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13 pages, 7209 KiB  
Article
Evolutionary Analysis of the Land Plant-Specific TCP Interactor Containing EAR Motif Protein (TIE) Family of Transcriptional Corepressors
by Agustín Arce, Camila Schild, Delfina Maslein and Leandro Lucero
Plants 2025, 14(15), 2423; https://doi.org/10.3390/plants14152423 - 5 Aug 2025
Abstract
The plant-specific TCP transcription factor family originated before the emergence of land plants. However, the timing of the appearance of their specific transcriptional repressor family, the TCP Interactor containing EAR motif protein (TIE), remains unknown. Here, through phylogenetic analyses, we traced the origin [...] Read more.
The plant-specific TCP transcription factor family originated before the emergence of land plants. However, the timing of the appearance of their specific transcriptional repressor family, the TCP Interactor containing EAR motif protein (TIE), remains unknown. Here, through phylogenetic analyses, we traced the origin of the TIE family to the early evolution of the embryophyte, while an earlier diversification in algae cannot be ruled out. Strikingly, we found that the number of TIE members is highly constrained compared to the expansion of TCPs in angiosperms. We used co-expression data to identify potential TIE-TCP regulatory targets across Arabidopsis thaliana and rice. Notably, the expression pattern between these species is remarkably similar. TCP Class I and Class II genes formed two distinct clusters, and TIE genes cluster within the TCP Class I group. This study provides a comprehensive evolutionary analysis of the TIE family, shedding light on its conserved role in the regulation of gene transcription in flowering plant development. Full article
(This article belongs to the Special Issue Plant Molecular Phylogenetics and Evolutionary Genomics III)
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21 pages, 6621 KiB  
Article
Genome-Wide Identification and Expression Pattern Analysis of the Late Embryogenesis Abundant (LEA) Family in Foxtail Millet (Setaria italica L.)
by Yingying Qin, Yiru Zhao, Xiaoyu Li, Ruifu Wang, Shuo Chang, Yu Zhang, Xuemei Ren and Hongying Li
Genes 2025, 16(8), 932; https://doi.org/10.3390/genes16080932 (registering DOI) - 4 Aug 2025
Abstract
Background/Objectives: Late embryogenesis abundant (LEA) proteins regulate stress responses and contribute significantly to plant stress tolerance. As a model species for stress resistance studies, foxtail millet (Setaria italica) lacks comprehensive characterization of its LEA gene family. This study aimed to [...] Read more.
Background/Objectives: Late embryogenesis abundant (LEA) proteins regulate stress responses and contribute significantly to plant stress tolerance. As a model species for stress resistance studies, foxtail millet (Setaria italica) lacks comprehensive characterization of its LEA gene family. This study aimed to comprehensively identify SiLEA genes in foxtail millet and elucidate their functional roles and tissue-specific expression patterns. Methods: Genome-wide identification of SiLEA genes was conducted, followed by phylogenetic reconstruction, cis-acting element analysis of promoters, synteny analysis, and expression profiling. Results: Ninety-four SiLEA genes were identified and classified into nine structurally distinct subfamilies, which are unevenly distributed across all nine chromosomes. Phylogenetic analysis showed closer clustering of SiLEA genes with sorghum and rice orthologs than with Arabidopsis thaliana AtLEA genes. Synteny analysis indicated the LEA gene family expansion through tandem and segmental duplication. Promoter cis-element analysis linked SiLEA genes to plant growth regulation, stress responses, and hormone signaling. Transcriptome analysis revealed tissue-specific expression patterns among SiLEA members, while RT-qPCR verified ABA-induced transcriptional regulation of SiLEA genes. Conclusions: This study identified 94 SiLEA genes grouped into nine subfamilies with distinct spatial expression profiles. ABA treatment notably upregulated SiASR-2, SiASR-5, and SiASR-6 in both shoots and roots. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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30 pages, 3430 KiB  
Article
Stage-Specific Serum Proteomic Signatures Reveal Early Biomarkers and Molecular Pathways in Huntington’s Disease Progression
by Christiana C. Christodoulou, Christiana A. Demetriou and Eleni Zamba-Papanicolaou
Cells 2025, 14(15), 1195; https://doi.org/10.3390/cells14151195 - 4 Aug 2025
Viewed by 41
Abstract
Background: Huntington’s Disease (HD) is a monogenic neurodegenerative disease resulting in a CAG repeat expansion in the HTT gene. Despite this genetic simplicity, its molecular mechanisms remain highly complex. Methods: In this study, untargeted serum proteomics, bioinformatics analysis, biomarker filtering and ELISA validation [...] Read more.
