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17 pages, 2582 KiB  
Article
Transcriptional Regulatory Mechanisms of Blueberry Endophytes in Enhancing Aluminum (Al) Tolerance in Pumpkins
by Qiang Chen, Xinqi Guo, Hongbo Pang, Ying Zhang, Haiyan Lv and Chong Zhang
Horticulturae 2025, 11(8), 887; https://doi.org/10.3390/horticulturae11080887 (registering DOI) - 1 Aug 2025
Abstract
Aluminum (Al) stress is an important factor that inhibits crop growth in acidic soils and poses a threat to pumpkin (Cucurbita moschata) production. In this study, we investigated the effect of endophyte (endophyte) strain J01 of blueberry (Vaccinium uliginosum) [...] Read more.
Aluminum (Al) stress is an important factor that inhibits crop growth in acidic soils and poses a threat to pumpkin (Cucurbita moschata) production. In this study, we investigated the effect of endophyte (endophyte) strain J01 of blueberry (Vaccinium uliginosum) on the growth, development, and transcriptional regulatory mechanisms of pumpkin under aluminum stress. The results showed that the blueberry endophyte strain J01 significantly increased the root length of pumpkin under aluminum stress, promoted the growth of lateral roots, and increased root vigor; strain J01 reduced the content of MDA and the relative conductivity in the root system; strain J01 enhanced the activities of superoxide dismutase and catalase in the root system but inhibited ascorbate peroxidase activity. Transcriptome analysis further revealed that strain J01 significantly regulated the expression of key genes associated with aluminum tolerance, including the upregulation of transporter protein genes (aluminum-activated malate transporter and aquaporin), affecting the gene expression levels of genes encoding antioxidant enzymes (ascorbate peroxidase and glutathione S-transferase) and cell wall modification genes (xyloglucan endotransglucosylase/hydrolase and pectin methylesterase). This study provides a theoretical basis and practical guidance for using microbial resources to improve aluminum tolerance in cucurbit crops. Full article
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59 pages, 3467 KiB  
Review
Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer’s Disease? A Review of Recent Pertinent Observations from Molecular Biology
by Valerie Walker
Int. J. Mol. Sci. 2025, 26(15), 7328; https://doi.org/10.3390/ijms26157328 (registering DOI) - 29 Jul 2025
Viewed by 152
Abstract
Alzheimer’s dementia (AD) is a disease of the ageing brain. It begins in the hippocampal region with the epicentre in the entorhinal cortex, then gradually extends into adjacent brain areas involved in memory and cognition. The events which initiate the damage are unknown [...] Read more.
Alzheimer’s dementia (AD) is a disease of the ageing brain. It begins in the hippocampal region with the epicentre in the entorhinal cortex, then gradually extends into adjacent brain areas involved in memory and cognition. The events which initiate the damage are unknown and under intense investigation. Localization to the hippocampus can now be explained by anatomical features of the blood vessels supplying this region. Blood supply and hence oxygen delivery to the area are jeopardized by poor flow through narrowed arteries. In genomic and metabolomic studies, the respiratory chain and mitochondrial pathways which generate ATP were leading pathways associated with AD. This review explores the notion that ATP depletion resulting from hippocampal hypoperfusion has a prime role in initiating damage. Sections cover sensing of ATP depletion and protective responses, vulnerable processes with very heavy ATP consumption (the malate shuttle, the glutamate/glutamine/GABA (γ-aminobutyric acid) cycle, and axonal transport), phospholipid disturbances and peroxidation by reactive oxygen species, hippocampal perfusion and the effects of hypertension, chronic hypoxia, and arterial vasospasm, and an overview of recent relevant genomic studies. The findings demonstrate strong scientific arguments for the proposal with increasing supportive evidence. These lines of enquiry should be pursued. Full article
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21 pages, 2631 KiB  
Article
Characterization of a Periplasmic D-Malate:Cytochrome c Oxidoreductase from Ectopseudomonas oleovorans CECT 5344 and Its Role in Extracytoplasmic Respiration and Cyanide Detoxification
by Faustino Merchán, Ana G. Población, María Isabel Guijo, Mar Gómez-Ortega, Felipe Morales-Durán, Irene Alonso-Ríos, Rubén Sánchez-Clemente and Rafael Blasco
Int. J. Mol. Sci. 2025, 26(14), 6575; https://doi.org/10.3390/ijms26146575 - 8 Jul 2025
Viewed by 270
Abstract
A periplasmic D-malate:cytochrome c oxidoreductase (DMCO) was identified in Ectopseudomonas oleovorans CECT5344, utilizing 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-phenyl tetrazolium chloride (INT) as an artificial electron acceptor. The assay was adapted for a spectrophotometric or native polyacrylamide gel electrophoresis (PAGE) analysis. The DMCO-encoding gene (BN5_4044) was cloned and [...] Read more.
