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Flowers are icons in developmental studies of complex structures. The vast majority of 250,000 angiosperm plant species have flowers with a conserved organ plan bearing sepals, petals, stamens, and carpels in the center. The combinatorial model for the activity of the so-called ABC homeotic floral genes has guided extensive experimental studies in Arabidopsis thaliana and many other plant species. However, a mechanistic and dynamical explanation for the ABC model and prevalence among flowering plants is lacking. Here, we put forward a simple discrete model that postulates logical rules that formally summarize published ABC and non-ABC gene interaction data for Arabidopsis floral organ cell fate determination and integrates this data into a dynamic network model. This model shows that all possible initial conditions converge to few steady gene activity states that match gene expression profiles observed experimentally in primordial floral organ cells of wild-type and mutant plants. Therefore, the network proposed here provides a dynamical explanation for the ABC model and shows that precise signaling pathways are not required to restrain cell types to those found in Arabidopsis, but these are rather determined by the overall gene network dynamics. Furthermore, we performed robustness analyses that clearly show that the cell types recovered depend on the network architecture rather than on specific values of the model's gene interaction parameters. These results support the hypothesis that such a network constitutes a developmental module, and hence provide a possible explanation for the overall conservation of the ABC model and overall floral plan among angiosperms. In addition, we have been able to predict the effects of differences in network architecture between Arabidopsis and Petunia hybrida.

Background Flower phylogenetics and genetically controlled development have been revolutionised during the last two decades. However, some of these evolutionary aspects are still debatable. MADS-box genes are known to play essential role in specifying the floral organogenesis and differentiation in numerous model plants like Petunia hybrida , Arabidopsis thaliana and Antirrhinum majus . SEPALLATA (SEP) genes, belonging to the MADS-box gene family, are members of the ABCDE and quartet models of floral organ development and play a vital role in flower development. However, few studies of the genes in Prunus mume have yet been conducted. Results In this study, we cloned four PmSEPs and investigated their phylogenetic relationship with other species. Expression pattern analyses and yeast two-hybrid assays of these four genes indicated their involvement in the floral organogenesis with PmSEP4 specifically related to specification of the prolificated flowers in P. mume . It was observed that the flower meristem was specified by PmSEP1 and PmSEP4 , the sepal by PmSEP1 and PmSEP4 , petals by PmSEP2 and PmSEP3 , stamens by PmSEP2 and PmSEP3 and pistils by PmSEP2 and PmSEP3 . Conclusion With the above in mind, flower development in P. mume might be due to an expression of SEP genes. Our findings can provide a foundation for further investigations of the transcriptional factors governing flower development, their molecular mechanisms and genetic basis.

SEP genes are famous for their function in the morphological novelty of bisexual flowers. Although the diverse functions of SEP genes were reported, only the regulatory mechanisms underlying floral organ development have been addressed. In this study, we identified SEP -like genes in Gossypium and found that SEP3 genes were duplicated in diploid cotton varieties. GhSEP4.1 and GhSEP4.2 were abundantly transcribed in the shoot apical meristem (SAM), but only GhSEP4.2 was expressed in the leaf vasculature. The expression pattern of GhSEP s in floral organs was conserved with that of homologs in Arabidopsis , except for GhSEP2 that was preponderantly expressed in ovules and fibers. The overexpression and silencing of each single GhSEP gene suggested their distinct role in promoting flowering via direct binding to GhAP1 and GhLFY genomic regions. The curly leaf and floral defects in overexpression lines with a higher expression of GhSEP genes revealed the concentration-dependent target gene regulation of GhSEP proteins. Moreover, GhSEP proteins were able to dimerize and interact with flowering time regulators. Together, our results suggest the dominant role of GhSEP4.2 in leaves to promote flowering via GhAP1-A04 , and differently accumulated GhSEP proteins in the SAM alternately participate in forming the dynamic tetramer complexes to target at the different loci of GhAP1 and GhLFY to maintain reproductive growth. The regulatory roles of cotton SEP genes reveal their conserved and diversified functions.

The MADS box genes are essential for floral development of Arabidopsis because they regulate flowering time and the development of floral organs. In this study, a MADS box gene, TaMADS1, was isolated and characterized from wheat (Triticum aestivum L.). The analysis of amino acid sequences and phylogenetic tree suggested that the TaMADS1 gene might be a SEPALLATA (SEP)-like gene. RNA hybridization indicated that the TaMADS1 transcripts began to accumulate in spikelets, and then, in floret primordia and floral organ primordia in wheat. In the later stage of floret development, the TaMADS1 transcripts accumulated in four whorls of young floral organs. The ectopic expression of TaMADS1 in Arabidopsis caused early flowering and altered the development of all floral organs. Further studies demonstrated that the early flowering phenotype in transgenic plants could be correlated with the upregulation of some flowering time genes and flower meristem identity genes. Our results suggest that TaMADS1 could be a putative SEP-like gene, and has diverse roles in flower development.

