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19 pages, 17084 KB  
Article
SPADE: Superpixel Adjacency Driven Embedding for Three-Class Melanoma Segmentation
by Pablo Ordóñez, Ying Xie, Xinyue Zhang, Chloe Yixin Xie, Santiago Acosta and Issac Guitierrez
Algorithms 2025, 18(9), 551; https://doi.org/10.3390/a18090551 - 2 Sep 2025
Abstract
The accurate segmentation of pigmented skin lesions is a critical prerequisite for reliable melanoma detection, yet approximately 30% of lesions exhibit fuzzy or poorly defined borders. This ambiguity makes the definition of a single contour unreliable and limits the effectiveness of computer-assisted diagnosis [...] Read more.
The accurate segmentation of pigmented skin lesions is a critical prerequisite for reliable melanoma detection, yet approximately 30% of lesions exhibit fuzzy or poorly defined borders. This ambiguity makes the definition of a single contour unreliable and limits the effectiveness of computer-assisted diagnosis (CAD) systems. While clinical assessment based on the ABCDE criteria (asymmetry, border, color, diameter, and evolution), dermoscopic imaging, and scoring systems remains the standard, these methods are inherently subjective and vary with clinician experience. We address this challenge by reframing segmentation into three distinct regions: background, border, and lesion core. These regions are delineated using superpixels generated via the Simple Linear Iterative Clustering (SLIC) algorithm, which provides meaningful structural units for analysis. Our contributions are fourfold: (1) redefining lesion borders as regions, rather than sharp lines; (2) generating superpixel-level embeddings with a transformer-based autoencoder; (3) incorporating these embeddings as features for superpixel classification; and (4) integrating neighborhood information to construct enhanced feature vectors. Unlike pixel-level algorithms that often overlook boundary context, our pipeline fuses global class information with local spatial relationships, significantly improving precision and recall in challenging border regions. An evaluation on the HAM10000 melanoma dataset demonstrates that our superpixel–RAG–transformer (region adjacency graph) pipeline achieves exceptional performance (100% F1 score, accuracy, and precision) in classifying background, border, and lesion core superpixels. By transforming raw dermoscopic images into region-based structured representations, the proposed method generates more informative inputs for downstream deep learning models. This strategy not only advances melanoma analysis but also provides a generalizable framework for other medical image segmentation and classification tasks. Full article
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14 pages, 1122 KB  
Article
Optimization of the Performance of Newborn Screening for X-Linked Adrenoleukodystrophy by Flow Injection Analysis Tandem Mass Spectrometry
by Chengfang Tang, Minyi Tan, Yanna Cai, Sichi Liu, Ting Xie, Xiang Jiang, Li Tao, Yonglan Huang and Fang Tang
Int. J. Neonatal Screen. 2025, 11(3), 71; https://doi.org/10.3390/ijns11030071 - 29 Aug 2025
Viewed by 184
Abstract
The aim of this study was to improve screening efficiency by establishing reasonable interpretation criteria for the use of flow injection analysis tandem mass spectrometry (FIA-MS/MS) in newborn screening (NBS) for X-linked adrenoleukodystrophy (X-ALD). FIA-MS/MS was employed to analyze very-long-chain acylcarnitines (ACs) and [...] Read more.