A periplasmic D-malate:cytochrome c oxidoreductase (DMCO) was identified in Ectopseudomonas oleovorans CECT5344, utilizing 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-phenyl tetrazolium chloride (INT) as an artificial electron acceptor. The assay was adapted for a spectrophotometric or native polyacrylamide gel electrophoresis (PAGE) analysis. The DMCO-encoding gene (BN5_4044) was cloned and expressed in Escherichia coli, enabling a partial purification and biochemical characterization. In addition to D-malate, the enzyme oxidizes D-2-hydroxyglutarate and, to a lesser extent, D-lactate, with cytochrome c also serving as an electron acceptor. DMCO requires Zn2+ for activity and exists as a dimer, as determined by gel filtration. The in vitro reconstitution of the electron transfer from D-malate to oxygen was achieved using spheroplasts, enriched periplasmic fractions, and cytochrome c. This extracytoplasmic respiration, unique among homologs of this protein, may eliminate the need for a dedicated inner membrane transporter, thereby avoiding potential upstream respiratory bottlenecks. In the context of bioremediation, and particularly regarding the cyanide metabolism, this D-malate oxidation to oxaloacetate facilitates detoxification by forming the corresponding cyanohydrin, which can be subsequently assimilated for growth. Full article
(This article belongs to the Special Issue Current Advances and Perspectives in Microbial Genetics and Genomics)
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21 pages, 3636 KiB  
Article
Antioxidant System Disturbances, Bioenergetic Disruption, and Glial Reactivity Induced by Methylmalonic Acid in the Developing Rat Brain
by Cristiano Antonio Dalpizolo, Josyane de Andrade Silveira, Manuela Bianchin Marcuzzo, Vitor Gayger-Dias, Vanessa-Fernanda Da Silva, Camila Vieira Pinheiro, Bruno Pereira dos Santos, Tiago Franco de Oliveira, Carlos-Alberto Gonçalves and Guilhian Leipnitz
Neuroglia 2025, 6(3), 25; https://doi.org/10.3390/neuroglia6030025 - 30 Jun 2025
Viewed by 353
Abstract
Background: Elevated levels of methylmalonic acid (MMA) are observed in the bodily fluids and tissues of patients with methylmalonic aciduria, a metabolic disorder characterized by manifestations such as vomiting, lethargy, muscle weakness, seizures, and coma. Objectives and Methods: To better understand the neuropathological [...] Read more.
