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M J Paul

Publications and source records attributed to M J Paul.

10 recordsLinked to original sources

Products of leaf primary carbon metabolism modulate the developmental programme determining plant morphology.

Considerable effort has been expended on understanding the genetic networks that regulate leaf development and morphology, however, less attention has been given to the role of leaf carbon status in modulating the plant developmental programme. Unexpected changes in plant development have been observed in response to changes in leaf metabolism. The focus of this review will be to discuss how manipulation of leaf carbon metabolic pathways, such as the photosynthetic carbon reduction cycle and trehalose biosynthesis, has provided insights into links between metabolism and development.

Carbohydrate Metabolism↗

Effect of temozolomide on central nervous system relapse in patients with advanced melanoma.

Temozolomide has shown efficacy in the treatment of metastatic melanoma similar to that of dacarbazine (DTIC), the standard chemotherapy, but with the added benefit of penetration into the central nervous system (CNS). Isolated CNS relapse is increasingly a problem for patients who respond to biochemotherapy. By replacing DTIC with temozolomide in treatment regimens, the incidence of CNS relapse might be reduced. This hypothesis is difficult to test in a prospective randomized controlled trial because of the large number of patients that would be required. We have examined this question in a retrospective case control study, observing the rates of CNS relapse in advanced metastatic melanoma patients responding to DTIC- or temozolomide-based chemotherapy in three institutions. Twenty-one DTIC and 20 temozolomide responders were identified, and have been followed up for a median of 19.0 months (range 6.0-74.3 months). CNS relapse occurred in nine DTIC- and two temozolomide-treated patients, a statistically significant difference in favour of the new agent (P = 0.03). These results support the investigation of temozolomide as a replacement for DTIC in systemic treatment regimens for melanoma.

Adult↗

Low sink demand limits photosynthesis under P(i) deficiency.

The role of the demand for carbon assimilates (the 'sink') in regulating photosynthetic carbon assimilation (Pn: the 'source') in response to phosphate (P(i)) deficiency was examined in tobacco (Nicotiana tabacum L.). P(i) supply was maintained or withdrawn from plants, and in both treatments the source/sink ratio was decreased in some plants by darkening all but two source leaves (partially darkened plants). The remaining plants were kept fully illuminated. P(i)-sufficient plants showed little variation in rate of Pn, amounts of P(i) or phosphorylated intermediates. Withdrawal of P(i) decreased Pn by 75% under the growing conditions and at both low and high internal CO2 concentration. Concomitantly, P(i), phosphorylated intermediates and ATP contents decreased and starch increased. RuBP and activity of phosphoribulokinase closely matched the changes in Pn, but Rubisco activity remained high. Partial darkening P(i)-deficient plants delayed the loss of photosynthetic activity; Rubisco and phosphoribulokinase activities and amounts of sucrose and metabolites, particularly RuBP and G6P, were higher than in fully illuminated Pi-deficient plants. Rates of sucrose export from leaves were more than 2-fold greater than in fully illuminated P(i)-deficient plants. Greater sucrose synthesis, facilitated by increased G6P content, an activator of SPS, would recycle P(i) from the cytosol back to the chloroplast, maintaining ATP, RuBP and hence Pn. It is concluded that low sink strength imposes the primary limitation on photosynthesis in P(i)-deficient plants which restricts sucrose export and sucrose synthesis imposing an end-product synthesis limitation of photosynthesis.

Adenosine Triphosphate↗

Sink regulation of photosynthesis.

The concept that photosynthetic flux is influenced by the accumulation of photo-assimilate persisted for 100 years before receiving any strong experimental support. Precise analysis of the mechanisms of photosynthetic responses to sink activity required the development of a battery of appropriate molecular techniques and has benefited from contemporary interest in the effects of elevated CO2 on photosynthesis. Photosynthesis is one of the most highly integrated and regulated metabolic processes to maximize the use of available light, to minimize the damaging effects of excess light and to optimize the use of limiting carbon and nitrogen resources. Hypotheses of feedback regulation must take account of this integration. In the short term, departure from homeostasis can lead to redox signals, which cause rapid changes in the transcription of genes encoding photosystems I and II. End-product synthesis can exert short-term metabolic feedback control through Pi recycling. Beyond this, carbohydrate accumulation in leaves when there is an imbalance between source and sink at the whole plant level can lead to decreased expression of photosynthetic genes and accelerated leaf senescence. In a high CO2 world this may become a more prevalent feature of photosynthetic regulation. However, sink regulation of photosynthesis is highly dependent on the physiology of the rest of the plant. This physiological state regulates photosynthesis through signal transduction pathways that co-ordinate the plant carbon : nitrogen balance, which match photosynthetic capacity to growth and storage capacity and underpin and can override the direct short-term controls of photosynthesis by light and CO2. Photosynthate supply and phytohormones, particularly cytokinins, interact with nitrogen supply to control the expression of photosynthesis genes, the development of leaves and the whole plant nitrogen distribution, which provides the dominant basis for sink regulation of photosynthesis.

