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Biomedical subjects

Stuart Graham

Publications and source records attributed to Stuart Graham.

9 recordsLinked to original sources

Arabidopsis ABA INSENSITIVE4 regulates lipid mobilization in the embryo and reveals repression of seed germination by the endosperm.

Regulation of seed germination requires coordinate action by the embryo and surrounding endosperm. We used Arabidopsis thaliana to establish the relative roles of embryo and endosperm in the control of seed germination and seedling establishment. We previously showed that endospermic oil reserves are used postgerminatively via gluconeogenesis to fuel seedling establishment and that lipid breakdown is repressed by abscisic acid (ABA) in embryo but not endosperm tissues. Here, we use RNA amplification to describe the transcriptome of the endosperm and compare the hormone responses of endosperm and embryo tissues. We show that the endosperm responds to both ABA and gibberellin but that ABA in particular regulates nuclear but not plastid-encoded photosynthetic gene expression in the embryo. We also show that ABA INSENSITIVE4 (ABI4) expression is confined to the embryo, accounts for the major differences in embryo response to ABA, and defines a role for ABI4 as a repressor of lipid breakdown. Furthermore, ABI5 expression in the endosperm defines a second region of altered ABA signaling in the micropylar endosperm cap. Finally, embryo and endosperm ABA signaling mutants demonstrate the spatial specificity of ABA action in seed germination. We conclude that the single cell endosperm layer plays an active role in the regulation of seed germination in Arabidopsis.

Abscisic Acid↗

Multifocal visual evoked potential latency analysis: predicting progression to multiple sclerosis.

OBJECTIVE: To monitor the difference in conversion rates to multiple sclerosis (MS) in 46 patients with optic neuritis between patients with multifocal visual evoked potential latency delay and those with normal latency. DESIGN: Prospective case series. SETTING: Metropolitan neuro-ophthalmology clinic. PARTICIPANTS: Forty-six patients with optic neuritis who did not have a diagnosis of MS on enrollment in the study. MAIN OUTCOME MEASURES: Conversion to MS according to the McDonald criteria. RESULTS: Analysis revealed that only 22 subjects had multifocal visual evoked potential latency delay. Over 1 year, 36.4% of patients with optic neuritis with latency delays progressed clinically to MS compared with 0% of those with normal latencies (P = .03, chi2). CONCLUSION: This may indicate that multifocal visual evoked potential latency delay can assist in predicting progression to future MS.

Analysis of Variance↗

A comparison of diagnostic protocols for interpretation of frequency doubling perimetry visual fields in glaucoma.

BACKGROUND: Frequency doubling perimetry (FDP) shows good correlation with achromatic automated perimetry in the assessment of glaucoma. However, many recommended protocols lead to a significant number of false positives and negatives. Therefore, it may be difficult to identify visual field loss owing to glaucoma. We investigated the accuracy of a diagnostic protocol that only considered either temporal wedge, arcuate, or nasal step field loss on an FDP field as significant. METHODS: Sixty-eight subjects who were glaucoma suspects, glaucoma patients or normal controls were recruited selectively. After achromatic automated perimetry and FDP visual field testing, results were compared between a conventional protocol and ones that took into account the position of FDP visual field loss. RESULTS: If an FDP field was considered abnormal only when either a temporal wedge, an arcuate or a nasal step defect was present, the presence of a nasal step yielded the most accurate results with the least false positives (kappa coefficient=0.76) and with only minimal increase in false negatives, compared with a conventional FDP protocol (kappa coefficient=0.70). CONCLUSIONS: Although, not statistically significant in this case, our results suggested a trend that a diagnostic protocol which considers nasal step FDP field loss significant may have a greater degree of accuracy when compared with conventional protocols and may facilitate interpretation in a clinical setting.

Female↗

Sucrose rescues seedling establishment but not germination of Arabidopsis mutants disrupted in peroxisomal fatty acid catabolism.