Background: Elevated levels of methylmalonic acid (MMA) are observed in the bodily fluids and tissues of patients with methylmalonic aciduria, a metabolic disorder characterized by manifestations such as vomiting, lethargy, muscle weakness, seizures, and coma. Objectives and Methods: To better understand the neuropathological mechanisms underlying this condition, we investigated the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of MMA on antioxidant defenses, citric acid cycle functioning, and glial reactivity in the cerebral cortex and striatum of Wistar rats. Amino acid levels were also quantified. Results: i.p. and i.c.v. administration of MMA decreased reduced glutathione levels and altered the activities of different antioxidant enzymes in the cortex and striatum. The activity of the citric acid cycle enzyme succinate dehydrogenase was diminished in both brain regions by i.p. and i.c.v. administration. Citrate synthase, isocitrate dehydrogenase, and malate dehydrogenase activities were further inhibited in the striatum. Furthermore, the i.p. administration increased glial fibrillary acidic protein (GFAP) and glucose transporter 1 (GLUT1) levels, whereas i.c.v. administration elevated GFAP and ionized calcium-binding adaptor molecule 1 (IBA1) levels in the striatum, suggesting glial activation. In contrast, no significant changes in glial markers were detected in the cortex. Moreover, synaptophysin levels remained unaltered in both regions. Finally, i.p. administration increased glutamate, glycine, and serine levels and reduced tyrosine concentrations in the striatum. Conclusions: Our findings indicate that oxidative stress, bioenergetic dysfunction, and glial reactivity induced by MMA may contribute to the neurological deficits observed in methylmalonic aciduria. Full article
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39 pages, 7561 KiB  
Article
Aluminum Stress Response Is Regulated Through a miR156/SPL13 Module in Medicago sativa
by Gamalat Allam, Solihu K. Sakariyahu, Binghui Shan, Banyar Aung, Tim McDowell, Yousef Papadopoulos, Mark A. Bernards and Abdelali Hannoufa
Genes 2025, 16(7), 751; https://doi.org/10.3390/genes16070751 - 27 Jun 2025
Viewed by 1123
Abstract
Background: Aluminum (Al) toxicity severely limits Medicago sativa (alfalfa) production on acidic soils, resulting in major yield losses worldwide. The highly conserved miRNA156 (miR156) functions by downregulating at least 11 SQUAMOSA promoter-binding protein-like (SPL) transcription factors in alfalfa, including SPL13, but its role [...] Read more.
Background: Aluminum (Al) toxicity severely limits Medicago sativa (alfalfa) production on acidic soils, resulting in major yield losses worldwide. The highly conserved miRNA156 (miR156) functions by downregulating at least 11 SQUAMOSA promoter-binding protein-like (SPL) transcription factors in alfalfa, including SPL13, but its role in Al stress remains unclear. This study aimed to investigate the miR156/SPL regulatory network’s function in alfalfa under Al stress. Methods: Gene expression analyses, histochemical staining, nutrient profiling, phenotypic assays, transcriptome profiling, and ChIP-seq were conducted on alfalfa plants with altered miR156 and SPL13 expression to assess their roles in the Al stress response. Results: Al stress induced SPL13 expression while repressing miR156 in the roots. Elevated miR156 intensified Al accumulation, lipid peroxidation, and plasma membrane damage, accompanied by reduced leaf nitrogen, magnesium, sulfur, and phosphorus content. Phenotypically, increased SPL13 enhanced the root length and Al tolerance, whereas SPL13 silencing reduced tolerance. Transcriptome profiling of SPL13-silenced plants identified differentially expressed genes involved in the Al response, including aluminum-activated malate transporters and various transcription factors (GRAS, Myb-related, bHLH041, NAC, WRKY53, bZIP, and MADS-box). ChIP-seq revealed that SPL13 directly regulates genes encoding a protein kinase, cytochrome P450, and fasciclin-like arabinogalactan proteins. Conclusions: The MsmiR156/MsSPL13 network plays a crucial regulatory role in alfalfa’s response to Al toxicity. These findings provide novel genetic targets and foundational knowledge to advance molecular breeding for enhanced Al tolerance in alfalfa. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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23 pages, 2372 KiB  
Article
Uropathogenic Escherichia coli Associated with Risk of Urosepsis—Genetic, Proteomic, and Metabolomic Studies
by Beata Krawczyk, Paweł Wityk, Magdalena Burzyńska, Tomasz Majchrzak and Michał Jan Markuszewski
Int. J. Mol. Sci. 2025, 26(12), 5681; https://doi.org/10.3390/ijms26125681 - 13 Jun 2025
Viewed by 711
Abstract
In the absence of fully effective therapies and preventive strategies against the development of urosepsis, a deeper understanding of the virulence mechanisms of Uropathogenic Escherichia coli (UPEC) strains is needed. UPEC strains employ a wide range of virulence factors (VFs) to persist in [...] Read more.
