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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
Viewed by 72
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 205
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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22 pages, 3429 KiB  
Article
Indoor Positioning and Tracking System in a Multi-Level Residential Building Using WiFi
by Elmer Magsino, Joshua Kenichi Sim, Rica Rizabel Tagabuhin and Jan Jayson Tirados
Information 2025, 16(8), 633; https://doi.org/10.3390/info16080633 - 24 Jul 2025
Viewed by 289
Abstract
The implementation of an Indoor Positioning System (IPS) in a three-storey residential building employing WiFi signals that can also be used to track indoor movements is presented in this study. The movement of inhabitants is monitored through an Android smartphone by detecting the [...] Read more.
The implementation of an Indoor Positioning System (IPS) in a three-storey residential building employing WiFi signals that can also be used to track indoor movements is presented in this study. The movement of inhabitants is monitored through an Android smartphone by detecting the Received Signal Strength Indicator (RSSI) signals from WiFi Anchor Points (APs).Indoor movement is detected through a successive estimation of a target’s multiple positions. Using the K-Nearest Neighbors (KNN) and Particle Swarm Optimization (PSO) algorithms, these RSSI measurements are trained for estimating the position of an indoor target. Additionally, the Density-based Spatial Clustering of Applications with Noise (DBSCAN) has been integrated into the PSO method for removing RSSI-estimated position outliers of the mobile device to further improve indoor position detection and monitoring accuracy. We also employed Time Reversal Resonating Strength (TRRS) as a correlation technique as the third method of localization. Our extensive and rigorous experimentation covers the influence of various weather conditions in indoor detection. Our proposed localization methods have maximum accuracies of 92%, 80%, and 75% for TRRS, KNN, and PSO + DBSCAN, respectively. Each method also has an approximate one-meter deviation, which is a short distance from our targets. Full article
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13 pages, 672 KiB  
Article
Exploratory Meta-Analysis of the Effect of Malic Acid or Malate Addition on Ruminal Parameters, Nutrient Digestibility, and Blood Characteristics of Cattle
by Leonardo Tombesi da Rocha, Tiago Antonio Del Valle, Fernando Reimann Skonieski, Stela Naetzold Pereira, Paola Selau de Oliveira, Francine Basso Facco and Julio Viégas
Animals 2025, 15(15), 2177; https://doi.org/10.3390/ani15152177 - 24 Jul 2025
Viewed by 185
Abstract
The aim of this study was to determine, through meta-analysis, the effects of malic acid/malate addition on ruminal and blood parameters and diet digestibility in cattle. The literature search was conducted in Web of Science, Science Direct, and Google Scholar using the terms [...] Read more.
The aim of this study was to determine, through meta-analysis, the effects of malic acid/malate addition on ruminal and blood parameters and diet digestibility in cattle. The literature search was conducted in Web of Science, Science Direct, and Google Scholar using the terms “organic acids”, “malic acid”, “malate”, and “bovine”. The database was composed of papers published between 1980 and 2023. The average effect of malate/malic acid inclusion was calculated using the “DerSimonian and Laird” random effects model. Meta-regression and subgroup analyses were conducted to explore sources of heterogeneity. Overall, malic acid (MAC) addition did not significantly affect rumen pH (ES = 0.310, p = 0.17), but subgroup analysis showed that malate increased pH (ES = 1.420, p < 0.01). MAC increased rumen propionate (ES = 0.560, p < 0.01) and total volatile fatty acids (VFAs; ES = 0.508, p = 0.03), while reducing the acetate-to-propionate ratio (p < 0.01). Starch and NDF intake were significant covariates affecting pH and VFA-related variables. MAC improved total-tract digestibility of dry matter (DM; ES = 0.547, p ≤ 0.05), crude protein (CP; ES = 0.422, p ≤ 0.05), and acid detergent fiber (ADF; ES = 0.635, p ≤ 0.05). It increased glucose levels (Overall ES = 0.170, p = 0.05) and reduced NEFA (Overall ES = −0.404, p = 0.03). In conclusion, the effectiveness of MAC depends on its chemical form. Improvements in rumen pH, fiber degradation, and blood parameters suggest more efficient energy use and potential metabolic benefits. The influence of diet-related covariates suggests that the response to MAC may vary depending on the nutritional composition of the diet. Full article
(This article belongs to the Special Issue Feed Additives in Animal Nutrition)
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22 pages, 527 KiB  
Article
Impact of Chronic Nitrate and Citrulline Malate Supplementation on Performance and Recovery in Spanish Professional Female Soccer Players: A Randomized Controlled Trial
by Marta Ramírez-Munera, Raúl Arcusa, Francisco Javier López-Román, Vicente Ávila-Gandía, Silvia Pérez-Piñero, Juan Carlos Muñoz-Carrillo, Antonio Jesús Luque-Rubia and Javier Marhuenda
Nutrients 2025, 17(14), 2381; https://doi.org/10.3390/nu17142381 - 21 Jul 2025
Viewed by 611
Abstract
Background: Pre-season training is critical for developing tolerance to high physical demands in professional soccer, and nitric oxide (NO) precursors such as dietary nitrate (NO3) and citrulline malate (CM) can support performance and recovery during this demanding phase. This [...] Read more.
