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Superoxide Dismutase 3 (SOD3) scavenges extracellular superoxide giving a hydrogen peroxide metabolite. Both Reactive Oxygen Species diffuse through aquaporins causing oxidative stress and biomolecular damage. SOD3 is differentially expressed in cancer and this research utilises Gene Expression Omnibus data series GSE2109 with 2,158 cancer samples. Genome-wide expression correlation analysis was conducted with SOD3 as the seed gene. Categorical SOD3 Pearson Correlation gene lists incrementing in correlation strength by 0.01 from ρ≥|0.34| to ρ≥|0.41| were extracted from the data. Positively and negatively SOD3 correlated genes were separated for each list and checked for significance against disease overlapping genes in the ClinVar and Orphanet databases via Enrichr. Disease causal genes were added to the relevant gene list and checked against Gene Ontology, Phenotype Ontology, and Elsevier Pathways via Enrichr before the significant ontologies containing causal and non-overlapping genes were reviewed with a literature search for possible disease and oxidative stress associations. 12 significant individually discriminated disorders were identified: Autosomal Dominant Cutis Laxa (p = 6.05x10 -7 ), Renal Tubular Dysgenesis of Genetic Origin (p = 6.05x10 -7 ), Lethal Arteriopathy Syndrome due to Fibulin-4 Deficiency (p = 6.54x10 -9 ), EMILIN-1-related Connective Tissue Disease (p = 6.54x10 -9 ), Holt-Oram Syndrome (p = 7.72x10 -10 ), Multisystemic Smooth Muscle Dysfunction Syndrome (p = 9.95x10 -15 ), Distal Hereditary Motor Neuropathy type 2 (p = 4.48x10 -7 ), Congenital Glaucoma (p = 5.24x210 -9 ), Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (p = 3.77x10 -16 ), Classical-like Ehlers-Danlos Syndrome type 1 (p = 3.77x10 -16 ), Retinoblastoma (p = 1.9x10 -8 ), and Lynch Syndrome (p = 5.04x10 -9 ). 35 novel (21 unique) genes across 12 disorders were identified: ADNP , AOC3 , CDC42EP2 , CHTOP , CNN1 , DES , FOXF1 , FXR1 , HLTF , KCNMB1 , MTF2 , MYH11 , PLN , PNPLA2 , REST , SGCA , SORBS1 , SYNPO2 , TAGLN , WAPL , and ZMYM4 . These genes are proffered as potential biomarkers or therapeutic targets for the corresponding rare diseases discussed.

Phylogenetic relationships in Rosaceae have long been problematic because of frequent hybridisation, apomixis and presumed rapid radiation, and their historical diversification has not been clarified. With 87 genera representing all subfamilies and tribes of Rosaceae and six of the other eight families of Rosales (outgroups), we analysed 130 newly sequenced plastomes together with 12 from GenBank in an attempt to reconstruct deep relationships and reveal temporal diversification of this family. Our results highlight the importance of improving sequence alignment and the use of appropriate substitution models in plastid phylogenomics. Three subfamilies and 16 tribes (as previously delimited) were strongly supported as monophyletic, and their relationships were fully resolved and strongly supported at most nodes. Rosaceae were estimated to have originated during the Late Cretaceous with evidence for rapid diversification events during several geological periods. The major lineages rapidly diversified in warm and wet habits during the Late Cretaceous, and the rapid diversification of genera from the early Oligocene onwards occurred in colder and drier environments. Plastid phylogenomics offers new and important insights into deep phylogenetic relationships and the diversification history of Rosaceae. The robust phylogenetic backbone and time estimates we provide establish a framework for future comparative studies on rosaceous evolution.

Angiosperms are by far the most species-rich clade of land plants, but their origin and early evolutionary history remain poorly understood. We reconstructed angiosperm phylogeny based on 80 genes from 2,881 plastid genomes representing 85% of extant families and all orders. With a well-resolved plastid tree and 62 fossil calibrations, we dated the origin of the crown angiosperms to the Upper Triassic, with major angiosperm radiations occurring in the Jurassic and Lower Cretaceous. This estimated crown age is substantially earlier than that of unequivocal angiosperm fossils, and the difference is here termed the ‘Jurassic angiosperm gap’. Our time-calibrated plastid phylogenomic tree provides a highly relevant framework for future comparative studies of flowering plant evolution. A study reconstructed angiosperm phylogeny on the basis of plastome data representing 2,351 angiosperm and 187 gymnosperm species, and dated the origin of crown angiosperms to be significantly earlier than the estimates based on fossil data.

