Cloning of the Arabidopsis ent-kaurene oxidase gene GA3 Helliwell, C.A; Sheldon, C.C; Olive, M.R ...
Proceedings of the National Academy of Sciences - PNAS,
(21 Jul 1998), 19980721, 1998-Jul-21, Letnik:
95, Številka:
15
Journal Article
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The ga3 mutant of Arabidopsis is a gibberellin-responsive dwarf. We present data showing that the ga3-1 mutant is deficient in ent-kaurene oxidase activity, the first cytochrome P450-mediated step in ...the gibberellin biosynthetic pathway. By using a combination of conventional map-based cloning and random sequencing we identified a putative cytochrome P450 gene mapping to the same location as GA3. Relative to the progenitor line, two ga3 mutant alleles contained single base changes generating in-frame stop codons in the predicted amino acid sequence of the P450. A genomic clone spanning the P450 locus complemented the ga3-2 mutant. The deduced GA3 protein defines an additional class of cytochrome P450 enzymes. The GA3 gene was expressed in all tissues examined, RNA abundance being highest in inflorescence tissue
Purpose: Grounded in self-determination theory, this study examined factors of secondary early field experiences that preservice teachers consider significant and how these experiences impact them as ...educators. Method: Preservice teachers (N = 13) completed two 10-week early field experiences, one at each level--middle school and high school. Data sources included weekly reflections, interviews, emails, and nonparticipant observations. Data were analyzed inductively through constant comparison and deductively to establish meaning through self-determination theory. Results: The cooperating teachers were substantially influential for the preservice teachers, as were establishing connections with concepts learned in methods courses and tending to students' well-being. The way the early field experiences influenced the preservice teachers as educators was unique to the individual, as negative experiences were channeled positively for some and negatively for others. Conclusion: Early field experiences are quite influential, thus physical education teacher education programs should strongly consider vetting placements or strategically pairing students with placements, particularly at the secondary level, to optimize professional development.
Abstract Objectives This study evaluated the scale-up of a remote monitoring service, capturing monthly Rheumatoid Arthritis Impact of Disease scores and patient-generated text messages, for patients ...with rheumatoid arthritis (RA; in remission or with low disease activity) attending routine outpatient clinics across six hospitals. We explored patients and staff experiences and implementation outcomes. Methods A pragmatic, mixed methods approach was used, with active patient involvement throughout. We undertook a rapid review, analysed service-level data, and conducted a patient survey and patient and staff interviews, informed by the Capability, Opportunity, Motivation, Behaviour (COM-B) and Exploration, Preparation, Implementation, Sustainment (EPIS) theoretical frameworks. Results The review included 37 articles, covering themes of patient and clinician acceptability, engagement, feasibility and clinical impact. Service-level data (n = 202) showed high levels of patient engagement with the service. The patient survey (n = 155) showed patients felt the service was easy to use, had confidence in it and felt it improved access to care. Patient interview (n = 22) findings mirrored those of the survey. Motivating factors included increased responsiveness and ease of contact with clinical teams. Views from staff interviews (n = 16) were more mixed. Some implementation barriers were specific to roll-out sites. Prioritization of staff needs was emphasized. Conclusion Patients were positive about the service and engagement was high. Staff views and engagement were more mixed. Results suggest that equal levels of patient and staff engagement are required for sustainability. These findings further our understanding of the implementation challenges to scaling remote monitoring interventions for patients with rheumatoid arthritis in routine care settings.
Pharmacokinetic properties of our first-generation HIF-2α antagonist PT2385, including modest solubility, resulted in a high recommended phase 2 dose (RP2D) of 800 mg BID and motivated the pursuit of ...novel scaffolds which could improve solubility and formulation parameters with the goal of improved pharmacokinetics. Herein we disclose our successful efforts to identify such HIF-2α antagonists through an optimization strategy characterized by: (1) increasing the fraction of sp
3
hybridized carbons (Fsp
3
), (2) replacing the aromatic portion of the indane core with pyridine heterocycles, and (3) improving a putative O
lp
→π*
Ar
interaction, an underutilized electrostatic contact in medicinal chemistry. These efforts emphasize the importance of employing multiple strategies in parameter optimization. In isolation, modifications to areas (1) and (2) improved solubility, but with the compromise of reduced potency. In area (3), understanding the importance of an O
lp
→π*
Ar
interaction, as documented through a wealth of crystal structures and retrospective calculations, proved essential in guiding SAR and identifying the trifluoromethyl group as a suitable replacement of the sulfone. Only by combining these three strategies could inhibitors with substantially improved solubility and comparable potency be discovered. Finally, the overall improvement in pharmacokinetic properties of the newly identified inhibitors is highlighted through a battery of ADME and in vivo data, including use of pharmacodynamic biomarkers indicative of HIF-2α antagonism.
We present and compare three different amorphous materials for robotic construction. By conforming to surfaces they are deposited on, such materials allow robots to reliably construct in unstructured ...terrain. However, using amorphous materials presents a challenge to robotic manipulation. We demonstrate how deposition of each material can be automated and compare their material properties, cost, and cost in time in order to evaluate their suitability for developing amorphous robotic construction system.