Background: Pre-season training is critical for developing tolerance to high physical demands in professional soccer, and nitric oxide (NO) precursors such as dietary nitrate (NO3) and citrulline malate (CM) can support performance and recovery during this demanding phase. This study aimed to examine the effects of a four-week supplementation protocol combining 500 mg of NO3 from amaranth extract and 8 g of CM (NIT + CM) on external training load and post-match recovery in professional female soccer players during pre-season. Methods: A randomized, double-blind, placebo-controlled trial was conducted with 34 female soccer players who received either the NIT + CM product or a placebo for four weeks during pre-season. Global positioning system (GPS)-derived external load was recorded throughout the intervention. Performance tests—a countermovement jump (CMJ) test and the Wingate anaerobic test (WAnT)—and blood sampling for plasma NO3 and nitrite (NO2) concentrations were conducted at baseline and the day after a competitive match. Results: The supplementation with NIT + CM increased maximal speed (Vmax) throughout training and match play. During post-match testing, the NIT + CM group exhibited a significantly smaller decline in mean (Pmean) and minimum (Pmin) power during the WAnT, along with reduced power loss in both the first (0–15 s) and second (15–30 s) intervals. Plasma NO3 concentrations significantly increased from baseline in the NIT + CM group and remained elevated 24 h after the final dose, confirming sustained systemic exposure. Conclusions: Chronic NIT + CM supplementation may enhance Vmax and help preserve anaerobic performance the day after a match. These effects could reflect improved tolerance to high training loads and sustained NO3 availability during recovery. Full article
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19 pages, 361 KiB  
Review
Long Non-Coding RNAs in Psoriasis and Cutaneous Squamous Cell Carcinoma
by Ioana Irina Trufin, Loredana Ungureanu, Salomea-Ruth Halmágyi, Adina Patricia Apostu and Simona Corina Șenilă
J. Clin. Med. 2025, 14(14), 5081; https://doi.org/10.3390/jcm14145081 - 17 Jul 2025
Viewed by 239
Abstract
Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as pivotal regulators in both inflammatory and neoplastic skin disorders. Their implications in numerous biological processes, including gene expression, immune responses, and epidermal homeostasis, suggest potential applications as diagnostic and prognostic markers, as well as [...] Read more.
Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as pivotal regulators in both inflammatory and neoplastic skin disorders. Their implications in numerous biological processes, including gene expression, immune responses, and epidermal homeostasis, suggest potential applications as diagnostic and prognostic markers, as well as therapeutic targets. Methods: We conducted a literature search on lncRNAs involved in both psoriasis and cutaneous squamous cell carcinoma (cSCC), highlighting overlapping pathogenic mechanisms. Results: Several lncRNAs, such as HOTAIR, MALAT-1, H19, and uc.291, display dysregulated expression in both psoriasis and cSCC, influencing keratinocyte proliferation and apoptosis, immune modulation, cytokine signaling, and the synthesis of epidermal proteins. Conclusions: The intersection of lncRNA function in chronic inflammation and skin carcinogenesis underscores their role in mediating the transition from psoriatic inflammation to tumorigenesis, offering new insights into disease susceptibility; further investigation through functional studies and clinical validation are required. The study of lncRNA-mediated molecular pathways is particularly relevant given the increased risk of non-melanoma skin cancers and lymphoproliferative disorders among patients with chronic and severe forms of psoriasis. Full article
(This article belongs to the Special Issue New Insights in Skin Tumors: From Pathogenesis to Therapy)
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 277
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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17 pages, 3309 KiB  
Article
Mitochondrial Fragmentation and Long Noncoding RNA MALAT1 in Diabetic Retinopathy
by Renu A. Kowluru and Jay Kumar
Int. J. Mol. Sci. 2025, 26(13), 6429; https://doi.org/10.3390/ijms26136429 - 3 Jul 2025
Viewed by 471
Abstract
Mitochondria are dynamic in nature and depending on the energy demand they fuse and divide. This fusion-fission process is impaired in diabetic retinopathy and the promoter DNA of Mfn2, a fusion gene, is hypermethylated and its expression is downregulated. Long noncoding RNAs [...] Read more.