Background: Huntington’s Disease (HD) is a monogenic neurodegenerative disease resulting in a CAG repeat expansion in the HTT gene. Despite this genetic simplicity, its molecular mechanisms remain highly complex. Methods: In this study, untargeted serum proteomics, bioinformatics analysis, biomarker filtering and ELISA validation were implemented to characterize the proteomic landscape across the three HD stages—asymptomatic, early symptomatic and symptomatic advanced—alongside gender/age-matched controls. Results: We identified 84 over-expressed and 118 under-expressed differentially expressed proteins. Enrichment analysis revealed dysregulation in pathways including the complement cascade, LXR/RXR activation and RHOGDI signaling. Biomarker analysis highlighted key proteins with diagnostic potential, including CAP1 (AUC = 0.809), CAPZB (AUC = 0.861), TAGLN2 (AUC = 0.886), THBS1 (AUC = 0.883) and CFH (AUC = 0.948). CAP1 and CAPZB demonstrated robust diagnostic potential in linear mixed-effects models. CAP1 decreased in the asymptomatic stage, suggesting early cytoskeletal disruption, while CAPZB was consistently increased across HD stages. Conclusions: Our findings illuminate the dynamic proteomic and molecular landscape of HD. Future studies should validate these candidates in larger, more diverse cohorts and explore their mechanistic roles in HD pathology and progression. Full article
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14 pages, 4690 KiB  
Article
Systematic Analysis of Dof Gene Family in Prunus persica Unveils Candidate Regulators for Enhancing Cold Tolerance
by Zheng Chen, Xiaojun Wang, Juan Yan, Zhixiang Cai, Binbin Zhang, Jianlan Xu, Ruijuan Ma, Mingliang Yu and Zhijun Shen
Int. J. Mol. Sci. 2025, 26(15), 7509; https://doi.org/10.3390/ijms26157509 - 4 Aug 2025
Viewed by 65
Abstract
Late-spring frost events severely damage low-chill peach blossoms, causing significant yield losses. Although 5-aminolevulinic acid (ALA) enhances cold tolerance through the PpC3H37-PpWRKY18 module, the regulatory mechanism of ALA on PpC3H37 remains to be elucidated. Using yeast one-hybrid screening with the PpC3H37 promoter as [...] Read more.
Late-spring frost events severely damage low-chill peach blossoms, causing significant yield losses. Although 5-aminolevulinic acid (ALA) enhances cold tolerance through the PpC3H37-PpWRKY18 module, the regulatory mechanism of ALA on PpC3H37 remains to be elucidated. Using yeast one-hybrid screening with the PpC3H37 promoter as bait, we identified PpDof9 as a key interacting transcription factor. A genome-wide analysis revealed 25 PpDof genes in peaches (Prunus persica). These genes exhibited variable physicochemical properties, with most proteins predicted as nuclear-localized. Subcellular localization experiments in tobacco revealed that PpDof9 was localized to the nucleus, consistent with predictions. A synteny analysis indicated nine segmental duplication pairs and tandem duplications on chromosomes 5 and 6, suggesting duplication events drove family expansion. A conserved motif analysis confirmed universal presence of the Dof domain (Motif 1). Promoter cis-element screening identified low-temperature responsive (LTR) elements in 12 PpDofs, including PpDof1, PpDof8, PpDof9, and PpDof25. The quantitative real-time PCR (qRT-PCR) results showed that PpDof1, PpDof8, PpDof9, PpDof15, PpDof16, and PpDof25 were significantly upregulated under low-temperature stress, and this upregulation was further enhanced by ALA pretreatment. Our findings demonstrate ALA-mediated modulation of specific PpDof TFs in cold response and provide candidates (PpDof1, PpDof9, PpDof8, PpDof25) for enhancing floral frost tolerance in peaches. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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14 pages, 6927 KiB  
Article
Physiological and Transcriptomic Mechanisms Underlying Vitamin C-Mediated Cold Stress Tolerance in Grafted Cucumber
by Panpan Yu, Junkai Wang, Xuyang Zhang, Zhenglong Weng, Kaisen Huo, Qiuxia Yi, Chenxi Wu, Sunjeet Kumar, Hao Gao, Lin Fu, Yanli Chen and Guopeng Zhu
Plants 2025, 14(15), 2398; https://doi.org/10.3390/plants14152398 - 2 Aug 2025
Viewed by 266
Abstract
Cucumbers (Cucumis sativus L.) are highly sensitive to cold, but grafting onto cold-tolerant rootstocks can enhance their low-temperature resilience. This study investigates the physiological and molecular mechanisms by which exogenous vitamin C (Vc) mitigates cold stress in grafted cucumber seedlings. Using cucumber [...] Read more.
