We investigated the physiological function of three Arabidopsis thaliana homologs of the gibberellin (GA) receptor GIBBERELLIN-INSENSITIVE DWARF1 (GID1) by determining the developmental consequences of GID1 inactivation in insertion mutants. Although single mutants developed normally, gid1a gid1c and gid1a gid1b displayed reduced stem height and lower male fertility, respectively, indicating some functional specificity. The triple mutant displayed a dwarf phenotype more severe than that of the extreme GA-deficient mutant ga1-3. Flower formation occurred in long days but was delayed, with severe defects in floral organ development. The triple mutant did not respond to applied GA. All three GID1 homologs were expressed in most tissues throughout development but differed in expression level. GA treatment reduced transcript abundance for all three GID1 genes, suggesting feedback regulation. The DELLA protein REPRESSOR OF ga1-3 (RGA) accumulated in the triple mutant, whose phenotype could be partially rescued by loss of RGA function. Yeast two-hybrid and in vitro pull-down assays confirmed that GA enhances the interaction between GID1 and DELLA proteins. In addition, the N-terminal sequence containing the DELLA domain is necessary for GID1 binding. Furthermore, yeast three-hybrid assays showed that the GA-GID1 complex promotes the interaction between RGA and the F-box protein SLY1, a component of the SCF^SLY1 E3 ubiquitin ligase that targets the DELLA protein for degradation.

Objectives: To evaluate the evidence relating to the effectiveness of breast self-examination (BSE) to screen for breast cancer and to provide recommendations for routine teaching of BSE to women in various age groups as part of a periodic health examination. Options: Routine teaching of BSE to women. Evidence: The electronic databases MEDLINE, PreMEDLINE, CINAHL, HealthSTAR, Current Contents and the Cochrane Library were searched for abstracts and full reports of studies published from 1966 to October 2000 that evaluated the effectiveness of BSE in reducing breast cancer mortality. In addition, references of key papers were searched and experts consulted to ensure that all relevant articles had been identified. Outcomes: Prevention of death from breast cancer was viewed as the most important outcome; other outcomes examined included the stage of cancer detected, the rate of benign biopsy results, the number of patient visits for breast complaints, and psychological benefits and harms. Values: The recommendations of this report reflect the commitment of the Canadian Task Force on Preventive Health Care to provide a structured, evidence-based appraisal of whether a manoeuvre should be included in the periodic health examination. Benefits, harms and costs: Breast cancer is the most frequently diagnosed cancer among Canadian women, accounting for 30% of all new cancer cases each year. In 2000 an estimated 19 200 Canadian women would have been diagnosed with breast cancer, and 5500 would have died from the disease. To date, 2 large randomized controlled trials, a quasi-randomized trial, a large cohort study and several case–control studies have failed to show a benefit for regular performance of BSE or BSE education, compared with no BSE. In contrast, there is good evidence of harm from BSE instruction, including significant increases in the number of physician visits for the evaluation of benign breast lesions and significantly higher rates of benign biopsy results. Recommendations: · Women aged 40–49 years: Because there is fair evidence of no benefit, and good evidence of harm, there is fair evidence to recommend that routine teaching of BSE be excluded from the periodic health examination of women in this age group (grade D recommendation).· Women aged 50–69 years: Because there is fair evidence of no benefit, and good evidence of harm, there is fair evidence to recommend that routine teaching of BSE be excluded from the periodic health examination of women in this age group (grade D recommendation).· The lack of sufficient evidence to evaulate the effectiveness of the manoeuvre in women younger than 40 years and those 70 years and older precludes making recommendations for teaching BSE to women in these age groups. The following issues may be important to consider: Women younger than 40 years: There is little evidence for effectiveness specific to this group. Because the incidence of breast cancer is low in this age group, the risk of net harm from BSE and BSE instruction is even more likely. Women 70 years and older: Although the incidence of breast cancer is high in this group, there is insufficient evidence to make a recommendation concerning BSE for women 70 years and older.· Important note: Although the evidence indicates no benefit from routine instruction, some women will ask to be taught BSE. The potential benefits and harms should be discussed with the woman, and if BSE is taught, care must be taken to ensure she performs BSE in a proficient manner. Validation: The findings of this analysis were reviewed through an iterative process by the members of the Canadian Task Force on Preventive Health Care. The task force sent the final review and recommendations to 4 independent experts, and their feedback was incorporated in the final draft of the manuscript. Sponsors: The Canadian Task Force on Preventive Health Care is funded through a partnership between the Provincial and Territorial Ministries of Health and Health Canada.