In the absence of fully effective therapies and preventive strategies against the development of urosepsis, a deeper understanding of the virulence mechanisms of Uropathogenic Escherichia coli (UPEC) strains is needed. UPEC strains employ a wide range of virulence factors (VFs) to persist in the urinary tract and bloodstream. UPEC strains were isolated from patients with sepsis and a control group without sepsis. PCR was used to detect 36 genes encoding various groups of virulence and fitness factors. Profiling of both intracellular and extracellular bacterial proteins was also included in our approach. Bacterial metabolites were identified and quantified using GC-MS and LC-MS techniques. The UpaG autotransporter, a trimeric E. coli AT adhesin, was significantly more prevalent in urosepsis strains (p = 0.00001). Iron uptake via aerobactin and the Iha protein also appeared to be predictive of urosepsis (p = 0.03 and p = 0.002, respectively). While some studies suggest an association between S fimbriae and the risk of urosepsis, we observed no such correlation (p = 0.0001). Proteomic and metabolomic analyses indicated that elevated levels of bacterial citrate, malate, coenzyme Q10, pectinesterase (YbhC), and glutamate transport proteins, as well as the regulators PhoP two-component system, CpxR two-component system, Nitrate/nitrite response regulator protein NarL, and the Ferrienterobactin receptor FepA, may play a role in sepsis. These genetic biomarkers, proteins, and metabolites derived from UPEC could potentially serve as indicators for assessing the risk of developing sepsis. Full article
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13 pages, 11396 KiB  
Article
Morphometric and Enzymatic Changes in Gills of Rainbow Trout After Exposure to Suboptimal Low Temperature
by Elias Lahnsteiner, Nooshin Zamannejad, Anna Dünser and Franz Lahnsteiner
Curr. Issues Mol. Biol. 2025, 47(6), 457; https://doi.org/10.3390/cimb47060457 - 13 Jun 2025
Viewed by 845
Abstract
The present study investigated the influence of a 30 day exposure of rainbow trout (Oncorhynchus mykiss) to a suboptimal low temperature of 1.8 ± 1.0 °C on their different gill characteristics (morphometry, enzyme activities, and expression of genes) in comparison to [...] Read more.
The present study investigated the influence of a 30 day exposure of rainbow trout (Oncorhynchus mykiss) to a suboptimal low temperature of 1.8 ± 1.0 °C on their different gill characteristics (morphometry, enzyme activities, and expression of genes) in comparison to fish acclimated to 9.4 ± 0.1 °C. Morphometric analysis revealed a significant decrease in the distance between the secondary lamellae at the low temperature, which can be interpreted as a decrease in the effective gill surface. The epithelial thickness increased at the lower temperatures, which is considered a mechanism to reduce ion fluxes and save the energy costs for osmoregulation. The length of the primary lamellae, distance between the primary lamellae, length of the secondary lamellae, as well as the number of mucus cells, chloride cells, and capillaries per mm of the secondary lamella were similar between the temperature regimes. The enzymatic activities of pyruvate kinase and malate dehydrogenase were significantly increased in cold-exposed fish, whereas lactate dehydrogenase activity was higher in controls, indicating increased energy expenditure and adjustments in energy metabolism. The activities of carbonic anhydrase, caspase, Na+/K+ ATPase, and H+ ATPase, and the gene expressions of hif1a, ca2, rhCG, slc26a6, and slc9a1 showed no statistically significant differences between the two temperature regimes. Therefore, it can be concluded that ammonia transport, acid–base regulation, and osmoregulation were not affected by the tested low temperature regime. These findings highlight that exposure to suboptimal temperatures induces structural and metabolic modifications in rainbow trout gills, potentially as an adaptive response to thermal stress. This study contributes to the understanding of fish acclimation to cold environments, with implications for aquaculture and ecological resilience in changing climates. Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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15 pages, 1235 KiB  
Article
Transcriptome Analysis Unveils the Molecular Mechanisms of Ethylene-Induced Ready-to-Eat Kiwifruit-Picking Ripening
by Jiayi Zhang, Shangqiao Cao, Na Li, Hongbo Li, Zhenbin Liu, Dan Xu and Haizhen Mo
Foods 2025, 14(12), 2026; https://doi.org/10.3390/foods14122026 - 8 Jun 2025
Viewed by 536
Abstract
Kiwifruit is a climacteric fruit that undergoes significant physiological and biochemical changes during ripening, with ethylene playing a central regulatory role. Understanding the molecular mechanisms underlying ethylene-induced ripening is crucial for improving the postharvest handling and quality of ready-to-eat kiwifruit. The primary objective [...] Read more.