Mitochondria are dynamic in nature and depending on the energy demand they fuse and divide. This fusion-fission process is impaired in diabetic retinopathy and the promoter DNA of Mfn2, a fusion gene, is hypermethylated and its expression is downregulated. Long noncoding RNAs (RNAs with >200 nucleotides that do not encode proteins) can regulate gene expression by interacting with DNA, RNA, and proteins. Several LncRNAs are aberrantly expressed in diabetes, and among them, MALAT1 is upregulated in the retina, altering the expression of the genes associated with inflammation. Our aim was to investigate MALAT1’s role in mitochondrial dynamics in diabetic retinopathy. Using MALAT1-siRNA-transfected human retinal endothelial cells (HRECs) and human retinal Muller cells (RMCs) incubated in 20 mM D-glucose, Mfn2 expression and activity and its promoter DNA methylation were quantified. Mitochondrial integrity was evaluated by analyzing their fragmentation, ultrastructure, membrane potential, and oxygen consumption rate. Compared to normal glucose, high glucose upregulated MALAT1 expression and downregulated Mfn2 expression and activity in both HRECs and RMCs. MALAT1-siRNA ameliorated the glucose-induced increase in Mfn2 promoter DNA hypermethylation and its activity. MALAT1-siRNA also protected against mitochondrial fragmentation, structural damage, and reductions in the oxygen consumption rate. In conclusion, the upregulation of MALAT1 in diabetes facilitates Mfn2 promoter DNA hypermethylation in retinal vascular and nonvascular cells, leading to its suppression and the accumulation of the fragmented/damaged mitochondria. Thus, the regulation of MALAT1 has the potential to protect mitochondria and provide a possible new target to inhibit/prevent the blinding disease in diabetic patients. Full article
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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 357
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 1131
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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19 pages, 5924 KiB  
Article
Development of a Secured IoT-Based Flood Monitoring and Forecasting System Using Genetic-Algorithm-Based Neuro-Fuzzy Network
by Hero Rafael Castillo Arante, Edwin Sybingco, Maria Antonette Roque, Leonard Ambata, Alvin Chua and Alvin Neil Gutierrez
Sensors 2025, 25(13), 3885; https://doi.org/10.3390/s25133885 - 22 Jun 2025
Viewed by 973
Abstract
The paper aims to provide a flood prediction system in the Philippines to increase flood awareness, which may help reduce property damage and save lives. Real-time flood status can significantly increase community awareness and preparedness. A flood model will simulate the flood level [...] Read more.
The paper aims to provide a flood prediction system in the Philippines to increase flood awareness, which may help reduce property damage and save lives. Real-time flood status can significantly increase community awareness and preparedness. A flood model will simulate the flood level with secured data flow from the sensor to the cloud. The algorithms embedded in the flood predicting model include fuzzy logic, LSTM neural network, and genetic algorithm. The project used the Infineon security module (Infineon Technologies Philippines Inc., Metro Manila, Philippines) to create a secure connection from the setup to the AWS. All data transmitted were encrypted when being sent to AWS IoT Core, Timestream, and Grafana. After training and testing, the neuro-fuzzy LSTM network with genetic algorithm solution showed improved flood prediction accuracy of 92.91% compared to the ADAM solver that predicts every 2 h using an 0.02 initial learning rate, 1000 LSTM hidden layers, and 1000 epochs. The best solution predicts a flood every 3 h using an ADAM solver, a 0.01 initial learning rate, and 244 LSTM hidden layers for 158 epochs. Full article
(This article belongs to the Section Internet of Things)
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18 pages, 2683 KiB  
Article
FpFumB Is Required for Basic Biological Processes and Virulence in Fusarium proliferatum by Modulating DNA Repair Through Interaction with FpSae2
by Yizhou Gao, Haibo Li, Yong Liu, Yuqing Wang, Jingwen Xue, Yitong Wang and Zhihong Wu
Microorganisms 2025, 13(6), 1433; https://doi.org/10.3390/microorganisms13061433 - 19 Jun 2025
Viewed by 433
Abstract
Fumarase plays a pivotal role in the tricarboxylic acid cycle, but its functions in plant pathogenic fungi are not well understood. We identified two fumarase genes in Fusarium proliferatum and generated individual deletion mutants. Loss of FpFumB led to defects in growth, sporulation, [...] Read more.