Cucumbers (Cucumis sativus L.) are highly sensitive to cold, but grafting onto cold-tolerant rootstocks can enhance their low-temperature resilience. This study investigates the physiological and molecular mechanisms by which exogenous vitamin C (Vc) mitigates cold stress in grafted cucumber seedlings. Using cucumber ‘Chiyu 505’ as the scion and pumpkin ‘Chuangfan No.1’ as the rootstock, seedlings were grafted using the whip grafting method. In the third true leaf expansion stage, seedlings were foliar sprayed with Vc at concentrations of 50, 100, 150, and 200 mg L−1. Three days after initial spraying, seedlings were subjected to cold stress (8 °C) for 3 days, with continued spraying. After that, morphological and physiological parameters were assessed. Results showed that 150 mg L−1 Vc treatment was most impactive, significantly reducing the cold damage index while increasing the root-to-shoot ratio, root vitality, chlorophyll content, and activities of antioxidant enzymes (SOD, POD, CAT). Moreover, this treatment enhanced levels of soluble sugars, soluble proteins, and proline compared to control. However, 200 mg L−1 treatment elevated malondialdehyde (MDA) content, indicating potential oxidative stress. For transcriptomic analysis, leaves from the 150 mg L−1 Vc and CK treatments were sampled at 0, 1, 2, and 3 days of cold stress. Differential gene expression revealed that genes associated with photosynthesis (LHCA1), stress signal transduction (MYC2-1, MYC2-2, WRKY22, WRKY2), and antioxidant defense (SOD-1, SOD-2) were initially up-regulated and subsequently down-regulated, as validated by qRT-PCR. Overall, we found that the application of 150 mg L−1 Vc enhanced cold tolerance in grafted cucumber seedlings by modulating gene expression networks related to photosynthesis, stress response, and the antioxidant defense system. This study provides a way for developing Vc biostimulants to enhance cold tolerance in grafted cucumbers, improving sustainable cultivation in low-temperature regions. Full article
(This article belongs to the Section Plant Response to Abiotic Stress and Climate Change)
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21 pages, 3959 KiB  
Article
Unveiling Stage-Specific Flavonoid Dynamics Underlying Drought Tolerance in Sweet Potato (Ipomoea batatas L.) via Integrative Transcriptomic and Metabolomic Analyses
by Tao Yin, Chaoyu Song, Huan Li, Shaoxia Wang, Wenliang Wei, Jie Meng and Qing Liu
Plants 2025, 14(15), 2383; https://doi.org/10.3390/plants14152383 - 2 Aug 2025
Viewed by 233
Abstract
Drought stress severely limits the productivity of sweet potato (Ipomoea batatas L.), yet the stage-specific molecular mechanisms of its adaptation remain poorly understood. Therefore, we integrated transcriptomics and extensive targeted metabolomics analysis to investigate the drought responses of the sweet potato cultivar [...] Read more.