Arabidopsis↗

Decrease of phosphoribulokinase activity by antisense RNA in transgenic tobacco: definition of the light environment under which phosphoribulokinase is not in large excess.

To test the hypothesis that the contribution of phosphoribulokinase (PRK) to the control of photosynthesis changes depending on the light environment of the plant, the response of transgenic tobacco (Nicotiana tabacum L.) transformed with antisense PRK constructs to irradiance was determined. In plants grown under low irradiance (330 micromol m(-2) s(-1)) steady-state photosynthesis was limited in plants with decreased PRK activity upon exposure to higher irradiance, with a control coefficient of PRK for CO2 assimilation of 0.25 at and above 800 micromol m(-2) s(-1). The flux control coefficient of PRK for steady-state CO2 assimilation was zero, however, at all irradiances in plant material grown at 800 micromol m(-2) s(-1) and in plants grown in a glasshouse during mid-summer (alternating shade and sun 300-1600 micromol m(-2) s(-1)). To explain these differences between plants grown under low and high irradiances, Calvin cycle enzyme activities and metabolite content were determined. Activities of PRK and other non-equilibrium Calvin cycle enzymes fructose-1,6-bisphosphatase, sedoheptulose-1,7-bisphosphatase and ribulose-1,5-bisphosphate carboxylase-oxygenase were twofold higher in plants grown at 800 micromol m(-2) s(-1) or in the glasshouse than in plants grown at 330 micromol m(-2) s(-1). Activities of equilibrium enzymes transketolase, aldolase, ribulose-5-phosphate epimerase and isomerase were very similar under all growth irradiances. The flux control coefficient of 0.25 in plants grown at 330 micromol m(-2) s(-1) can be explained because low ribulose-5-phosphate content in combination with low PRK activity limits the synthesis of ribulose-1,5-bisphosphate. This limitation is overcome in high-light-grown plants because of the large relative increase in activities of sedoheptulose-1,7-bisphosphatase and fructose-1,6-bisphosphatase under these conditions, which facilitates the synthesis of larger amounts of ribulose-5-phosphate. This potential limitation will have maintained evolutionary selection pressure for high concentrations of PRK within the chloroplast.

Light↗

Relationship of measured external tocodynamometry with measured internal uterine activity.

The use of home uterine activity monitoring for patients at high risk for preterm labor and delivery has become common in clinical perinatology. The ability of the monitoring devices to detect accurately uterine contractions in early pregnancy has not previously been reported. Ten women in labor between 20 and 35 weeks' gestation underwent simultaneous monitoring of uterine activity with a guard-ring tocodynamometer and an intrauterine pressure monitor. When compared with internal monitoring, the external monitor detected 90.8% of uterine contractions with a specificity for uterine quiescence of 98.1%. The predictive value of external monitoring was 97.3% for detecting uterine contractions and 93.6% for recording the absence of uterine contractions. The contractions detected externally were similar in duration: mean 63.7 +/- 23.0 seconds for internal monitoring and 62.2 +/- 22.6 seconds for external monitoring (p greater than 0.05). The intensity of contractions detected externally was less than internally measured contractions, mean difference, 19.7 +/- 15.9 mmHg (p less than 0.001). External tocodynamometry using this guarding tocodynamometer reliably distinguishes between uterine contractions and uterine quiescence in preterm pregnancies but does not adequately measure the intensity of contractions.

Adolescent↗

Characterization of two Ca-ATPases in gill epithelium from the killifish (Fundulus heteroclitus).

1. Two Ca-ATPases in the gill microsomal fraction from the killifish (Fundulus heteroclitus) have been characterized. 2. A (Ca2+ + Mg2+)-ATPase which has a high affinity for Ca2+, requires Mg2+ for activity and may be stimulated by calmodulin. 3. A (Ca2+ + Na+)-ATPase which has a low affinity for Ca2+ requires Na+ for activity, does not require Mg2+ and is probably not stimulated by calmodulin. 4. These enzymes may play a physiological role in killifish calcium regulation.

Adenosine Triphosphatases↗