The Arabidopsis acyl-CoA oxidase (ACX) family comprises isozymes with distinct fatty acid chain-length specificities that together catalyse the first step of peroxisomal fatty acid beta-oxidation. We have isolated and characterized T-DNA insertion mutants in the medium to long-chain (ACX1) and long-chain (ACX2) acyl-CoA oxidases, and show that the corresponding endogenous activities are decreased in the mutants. Lipid catabolism during germination and early post-germinative growth was unaltered in the acx1-1 mutant, but slightly delayed in the acx2-1 mutant, with 3-day-old acx2-1 seedlings accumulating long-chain acyl-CoAs. In acx1-1 and acx2-1, seedling growth and establishment in the absence of an exogenous supply of sucrose was unaffected. Seedlings of the double mutant acx1-1 acx2-1 were unable to catabolize seed storage lipid, and accumulated long-chain acyl-CoAs. The acx1-1 acx2-1 seedlings were also unable to establish photosynthetic competency in the absence of an exogenous carbon supply, a phenotype that is shared with a number of other Arabidopsis mutants disrupted in storage lipid breakdown. Germination frequency of the double mutant was significantly reduced compared with wild-type seeds. This was unaffected by the addition of exogenous sucrose, but was improved by dormancy-breaking treatments such as cold stratification and after-ripening. We show that the acx1-1, acx2-1 and acx1-2 acx2-1 double mutants and the ketoacyl-CoA thiolase-2 (kat2) mutant exhibit a sucrose-independent germination phenotype comparable with that reported for comatose (cts-2), a mutant in a peroxisomal ABC transporter which exhibits enhanced dormancy. This demonstrates an additional role beyond that of carbon provision for the beta-oxidation pathway during germination or in dormant seeds.

Acyl Coenzyme A↗

Effect of fixation tasks on multifocal visual evoked potentials.

PURPOSE: This study investigated the effects of cognitive influence on the multifocal visual evoked potential (mVEP) at different levels of eccentricity. Three different foveal fixation conditions were utilized involving varying levels of task complexity. A more complex visual fixation task has been known to suppress peripheral signals in subjective testing. METHODS: Twenty normal subjects had monocular mVEPs recorded using the AccuMap objective perimeter. This allowed simultaneous stimulation of 58 segments of the visual field to an eccentricity of 24 degrees. The mVEP was recorded using three different fixation conditions in random order. During task 1 the subject passively viewed the central fixation area. For task 2 alternating numbers were displayed within the fixation area; the subject on viewing the number '3' in the central fixation area indicated recognition by pressing a button. Throughout task 3, numbers were displayed as in task 2. The subject had the cognitive task of summating all the numbers. RESULTS: Analysis revealed that the increased attention and concentration demanded by tasks 2 and 3 in comparison with task 1 resulted in significantly enhanced central amplitudes of 9.41% (Mann-Whitney P = 0.0002) and 13.45% (P = 0.0002), respectively. These amplitudes became reduced in the periphery and approached those of task 1, resulting in no significant difference between the three tasks. Latencies demonstrated no significant difference between each task nor at any eccentricity (P > 0.05). As the complexity of each task increased the amount of alpha rhythm was significantly reduced. CONCLUSIONS: Our findings indicate that task 1 required a minimal demand of cognition and was associated with the greatest amount of alpha rhythm. It was also the most difficult to perform because of loss of interest. The other two tasks required a greater demand of higher order cognitive skills resulting in significantly enhanced amplitudes centrally and the attenuation of alpha rhythm. Therefore, amplitudes are increased around the area of attention.

Adult↗

Reserve mobilization in the Arabidopsis endosperm fuels hypocotyl elongation in the dark, is independent of abscisic acid, and requires PHOSPHOENOLPYRUVATE CARBOXYKINASE1.

Arabidopsis thaliana is used as a model system to study triacylglycerol (TAG) accumulation and seed germination in oilseeds. Here, we consider the partitioning of these lipid reserves between embryo and endosperm tissues in the mature seed. The Arabidopsis endosperm accumulates significant quantities of storage lipid, and this is effectively catabolized upon germination. This lipid differs in composition from that in the embryo and has a specific function during germination. Removing the endosperm from the wild-type seeds resulted in a reduction in hypocotyl elongation in the dark, demonstrating a role for endospermic TAG reserves in fueling skotomorphogenesis. Seedlings of two allelic gluconeogenically compromised phosphoenolpyruvate carboxykinase1 (pck1) mutants show a reduction in hypocotyl length in the dark compared with the wild type, but this is not further reduced by removing the endosperm. The short hypocotyl phenotypes were completely reversed by the provision of an exogenous supply of sucrose. The PCK1 gene is expressed in both embryo and endosperm, and the induction of PCK1:beta-glucuronidase at radicle emergence occurs in a robust, wave-like manner around the embryo suggestive of the action of a diffusing signal. Strikingly, the induction of PCK1 promoter reporter constructs and measurements of lipid breakdown demonstrate that whereas lipid mobilization in the embryo is inhibited by abscisic acid (ABA), no effect is seen in the endosperm. This insensitivity of endosperm tissues is not specific to lipid breakdown because hydrolysis of the seed coat cell walls also proceeded in the presence of concentrations of ABA that effectively inhibit radicle emergence. Both processes still required gibberellins, however. These results suggest a model whereby the breakdown of seed carbon reserves is regulated in a tissue-specific manner and shed new light on phytohormonal regulation of the germination process.

