of certain clinical genotype families of Mycobacterium tuberculosis, we hypothesize that different strains may have distinct mechanisms of adaptation and tolerance. We used an in vitro carbon starvation model to determine the propensity of strains from lineages 2 and 4 that included the Beijing and LAM families respectively, to generate DCTB. Beijing strains were associated with a greater propensity to produce DCTB compared to LAM strains. Furthermore, LAM strains required culture filtrate (CF) for resuscitation whilst starved Beijing strains were not dependent on CF. Moreover, Beijing strains showed improved resuscitation with cognate CF, suggesting the presence of unique growth stimulatory molecules in this family. Analysis of starved Beijing and LAM strains showed longer cells, which with resuscitation were restored to a shorter length. Cell wall staining with fluorescent D-amino acids identified strain-specific incorporation patterns, indicating that cell surface remodeling during resuscitation was distinct between clinical strains. Collectively, our data demonstrate that M. tuberculosis clinical strains from different genotype lineages have differential propensities to generate DCTB, which may have implications for TB treatment success. Full article