Kiwifruit is a climacteric fruit that undergoes significant physiological and biochemical changes during ripening, with ethylene playing a central regulatory role. Understanding the molecular mechanisms underlying ethylene-induced ripening is crucial for improving the postharvest handling and quality of ready-to-eat kiwifruit. The primary objective of the present study was to comprehensively analyze the transcriptome to investigate the ripening mechanism of ethylene-induced ready-to-eat kiwifruit. During the rapid maturation phase, it was observed that the gene Acc26812, responsible for regulating malate synthase activity, showed a significant upregulation at 84 h. Similarly, the gene Acc07097, which encodes arginine decarboxylase, also showed a significant upregulation during this period. A canonical correlation analysis (CCA) was performed to ascertain the relevance of genes associated with fruit firmness. Through transcriptome sequencing and bioinformatics analysis, approximately 2000 differentially expressed genes (DEGs) were identified. These genes were primarily involved in various pathways such as pentose and glucuronic acid interconversion, DNA replication, and others. A further investigation of these DEGs provided insights into several biological processes and molecular activities that contribute to the regulation of kiwifruit firmness. Notably, genes associated with fruit softening, including pectinesterase and cellulase, demonstrated significant upregulation, thereby indicating the degradation and remodeling of cell wall components during ripening. Additionally, highly expressed genes involved in glucose synthesis and transport highlighted the crucial role of sugar synthesis in the maturation process of ready-to-eat kiwifruit. Consequently, this study offers valuable insights into the mechanisms underlying the maturation of ready-to-eat kiwifruit. Full article
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22 pages, 1123 KiB  
Article
DNA Methylation Changes Reflect Aluminum Stress in Triticale and Epigenetic Control of the Trait
by Agnieszka Niedziela, Renata Orłowska and Piotr Tomasz Bednarek
Int. J. Mol. Sci. 2025, 26(11), 4995; https://doi.org/10.3390/ijms26114995 - 22 May 2025
Viewed by 397
Abstract
Aluminum (Al) stress is typical for acidic soils and may affect cereals’ yield. Al tolerance in triticale is mostly affected by the aluminum-activated malate transporter (ALMT) gene (7R) and some other QTLs (3R, 5R, and 6R). The trait is heritable in about 36% [...] Read more.
Aluminum (Al) stress is typical for acidic soils and may affect cereals’ yield. Al tolerance in triticale is mostly affected by the aluminum-activated malate transporter (ALMT) gene (7R) and some other QTLs (3R, 5R, and 6R). The trait is heritable in about 36% of cases, indicating that epigenetic factors may impact the phenomenon. This study demonstrates that utilizing different methods to quantify DNA methylation changes induced by Al stress results in detail differences, and the results evaluated should be compared critically. The Common and the basic General approaches are sufficient if general information is needed. The General (extended variant) approach may deliver data on methylation changes affecting symmetric sequence contexts. The markers assigned to DN-CG, DM-CG, and DN-CHG were suggested as the most important in explaining Al tolerance in triticale. Analysis of the maps constructed based on root tips and leaf tissues showed different densities of the epigenetic markers but reflected the comparable patterns of their distribution, supporting the hypothesis that Al stress could be transmitted to other plant tissues due to somatic memory. Methylation changes occur throughout the genome and are not associated with specific genes related to aluminum stress. Full article
(This article belongs to the Special Issue Plant Responses to Abiotic and Biotic Stresses)
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20 pages, 2275 KiB  
Article
The Regulatory Role of Exogenous Carnitine Applications in Lipid Metabolism, Mitochondrial Respiration, and Germination in Maize Seeds (Zea mays L.)
by Hulya Turk, Mucip Genisel and Rahmi Dumlupinar
Life 2025, 15(4), 631; https://doi.org/10.3390/life15040631 - 9 Apr 2025
Viewed by 647
Abstract
The present study aimed to investigate the effects of exogenous carnitine treatments on maize seed germination by stimulating lipid metabolism and regulating the mitochondrial respiratory pathway. Maize seeds were grown as control, 5, 7.5, and 10 μM carnitine treatment groups in a germination [...] Read more.