The aim of this study was to improve screening efficiency by establishing reasonable interpretation criteria for the use of flow injection analysis tandem mass spectrometry (FIA-MS/MS) in newborn screening (NBS) for X-linked adrenoleukodystrophy (X-ALD). FIA-MS/MS was employed to analyze very-long-chain acylcarnitines (ACs) and lysophosphatidylcholines (LPCs) and their ratios in dried blood spot (DBS) obtained from five X-ALD patients in the neonatal period (0–7 days old) and 7123 healthy neonate controls. By comparing these results and analyzing receiver operating characteristic (ROC) curves, we identified sensitive indicators for X-ALD screening in newborns. To evaluate the performance of different FIA-MS/MS screening indicators, we simultaneously analyzed 7712 neonatal DBS samples obtained for X-ALD screening using FIA-MS/MS and the established liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantitative detection of C26:0-lysophosphatidylcholine (C26:0-LPC). Furthermore, 84,268 newborn X-ALD screening results were retrospectively analyzed to further evaluate the screening performance of FIA-MS/MS. After the three-step optimization evaluation, the optimized first-tier sensitive screening indicators of FIA-MS/MS were C24:0-AC, C26:0LPC, and C24:0/C22:0-AC. Among the 7712 newborns screened, one case was confirmed to be double-positive. Within separate statistical analyses, based on LC-MS/MS screening alone (positive cutoff > 0.17 µmol/L), only seven cases (0.09%) were initially positive, with a positive predictive value (PPV) of 42.8%, and two additional ABCD1 VUS hemizygous males were detected. Through the retrospective analysis of 84,268 newborns, eight ABCD1 variants (six hemizygous males and two heterozygous females) were ultimately identified. Our study showed that the optimization of first-tier screening performance is particularly important if second-tier screening is not performed. Using LC-MS/MS for second-tier screening for X-ALD can significantly reduce the number of false positives, but the method still misses some false negatives. If it is used as a first-tier assessment, more VUS variant neonates can be detected. Full article
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15 pages, 7464 KB  
Article
Regulatory Characterization of Two Cop Systems for Copper Resistance in Pseudomonas putida
by Huizhong Liu, Yafeng Song, Ping Yang, Qian Wang, Ping Huang, Zhiqing Zhang, Gang Zhou, Qingshan Shi and Xiaobao Xie
Int. J. Mol. Sci. 2025, 26(17), 8172; https://doi.org/10.3390/ijms26178172 - 22 Aug 2025
Viewed by 308
Abstract
Copper ions serve as essential cofactors for many enzymes but exhibit toxicity at elevated concentrations. In Gram-negative bacteria, the Cop system, typically encoded by copABCD, plays a crucial role in maintaining copper homeostasis and detoxification. The chromosome of Pseudomonas putida harbors two [...] Read more.
Copper ions serve as essential cofactors for many enzymes but exhibit toxicity at elevated concentrations. In Gram-negative bacteria, the Cop system, typically encoded by copABCD, plays a crucial role in maintaining copper homeostasis and detoxification. The chromosome of Pseudomonas putida harbors two copAB clusters but lacks copCD, along with two copR-copS clusters that encode the cognate two-component system. Here, the roles of these Cop components in countering copper toxicity were studied. We found that copAB2 was essential for full resistance to Cu2+ in P. putida, while copAB1 made only a minor contribution, partially due to its low expression. The two-component systems CopRS1 and CopRS2 both played significant regulatory roles in copper resistance. Although they could compensate for the absence of each other to mediate copper resistance, they exhibited distinct regulatory effects. CopR1 bound to all four cop promoters and activated their transcription under copper stress. In contrast, though CopR2 bound to the same sites as CopR1 in each cop promoter, it significantly activated only copAB2 and copRS2 expression. Its competitive binding at the copAB1 and copRS1 promoters likely impeded CopR1-mediated activation of these genes. Overall, this study reveals the distinct contributions of the two Cop systems to copper resistance and their regulatory interplay in P. putida. Full article
(This article belongs to the Section Molecular Biology)
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20 pages, 3686 KB  
Article
Comparative Analysis of Correction Methods for Multi-Camera 3D Image Processing System and Its Application Design in Safety Improvement on Hot-Working Production Line
by Joanna Gąbka
Appl. Sci. 2025, 15(16), 9136; https://doi.org/10.3390/app15169136 - 19 Aug 2025
Viewed by 303
Abstract
The paper presents the results of research focused on configuring a system for stereoscopic view capturing and processing. The system is being developed for use in staff training scenarios based on Virtual Reality (VR), where high-quality, distortion-free imagery is essential. This research addresses [...] Read more.
