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132 records · Page 8Linked to original sources

Analysis of end-stage renal disease mediated by cuproptosis-related genes.

OBJECTIVE: The complex pathophysiological mechanism of end-stage renal disease (ESRD) has not been fully understood. Cuproptosis is a newly discovered type of programmed cell death. Therefore, this study attempts to clarify the relationship between cuproptosis-related genes (CRGs) and the phenotype of ESRD. MATERIALS AND METHODS: The National Center for Biological Information Gene Expression Omnibus database was applied to obtain the GSE37171 dataset comprising whole-genome microarray analysis of peripheral blood samples. A 3 : 1 case-control design was employed with 75 ESRD patients and 20 healthy controls who were frequency-matched for age, sex, and ethnicity. Based on differentially expressed genes (DEGs) and genes related to cuproptosis, CRGs were identified. Thereafter, we explored two different subpopulations based on the cuproptosis gene and analyzed their expression and immune infiltration. Genes specific to the CRG cluster were identified through the weighted gene co-expression network analysis algorithm, and the best prediction model was determined and verified by four machine learning methods. RESULTS: The study identified 14 differentially expressed CRGs, among which ATP7B, SLC31A1, LIAS, LIPT1, DLD, MTF1, CDKN2A, DBT, and DLST had relatively high expression levels in the ESRD samples. Compared with the control group, expression levels of FDX1, DLAT, PDHA1, PDHB, and GLS were significantly lower in the ESRD group, and CRGs played a key role in the regulation of immune infiltration in ESRD. Two cuproptosis-related molecular clusters were identified in the ESRD samples. Cluster2 was more correlated with the immune infiltration of ESRD. By analyzing the intersection points between CRG cluster and key genes of ESRD, a total of 888 specific DEGs were identified. Functional differences related to specific DEGs were further explored using gene set variation analysis. Five significant genes (SMC5, USP47, USP53, AGA, and DMXL1) were identified by the support vector machine model as key predictors for ESRD disease risk, achieving an area under the curve (AUC) of 1.00 in internal validation. However, external validation in independent cohorts is required prior to clinical application. Individual gene analysis showed an AUC > 0.81 in discriminating ESRD patients from healthy controls, and the expression of all 5 genes in ESRD patients was significantly lower than in the control group. CONCLUSION: This study clarified the relationship between CRGs and the phenotype of ESRD, analyzed their specific roles in the immune microenvironment, and obtained a predictive model, providing new insights for the study of its potential therapeutic targets.

Humans

Cytonuclear conflict and reticulate evolution in the Morelloid clade (Solanum, Solanaceae): Insights from genome skimming and network Phylogenomics.

The Morelloid clade (black nightshades) is one of the most strongly supported clades within the megadiverse Solanum genus. It comprises 76 globally distributed, non-spiny herbaceous and suffrutescent species. While often erroneously considered poisonous weeds, several species are economically important as orphan crops. The clade is closely related to tomato and potato but, due to a lack of focused breeding efforts, remains a putative reservoir of genetic diversity for crop improvement. Despite this potential, we lack fundamental knowledge on the evolution of the Morelloid clade. The group includes polyploid species with unknown parental origins-likely reflecting reticulate processes such as hybridization, introgression, and associated backcrossing events. Prior analyses have been unable to disentangle these processes, leaving the mechanisms underlying reticulate evolution in the Morelloid clade poorly understood. Here, we use genome skimming to produce a well-supported maximum likelihood plastid phylogeny from complete circularized plastomes and a coalescent-based species tree from combined Angiosperms353 and conserved ortholog set nuclear markers. Our dataset, composed of previously published data and deep genome skimming from herbarium samples, spans 26 Morelloid species. To investigate phylogenetic discordance, we used a nuclear phylogenetic network, multispecies coalescent simulations, a fused rooted nuclear chloroplast tree, and quantification of nuclear gene tree concordance. We show that incongruence between nuclear and plastid trees is pervasive and cannot be explained by incomplete lineage sorting alone. Instead, our results demonstrate that events consistent with repeated chloroplast capture have shaped the reticulate evolutionary history of the clade, especially among African polyploid and Pan-American diploid lineages.

Phylogeny

Assembly and Characterization of the First Complete Mitochondrial Genome of Tussilago farfara L.: Insights into Biological Functions and Phylogenetic Relationships within the Asteraceae Family.

Tussilago farfara L., a member of the Asteraceae family, is an economically valuable species due to its edible and medicinal properties. To elucidate the structural characteristics, genetic mechanisms, and evolutionary pathways of the organelle genomes of T. farfara, we sequenced, assembled, and annotated its mitochondrial genome for the first time. The complete mitochondrial genome of T. farfara spans 306,024 bp and contains 33 mitochondrial protein-coding genes (PCGs), 3 rRNAs, and 22 tRNAs. Analysis of the nucleotide substitution rate and genetic diversity revealed that most mitochondrial genome genes may have undergone purifying selection, indicating a slow evolutionary rate and a relatively conserved genomic structure. We further identified 13 fragments of chloroplast-derived DNA integrated into the mitochondrial genome, evidencing intracellular gene transfer. Collinearity analysis showed that Arctium lappa shares the most extensive mitochondrial homologous sequences and the highest sequence similarity with T. farfara. Phylogenetic analysis based on the mitochondrial genome helped to clarify the evolutionary and taxonomic position of T. farfara within the Asteraceae family. The mitochondrial genome sequence of T. farfara provides a valuable genomic resource for species identification and for evolutionary studies within the Asteraceae family.

Genome, Mitochondrial

Exploratory identification and cellular functional characterization of ppiabl as a candidate gene associated with growth traits in Paralichthys olivaceus.