The present study aimed to investigate the effects of exogenous carnitine treatments on maize seed germination by stimulating lipid metabolism and regulating the mitochondrial respiratory pathway. Maize seeds were grown as control, 5, 7.5, and 10 μM carnitine treatment groups in a germination chamber at 25 °C under dark conditions for 5 d. It was determined that carnitine treatments increased the germination rate (GR), germination index (GI), germination potential (GP), vigor index (VI), root and hypocotyl length, fresh weight (FW), and content of total soluble protein but decreased the total carbohydrate content. It was also found that it increased the activities of α-amylase, isocitrate lyase (ICL), and malate synthase (MS) enzymes, which are critical in the germination process, and upregulated the expression of ICL and MS genes. To clarify the potential of carnitine treatments to promote the participation of lipids in respiration in roots and hypocotyls, lipase, carnitine acyltransferases (CATI and CATII), and citrate synthase (CS) enzyme activities were examined, and significant increases in these activities were detected. It was also found that gene levels of respiratory enzymes cytochrome oxidase (COX), pyruvate dehydrogenase (PDH), and Atp synthase, lipase, and CS proteins were upregulated by carnitine treatment. In support of the enzyme and gene change findings, significant changes were determined in fatty acid contents, free carnitine, and long-chain acylcarnitine levels in seeds, roots, and hypocotyls depending on carnitine application. In roots and hypocotyls, carnitine treatments significantly increased glutamine synthase (GS) and glutamate dehydrogenase (NADH-GDH) activities and gene expression levels, which are closely related to the tricarboxylic acid cycle (TCA). It was also noted that all proteins analyzed at the gene expression level were upregulated by carnitine applications in seeds. In addition, significant increases were recorded in antioxidant enzyme ascorbate peroxidase (APX) and superoxide dismutase (SOD) activities and total ascorbate (AsA) and glutathione (GSH) contents in roots and hypocotyls, while decreases were determined in guaiacol peroxidase (GPX) and catalase activities. Significant changes were recorded in all parameters examined, especially with 7.5 µM carnitine application. The findings suggest that carnitine may promote the transport of fatty acids to mitochondrial respiration by accelerating lipid catabolism in five-day-old maize and contribute to seed germination and growth and development processes by activating other metabolic pathways associated with respiration in this process. Full article
(This article belongs to the Section Plant Science)
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22 pages, 4376 KiB  
Article
Effects of Varying N, P, K, Mg, and Ca Concentrations on Nitrogen Transport in Xylem Sap of Rice Plants
by Shohei Watado, Kyoko Higuchi, Akihiro Saito and Takuji Ohyama
Plants 2025, 14(8), 1154; https://doi.org/10.3390/plants14081154 - 8 Apr 2025
Viewed by 1032
Abstract
The nutrients absorbed in the plant roots are transported to the shoots through the xylem. The effects of concentrations of N, P, K, Mg, and Ca in a culture solution on N transport forms have not been fully elucidated. In this study, rice [...] Read more.
The nutrients absorbed in the plant roots are transported to the shoots through the xylem. The effects of concentrations of N, P, K, Mg, and Ca in a culture solution on N transport forms have not been fully elucidated. In this study, rice plants were grown with five concentrations of N, P, K, Mg, and Ca for three days, and the concentrations of major N compounds in the xylem sap were determined. In the control plants, nitrate, glutamine, and asparagine were the principal N compounds. The concentrations of nitrate, glutamine, and asparagine decreased consistently with a decrease in the N concentration in the culture solution. Different P concentrations did not affect the N components. With lower K concentrations, only the nitrate concentration decreased. While the glutamine and asparagine concentrations decreased with a decrease in the Mg concentration. The Ca concentration did not affect the N concentration, except for Ca deprivation. The citrate and malate concentrations markedly increased when the plants grew with an N-free solution due to regulating the cation-anion balance. The results of this study indicate that changes in the concentrations of N, K, Mg, and Ca affected the concentrations of N transport forms, especially nitrate, glutamine, and asparagine. Full article
(This article belongs to the Special Issue Advances in Nitrogen Nutrition in Plants)
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20 pages, 3344 KiB  
Article
DNA Damage-Induced Ferroptosis: A Boolean Model Regulating p53 and Non-Coding RNAs in Drug Resistance
by Shantanu Gupta, Daner A. Silveira, José Carlos M. Mombach and Ronaldo F. Hashimoto
Proteomes 2025, 13(1), 6; https://doi.org/10.3390/proteomes13010006 - 20 Jan 2025
Cited by 3 | Viewed by 3325
Abstract
The tumor suppressor p53, in its wild-type form, plays a central role in cellular homeostasis by regulating senescence, apoptosis, and autophagy within the DNA damage response (DDR). Recent findings suggest that wild-type p53 also governs ferroptosis, an iron-dependent cell death process driven by [...] Read more.