Although AGAMOUS-LIKE6 （AGL6） MADS-box genes are ancient with wide distributions in gymnosperms and angiosperms, their functions remain poorly understood. Here, we show the biological role of the AGL6-1ike gene, OsMADS6, in specifying floral organ and meristem identities in rice （Oryza sativa L.）. OsMADS6 was strongly ex- pressed in the floral meristem at early stages. Subsequently, OsMADS6 transcripts were mainly detectable in paleas, lodicules, carpels and the integument of ovule, as well as in the receptacle. Compared to wild type plants, osmads6 mutants displayed altered palea identity, extra glume-like or mosaic organs, abnormal carpel development and loss of floral meristem determinacy. Strikingly, mutation of a SEPALLATA （SEP）-like gene, OsMADS1 （LHS1）, enhanced the defect of osmads6 flowers, and no inner floral organs or glume-like structures were observed in whorls 2 and 3 of osmadsl-z osmads6-1 flowers. Furthermore, the osmadsl-z osmads6-1 double mutants developed severely indetermi- nate floral meristems. Our finding, therefore, suggests that the ancient OsMADS6 gene is able to specify ＂floral state＂ by determining floral organ and meristem identities in monocot crop rice together with OsMADS1.

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755 ), expression quantitative trait loci (eQTLs) (influencing GNG11 , RGS6 and NEO1 ), or are located in genes preferentially expressed in the sinoatrial node ( GNG11 , RGS6 and HCN4) . Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (−0.74< r g <−0.55) and blood pressure (−0.35< r g <−0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants ( GNG11 , RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization. Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

The diversity of floral forms in the plant order Zingiberales has evolved through alterations in floral organ morphology. One striking alteration is the shift from fertile, filamentous stamens to sterile, laminar (petaloid) organs in the stamen whorls, attributed to specific pollination syndromes. Here, we examine the role of the SEPALLATA (SEP) genes, known to be important in regulatory networks underlying floral development and organ identity, in the evolution of development of the diverse floral organs phenotypes in the Zingiberales. Phylogenetic analyses show that the SEP-like genes have undergone several duplication events giving rise to multiple copies. Selection tests on the SEP-like genes indicate that the two copies of SEP3 have mostly evolved under balancing selection, probably due to strong functional restrictions as a result of their critical role in floral organ specification. In contrast, the two LOFSEP copies have undergone differential positive selection, indicating neofunctionalization. Reverse transcriptase-polymerase chain reaction, gene expression from RNA-seq data, and in situ hybridization analyses show that the recovered genes have differential expression patterns across the various whorls and organ types found in the Zingiberales. Our data also suggest that AGL6, sister to the SEP-like genes, may play an important role in stamen morphology in the Zingiberales. Thus, the SEP-like genes are likely to be involved in some of the unique morphogenetic patterns of floral organ development found among this diverse order of tropical monocots. This work contributes to a growing body of knowledge focused on understanding the role of gene duplications and the evolution of entire gene networks in the evolution of flower development.

Selenoprotein P (SeP), a liver-derived secretory protein, functions as a selenium supply protein in the body. SeP has been reported to be associated with insulin resistance in humans through serial analysis of gene expression. Recently, SeP has been found to inhibit vascular endothelial growth factor-stimulated cell proliferation in human umbilical vein endothelial cells, and impair angiogenesis in a mouse hind limb model. In this study, the role of SeP in ischemia/reperfusion (I/R) injury has been investigated. SeP knockout (KO) and littermate wild-type (WT) mice were subjected to 30 min of myocardial ischemia followed by 24 h of reperfusion. The myocardial infarct area/area at risk (IA/AAR), evaluated using Evans blue (EB) and 2,3,5-triphenyltetrazolium chloride (TTC) staining, was significantly smaller in SeP KO mice than in WT mice. The number of terminal de-oxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive nuclei was significantly lower in SeP KO mice than in WT mice. In addition, caspase-3 activation was reduced in SeP KO mice compared to that in WT mice. Furthermore, phosphoinositide 3-kinase/Akt and Erk levels were examined for the reperfusion injury salvage kinase (RISK) pathway. Interestingly, SeP KO significantly increased the phosphorylation of IGF-1, Akt, and Erk compared to that in WT mice after I/R. Finally, I/R-induced myocardial IA/AAR was significantly increased in SeP KO mice overexpressing SeP in the liver compared to other SeP KO mice. These results, together, suggest that inhibition of SeP protects the heart from I/R injury through upregulation of the RISK pathway.