The paper presents the results of research focused on configuring a system for stereoscopic view capturing and processing. The system is being developed for use in staff training scenarios based on Virtual Reality (VR), where high-quality, distortion-free imagery is essential. This research addresses key challenges in image distortion, including the fish-eye effect and other aberrations. In addition, it considers the computational and bandwidth efficiency required for effective and economical streaming and real-time display of recorded content. Measurements and calculations were performed using a selected set of cameras, adapters, and lenses, chosen based on predefined criteria. A comparative analysis was conducted between the nearest-neighbour linear interpolation method and a third-order polynomial interpolation (ABCD polynomial). These methods were tested and evaluated using three different computational approaches, each aimed at optimizing data processing efficiency critical for real-time image correction. Images captured during real-time video transmission—processed using the developed correction techniques—are presented. In the final sections, the paper describes the configuration of an innovative VR-based training system incorporating an edge computing device. A case study involving a factory producing wheel rims is also presented to demonstrate the practical application of the system. Full article
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8 pages, 625 KB  
Brief Report
A Genome-Wide Association Study of Rib Number and Thoracolumbar Vertebra Number in a Landrace × Yorkshire Crossbred Pig Population
by Chunyan Bai, Junwen Fei, Xiaoran Zhang, Wuyang Liu, Juan Ke, Changyi Chen, Yu He, Shuang Liang, Boxing Sun and Hao Sun
Biology 2025, 14(8), 1068; https://doi.org/10.3390/biology14081068 - 16 Aug 2025
Viewed by 364
Abstract
The number of thoracolumbar vertebrae (NTLV) and the number of ribs (NR) are economically important traits in pigs due to their influence on carcass length and meat yield. Although VRTN is an established key gene, it fails to fully account for population-level variation [...] Read more.
The number of thoracolumbar vertebrae (NTLV) and the number of ribs (NR) are economically important traits in pigs due to their influence on carcass length and meat yield. Although VRTN is an established key gene, it fails to fully account for population-level variation in vertebral count, necessitating a further exploration of its genetic mechanisms. Given the efficacy of crossbred populations in mapping the genetic determinants of phenotypic variation, we analyzed 439 pigs from a Landrace × Yorkshire cross. Genotyping was performed via a 50 K SNP chip. Both NTLV and NR showed high heritability (0.700 and 0.752, respectively), while the number of lumbar vertebrae (NLV) showed limited variation (92.5% of pigs had NLV = 6). Using the BLINK model, four significant loci were identified. The most significant SNP, rs3469762345, located in the intergenic region between ABCD4 and VRTN, corresponds to a previously known QTL. Additionally, three novel variant sites (rs81211244, rs81347323, and rs81416674) were identified within or near the ALDH7A1, PTPRT, and PAK1 genes, which are known to play a role in bone development. This study uncovers novel swine candidate genes associated with vertebral and rib number variation, subsequently facilitating targeted research into their molecular mechanisms. Full article
(This article belongs to the Special Issue Advances in Animal Functional Genomics)
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27 pages, 414 KB  
Review
Contractions of Wigner’s Little Groups as Limiting Procedures
by Sibel Başkal, Young S. Kim and Marilyn E. Noz
Symmetry 2025, 17(8), 1257; https://doi.org/10.3390/sym17081257 - 7 Aug 2025
Viewed by 451
Abstract
Wigner’s little groups are the subgroups of the Poincaré group whose transformations leave the four-momentum of a relativistic particle invariant. The little group for a massive particle is SO(3)-like, whereas for a massless particle, it is E(2)-like. Multiple approaches to group [...] Read more.
Wigner’s little groups are the subgroups of the Poincaré group whose transformations leave the four-momentum of a relativistic particle invariant. The little group for a massive particle is SO(3)-like, whereas for a massless particle, it is E(2)-like. Multiple approaches to group contractions are discussed. It is shown that the Lie algebra of the E(2)-like little group for massless particles can be obtained from the SO(3) and from the SO(2, 1) group by boosting to the infinite-momentum limit. It is also shown that it is possible to obtain the generators of the E(2)-like and cylindrical groups from those of SO(3) as well as from those of SO(2, 1) by using the squeeze transformation. The contraction of the Lorentz group SO(3, 2) to the Poincaré group is revisited. As physical examples, two applications are chosen from classical optics. The first shows the contraction of a light ray from a spherical transparent surface to a straight line. The second shows that the focusing of the image in a camera can be formulated by the implementation of the focal condition to the [ABCD] matrix of paraxial optics, which can be regarded as a limiting procedure. Full article
(This article belongs to the Special Issue Symmetry and Lie Algebras)
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23 pages, 2081 KB  
Article
Rapid Soil Tests for Assessing Soil Health
by Jan Adriaan Reijneveld and Oene Oenema
Appl. Sci. 2025, 15(15), 8669; https://doi.org/10.3390/app15158669 - 5 Aug 2025
Viewed by 607
Abstract
Soil testing has long been used to optimize fertilization and crop production. More recently, soil health testing has emerged to reflect the growing interest in soil multifunctionality and ecosystem services. Soil health encompasses physical, chemical, and biological properties that support ecosystem functions and [...] Read more.
