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1.  Comparison of three approaches to model grapevine organogenesis in conditions of fluctuating temperature, solar radiation and soil water content 
Annals of Botany  2010;107(5):729-745.
Background and Aims
There is increasing interest in the development of plant growth models representing the complex system of interactions between the different determinants of plant development. These approaches are particularly relevant for grapevine organogenesis, which is a highly plastic process dependent on temperature, solar radiation, soil water deficit and trophic competition.
Methods
The extent to which three plant growth models were able to deal with the observed plasticity of axis organogenesis was assessed. In the first model, axis organogenesis was dependent solely on temperature, through thermal time. In the second model, axis organogenesis was modelled through functional relationships linking meristem activity and trophic competition. In the last model, the rate of phytomer appearence on each axis was modelled as a function of both the trophic status of the plant and the direct effect of soil water content on potential meristem activity.
Key Results
The model including relationships between trophic competition and meristem behaviour involved a decrease in the root mean squared error (RMSE) for the simulations of organogenesis by a factor nine compared with the thermal time-based model. Compared with the model in which axis organogenesis was driven only by trophic competition, the implementation of relationships between water deficit and meristem behaviour improved organogenesis simulation results, resulting in a three times divided RMSE. The resulting model can be seen as a first attempt to build a comprehensive complete plant growth model simulating the development of the whole plant in fluctuating conditions of temperature, solar radiation and soil water content.
Conclusions
We propose a new hypothesis concerning the effects of the different determinants of axis organogenesis. The rate of phytomer appearance according to thermal time was strongly affected by the plant trophic status and soil water deficit. Futhermore, the decrease in meristem activity when soil water is depleted does not result from source/sink imbalances.
doi:10.1093/aob/mcq173
PMCID: PMC3077974  PMID: 20852307
Thermal time; trophic competition; axis organogenesis; soil water deficit; plant growth models; phenotypic plasticity; grapevine; Vitis vinifera
2.  Mapping of hereditary mixed polyposis syndrome (HMPS) to chromosome 10q23 by genomewide high‐density single nucleotide polymorphism (SNP) scan and identification of BMPR1A loss of function 
Journal of Medical Genetics  2006;43(3):e13.
Background
Hereditary mixed polyposis syndrome (HMPS) is characterised by colonic polyps of mixed histological types that are autosomal dominantly inherited and eventually lead to colorectal cancer (CRC). Study of the molecular basis of HMPS will enhance our knowledge of the genetic basis of the mixed polyposis‐carcinoma sequence in both hereditary and sporadic CRC.
Methods/Results
We performed a genomewide linkage search on 15 members of a three‐generation HMPS family using the GeneChip Human Mapping 10K Array and identified a 7 cM putative linkage interval on chromosome 10q23. Subsequently, 32 members from two HMPS families were typed with nine microsatellite markers spanning the region and the linkage was confirmed with a maximum multi‐point logarithm of the odds (LOD) score of 4.6 (p<0.001). The 10q23.1–10q23.31 haplotypes segregate with the disease in both families. We screened for mutations in four candidate genes within the linkage region and identified an 11 bp deletion in the bone morphogenesis protein receptor 1A (BMPR1A) gene in one family.
Conclusions
Our results indicate that BMPR1A mutation accounts for HMPS. The data suggest that inactivating BMPR1A can initiate colorectal tumourigenesis via the mixed polyposis‐carcinoma sequence.
doi:10.1136/jmg.2005.034827
PMCID: PMC2563243  PMID: 16525031
colorectal cancer; haplotype; linkage; mixed polyposis; whole‐genome SNP genotyping
3.  Individual and combined effects of cimetidine and ciprofloxacin on theophylline metabolism in male nonsmokers. 
1. The individual and combined effects of cimetidine and ciprofloxacin on theophylline metabolism were examined in six young male nonsmokers. 2. Treatment sequence consisted of 7 days each of cimetidine 400 mg p.o. every 12 h. ciprofloxacin 500 mg p.o. every 12 h, and the combination of cimetidine and ciprofloxacin. 3. Studies of theophylline pharmacokinetics were performed at baseline and on the fifth day of each regimen. 4. Individually, cimetidine and ciprofloxacin decreased the clearance of theophylline by 25% and 32%, respectively. Therapy with the combined regimen resulted in a 41% reduction in theophylline clearance, which was greater than that achieved with each drug alone (P < 0.01). 5. Ciprofloxacin, in contrast to cimetidine, inhibited N-demethylations of theophylline to a significantly greater extent than the hydroxylation pathway. Combined treatment produced a further decline in formation of 1,3-dimethyluric acid than each drug alone. 6. These data suggest that coadministration of cimetidine and ciprofloxacin exerts a greater impairment of theophylline biotransformation than each inhibitor alone. The enhanced inhibitory effect from the two inhibitors will occur only when sub-maximal doses of each individual agent are used.
PMCID: PMC1364637  PMID: 9114903
4.  The effect of tocainide on theophylline metabolism. 
The effect of 5 days of oral tocainide (400 mg every 8 h) on the kinetics of theophylline given as a single 5 mg kg-1 i.v. infusion over 30 min was investigated in eight healthy male nonsmokers. Treatment with tocainide decreased the plasma clearance of theophylline from 37.5 +/- 6.9 (mean +/- s.d.) to 33.7 +/- 5.0 ml kg-1 h-1 (difference -3.8, 95% CI, -1.7 to -5.9; P = 0.004) and increased its terminal elimination half-life from 9.7 +/- 2.5 to 10.4 +/- 2.1 h (difference 0.7, 95% CI, 0.2 to 1.2; P = 0.011). Tocainide decreased the formation clearances of 3-methylxanthine and 1-methyluric acid, but the formation clearance of 1,3-dimethyluric acid was unaltered. These data indicate that tocainide exerts a modest inhibitory effect on theophylline metabolism. The magnitude of this change is substantially smaller than that reported to be produced by mexiletine.
PMCID: PMC1381557  PMID: 8485025

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