The tumor suppressor p53, in its wild-type form, plays a central role in cellular homeostasis by regulating senescence, apoptosis, and autophagy within the DNA damage response (DDR). Recent findings suggest that wild-type p53 also governs ferroptosis, an iron-dependent cell death process driven by lipid peroxidation. Post-translational modifications of p53 generate proteoforms that significantly enhance its functional diversity in regulating these mechanisms. A key target in this process is the cystine/glutamate transporter (xCT), which is essential for redox balance and ferroptosis resistance. Additionally, p53-induced miR-34c-5p suppresses cancer cell proliferation and drug resistance by modulating Myc, an oncogene further influenced by non-coding RNAs like circular RNA NOTCH1 (CricNOTCH1) and long non-coding RNA MALAT1. However, the exact role of these molecules in ferroptosis remains unclear. To address this, we introduce the first dynamic Boolean model that delineates the influence of these ncRNAs and p53 on ferroptosis, apoptosis, and senescence within the DDR context. Validated through gain- and loss-of-function perturbations, our model closely aligns with experimental observations in cancers such as oral squamous cell carcinoma, nasopharyngeal carcinoma, and osteosarcoma. The model identifies crucial positive feedback loops (CricNOTCH1/miR-34c/Myc, MALAT1/miR-34c/Myc, and Myc/xCT) and highlights the therapeutic potential of using p53 proteoforms and ncRNAs to combat drug resistance and induce cancer cell death. Full article
(This article belongs to the Section Multi-Omics Studies that Include Proteomics)
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18 pages, 7020 KiB  
Article
Genome-Wide Identification of the ALMT Gene Family in Nine Rosaceae Species and Functional Analysis Associated with Organic Acid Accumulation in Prunus mume
by Ximeng Lin, Pengyu Zhou, Yin Wu, Ziqi Wang, Yuying Lu, Silas Segbo, Feng Gao, Chengdong Ma, Xiao Huang, Zhaojun Ni, Ting Shi and Zhihong Gao
Horticulturae 2024, 10(12), 1305; https://doi.org/10.3390/horticulturae10121305 - 7 Dec 2024
Viewed by 1022
Abstract
ALMT (aluminum-activated malate transporter) proteins play crucial roles in the transport of organic acids and have significant implications for plant stress responses and development. While extensively studied in some plants, the characteristics and functional divergence of the ALMT gene family have not yet [...] Read more.
ALMT (aluminum-activated malate transporter) proteins play crucial roles in the transport of organic acids and have significant implications for plant stress responses and development. While extensively studied in some plants, the characteristics and functional divergence of the ALMT gene family have not yet been thoroughly explored in Prunus mume and some other Rosaceae species. In this study, we systematically analyzed the ALMT gene family across nine Rosaceae species to explore their evolutionary relationships, structural characteristics, and functional roles. A total of 138 ALMT genes were identified and categorized into four groups based on a phylogenetic analysis. The motif analysis confirmed the accuracy of the phylogenetic grouping. The collinearity analysis indicated that whole-genome duplication events were the primary drivers of ALMT gene expansion in these species. Furthermore, the cis-acting element analysis revealed diverse regulatory elements associated with environmental responses, including abscisic acid, light, and jasmonic acid. The gene expression correlation analysis showed that PmALMT1 is primarily associated with malic acid accumulation, whereas PmALMT8 is related to citric acid accumulation. Further transient expression in Nicotiana benthamiana validated the above conclusion. This comprehensive analysis provides valuable insights into the evolution, function, and regulation of the ALMT gene family in Rosaceae species. Full article
(This article belongs to the Section Genetics, Genomics, Breeding, and Biotechnology (G2B2))
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19 pages, 4898 KiB  
Article
Molecular Regulation of Photosynthetic Carbon Assimilation in Oat Leaves Under Drought Stress
by Yiqun Xu, Liling Jiang, Jia Gao, Wei Zhang, Meijun Zhang, Changlai Liu and Juqing Jia
Plants 2024, 13(23), 3317; https://doi.org/10.3390/plants13233317 - 26 Nov 2024
Viewed by 983
Abstract
Common oat (Avena sativa L.) is one of the important minor grain crops in China, and drought stress severely affects its yield and quality. To investigate the drought resistance characteristics of oat seedlings, this study used Baiyan 2, an oat cultivar at [...] Read more.