Drought stress severely limits the productivity of sweet potato (Ipomoea batatas L.), yet the stage-specific molecular mechanisms of its adaptation remain poorly understood. Therefore, we integrated transcriptomics and extensive targeted metabolomics analysis to investigate the drought responses of the sweet potato cultivar ‘Luoyu 11’ during the branching and tuber formation stage (DS1) and the storage root expansion stage (DS2) under controlled drought conditions (45 ± 5% field capacity). Transcriptome analysis identified 8292 and 13,509 differentially expressed genes in DS1 and DS2, respectively, compared with the well-watered control (75 ± 5% field capacity). KEGG enrichment analysis revealed the activation of plant hormone signaling, carbon metabolism, and flavonoid biosynthesis pathways, and more pronounced transcriptional changes were observed during the DS2 stage. Metabolomic analysis identified 415 differentially accumulated metabolites across the two growth periods, with flavonoids being the most abundant (accounting for 30.3% in DS1 and 23.7% in DS2), followed by amino acids and organic acids, which highlighted their roles in osmotic regulation and oxidative stress alleviation. Integrated omics analysis revealed stage-specific regulation of flavonoid biosynthesis under drought stress. Genes such as CYP75B1 and IF7MAT were consistently downregulated, whereas flavonol synthase and glycosyltransferases exhibited differential expression patterns, which correlated with the selective accumulation of trifolin and luteoloside. Our findings provide novel insights into the molecular basis of drought tolerance in sweet potato and offer actionable targets for breeding and precision water management in drought-prone regions. Full article
(This article belongs to the Section Plant Response to Abiotic Stress and Climate Change)
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32 pages, 1447 KiB  
Article
Haplotypes of Echinococcus granulosus sensu stricto in Chile and Their Comparison Through Sequences of the Mitochondrial cox1 Gene with Haplotypes from South America and Other Continents
by Nicole Urriola-Urriola, Gabriela Rossi-Vargas and Yenny Nilo-Bustios
Parasitologia 2025, 5(3), 40; https://doi.org/10.3390/parasitologia5030040 - 1 Aug 2025
Viewed by 167
Abstract
Cystic echinococcosis is a zoonosis caused by the cestode Echinococcus granulosus sensu stricto. Population genetic studies and phylogeographic patterns are essential to understanding the transmission dynamics of this parasite under varying environmental conditions. In this study, the genetic diversity of E. granulosus [...] Read more.
Cystic echinococcosis is a zoonosis caused by the cestode Echinococcus granulosus sensu stricto. Population genetic studies and phylogeographic patterns are essential to understanding the transmission dynamics of this parasite under varying environmental conditions. In this study, the genetic diversity of E. granulosus s.s. was evaluated using 46 hydatid cyst samples obtained from sheep, goats, cattle, and humans across three regions of Chile: Coquimbo, La Araucanía, and Magallanes. Mitochondrial cox1 gene sequences were analyzed and compared with reference sequences reported from South America, Europe, Africa, Asia, and Oceania. In Chile, the EG01 haplotype was the predominant haplotype. A total of four haplotypes were identified, with low haplotype diversity (Hd = 0.461 ± 0.00637) and low nucleotide diversity (π = 0.00181 ± 0.00036). The haplotype network displayed a star-like configuration, with the EG01 genotype at the center, suggesting a potentially ancestral or widely distributed lineage. In Coquimbo (Tajima’s D = −0.93302, p = 0.061; Fu’s Fs = −0.003, p = 0.502) and Magallanes (Tajima’s D = −0.17406, p = 0.386; Fu’s Fs = −0.121, p = 0.414), both neutrality tests were non-significant, indicating no strong evidence for recent population expansion or selection. Star-like haplotype network patterns were also observed in populations from Europe, the Middle East, Asia, Africa, and Oceania, with the EG01 genotype occupying the central position. The population genetic structure of Echinococcus granulosus s.s. in Chile demonstrates considerable complexity, with EG01 as the predominant haplotype. Further comprehensive studies are required to assess the intraspecific genetic variability of E. granulosus s.s. throughout Chile and to determine whether this variability influences the key biological traits of the parasite. This structure may prove even more complex when longer fragments are analyzed, which could allow for the detection of finer-scale microdiversity among isolates from different hosts. We recommended that future cystic echinococcosis control programs take into account the genetic variability of E. granulosus s.s. strains circulating in each endemic region, to better understand their epidemiological, immunological, and possibly pathological differences. Full article
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19 pages, 3631 KiB  
Article
Genome-Wide Analyses of the XTH Gene Family in Brachypodium distachyon and Functional Analyses of the Role of BdXTH27 in Root Elongation
by Hongyan Shen, Qiuping Tan, Wenzhe Zhao, Mengdan Zhang, Cunhao Qin, Zhaobing Liu, Xinsheng Wang, Sendi An, Hailong An and Hongyu Wu
Int. J. Mol. Sci. 2025, 26(15), 7457; https://doi.org/10.3390/ijms26157457 - 1 Aug 2025
Viewed by 110
Abstract
Xyloglucan endotransglucosylase/hydrolases (XTHs) are a class of cell wall-associated enzymes involved in the construction and remodeling of cellulose/xyloglucan crosslinks. However, knowledge of this gene family in the model monocot Brachypodium distachyon is limited. A total of 29 BdXTH genes were identified from the [...] Read more.