Background Spiraea is a genus of deciduous shrubs that contains 80-120 species, is mainly distributed in the Northern Hemisphere and has diversified in East Asia. Spiraea species are cultivated as ornamental plants and some are used in traditional herbal medicine. Based on morphological characteristics and genetic markers, phylogenetic classification exhibits low discriminatory power. Results In present study, we assembled and characterized the chloroplast (cp) genomes of ten Spiraea species and comparatively analysed with five reported cp genomes of this genus. The cp genomes of the fifteen Spiraea species, ranging from 155,904 to 158,637 bp in length, were very conserved and no structural rearrangements occurred. A total of 85 protein-coding genes (PCGs), 37 tRNAs and 8 rRNAs were annotated. We also examined 1,010 simple sequence repeat (SSR) loci, most of which had A/T base preference. Comparative analysis of cp genome demonstrated that single copy and non-coding regions were more divergent than the inverted repeats (IRs) and coding regions and six mutational hotspots were detected. Selection pressure analysis showed that all PCGs were under purifying selection. Phylogenetic analysis based on the complete cp genome data showed that Spiraea formed a monophyletic group and was further divided into two major clades. Infrageneric classification in each clade was supported with a high resolution value. Moreover, the phylogenetic trees based on each individual mutational hotspot segment and their combined dataset also consisted of two major clades, but most of the phylogenetic relationships of interspecies were not well supported. Conclusions Although the cp genomes of Spiraea species exhibited high conservation in genome structure, gene content and order, a large number of polymorphism sites and several mutation hotspots were identified in whole cp genomes, which might be sufficiently used as molecular markers to distinguish Spiraea species. Phylogenetic analysis based on the complete cp genome indicated that infrageneric classification in two major clades was supported with high resolution values. Therefore, the cp genome data of the genus Spiraea will be effective in resolving the phylogeny in this genus.

Phylogenomic analyses have helped resolve many recalcitrant relationships in the angiosperm tree of life, yet phylogenetic resolution of the backbone of the Leguminosae, one of the largest and most economically and ecologically important families, remains poor due to generally limited molecular data and incomplete taxon sampling of previous studies. Here, we resolve many of the Leguminosae’s thorniest nodes through comprehensive analysis of plastome-scale data using multiple modified coding and noncoding data sets of 187 species representing almost all major clades of the family. Additionally,we thoroughly characterize conflicting phylogenomic signal across the plastome in light of the family’s complex history of plastome evolution. Most analyses produced largely congruent topologies with strong statistical support and provided strong support for resolution of some long-controversial deep relationships among the early diverging lineages of the subfamilies Caesalpinioideae and Papilionoideae. The robust phylogenetic backbone reconstructed in this study establishes a framework for future studies on legume classification, evolution, and diversification. However, conflicting phylogenetic signal was detected and quantified at several key nodes that prevent the confident resolution of these nodes using plastome data alone.

Background MicroRNA (miRNA) is a crucial post-transcriptional regulatory factor in plant growth and development. Duplicated genes often exhibit functional divergence due to competition for the identical miRNA binding sites. Kiwifruit ( Actinidia spp.) is an economically significant horticultural crop renowned for its distinctive flavor, which is largely attributable to elevated citrate levels during fruit development. However, the mechanisms through which miRNA-targeted modules evolve following duplication events and regulate citrate biosynthesis, thereby influencing the unique flavor profile of kiwifruits, remain poorly understood. Results In this study, we examined the expression patterns of miRNAs and interactions with their targets in kiwifruit fruit samples from various pulp tissues and developmental stages. Our analysis identified 46 miRNAs, comprising 44 known miRNAs and two novel/kiwifruit-specific miRNAs, which targeted a total of 1,474 genes. Correlation analysis revealed weak relationships between the expression levels of miRNAs and their target genes. Among these targets, 27 tandemly duplicated genes, and 782 whole genome duplication (WGD) genes exhibited a loss of miRNA binding sites in one of their duplicated copies. Furthermore, weighted gene co-expression network analysis demonstrated that most duplicated genes clustered into distinct gene modules. These findings suggest that the loss of miRNA targets following duplications contributes to expression divergence among gene duplicates, thereby facilitating stable gene expression within the miRNA-targeted network. For instance, the aconitate hydratase genes AchAco4 and AchAco6 were each targeted by different miRNAs, ach-miR-3774 and ach-miR-10371 , respectively. Notably, these genes exhibited distinct expression patterns compared to their duplicated counterparts. Conclusions This study enhances our understanding of how the miRNA- AchAco module regulates citrate content and provides insights into the molecular network that influences the flavor profile of kiwifruit. Clinical trial number Not applicable.

Genus Filipendula (Rosoideae, Rosaceae) comprises about 15 species and mainly distributed in Northern Hemisphere. The phylogenetic relationships based on the nrITS marker are not consistent with the traditional taxonomic systems of the genus. Here, we first analysed the complete chloroplast (cp) genomes of seven Filipendula species (including two varieties of F. palmate ). Our results indicated that the cp genomes of Filipendula species had few changes in size, ranging from 154,205 bp to 154,633 bp and the average of 36.63% GC content. A total of 126 annotated genes had the identical order and orientation, implying that the cp genome structure of Filipendula species was rather conserved. However, the cp genomes of Filipendula species exhibited structural differences, including gene loss, transposition and inversion when compared to those of other genera of Rosoideae. Moreover, SSRs with the different number were observed in the cp genome of each Filipendula species and sequence divergence mainly occurred in noncoding regions, in which four mutational hotspots were identified. In contrast, only two positive selection genes ( matK and rps8 ) were found. Phylogenetic and molecular-dating analysis indicated that Filipendula species were divergent from other genera of Rosoideae at about 82.88 Ma. Additionally, Filipendula species from East Asia were split at about 9.64 Ma into two major clades. These results provide a basis for further studying the infrageneric classification of Filipendula .