Common oat (Avena sativa L.) is one of the important minor grain crops in China, and drought stress severely affects its yield and quality. To investigate the drought resistance characteristics of oat seedlings, this study used Baiyan 2, an oat cultivar at the three-leaf stage, as the experimental material. Drought stress was simulated using polyethylene glycol (PEG) to treat the seedlings. The photosynthetic parameters and physicochemical indices of the treatment groups at 6 h and 12 h were measured and compared with the control group at 0 h. The results showed that drought stress did not significantly change chlorophyll content, but it significantly reduced net photosynthetic rate and other photosynthetic parameters while significantly increasing proline content. Transcriptome analysis was conducted using seedlings from both the control and treatment groups, comparing the two treatment groups with the control group using Tbtool software (v2.136). This analysis identified 344 differentially expressed genes. Enrichment analysis of these differentially expressed genes revealed significant enrichment in physiological pathways such as photosynthesis and ion transport. Ten differentially expressed genes related to the physiological process of photosynthetic carbon assimilation were identified, all of which were downregulated. Additionally, seven differentially expressed genes were related to ion transport. Through gene co-expression analysis combined with promoter region structure analysis, 11 transcription factors (from MYB, AP2/ERF, C2C2-dof) were found to regulate the expression of 10 genes related to photosynthetic carbon assimilation. Additionally, five transcription factors regulate the expression of two malate transporter protein-related genes (from LOB, zf-HD, C2C2-Dof, etc.), five transcription factors regulate the expression of two metal ion transporter protein-related genes (from MYB, zf-HD, C2C2-Dof), five transcription factors regulate the expression of two chloride channel protein-related genes (from MYB, bZIP, AP2/ERF), and two transcription factors regulate the expression of one Annexin-related gene (from NAC, MYB). This study provides a theoretical foundation for further research on the molecular regulation of guard cells and offers a molecular basis for enhancing drought resistance in oats. Full article
(This article belongs to the Section Plant Response to Abiotic Stress and Climate Change)
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18 pages, 6414 KiB  
Article
Modulatory Effect of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) on the 2-Oxoglutarate Mitochondrial Carrier
by Anna Spagnoletta, Daniela Valeria Miniero, Nicola Gambacorta, Francesca Oppedisano, Anna De Grassi, Orazio Nicolotti, Ciro Leonardo Pierri and Annalisa De Palma
Molecules 2024, 29(21), 5154; https://doi.org/10.3390/molecules29215154 - 31 Oct 2024
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Abstract
The 2-oxoglutarate carrier (OGC), pivotal in cellular metabolism, facilitates the exchange of key metabolites between mitochondria and cytosol. This study explores the influence of NADPH on OGC transport activity using proteoliposomes. Experimental data revealed the ability of NADPH to modulate the OGC activity, [...] Read more.
The 2-oxoglutarate carrier (OGC), pivotal in cellular metabolism, facilitates the exchange of key metabolites between mitochondria and cytosol. This study explores the influence of NADPH on OGC transport activity using proteoliposomes. Experimental data revealed the ability of NADPH to modulate the OGC activity, with a significant increase of 60% at 0.010 mM. Kinetic analysis showed increased Vmax and a reduction in Km for 2-oxoglutarate, suggesting a direct regulatory role. Molecular docking pointed to a specific interaction between NADPH and cytosolic loops of OGC, involving key residues such as K206 and K122. This modulation was unique in mammalian OGC, as no similar effect was observed in a plant OGC structurally/functionally related mitochondrial carrier. These findings propose OGC as a responsive sensor for the mitochondrial redox state, coordinating with the malate/aspartate and isocitrate/oxoglutarate shuttles to maintain redox balance. The results underscore the potential role of OGC in redox homeostasis and its broader implications in cellular metabolism and oxidative stress responses. Full article
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