Xyloglucan endotransglucosylase/hydrolases (XTHs) are a class of cell wall-associated enzymes involved in the construction and remodeling of cellulose/xyloglucan crosslinks. However, knowledge of this gene family in the model monocot Brachypodium distachyon is limited. A total of 29 BdXTH genes were identified from the whole genome, and these were further divided into three subgroups (Group I/II, Group III, and the Ancestral Group) through evolutionary analysis. Gene structure and protein motif analyses indicate that closely clustered BdXTH genes are relatively conserved within each group. A highly conserved amino acid domain (DEIDFEFLG) responsible for catalytic activity was identified in all BdXTH proteins. We detected three pairs of segmentally duplicated BdXTH genes and five groups of tandemly duplicated BdXTH genes, which played vital roles in the expansion of the BdXTH gene family. Cis-elements related to hormones, growth, and abiotic stress responses were identified in the promoters of each BdXTH gene, and when roots were treated with two abiotic stresses (salinity and drought) and four plant hormones (IAA, auxin; GA3, gibberellin; ABA, abscisic acid; and BR, brassinolide), the expression levels of many BdXTH genes changed significantly. Transcriptional analyses of the BdXTH genes in 38 tissue samples from the publicly available RNA-seq data indicated that most BdXTH genes have distinct expression patterns in different tissues and at different growth stages. Overexpressing the BdXTH27 gene in Brachypodium led to reduced root length in transgenic plants, which exhibited higher cellulose levels but lower hemicellulose levels compared to wild-type plants. Our results provide valuable information for further elucidation of the biological functions of BdXTH genes in the model grass B. distachyon. Full article
(This article belongs to the Section Molecular Plant Sciences)
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15 pages, 7392 KiB  
Article
Genetic Diversity and Population Structure of Tufted Deer (Elaphodus cephalophus) in Chongqing, China
by Fuli Wang, Chengzhong Yang, Yalin Xiong, Qian Xiang, Xiaojuan Cui and Jianjun Peng
Animals 2025, 15(15), 2254; https://doi.org/10.3390/ani15152254 - 31 Jul 2025
Viewed by 157
Abstract
The tufted deer (Elaphodus cephalophus), a Near-Threatened (NT) species endemic to China and Myanmar, requires robust genetic data for effective conservation. However, the genetic landscape of key populations, such as those in Chongqing, remains poorly understood. This study aimed to comprehensively [...] Read more.
The tufted deer (Elaphodus cephalophus), a Near-Threatened (NT) species endemic to China and Myanmar, requires robust genetic data for effective conservation. However, the genetic landscape of key populations, such as those in Chongqing, remains poorly understood. This study aimed to comprehensively evaluate the genetic diversity, population structure, gene flow, and demographic history of tufted deer across this critical region. We analyzed mitochondrial DNA (mtDNA) from 46 non-invasively collected fecal samples from three distinct populations: Jinfo Mountain (JF, n = 13), Simian Mountain (SM, n = 21), and the Northeastern Mountainous region (NEM, n = 12). Genetic variation was assessed using the cytochrome b (Cyt b) and D-loop regions, with analyses including Fst, gene flow (Nm), neutrality tests, and Bayesian Skyline Plots (BSP). Our results revealed the highest genetic diversity in the SM population, establishing it as a genetic hub. In contrast, the JF population exhibited the lowest diversity and significant genetic differentiation (>0.23) from the SM and NEM populations, indicating profound isolation. Gene flow was substantial between SM and NEM but severely restricted for the JF population. Demographic analyses, including BSP, indicated a long history of demographic stability followed by a significant expansion beginning in the Middle to Late Pleistocene. We conclude that the SM/NEM metapopulation serves as the genetic core for the species in this region, while the highly isolated JF population constitutes a distinct and vulnerable Management Unit (MU). This historical demographic expansion is likely linked to climatic and environmental changes during the Pleistocene, rather than recent anthropogenic factors. These findings underscore the urgent need for a dual conservation strategy: targeted management for the isolated JF population and the establishment of ecological corridors to connect the Jinfo Mountain and Simian Mountain populations, ensuring the long-term persistence of this unique species. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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30 pages, 4119 KiB  
Article
Ubiquitination Regulates Reorganization of the Membrane System During Cytomegalovirus Infection
by Barbara Radić, Igor Štimac, Alen Omerović, Ivona Viduka, Marina Marcelić, Gordana Blagojević Zagorac, Pero Lučin and Hana Mahmutefendić Lučin
Life 2025, 15(8), 1212; https://doi.org/10.3390/life15081212 - 31 Jul 2025
Viewed by 263
Abstract
Background: During infection with the cytomegalovirus (CMV), the membrane system of the infected cell is remodelled into a megastructure called the assembly compartment (AC). These extensive changes may involve the manipulation of the host cell proteome by targeting a pleiotropic function of the [...] Read more.