Soil testing has long been used to optimize fertilization and crop production. More recently, soil health testing has emerged to reflect the growing interest in soil multifunctionality and ecosystem services. Soil health encompasses physical, chemical, and biological properties that support ecosystem functions and sustainable agriculture. Despite its relevance to several United Nations Sustainable Development Goals (SDGs 1, 2, 3, 6, 12, 13, and 15), comprehensive soil health testing is not widely practiced due to complexity and cost. The aim of the study presented here was to contribute to the further development, implementation, and testing of an integrated procedure for soil health assessment in practice. We developed and tested a rapid, standardized soil health assessment tool that combines near-infrared spectroscopy (NIRS) and multi-nutrient 0.01 M CaCl2 extraction with Inductive Coupled Plasma Mass Spectroscopy analysis. The tool evaluates a wide range of soil characteristics with high accuracy (R2 ≥ 0.88 for most parameters) and has been evaluated across more than 15 countries, including those in Europe, China, New Zealand, and Vietnam. The results are compiled into a soil health indicator report with tailored management advice and a five-level ABCDE score. In a Dutch test set, 6% of soils scored A (optimal), while 2% scored E (degraded). This scalable tool supports land users, agrifood industries, and policymakers in advancing sustainable soil management and evidence-based environmental policy. Full article
(This article belongs to the Special Issue Soil Analysis in Different Ecosystems)
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12 pages, 1076 KB  
Article
Rapid Identification of the SNP Mutation in the ABCD4 Gene and Its Association with Multi-Vertebrae Phenotypes in Ujimqin Sheep Using TaqMan-MGB Technology
by Yue Zhang, Min Zhang, Hong Su, Jun Liu, Feifei Zhao, Yifan Zhao, Xiunan Li, Yanyan Yang, Guifang Cao and Yong Zhang
Animals 2025, 15(15), 2284; https://doi.org/10.3390/ani15152284 - 5 Aug 2025
Viewed by 304
Abstract
Ujimqin sheep, known for its distinctive multi-vertebrae phenotypes (T13L7, T14L6, and T14L7) and economic value, has garnered significant attention. However, conventional phenotypic detection methods suffer from low efficiency and high costs. In this study, based on a key SNP locus (ABCD4 gene, [...] Read more.
Ujimqin sheep, known for its distinctive multi-vertebrae phenotypes (T13L7, T14L6, and T14L7) and economic value, has garnered significant attention. However, conventional phenotypic detection methods suffer from low efficiency and high costs. In this study, based on a key SNP locus (ABCD4 gene, Chr7:89393414, C > T) identified through a genome-wide association study (GWAS), a TaqMan-MGB (minor groove binder) genotyping system was developed. the objective was to establish a high-throughput and efficient molecular marker-assisted selection (MAS) tool. Specific primers and dual fluorescent probes were designed to optimize the reaction system. Standard plasmids were adopted to validate genotyping accuracy. A total of 152 Ujimqin sheep were subjected to TaqMan-MGB genotyping, digital radiography (DR) imaging, and Sanger sequencing. the results showed complete concordance between TaqMan-MGB and Sanger sequencing, with an overall agreement rate of 83.6% with DR imaging. For individuals with T/T genotypes (127/139), the detection accuracy reached 91.4%. This method demonstrated high specificity, simplicity, and cost-efficiency, significantly reducing the time and financial burden associated with traditional imaging-based approaches. the findings indicate that the TaqMan-MGB technique can accurately identify the T/T genotype at the SNP site and its strong association with the multi-vertebrae phenotypes, offering an effective and reliable tool for molecular breeding of Ujimqin sheep. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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27 pages, 1595 KB  
Review
Gene Therapy of Adrenomyeloneuropathy: Challenges, Target Cells, and Prospectives
by Pierre Bougnères, Catherine Le Stunff and Romina Aron Badin
Biomedicines 2025, 13(8), 1892; https://doi.org/10.3390/biomedicines13081892 - 4 Aug 2025
Viewed by 529
Abstract
Gene replacement using adeno-associated viral (AAV) vectors has become a major therapeutic avenue for neurodegenerative diseases (NDD). In single-gene diseases with loss-of-function mutations, the objective of gene therapy is to express therapeutic transgenes abundantly in cell populations that are implicated in the pathological [...] Read more.