CRNDE is considered an oncogene expressed as long non-coding RNA. Our previous paper is the only one reporting CRNDE as a micropeptide-coding gene. The amino acid sequence of this micropeptide (CRNDEP) has recently been confirmed by other researchers. This study aimed at providing a mass spectrometry (MS)-based validation of the CRNDEP sequence and an investigation of how the differential expression of CRNDE(P) influences the metabolism and chemoresistance of ovarian cancer (OvCa) cells. We also assessed cellular localization changes of CRNDEP, looked for its protein partners, and bioinformatically evaluated its RNA-binding capacities. Herein, we detected most of the CRNDEP sequence by MS. Moreover, our results corroborated the oncogenic role of CRNDE, portraying it as the gene impacting carcinogenesis at the stages of DNA transcription and replication, affecting the RNA metabolism, and stimulating the cell cycle progression and proliferation, with CRNDEP being detected in the centrosomes of dividing cells. We also showed that CRNDEP is located in nucleoli and revealed interactions of this micropeptide with p54, an RNA helicase. Additionally, we proved that high CRNDE(P) expression increases the resistance of OvCa cells to treatment with microtubule-targeted cytostatics. Furthermore, altered CRNDE(P) expression affected the activity of the microtubular cytoskeleton and the formation of focal adhesion plaques. Finally, according to our in silico analyses, CRNDEP is likely capable of RNA binding. All these results contribute to a better understanding of the CRNDE(P) role in OvCa biology, which may potentially improve the screening, diagnosis, and treatment of this disease.

SEPALLATA (SEP) genes have been well characterized in core eudicots and some monocots, and they play important and diverse roles in plant development, including flower meristem initiation, floral organ identity, and fruit development and ripening. However, the knowledge on the function and evolution of SEP-like genes in basal eudicot species is very limited. Here, we cloned and identified five SEP-like genes from London plane (Platanus acerifolia), a basal eudicot tree that is widely used for landscaping in cities. Sequence alignment and phylogenetic analysis indicated that three genes (PlacSEP1.1, PlacSEP1.2, and PlacSEP1.3) belong to the SEP1/2/4 clade, while the other two genes (PlacSEP3.1 and PlacSEP3.2) are grouped into the SEP3 clade. Quantitative real-time PCR (qRT-PCR) analysis showed that all PlacSEPs, except PlacSEP1.1 and PlacSEP1.2, were expressed during the male and female inflorescence initiation, and throughout the flower and fruit development process. PlacSEP1.2 gene expression was only detected clearly in female inflorescence at April. PlacSEP1.3 and PlacSEP3.1 were also expressed, although relatively weak, in vegetative buds of adult trees. No evident PlacSEPs transcripts were detected in various organs of juvenile trees. Overexpression of PlacSEPs in Arabidopsis and tobacco plants resulted in different phenotypic alterations. 35S: PlacSEP1.1, 35S: PlacSEP1.3, and 35S: PlacSEP3.2 transgenic Arabidopsis plants showed evident early flowering, with less rosette leaves but more cauline leaves, while 35S: PlacSEP1.2 and PlacSEP3.1 transgenic plants showed no visible phenotypic changes. 35S: PlacSEP1.1 and 35S: PlacSEP3.2 transgenic Arabidopsis plants also produced smaller and curled leaves. Overexpression of PlacSEP1.1 and PlacSEP3.1 in tobacco resulted in the early flowering and producing more lateral branches. Yeast two-hybrid analysis indicated that Plac-SEPs proteins can form homo-or hetero-dimers with the Platanus APETALA1 (AP1)/FRUITFULL (FUL), B-, C-, and D-class MADS-box proteins in different interacting patterns and intensities. Our results suggest that the five PlacSEP genes may play important and divergent roles during floral initiation and development, as well as fruit development, by collaborating with FUL, B-, C-, and D-class MADS-box genes in London plane; PlacSEP1.3 and PlacSEP3.1 genes might also involve in vegetative bud growth and dormancy. The results provide valuable data for us to understand the functional evolution of SEP like genes in basal eudicot species.