Background: During infection with the cytomegalovirus (CMV), the membrane system of the infected cell is remodelled into a megastructure called the assembly compartment (AC). These extensive changes may involve the manipulation of the host cell proteome by targeting a pleiotropic function of the cell such as ubiquitination (Ub). In this study, we investigate whether the Ub system is required for the establishment and maintenance of the AC in murine CMV (MCMV)-infected cells Methods: NIH3T3 cells were infected with wild-type and recombinant MCMVs and the Ub system was inhibited with PYR-41. The expression of viral and host cell proteins was analyzed by Western blot. AC formation was monitored by immunofluorescence with confocal imaging and long-term live imaging as the dislocation of the Golgi and expansion of Rab10-positive tubular membranes (Rab10 TMs). A cell line with inducible expression of hemagglutinin (HA)-Ub was constructed to monitor ubiquitination. siRNA was used to deplete host cell factors. Infectious virion production was monitored using the plaque assay. Results: The Ub system is required for the establishment of the infection, progression of the replication cycle, viral gene expression and production of infectious virions. The Ub system also regulates the establishment and maintenance of the AC, including the expansion of Rab10 TMs. Increased ubiquitination of WASHC1, which is recruited to the machinery that drives the growth of Rab10 TMs, is consistent with Ub-dependent rheostatic control of membrane tubulation and the continued expansion of Rab10 TMs. Conclusions: The Ub system is intensively utilized at all stages of the MCMV replication cycle, including the reorganization of the membrane system into the AC. Disruption of rheostatic control of the membrane tubulation by ubiquitination and expansion of Rab10 TREs within the AC may contribute to the development of a sufficient amount of tubular membranes for virion envelopment. Full article
(This article belongs to the Section Cell Biology and Tissue Engineering)
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18 pages, 300 KiB  
Review
Genetic Dissection of Energy Deficiency in Autism Spectrum Disorder
by John Jay Gargus
Genes 2025, 16(8), 923; https://doi.org/10.3390/genes16080923 (registering DOI) - 31 Jul 2025
Viewed by 345
Abstract
Background/Objectives: An important new consideration when studying autism spectrum disorder (ASD) is the bioenergetic mechanisms underlying the relatively recent rapid evolutionary expansion of the human brain, which pose fundamental risks for mitochondrial dysfunction and calcium signaling abnormalities and their potential role in [...] Read more.
Background/Objectives: An important new consideration when studying autism spectrum disorder (ASD) is the bioenergetic mechanisms underlying the relatively recent rapid evolutionary expansion of the human brain, which pose fundamental risks for mitochondrial dysfunction and calcium signaling abnormalities and their potential role in ASD, as recently highlighted by insights from the BTBR mouse model of ASD. The rapid brain expansion taking place as Homo sapiens evolved, particularly in the parietal lobe, led to increased energy demands, making the brain vulnerable to such metabolic disruptions as are seen in ASD. Methods: Mitochondrial dysfunction in ASD is characterized by impaired oxidative phosphorylation, elevated lactate and alanine levels, carnitine deficiency, abnormal reactive oxygen species (ROS), and altered calcium homeostasis. These dysfunctions are primarily functional, rather than being due to mitochondrial DNA mutations. Calcium signaling plays a crucial role in neuronal ATP production, with disruptions in inositol 1,4,5-trisphosphate receptor (ITPR)-mediated endoplasmic reticulum (ER) calcium release being observed in ASD patient-derived cells. Results: This impaired signaling affects the ER–mitochondrial calcium axis, leading to mitochondrial energy deficiency, particularly in high-energy regions of the developing brain. The BTBR mouse model, with its unique Itpr3 gene mutation, exhibits core autism-like behaviors and metabolic syndromes, providing valuable insights into ASD pathophysiology. Conclusions: Various interventions have been tested in BTBR mice, as in ASD, but none have directly targeted the Itpr3 mutation or its calcium signaling pathway. This review presents current genetic, biochemical, and neurological findings in ASD and its model systems, highlighting the need for further research into metabolic resilience and calcium signaling as potential diagnostic and therapeutic targets for ASD. Full article
(This article belongs to the Section Neurogenomics)
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20 pages, 5322 KiB  
Article
Regulation of Tetraspanin CD63 in Chronic Myeloid Leukemia (CML): Single-Cell Analysis of Asymmetric Hematopoietic Stem Cell Division Genes
by Christophe Desterke, Annelise Bennaceur-Griscelli and Ali G. Turhan
Bioengineering 2025, 12(8), 830; https://doi.org/10.3390/bioengineering12080830 - 31 Jul 2025
Viewed by 261
Abstract
(1) Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL oncoprotein. During the chronic phase, Philadelphia chromosome-positive hematopoietic stem cells generate proliferative myeloid cells with various stages of maturation. Despite this expansion, leukemic stem cells (LSCs) retain self-renewal capacity [...] Read more.