Gene replacement using adeno-associated viral (AAV) vectors has become a major therapeutic avenue for neurodegenerative diseases (NDD). In single-gene diseases with loss-of-function mutations, the objective of gene therapy is to express therapeutic transgenes abundantly in cell populations that are implicated in the pathological phenotype. X-ALD is one of these orphan diseases. It is caused by ABCD1 gene mutations and its main clinical form is adreno-myelo-neuropathy (AMN), a disabling spinal cord axonopathy starting in middle-aged adults. Unfortunately, the main cell types involved are yet poorly identified, complicating the choice of cells to be targeted by AAV vectors. Pioneering gene therapy studies were performed in the Abcd1-/y mouse model of AMN with AAV9 capsids carrying the ABCD1 gene. These studies tested ubiquitous or cell-specific promoters, various routes of vector injection, and different ages at intervention to either prevent or reverse the disease. The expression of one of these vectors was studied in the spinal cord of a healthy primate. In summary, gene therapy has made promising progress in the Abcd1-/y mouse model, inaugurating gene replacement strategies in AMN patients. Because X-ALD is screened neonatally in a growing number of countries, gene therapy might be applied in the future to patients before they become overtly symptomatic. Full article
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20 pages, 5041 KB  
Review
Aquatic Biomass-Based Carbon Dots: A Green Nanostructure for Marine Biosensing Applications
by Ahmed Dawood, Mohsen Ghali, Laura Micheli, Medhat H. Hashem and Clara Piccirillo
Clean Technol. 2025, 7(3), 64; https://doi.org/10.3390/cleantechnol7030064 - 1 Aug 2025
Viewed by 468
Abstract
Aquatic biomass—ranging from fish scales and crustacean shells to various algae species—offers an abundant, renewable source for carbon dot (CD) synthesis, aligning with circular economy principles. This review highlights recent studies for valorizing aquatic biomass into high-performance carbon-based nanomaterials—specifically aquatic biomass-based carbon dots [...] Read more.
Aquatic biomass—ranging from fish scales and crustacean shells to various algae species—offers an abundant, renewable source for carbon dot (CD) synthesis, aligning with circular economy principles. This review highlights recent studies for valorizing aquatic biomass into high-performance carbon-based nanomaterials—specifically aquatic biomass-based carbon dots (AB-CDs)—briefly summarizing green synthesis approaches (e.g., hydrothermal carbonization, pyrolysis, and microwave-assisted treatments) that minimize environmental impact. Subsequent sections highlight the varied applications of AB-CDs, particularly in biosensing (including the detection of marine biotoxins), environmental monitoring of water pollutants, and drug delivery systems. Physically AB-CDs show unique optical and physicochemical properties—tunable fluorescence, high quantum yields, enhanced sensitivity, selectivity, and surface bio-functionalization—that make them ideal for a wide array of applications. Overall, the discussion underlines the significance of this approach; indeed, transforming aquatic biomass into carbon dots can contribute to sustainable nanotechnology, offering eco-friendly solutions in sensing, environmental monitoring, and therapeutics. Finally, current challenges and future research directions are discussed to give a perspective of the potential of AB-CDs; the final aim is their integration into multifunctional, real-time monitoring and therapeutic systems—for sustainable nanotechnology innovations. Full article
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15 pages, 2504 KB  
Review
The Madangamines: Synthetic Strategies Toward Architecturally Complex Alkaloids
by Valentina Ríos, Cristian Maulen, Claudio Parra and Ben Bradshaw
Mar. Drugs 2025, 23(8), 301; https://doi.org/10.3390/md23080301 - 28 Jul 2025
Viewed by 539
Abstract
Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven [...] Read more.
Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven total syntheses—covering five of the six members—have been reported to date. These syntheses, involving 28 to 36 steps and global yields ranging from 0.006% to 0.029%, highlight the formidable challenge these compounds present. This review summarizes the key synthetic strategies developed to access critical fragments, including the construction of the ABC diazatricyclic core and the ACE ring systems. Approaches to assembling the ABCD and ABCE tetracyclic frameworks are also discussed. Finally, we highlight the completed total syntheses of madangamines A–E, with a focus on pivotal transformations and strategic innovations that have enabled progress in this field. Full article
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25 pages, 959 KB  
Article
Personality and Smartphone Addiction in Romania’s Digital Age: The Mediating Role of Professional Status and the Moderating Effect of Adaptive Coping
by Daniela-Elena Lițan
J. Intell. 2025, 13(7), 86; https://doi.org/10.3390/jintelligence13070086 - 15 Jul 2025
Viewed by 1110
Abstract
In this research, we aimed to evaluate the relationship between the main dimensions of personality (Extraversion, Maturity, Agreeableness, Conscientiousness, and Self-actualization) and mobile phone addiction, both directly and mediated by the professional context (professional status), and moderated by adaptive cognitive-emotional coping strategies. The [...] Read more.