The Japanese flounder (Paralichthys olivaceus) is an important mariculture species. However, the genetic mechanisms underlying its growth traits remain poorly understood. To explore the genetic basis of growth variation, whole-genome resequencing was performed in a cultured cohort of 60 individuals, followed by exploratory genome-wide association analysis and candidate-gene prioritization. The results revealed heritability estimates of 0.40 for body weight and 0.24 for body length, with substantial overlap in associated loci between the two traits. Exploratory association and variant-annotation analyses prioritized ppiabl, which carries a nonconservative missense variant, as a candidate gene for further investigation. Tissue expression analysis showed that ppiabl was highly expressed in muscle tissue. This gene encodes a protein belonging to the conserved peptidyl-prolyl cis-trans isomerase family. In Japanese flounder primary muscle cells, ppiabl knockdown was associated with altered expression of growth-related genes and an increased G1-phase fraction, whereas overexpression produced changes in the opposite direction. In line with this, fast-growing individuals were found to have significantly larger muscle fiber areas than slow-growing ones. These findings suggest that ppiabl may be involved in muscle-related cellular processes associated with growth variation in Japanese flounder, although its contribution to whole-animal growth requires further validation. Overall, this exploratory study prioritizes ppiabl as a candidate gene potentially associated with growth-related cellular processes in Japanese flounder, although validation in larger independent populations and in vivo models is required.

Animals

Genome-wide insights into the evolutionary and demographic history of the red alga Mazzaella laminarioides: Evidence for speciation with ancient migration along the southeast Pacific coast.

The mechanisms driving lineage divergence in red algae remain unexplored, despite the group's remarkable diversity and ancient evolutionary history. The red alga Mazzaella laminarioides, a Chilean intertidal species complex composed of three parapatric cryptic lineages (North, Center, South), offers a valuable system to evaluate these processes, as its life history combines severe dispersal limitation with a haploid-diploid cycle that may influence the emergence of reproductive barriers. We reconstructed its evolutionary history using whole-genome sequencing and nuclear genome assembly of representative individuals from each lineage. Phylogenomic analyses based on 1,507 single-copy orthologs recovered three deeply divergent lineages with limited nuclear discordance consistent with incomplete lineage sorting. For both splits, demographic modelling was most consistent with an Ancient Migration scenario, although support over strict isolation was moderate, suggesting that divergence may have begun with low asymmetric ancestral gene flow followed by subsequent loss of connectivity, demographic bottlenecks, and later population expansion. Coding sequence analyses revealed lineage-specific dN/dS heterogeneity; only one South-lineage locus passed FDR correction (metaxin-1, mitochondrial protein import), with two further South-lineage candidates in chlorophyll and heme biosynthesis falling below the FDR threshold. Together, these signals suggest that divergent selective pressures on energy acquisition may have contributed to divergence at the southern end of the distribution. These results add to the small but growing body of whole-genome data for red algae and, alongside recent macroalgal studies, suggest that ancestral connectivity could be a recurrent feature of lineage divergence even in marine organisms with extremely restricted dispersal.

Rhodophyta

Multi-omics integrative analysis provides insight into potential molecular responses to sustained high water flow in common carp (Cyprinus carpio) cultured in recirculating aquaculture.

To investigate the potential molecular responses by which water flow intensity affects the growth of common carp (Cyprinus carpio) in a recirculating aquaculture system (RAS), a control group (CG, actual water velocity 0.3&#xa0;cm/s) and three sustained flow treatment groups were established, including a low-flow group (LF, 1 body length per second, bl/s), a medium-flow group (MF, 2 bl/s), and a high-flow group (HF, 3 bl/s). After 12&#xa0;weeks of culture in the RAS, growth performance was compared among groups under different flow intensities. The best-performing group and the control group were then selected for the determination of intestinal digestive enzyme activities, as well as transcriptomic and whole-genome bisulfite sequencing analyses of muscle tissue. The results showed that the specific growth rate and feed intake of the HF group were significantly higher than those of the other groups (P&#xa0;<&#xa0;0.05), whereas no significant difference in feed conversion ratio was observed among groups. Compared with the CG group, lipase activity was significantly higher in the HF group (P&#xa0;<&#xa0;0.05), while &#x3b1;-amylase and trypsin activities showed increasing trends without significant differences. RNA-seq identified a total of 273 differentially expressed genes, including 72 upregulated genes and 201 downregulated genes in the HF group relative to the CG group. These genes were mainly enriched in glycolysis, pyruvate metabolism, ATP metabolism, the pentose phosphate pathway, the insulin signaling pathway, the PPAR signaling pathway, and the adipocytokine signaling pathway, indicating that sustained high water flow induced a muscle transcriptional response characterized by remodeling of energy metabolism and substrate utilization. Whole-genome bisulfite sequencing analysis showed that DNA methylation in common carp muscle occurred predominantly in the CpG context. Differentially methylated regions between the HF and CG groups were mainly distributed in transcription-related regulatory regions, including promoters, CpG islands, and CpG island shores. In promoter regions, the number of hypermethylated regions in the HF group relative to the CG group was markedly higher than that of hypomethylated regions. Integrated analysis further identified two candidate genes showing both promoter differential methylation and differential expression, namely LOC109094644 and bcorl1, suggesting that adaptation to high water flow may involve IGF-related growth regulation and remodeling of upstream transcriptional programs. The qPCR results were consistent with the transcriptomic data. Taken together, within the tested range, a sustained water flow of 3 bl/s was more conducive to the growth of common carp in the RAS, which may be associated with enhanced lipid digestion and utilization, remodeling of the muscle energy metabolic network, changes in promoter methylation, and the coordinated regulation of key candidate genes. This study provides a theoretical basis for clarifying the exercise adaptation mechanism of common carp in recirculating aquaculture and for optimizing flow velocity parameters.

Animals