The DNA repair capacity of human cells declines with age, in a process that is not clearly understood. Mutation of the nuclear envelope protein barrier-to-autointegration factor 1 (Banf1) has previously been shown to cause a human progeroid disorder, Néstor–Guillermo progeria syndrome (NGPS). The underlying links between Banf1, DNA repair and the ageing process are unknown. Here, we report that Banf1 controls the DNA damage response to oxidative stress via regulation of poly [ADP-ribose] polymerase 1 (PARP1). Specifically, oxidative lesions promote direct binding of Banf1 to PARP1, a critical NAD + -dependent DNA repair protein, leading to inhibition of PARP1 auto-ADP-ribosylation and defective repair of oxidative lesions, in cells with increased Banf1. Consistent with this, cells from patients with NGPS have defective PARP1 activity and impaired repair of oxidative lesions. These data support a model whereby Banf1 is crucial to reset oxidative-stress-induced PARP1 activity. Together, these data offer insight into Banf1-regulated, PARP1-directed repair of oxidative lesions. Mutation of the nuclear envelope protein, barrier-to-autointegration factor 1 (Banf1), has previously been associated with the development of ageing associated diseases in a human progeria syndrome. Here, the authors reveal the functional link between Banf1-regulated, PARP1-directed repair of oxidative lesions.

The Hippo pathway restricts the activity of transcriptional coactivators TAZ (WWTR1) and YAP. TAZ and YAP are reported to be overexpressed in various cancers, however, their prognostic significance in colorectal cancers remains unstudied. The expression levels of TAZ and YAP, and their downstream transcriptional targets, AXL and CTGF, were extracted from two independent colon cancer patient datasets available in the Gene Expression Omnibus database, totaling 522 patients. We found that mRNA expressions of both TAZ and YAP were positively correlated with those of AXL and CTGF (p<0.05). High level mRNA expression of TAZ, AXL or CTGF significantly correlated with shorter survival. Importantly, patients co-overexpressing all 3 genes had a significantly shorter survival time, and combinatorial expression of these 3 genes was an independent predictor for survival. The downstream target genes for TAZ-AXL-CTGF overexpression were identified by Java application MyStats. Interestingly, genes that are associated with colon cancer progression (ANTXR1, EFEMP2, SULF1, TAGLN, VCAN, ZEB1 and ZEB2) were upregulated in patients co-overexpressing TAZ-AXL-CTGF. This TAZ-AXL-CTGF gene expression signature (GES) was then applied to Connectivity Map to identify small molecules that could potentially be utilized to reverse this GES. Of the top 20 small molecules identified by connectivity map, amiloride (a potassium sparing diuretic), and tretinoin (all-trans retinoic acid) have shown therapeutic promise in inhibition of colon cancer cell growth. Using MyStats, we found that low level expression of either ANO1 or SQLE were associated with a better prognosis in patients who co-overexpressed TAZ-AXL-CTGF, and that ANO1 was an independent predictor of survival together with TAZ-AXL-CTGF. Finally, we confirmed that TAZ regulates Axl, and plays an important role in clonogenicity and non-adherent growth in vitro and tumor formation in vivo. These data suggest that TAZ could be a therapeutic target for the treatment of colon cancer.

Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with features that vary by ethnicity. A systematic characterization of the genomic landscape of Chinese ccRCC is lacking, and features of ccRCC associated with tumor thrombus (ccRCC-TT) remain poorly understood. Here, we applied whole-exome sequencing on 110 normal-tumor pairs and 42 normal-tumor-thrombus triples, and transcriptome sequencing on 61 tumor-normal pairs and 30 primary-thrombus pairs from 152 Chinese patients with ccRCC. Our analysis reveals that a mutational signature associated with aristolochic acid (AA) exposure is widespread in Chinese ccRCC. Tumors from patients with ccRCC-TT show a higher mutational burden and genomic instability; in addition, mutations in BAP1 and SETD2 are highly enriched in patients with ccRCC-TT. Moreover, patients with/without TT show distinct molecular characteristics. We reported the integrative genomic sequencing of Chinese ccRCC and identified the features associated with tumor thrombus, which may facilitate ccRCC diagnosis, prognosis and treatment. The genomic heterogeneity of clear cell renal cell carcinoma (ccRCC) across populations is poorly understood. Here, the authors analyse a cohort of Chinese ccRCC cases revealing a mutational signature associated with aristolochic acid exposure, and higher mutational burden and enrichment for BAP1 and SETD2 mutations in ccRCC cases associated with tumor thrombus.