Summary: The activity of the gibberellin (GA) biosynthetic enzymes GA 20‐oxidases (GA20ox) is of particular importance in determining GA concentration in many plant species. In Arabidopsis these enzymes are encoded by a family of five genes: AtGA20ox1–AtGA20ox5. Transcript analysis indicated that they have different expression patterns and may thus participate differentially in GA‐regulated developmental processes. We have used reverse genetics to determine the physiological roles of AtGA20ox1 and AtGA20ox2, the most highly expressed GA20ox genes during vegetative and early reproductive development. AtGA20ox1 and AtGA20ox2 act redundantly to promote hypocotyl and internode elongation, flowering time, elongation of anther filaments, the number of seeds that develop per silique and elongation of siliques, with AtGA20ox1 making the greater contribution to internode and filament elongation, and AtGA20ox2 making the greater contribution to flowering time and silique length. Pollination of the double mutant with wild‐type pollen indicated that the GA promoting silique elongation is of maternal origin. The ga20ox2 phenotype revealed that GA promotes the number of stem internodes that elongate upon bolting, and does so independently of its effect on internode elongation. Comparison of the phenotype of the double mutant with that of the highly GA‐deficient ga1‐3 mutant indicates that other GA20ox genes contribute to all the developmental processes examined, and, in some cases such as root growth and leaf expansion, make major contributions, as these processes were unaffected in the double mutant. In addition, the effects of the mutations are mitigated by the homeostatic mechanism that acts on expression of other GA dioxygenase and GID1 receptor genes.

Adaptive plant responses to specific abiotic stresses or biotic agents are fine-tuned by a network of hormonal signaling cascades, including abscisic acid (ABA), ethylene, jasmonic acid (JA) and salicylic acid. Moreover, hormonal cross-talk modulates plant responses to abiotic stresses and defenses against insect herbivores when they occur simultaneously. How such interactions affect plant responses under multiple stresses, however, is less understood, even though this may frequently occur in natural environments. Here, we review our current knowledge on how hormonal signaling regulates abiotic stress responses and defenses against insects, and discuss the few recent studies that attempted to dissect hormonal interactions occurring under simultaneous abiotic stress and herbivory. Based on this we hypothesize that drought stress enhances insect resistance due to synergistic interactions between JA and ABA signaling. Responses to flooding or waterlogging involve ethylene signaling, which likely reduces plant resistance to chewing herbivores due to its negative cross-talk with JA. However, the outcome of interactions between biotic and abiotic stress signaling is often plant and/or insect species-dependent and cannot simply be predicted based on general knowledge on the involvement of signaling pathways in single stress responses. More experimental data on non-model plant and insect species are needed to reveal general patterns and better understand the molecular mechanisms allowing plants to optimize their responses in complex environments.

Bioactive hormone concentrations are regulated both at the level of hormone synthesis and through controlled inactivation. Based on the ubiquitous presence of 2β-hydroxylated gibberellins (GAs), a major inactivating pathway for the plant hormone GA seems to be via GA 2-oxidation. In this study, we used various approaches to determine the role of C19-GA 2-oxidation in regulating GA concentration and GA-responsive plant growth and development. We show that Arabidopsis thaliana has five C19-GA 2-oxidases, transcripts for one or more of which are present in all organs and at all stages of development examined. Expression of four of the five genes is subject to feed-forward regulation. By knocking out all five Arabidopsis C19-GA 2-oxidases, we show that C19-GA 2-oxidation limits bioactive GA content and regulates plant development at various stages during the plant life cycle: C19-GA 2-oxidases prevent seed germination in the absence of light and cold stimuli, delay the vegetative and floral phase transitions, limit the number of flowers produced per inflorescence, and suppress elongation of the pistil prior to fertilization. Under GA-limited conditions, further roles are revealed, such as limiting elongation of the main stem and side shoots. We conclude that C19-GA 2-oxidation is a major GA inactivation pathway regulating development in Arabidopsis.