In this research, we aimed to evaluate the relationship between the main dimensions of personality (Extraversion, Maturity, Agreeableness, Conscientiousness, and Self-actualization) and mobile phone addiction, both directly and mediated by the professional context (professional status), and moderated by adaptive cognitive-emotional coping strategies. The participants, adult Romanian citizens, completed measures of personality—Big Five ABCD-M, a mobile phone addiction questionnaire, and the CERQ for adaptive coping strategies. They also responded to a question about current professional status (employed, student, etc.). Data were analyzed using Jamovi, and the findings were somewhat unexpected, though it aligned with the existing literature. Maturity emerged as a consistent inverse predictor of smartphone addiction (r = −0.45, β = −0.43, p < 0.001) across all three analyses. Extraversion showed an indirect effect mediated by professional status (β = −0.077, p < 0.05). Self-actualization was also found to predict smartphone addiction positively through full mediation by professional status (β = 0.05, p < 0.05). Agreeableness became a significant negative predictor (β = −0.13, p < 0.05) only when adaptive coping strategies were included. These findings highlight that the transition from frequent smartphone use—whether for work or personal reasons—to addiction can be subtle. This study may support both the general population in understanding smartphone use from a psycho-emotional perspective and organizations in promoting a healthy work-life balance. Full article
(This article belongs to the Special Issue Social Cognition and Emotions)
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24 pages, 14733 KB  
Article
Disentangling the Source of Uncertainty in Monthly Streamflow Predictions: A Case Study of Riu Mannu di Narcao Basin, Sardinia Region, Italy
by Aklilu Assefa Tilahun, Ouafik Boulariah, Francesco Viola and Roberto Deidda
Water 2025, 17(13), 2036; https://doi.org/10.3390/w17132036 - 7 Jul 2025
Viewed by 541
Abstract
This study quantifies the uncertainty in monthly streamflow predictions under future climate scenarios in two periods (near and far future) for the Riu Mannu di Narcao basin in Sardinia, Italy. The sources of uncertainty include the hydrological model structure, model parameters, and variability [...] Read more.
This study quantifies the uncertainty in monthly streamflow predictions under future climate scenarios in two periods (near and far future) for the Riu Mannu di Narcao basin in Sardinia, Italy. The sources of uncertainty include the hydrological model structure, model parameters, and variability in climatic inputs derived from global and regional climate models (GCM-RCM coupling) and representative concentration pathways (RCPs). Three conceptual and lumped hydrological models (GR3M, ABCD, and IHACRES) were combined with four climate models and two RCPs (RCP 4.5 and RCP 8.5) to assess future streamflow. Monte Carlo simulations were performed to evaluate parameter uncertainty, and the analysis of variance (ANOVA) method was applied to quantify the different sources of uncertainty. The results reveal that, as a single source, GCM-RCM coupling is the largest contributor, accounting for 47.32% (54.64%) of total near (far) future monthly streamflow projection uncertainties, followed by the hydrological model structure at 16.02% (21.09%), RCP scenarios at 15.35% (8.54%), and parameter uncertainty at 0.79% (1.39%). A consistent decline in median monthly streamflow is projected, especially during winter months (December to February), raising a concern about water availability in the region. Our study quantified different sources of uncertainty in monthly streamflow predictions under climate change, disentangling the roles of the hydrological model, model parameters, climate model, and climate scenario for reliable future streamflow projections. Full article
(This article belongs to the Section Hydrology)
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21 pages, 1766 KB  
Article
MvfR Shapes Pseudomonas aeruginosa Interactions in Polymicrobial Contexts: Implications for Targeted Quorum-Sensing Inhibition
by Kelsey M. Wheeler, Myung Whan Oh, Julianna Fusco, Aishlinn Mershon, Erin Kim, Antonia De Oliveira and Laurence G. Rahme
Cells 2025, 14(10), 744; https://doi.org/10.3390/cells14100744 - 20 May 2025
Viewed by 1166
Abstract
Infections often occur in complex niches consisting of multiple bacteria. Despite the increasing awareness, there is a fundamental gap in understanding which interactions govern microbial community composition. Pseudomonas aeruginosa is frequently isolated from monomicrobial and polymicrobial human infections. This pathogen forms polymicrobial infections [...] Read more.