(1) Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL oncoprotein. During the chronic phase, Philadelphia chromosome-positive hematopoietic stem cells generate proliferative myeloid cells with various stages of maturation. Despite this expansion, leukemic stem cells (LSCs) retain self-renewal capacity via asymmetric cell divisions, sustaining the stem cell pool. Quiescent LSCs are known to be resistant to tyrosine kinase inhibitors (TKIs), potentially through BCR::ABL-independent signaling pathways. We hypothesize that dysregulation of genes governing asymmetric division in LSCs contributes to disease progression, and that their expression pattern may serve as a prognostic marker during the chronic phase of CML. (2) Methods: Genes related to asymmetric cell division in the context of hematopoietic stem cells were extracted from the PubMed database with the keyword “asymmetric hematopoietic stem cell”. The collected relative gene set was tested on two independent bulk transcriptome cohorts and the results were confirmed by single-cell RNA sequencing. (3) Results: The expression of genes involved in asymmetric hematopoietic stem cell division was found to discriminate disease phases during CML progression in the two independent transcriptome cohorts. Concordance between cohorts was observed on asymmetric molecules downregulated during blast crisis (BC) as compared to the chronic phase (CP). This downregulation during the BC phase was confirmed at single-cell level for SELL, CD63, NUMB, HK2, and LAMP2 genes. Single-cell analysis during the CP found that CD63 is associated with a poor prognosis phenotype, with the opposite prediction revealed by HK2 and NUMB expression. The single-cell trajectory reconstitution analysis in CP samples showed CD63 regulation highlighting a trajectory cluster implicating HSPB1, PIM2, ANXA5, LAMTOR1, CFL1, CD52, RAD52, MEIS1, and PDIA3, known to be implicated in hematopoietic malignancies. (4) Conclusion: Regulation of CD63, a tetraspanin involved in the asymmetric division of hematopoietic stem cells, was found to be associated with poor prognosis during CML progression and could be a potential new therapeutic target. Full article
(This article belongs to the Special Issue Micro- and Nano-Technologies for Cell Analysis)
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17 pages, 1204 KiB  
Article
The Great Wanderer: The Phylogeographic History of the Bicolor Pyramid Ant (Dorymyrmex bicolor Wheeler, 1906) in Central Veracruz, Mexico
by Maria Gómez-Lazaga and Alejandro Espinosa de los Monteros
Insects 2025, 16(8), 785; https://doi.org/10.3390/insects16080785 - 31 Jul 2025
Viewed by 246
Abstract
The goal of phylogeography is to explain how microevolutionary forces shape the gene pool of a lineage into the geography. In this study we have evaluated the amount of genetic variation in 13 populations of Dorymyrmex bicolor distributed in a mountainous region in [...] Read more.