Abscisic Acid↗

Effect of check size and stimulation rate on blue-yellow multifocal visual evoked potentials.

BACKGROUND: To determine the effect of different stimulus frame rates and check sizes on blue-yellow multifocal visual evoked potentials (mVEP). METHODS: Subjects were examined at the Save Sight Institute at the University Sydney. Experiment 1 involved five adult subjects who underwent binocular stimulation by the Accumap multifocal objective perimeter. The eyes were stimulated with a cortically scaled dartboard pattern consisting of isoluminant blue and yellow checks. These were arranged in three concentric rings extending to an eccentricity of 26 degrees in the visual field. The stimulus pattern was driven by binary sequences resulting in pseudorandom binary exchange of two opposite checkerboard patterns at each of the 32 sites in the visual field. The mVEP were recorded at two different rates of display of the pattern stimulus. In experiment 2, mVEP were tested on 10 normal subjects. Each of the 36 stimulation sites contained a checkerboard pattern of 20, 30, 42 or 56 checks/site, the stimulation pattern was displayed at the optimum rate found in experiment 1. The size of the checks was inversely proportional to the number of checks per site. RESULTS: In experiment 1, the slow frame rate significantly increased the average amplitude throughout the field tested by 50 +/- 10.1% (P = 0.001). Latency was significantly shortened by 6.3% (P < 0.01). In experiment 2, the average amplitude peaked at 30 checks per segment; however, this was only calculated to be significantly different from the smallest check size (F(crit range 4,27) = 0.09 P < 0.05, anova, Tukey's T method). A similar difference was found in ring 1 (F(crit range 4,27) = 0.09, P < 0.05, anova, Tukey's T method). In ring 2, however, there was also a significant difference between 56 checks and 20, 30 and 42 (F(crit range 4,27) = 0.09, anova, P < 0.05). Altering the check sizes did not significantly affect the amplitudes in ring 3. The latencies were not significantly modified by altering check size at any eccentricity. CONCLUSIONS: These findings suggest that slowing the stimulation rate and displaying 30 checks per stimulation segment optimizes the blue-yellow mVEP stimulus.

Adult↗

Does a family history of glaucoma affect disease severity at the time of diagnosis?

PURPOSE: Progressive glaucomatous optic neuropathy is an asymptomatic process with an insidious onset. Patients who are aware of glaucomatous signs and who suspect that they may have the disease may present earlier. If a person has glaucoma, this may alert his or her other family members to seek assessment and thereby permit earlier diagnosis. The authors sought to determine whether glaucoma patients with a family history of the disease were younger and showed less evidence of glaucomatous optic neuropathy at diagnosis than glaucoma patients without a family history of the disease. PATIENTS AND METHODS: Family history of glaucoma, age at diagnosis, and visual field mean defect within 2 years after diagnosis were recorded in 292 patients with primary open-angle glaucoma. Results were analyzed to compare visual field loss with age and family history. RESULTS: At diagnosis, patients with a family history of glaucoma were younger than those without such a history (mean +/- SD, 58 +/- 12.7 years versus 63 +/- 10.8 years; = 3.68, P<0.001). Patients who were younger than 50 years at the time of diagnosis and had a positive family history were significantly less likely to have a worse visual field than those with a negative family history (OR = 0.3; 95% CI, 0.1-0.6; P<0.001), whereas those aged 50 years or older showed no such correlation (OR = 0.9; 95% CI, 0.7-1.3; P = 0.6). CONCLUSION: A family history of glaucoma was associated with a better visual field at diagnosis in patients younger than 50 years, but not in patients 50 years or older.

Adult↗