Serum insulin-like growth factor-I (IGF-I) and procollagen type III peptide (P-III-P) have been proposed as indirect biomarkers of rhGH misuse in sports. The purpose of the present study was to ...investigate concentrations of these biomarkers in athletes at different levels of physical fitness and endurance exercise. Serum total IGF-I and P-III-P were measured in 96 elite athletes of various sports along the training season; in 21 recreational athletes at baseline non-exercising conditions and in another 129 recreational athletes before and after long-distance races (10 and 21 km). No differences were evidenced for IGF-I concentrations, but statistically higher values of serum P-III-P were found in elite athletes compared to recreational ones. Among elite athletes, the specific sport did not affect serum IGF-I. However, P-III-P was statistically higher in the sport performed by the youngest athletes (rhythmic gymnastics), even after correction of the logarithm of the concentration by the reciprocal of age. Over the training season, the within-athlete variabilities of IGF-I and P-III-P in elite athletes were low (22.8 % and 21.7 %, respectively). Recreational athletes taking part in a 21 km competition race showed a significant increase in serum values of IGF-I and P-III-P immediately after the event. Exercise workload and age had a significant effect on serum concentration of P-III-P, while age alone affected IGF-I serum concentrations. Therefore, athlete's reference concentration ranges for doping detection should include subjects from as many different ages and sports as possible.
Erythropoietin (EPO) and soluble transferrin receptor (sTfR) in serum have been proposed as indirect biomarkers for the detection of recombinant human EPO (rhEPO) misuse in sport. The purpose of the ...present study was to investigate the influence of different levels of physical fitness, sport, different training workload during the sport season, and endurance exercise in the concentrations of these serum biomarkers for their application into mathematical models to indirectly detect rhEPO misuse. Serum EPO and sTfR concentrations were measured in 96 elite athletes of various sports along the sport season, in 21 recreational athletes at baseline (non exercising) conditions and in 129 other recreational athletes before and after long-distance races (10 and 21 km). In elite athletes, hemoglobin concentrations and percentage of reticulocytes were also measured, and indirect detection models applied. In recreational athletes, for EPO and sTfR, significant differences were only observed after the 21-km race. In baseline conditions, no differences were observed between recreational and elite athletes for EPO and sTfR. In elite athletes, individual EPO and sTfR concentrations slightly changed over the sport season, with coefficients of variation (CV) of 26.1 % and 9.0 %, respectively. Hemoglobin and reticulocytes were influenced by sport, but their individual variation over the sport season was not physiologically relevant (CV of 3.7 % and 21.3 %, respectively). When applying mathematical models for detection of rhEPO administration, only one elite athlete obtained an individual model score above the established thresholds. Physical fitness, sport and different training workload during the sport season had no substantial effect on serum EPO and sTfR concentrations, except in recreational athletes after a 21-km race. Variations observed in mathematical models to detect EPO administration were mainly due to fluctuation in hemoglobin concentrations, commonly observed in elite athletes.
The construction of a solar sail from commercially available metallized film presents several challenges. The solar sail membrane is made by seaming together precut lengths of ultrathin metallized ...polymer film into the required geometry. This assembled sail membrane is then folded into a small stowage volume prior to launch. The sail membranes must have additional features for connecting to rigid structural elements (e.g., sail booms) and must be electrically grounded to the spacecraft bus to prevent charge build up. Space durability of the material and mechanical interfaces of the sail membrane assemblies will be critical for the success of any solar sail mission. In this study, interfaces of polymer/metal joints in a representative solar sail membrane assembly were tested to ensure that the adhesive interfaces and the fastening grommets could withstand the temperature range and expected loads required for mission success. Various adhesion methods, such as surface treatment, commercial adhesives, and fastening systems, were experimentally tested in order to determine the most suitable method of construction.
Two genes cloned from Eucalyptus globulus, Eucalyptus LeaFy (ELF1 and ELF2), have sequence homology to the floral meristem identity genes LEAFY from Arabidopsis and FLORICAULA from Antirrhinum. ELF1 ...is expressed in the developing eucalypt floral organs in a pattern similar to LEAFY while ELF2 appears to be a pseudo gene. ELF1 is expressed strongly in the early floral primordium and then successively in the primordia of sepals, petals, stamens and carpels. It is also expressed in the leaf primordia and young leaves and adult and juvenile trees. The ELF1 promoter coupled to a GUS reporter gene directs expression in transgenic Arabidopsis in a temporal and tissue-specific pattern similar to an equivalent Arabidopsis LEAFY promoter construct. Strong expression is seen in young flower buds and then later in sepals and petals. No expression was seen in rosette leaves or roots of flowering plants or in any non-flowering plants grown under long days. Furthermore, ectopic expression of the ELF1 gene in transgenic Arabidopsis causes the premature conversion of shoots into flowers, as does an equivalent 35S-LFY construct. These data suggest that ELF1 plays a similar role to LFY in flower development and that the basic mechanisms involved in flower initiation and development in Eucalyptus are similar to those in Arabidopsis.