The goal of phylogeography is to explain how microevolutionary forces shape the gene pool of a lineage into the geography. In this study we have evaluated the amount of genetic variation in 13 populations of Dorymyrmex bicolor distributed in a mountainous region in Central Veracruz, Mexico. To do so, we sequenced fragments from the mitochondrial COI, COII, and nuclear LWRh genes. Segregated sites were found only at the mitochondrial markers, recovering a total of 21 different haplotypes. The nucleotide diversity ranged from 0 to 0.5% at the different sampling sites. Phylogenetic and spatial analyses of molecular variance revealed a weak but significant phylogeographic structure associated with lowland and mountainous zones. Molecular clock analysis suggests that radiation in the mountain area started 7500 years ago, whereas lineage radiation in the lowland started more recently, around 2700 years ago. The phylogeographic structure is incipient, with nests from lowlands more closely related to mountain nests than to other lowland nests, and vice versa. This seems to be consistent with a model of incomplete lineage sorting. The obtained patterns appear to be the result of restricted gene flow mediated by a complex topographic landscape that has been shaped by a dynamic geologic history. Full article
(This article belongs to the Special Issue Ant Population Genetics, Phylogeography and Phylogeny)
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18 pages, 1267 KiB  
Article
Characterization of Antibiotic Administration Factors Associated with Microbiome Disruption and Subsequent Antibiotic-Resistant Infection and Colonization Events in Acute Myeloid Leukemia Patients Receiving Chemotherapy
by Samantha Franklin, Corina Ramont, Maliha Batool, Stephanie McMahon, Pranoti Sahasrabhojane, John C. Blazier, Dimitrios P. Kontoyiannis, Yang Ni and Jessica Galloway-Peña
Antibiotics 2025, 14(8), 770; https://doi.org/10.3390/antibiotics14080770 - 30 Jul 2025
Viewed by 320
Abstract
Background: Broad-spectrum antibiotics are often used for suspected infections in patients with hematologic malignancies due to the risk of severe infections. Although antibiotic use can lead to antimicrobial resistance and microbiome dysbiosis, the effects of antibiotics on the microbiome and resistome in patients [...] Read more.
Background: Broad-spectrum antibiotics are often used for suspected infections in patients with hematologic malignancies due to the risk of severe infections. Although antibiotic use can lead to antimicrobial resistance and microbiome dysbiosis, the effects of antibiotics on the microbiome and resistome in patients with acute myeloid leukemia (AML) undergoing remission induction chemotherapy (RIC) are not well understood. Methods: Various statistical models were utilized to examine the effects of antibiotic administration on the microbiome and resistome over time, as well as differences in AR-infection (ARI) and colonization (ARC) by important CDC-threats in 119 AML patients. Results: A greater number of unique antibiotic classes administered correlated with a loss of unique antibiotic resistance genes (ARGs) (R = −0.39, p = 0.008). Specifically, although a greater number of oxazolidinone administrations was correlated with a greater loss of diversity (R = −0.58, p < 0.001), each additional day of linezolid reduced the risk of ARC by ~30% (HR: 0.663, p = 0.047) and decreased the odds of acquiring genes predicted to confer macrolide (HR: 0.50, p = 0.026) resistance. Conclusions: The number of antibiotic administrations and the types of antibiotics used can influence the risk of antibiotic resistance gene (ARG) expansion and ARC events in AML patients undergoing RIC. While certain antibiotics may reduce microbial diversity, they are not always linked to an increase in ARGs or ARC events. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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14 pages, 2074 KiB  
Article
Special Regulation of GhANT in Ovules Increases the Size of Cotton Seeds
by Ning Liu, Yuping Chen, Yangbing Guan, Geyi Guan, Jian Yang, Feng Nie, Kui Ming, Wenqin Bai, Ming Luo and Xingying Yan
Genes 2025, 16(8), 912; https://doi.org/10.3390/genes16080912 - 30 Jul 2025
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Abstract
Background: Gossypium hirsutum L. is one of the main economic crops worldwide, and increasing the size/weight of its seeds is a potential strategy to improve its seed-related yield. AINTEGUMENTA (ANT) is an organogenesis transcription factor mediating cell proliferation and expansion in Arabidopsis, [...] Read more.
Background: Gossypium hirsutum L. is one of the main economic crops worldwide, and increasing the size/weight of its seeds is a potential strategy to improve its seed-related yield. AINTEGUMENTA (ANT) is an organogenesis transcription factor mediating cell proliferation and expansion in Arabidopsis, but little is known about its candidate function in upland cotton seed. Results: In this study, functional characterization of GhANT in the cotton seed development stage was performed. The expression pattern analysis showed that GhANT was predominantly expressed in the ovules, and its expression was consistent with the ovules’ development stage. Heterologous expression of GhANT in Arabidopsis promoted plant organ growth and led to larger seeds. Importantly, specific expression of GhANT by the TFM7 promoter in the cotton ovules enlarged the seeds and increased the cotton seed yield, as compared with the wild-type in a three-year field trial. Furthermore, transcription level analysis showed that numerous genes involved in cell division were up-regulated in the ovules of TFM7::GhANT lines in comparison to the wild-type. These results indicate that GhANT is a potential genetic resource for improving cotton seed yield through its molecular links with cell cycle controllers. Full article
(This article belongs to the Special Issue 5Gs in Crop Genetic and Genomic Improvement: 2nd Edition)
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