DELLA degradation by gibberellin promotes flowering via GAF1-TPR-dependent repression of floral repressors in Arabidopsis.

Flowering is the developmental transition from the vegetative to the reproductive phase. FLOWERING LOCUS T (FT), SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1), and LEAFY (LFY) are floral integrators. These genes are repressed by several floral repressors including EARLY FLOWERING3 (ELF3), SHORT VEGETATIVE PHASE (SVP), TEMPRANILLO1 (TEM1), and TEM2. Although gibberellin (GA) promotes flowering by activating the floral integrator genes, the exact molecular mechanism remains unclear. DELLAs are negative regulators in GA signaling and act as coactivators of the transcription factor GAI ASSOCIATED FACTOR 1 (GAF1). GAs convert the GAF1 complex from a transcriptional activator to a repressor. Here, we show that GAF1 functions in the GA-dependent flowering pathway by regulating FT and SOC1 expression in Arabidopsis thaliana. We identified four flowering repressors, ELF3, SVP, TEM1, and TEM2, as GAF1-target genes. In response to GAs, GAF1 forms a transcriptional repressor complex and promotes the expression of FT and SOC1 through the repression of four flowering repressor genes, ELF3, SVP, TEM1, and TEM2.

Tumor recognition of peanut agglutinin-immobilized fluorescent nanospheres in biopsied human tissues.

We are investigating an imaging agent for early detection of colorectal cancer. The agent, named the nanobeacon, is coumarin 6-encapsulated polystyrene nanospheres whose surfaces are covered with poly(N-vinylacetamide) and peanut agglutinin that reduces non-specific interactions with the normal mucosa and exhibits high affinity for terminal sugars of the Thomsen-Friedenreich antigen, which is expressed cancer-specifically on the mucosa, respectively. We expect that cancer can be diagnosed by detecting illumination of intracolonically administered nanobeacon on the mucosal surface. In the present study, biopsied human tissues were used to evaluate the potential use of the nanobeacon in the clinic. Prior to the clinical study, diagnostic capabilities of the nanobeacon for detection of colorectal cancer were validated using 20 production batches whose characteristics were fine-tuned chemically for the purpose. Ex vivo imaging studies on 66 normal and 69 cancer tissues removed from the colons of normal and orthotopic mouse models of human colorectal cancer, respectively, demonstrated that the nanobeacon detected colorectal cancer with excellent capabilities whose rates of true and false positives were 91% and 5%, respectively. In the clinical study, normal and tumor tissues on the large intestinal mucosa were biopsied endoscopically from 11 patients with colorectal tumors. Histological evaluation revealed that 9 patients suffered from cancer and the rest had adenoma. Mean fluorescence intensities of tumor tissues treated with the nanobeacon were significantly higher than those of the corresponding normal tissues. Correlation of magnitude relation of the intensity in individuals was observed in cancer patients with a high probability (89%); however, the probability reduced to 50% in adenoma patients. There was a reasonable likelihood for diagnosis of colorectal cancer by the nanobeacon applied to the mucosa of the large intestine.