Infections often occur in complex niches consisting of multiple bacteria. Despite the increasing awareness, there is a fundamental gap in understanding which interactions govern microbial community composition. Pseudomonas aeruginosa is frequently isolated from monomicrobial and polymicrobial human infections. This pathogen forms polymicrobial infections with other ESKAPEE pathogens and defies eradication by conventional therapies. By analyzing the competition within co-cultures of P. aeruginosa and representative secondary pathogens that commonly co-infect patients, we demonstrate the antagonism of P. aeruginosa against other ESKAPEE pathogens and the contribution of this pathogen’s multiple quorum-sensing (QS) systems in these interactions. QS is a highly conserved bacterial cell-to-cell communication mechanism that coordinates collective gene expressions at the population level, and it is also involved in P. aeruginosa virulence. Using a collection of P. aeruginosa QS mutants of the three major systems, LasR/LasI, MvfR/PqsABCDE, and RhlR/RhlI, and mutants of several QS-regulated functions, we reveal that MvfR and, to a lesser extent, LasR and RhlR, control competition between P. aeruginosa and other microbes, possibly through their positive impact on pyoverdine, pyochelin, and phenazine genes. We show that MvfR inhibition alters competitive interspecies interactions and preserves the coexistence of P. aeruginosa with the ESKAPEE pathogens tested while disarming the pathogens’ ability to form biofilm and adhere to lung epithelial cells. Our results highlight the role of MvfR inhibition in modulating microbial competitive interactions across multiple species, while simultaneously attenuating virulence traits. These findings reveal the complexity and importance of QS in interspecies interactions and underscore the impact of the anti-virulence approach in microbial ecology and its importance for treating polymicrobial infections. Full article
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53 pages, 1175 KB  
Review
Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy
by Pierre Bougnères and Catherine Le Stunff
Genes 2025, 16(5), 590; https://doi.org/10.3390/genes16050590 - 17 May 2025
Cited by 2 | Viewed by 2185
Abstract
Background: X-ALD is a white matter (WM) disease caused by mutations in the ABCD1 gene encoding the transporter of very-long-chain fatty acids (VLCFAs) into peroxisomes. Strikingly, the same ABCD1 mutation causes either devastating brain inflammatory demyelination during childhood or, more often, progressive spinal [...] Read more.
Background: X-ALD is a white matter (WM) disease caused by mutations in the ABCD1 gene encoding the transporter of very-long-chain fatty acids (VLCFAs) into peroxisomes. Strikingly, the same ABCD1 mutation causes either devastating brain inflammatory demyelination during childhood or, more often, progressive spinal cord axonopathy starting in middle-aged adults. The accumulation of undegraded VLCFA in glial cell membranes and myelin has long been thought to be the central mechanism of X-ALD. Methods: This review discusses studies in mouse and drosophila models that have modified our views of X-ALD pathogenesis. Results: In the Abcd1 knockout (KO) mouse that mimics the spinal cord disease, the late manifestations of axonopathy are rapidly reversed by ABCD1 gene transfer into spinal cord oligodendrocytes (OLs). In a peroxin-5 KO mouse model, the selective impairment of peroxisomal biogenesis in OLs achieves an almost perfect phenocopy of cerebral ALD. A drosophila knockout model revealed that VLCFA accumulation in glial myelinating cells causes the production of a toxic lipid able to poison axons and activate inflammatory cells. Other mouse models showed the critical role of OLs in providing energy substrates to axons. In addition, studies on microglial changing substates have improved our understanding of neuroinflammation. Conclusions: Animal models supporting a primary role of OLs and axonal pathology and a secondary role of microglia allow us to revisit of X-ALD mechanisms. Beyond ABCD1 mutations, pathogenesis depends on unidentified contributors, such as genetic background, cell-specific epigenomics, potential environmental triggers, and stochasticity of crosstalk between multiple cell types among billions of glial cells and neurons. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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