No abstract

Two of the important traits for wheat yield are tiller and fertile tiller number, both of which have been thought to increase cereal yield in favorable and unfavorable environments. A total of 6,349 single nucleotide polymorphism (SNP) markers from the 15 K wheat Infinium array were employed for genome-wide association study (GWAS) of tillering number traits, generating a physical distance of 14,041.6 Mb based on the IWGSC wheat genome sequence. GWAS analysis using Fixed and random model Circulating Probability Unification (FarmCPU) identified a total of 47 significant marker-trait associations (MTAs) for total tiller number (TTN) and fertile tiller number (FTN) in Iranian bread wheat under different water regimes. After applying a 5% false discovery rate (FDR) threshold, a total of 13 and 11 MTAs distributed on 10 chromosomes were found to be significantly associated with TTN and FTN, respectively. Linked single nucleotide polymorphisms for IWB39005 (2A) and IWB44377 (7A) were highly significantly associated (FDR < 0.01) with TTN and FTN traits. Moreover, to validate GWAS results, meta-analysis was performed and 30 meta-QTL regions were identified on 11 chromosomes. The integration of GWAS and meta-QTLs revealed that tillering trait in wheat is a complex trait which is conditioned by the combined effects of minor changes in multiple genes. The information provided by this study can enrich the currently available candidate genes and genetic resources pools, offering evidence for subsequent analysis of genetic adaptation of wheat to different climatic conditions of Iran and other countries. Bread wheat (Triticum aestivum L., genomes AABBDD, 2n = 6x = 42), is a major cereal crop, supplying 20% of the total energy and protein of the world's diet 1. Its production and productivity, especially in arid and semiarid regions such as Iran, are considerably constrained by extreme drought and heat stresses. Breeding for grain yield is the final step to produce stress-tolerant crop plants, since grain yield is a complex trait with low heritability, which is controlled by multiple genes and is affected by a lot of environmental factors, other traits such as yield components can be employed to overcome the limitations. Tillering is a crucial factor for wheat yield because of its involvement in grain weight and grain number determination. Moreover, it is a determinant of grain yield,

Cratoxylum arborescens is an equatorial plant belonging to the family Guttiferae. In the current study, α-Mangostin (AM) was isolated and its cell death mechanism was studied. HCS was undertaken to detect the nuclear condensation, mitochondrial membrane potential, cell permeability, and the release of cytochrome c. An investigation for reactive oxygen species formation was conducted using fluorescent analysis. To determine the mechanism of cell death, human apoptosis proteome profiler assay was conducted. In addition, using immunofluorescence and immunoblotting, the levels of Bcl-2-associated X protein (Bax) and B-cell lymphoma (Bcl)-2 proteins were also tested. Caspaces such as 3/7, 8, and 9 were assessed during treatment. Using HCS and Western blot, the contribution of nuclear factor kappa-B (NF-κB) was investigated. AM had showed a selective cytotoxicity toward the cancer cells with no toxicity toward the normal cells even at 30 μg/mL, thereby indicating that AM has the attributes to induce cell death in tumor cells. The treatment of MCF-7 cells with AM prompted apoptosis with cell death-transducing signals. This regulated the mitochondrial membrane potential by down-regulation of Bcl-2 and up-regulation of Bax, thereby causing the release of cytochrome c from the mitochondria into the cytosol. The liberation of cytochrome c activated caspace-9, which, in turn, activated the downstream executioner caspace-3/7 with the cleaved poly (ADP-ribose) polymerase protein, thereby leading to apoptotic alterations. Increase of caspace 8 had showed the involvement of an extrinsic pathway. This type of apoptosis was suggested to occur through both extrinsic and intrinsic pathways and prevention of translocation of NF-κB from the cytoplasm to the nucleus. Our results revealed AM prompt apoptosis of MCF-7 cells through NF-κB, Bax/Bcl-2 and heat shock protein 70 modulation with the contribution of caspaces. Moreover, ingestion of AM at (30 and 60 mg/kg) significantly reduced tumor size in an animal model of breast cancer. Our results suggest that AM is a potentially useful agent for the treatment of breast cancer.

β-Mangostin (βM) was isolated from Cratoxylum arborescens to investigate its anti-cancer effect in MCF-7 cells. βM induced apoptosis by down-regulation of Bcl2 and up-regulation of Bax, triggering the cytochrome c release from mitochondria to cytosol. The release of caspase-9 and -7 and consequently cleaved PARP leading to apoptotic was observed upon treatment. Reduction of both bid and caspase 8 and the up regulation of Fas showed the involvement of the extrinsic pathway. Significantly up regulated GADD45A and HRK genes were observed upon treatment, with concomitant inhibition of NF-kB to nucleus. The protein array had demonstrated the expression of HSP 70, HSP 60, XIAP, Survivin, p53 and Bax. Moreover, βM had showed p53-dependent G2/M cell cycle arrest by down regulation of cdc2 and PCNA. Together, the results demonstrated that the βM induced anti-proliferative effect, leading to G2/M phase cell cycle arrest and apoptosis through both the extrinsic and mitochondrial pathways with the involvement of the multiple pro and anti-apoptosis and NF-kB signalling pathways.

BackgroundCratoxylum arborescens has been used traditionally in Malaysia for the treatment of various ailments.Methodsα-Mangostin (AM) was isolated from C. arborescens and its cell death mechanism was investigated. AM-induced cytotoxicity was observed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Acridine orange/propidium iodide staining and annexin V were used to detect cells in early phases of apoptosis. High-content screening was used to observe the nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release. The role of caspases-3/7, -8, and -9, reactive oxygen species, Bcl-2 and Bax expression, and cell cycle arrest were also investigated. To determine the role of the central apoptosis-related proteins, a protein array followed by immunoblot analysis was conducted. Moreover, the involvement of nuclear factor-kappa B (NF-κB) was also analyzed.ResultsApoptosis was confirmed by the apoptotic cells stained with annexin V and increase in chromatin condensation in nucleus. Treatment of cells with AM promoted cell death-transducing signals that reduced MMP by downregulation of Bcl-2 and upregulation of Bax, triggering cytochrome c release from the mitochondria to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by the executioner caspase-3/7 and then cleaved the PARP protein. Increase of caspase-8 showed the involvement of extrinsic pathway. AM treatment significantly arrested the cells at the S phase (P<0.05) concomitant with an increase in reactive oxygen species. The protein array and Western blotting demonstrated the expression of HSP70. Moreover, AM significantly blocked the induced translocation of NF-κB from cytoplasm to nucleus.ConclusionTogether, the results demonstrate that the AM isolated from C. arborescens inhibited the proliferation of MDA-MB-231 cells, leading to cell cycle arrest and programmed cell death, which was suggested to occur through both the extrinsic and intrinsic apoptosis pathways with involvement of the NF-κB and HSP70 signaling pathways.