Fumarase plays a pivotal role in the tricarboxylic acid cycle, but its functions in plant pathogenic fungi are not well understood. We identified two fumarase genes in Fusarium proliferatum and generated individual deletion mutants. Loss of FpFumB led to defects in growth, sporulation, stress tolerance, and virulence. Exogenous malate supplementation restored growth defects. Site-directed mutagenesis of residues G452 and A463 reduced FpFumB enzyme activity. Transcriptomic analysis identified significant changes in gene expression related to different metabolic pathways. Protein interaction assays showed that FpFumB interacts with the DNA repair protein FpSae2. Both ΔFpFumB and ΔFpSae2 mutants displayed altered sensitivity to DNA-damaging agents and reduced virulence, indicating that FpFumB modulates DNA repair and pathogenicity through its interaction with FpSae2. Together, these findings highlight FpFumB as a key regulator of basic biological processes, DNA damage repair, and virulence in Fusarium proliferatum. Full article
(This article belongs to the Section Plant Microbe Interactions)
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18 pages, 4053 KiB  
Article
Molecular Insights into Outer Dynein Arm Defects in Primary Ciliary Dyskinesia: Involvement of ZMYND10 and GRP78
by İlker Levent Erdem, Zeynep Bengisu Kaya, Pergin Atilla, Nagehan Emiralioğlu, Cemil Can Eylem, Emirhan Nemutlu, Uğur Özçelik, Halime Nayır Büyükşahin, Ayşenur Daniş and Elif Karakoç
Cells 2025, 14(12), 916; https://doi.org/10.3390/cells14120916 - 17 Jun 2025
Viewed by 605
Abstract
Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by recurrent sinopulmonary infections due to motile cilia defects. The disease is genetically heterogeneous, with abnormalities in structural ciliary proteins. Zinc finger MYND-type containing 10 (ZMYND10) is essential for the assembly of [...] Read more.
Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by recurrent sinopulmonary infections due to motile cilia defects. The disease is genetically heterogeneous, with abnormalities in structural ciliary proteins. Zinc finger MYND-type containing 10 (ZMYND10) is essential for the assembly of outer dynein arms (ODA), with chaperones like Glucose-regulated protein 78 (GRP78) facilitating protein folding. This study investigates ZMYND10 and Dynein axonemal heavy chain 5 (DNAH5) mutations in individuals with PCD. Methods: Eight individuals aged 14–22 with clinical PCD symptoms and confirmed DNAH5 mutations were included. We analyzed the correlation between DNAH5 abnormalities and preassembly/chaperone proteins using immunofluorescence labeling. Nasal swabs were double-labeled (DNAH5–β-tubulin, β-tubulin–ZMYND10, β-tubulin–GRP78) and examined via fluorescence microscopy. Serum metabolomics and proteomics were also assessed. Results: The corrected total cell fluorescence (CTCF) levels of DNAH5, ZMYND10, and GRP78 were significantly different between PCD individuals and controls. Metabolomic analysis showed reduced valine, leucine, and isoleucine biosynthesis, with increased malate and triacylglycerol biosynthesis, malate-aspartate and glycerol phosphate shuttles, and arginine/proline metabolism, suggesting mitochondrial and ER stress. Conclusions: The altered expression of DNAH5, ZMYND10, and GRP78, along with metabolic shifts, points to a complex link between ciliary dysfunction and cellular stress in PCD. Further studies are needed to clarify the underlying mechanisms. Full article
(This article belongs to the Special Issue The Role of Cilia in Health and Diseases—2nd Edition)
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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 723
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 848
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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