Identification of alleles of carotenoid pathway genes important for zeaxanthin accumulation in potato tubers

We have investigated the genetics and molecular biology of orange flesh colour in potato (Solanum tuberosum L.). To this end the natural diversity in three genes of the carotenoid pathway was assessed by SNP analyses. Association analysis was performed between SNP haplotypes and flesh colour phenotypes in diploid and tetraploid potato genotypes. We observed that among eleven beta-carotene hydroxylase 2 (Chy2) alleles only one dominant allele has a major effect, changing white into yellow flesh colour. In contrast, none of the lycopene epsilon cyclase (Lcye) alleles seemed to have a large effect on flesh colour. Analysis of zeaxanthin epoxidase (Zep) alleles showed that all (diploid) genotypes with orange tuber flesh were homozygous for one specific Zep allele. This Zep allele showed a reduced level of expression. The complete genomic sequence of the recessive Zep allele, including the promoter, was determined, and compared with the sequence of other Zep alleles. The most striking difference was the presence of a non-LTR retrotransposon sequence in intron 1 of the recessive Zep allele, which was absent in all other Zep alleles investigated. We hypothesise that the presence of this large sequence in intron 1 caused the lower expression level, resulting in reduced Zep activity and accumulation of zeaxanthin. Only genotypes combining presence of the dominant Chy2 allele with homozygosity for the recessive Zep allele produced orange-fleshed tubers that accumulated large amounts of zeaxanthin

Effects of dopamine on networks of barrel cortex

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Effect of 1,8-dihydroxy-9-anthrone (anthralin) on rat hepatic ornithine decarboxylase activity in vivo

Intraperitoneal injection of the non-phorbol tumor promoter anthralin (1,8-dihydroxy-9-anthrone) in male rats resulted in an increase of hepatic ornithine decarboxylase (ODC) activity. Maximal activity was observed 8 h after promoter administration reaching levels about 30 times over control. The kinetics of anthralin dependent ODC induction differed markedly from that by either 12-O-tetradecanoylphorbol-13-acetate (TPA) or phenobarbital (PB) (Bisschop et al., Carcinogenesis 2 (1981) 1282). With anthralin a slow decrease of ODC back to control level is observed approximately within 22 h. In contrast, ODC induction mediated by other tumor promoters like TPA and PB decreased to control levels within 4–6 hours. Administration of a second dose of anthralin 8 h after the first dose prevented the activity decrease as normally observed after a single dose of a tumor promoter. This effect lasted at least 10 h. ODC activity induction occurred in a dose-dependent manner being linear from 10–2000 μg anthralin/kg body wt. Pretreatment of the animals either with actinomycin D or with cycloheximide completely blocked anthralin mediated ODC induction suggesting that de novo ODC-mRNA synthesis and subsequent translation is involved in this process

Training for more accurate visual fat estimation in meat

Much animal fat in the diet is contained in meat. As fat intake is considered too high in western societies, a more fat-conscious attitude may be desirable. One of the parties involved is the butcher, who sells fresh meat directly to the consumer. In a pre-post experimental design, with an interpolated training phase, the possibility to improve the ability of student butchers to visually estimate fat content of meat, was investigated. A limited number of training sessions, in which immediate feed-back was given of the actual fat percentage after each estimation, led to a large improvement in fat estimation accuracy. A delayed post-test indicated that most of the training effect was preserved after six weeks. Similarities between the observed learning process and informational feed-back learning with numerosity stimuli were discussed. On the basis of these results it is recommended that courses for trainee butchers include a short course on fat estimation in their curriculum. If butchers sell what they think they sell, consumers are more likely to get what they think they get. Increased `fat awareness' may indirectly contribute to healthier eating habits

Real-time cardiorespiratory motion management for MRI-guided stereotactic arrythmia radioablation

Purpose or Objective Stereotactic arrhythmia radioablation (STAR) serves as a novel alternative approach for the treatment of refractory ventricular tachycardia (VT). Early evidence demonstrates impressive reductions (>90%) in VT burden with a single 25 Gy fraction. Clearly, toxicity is a major concern and should be proactively minimised by cardiorespiratory motion management. While respiratory motion mitigation is widely applied in stereotactic radiotherapy, cardiac motion presents a unique challenge due to its rapid periodicity. In this study, we provide the first experimental demonstration of real-time adaptive MRI-guided STAR. Materials and Methods An MRI-guided real-time adaptive STAR workflow was developed on the 1.5 T Unity MR-linac (Elekta AB, Stockholm, SE) in research mode (Fig. 1). The Quasar MRI4D phantom was used with a cardiorespiratory motion pattern consisting of a respiratory (sine, 12 bpm, 20 mm peak-to-peak) and a cardiac (cos4, 60 bpm, 10 mm peak-to-peak) component. Embedded in the water-filled body oval was a moveable film dosimetry insert with a spherical 3 cm target. An IMRT treatment plan for Unity (1x25 Gy) was created in Monaco v.5.40.01 (Elekta AB). MR-guidance was performed by using 2D cine-MRI (bSSFP, 13 Hz, TR/TE=3/1.48 ms, SENSE=1.5, FOV = 400x207 mm2, voxel size = 3x3x15 mm, PF factor = 0.65). The detected cardiorespiratory motion was deconvoluted by prospective linear Kalman filtering. The respiratory motion was then used as input for MLC tracking, while the cardiac motion was used as input for beam gating (“track+gate”). Alternative delivery scenarios were created either without any motion (“static”), or by ignoring cardiac motion (“track-only”), or by gating independently on both cardiac and respiratory motion (“dual-gate”). To fit the dynamic range of the Gafchromic EBT3 film, MUs were quartered before the delivery. For cardiac motion, a gating window of 3.8 mm was defined to simulate delivery in diastole. For dual-gating, the exhale gating window was set to 10 mm to limit excessive treatment times. System latencies were quantified by using the portal imager on Unity. Results The system latencies of 175 ms (MLC tracking) and 70 ms (gating) were effectively eliminated by using a linear regression predictor. The treatment delivery times were 5.7 mins (static, track-only), 8.8 mins (track+gate), and 20 mins (dual-gate). Dose difference maps confirm that the track+gate scenario best mimics the static dose distribution (Fig. 2). Dose profiles on the 2 (6.25) Gy isolines along the CC direction showed widening of 3.9 (-3.2) mm for track-only, 2.5 (-2.7) mm for dual-gate, and 0.5 (0) mm for track+gate deliveries with respect to the static reference. The gamma pass rates (2%/2mm) were 96.6% (track-only), 96.7% (dual-gate) and 99.4% (track+gate). Conclusion This is the first experimental demonstration of simultaneous cardiorespiratory motion management for MRI- guided STAR resulting in very high dosimetric accuracy

First VMAT delivery with MLC-tracking for single and multi fraction lung SBRT on a Unity MR-linac

Purpose or Objective Conventional lung SBRT requires large treatment margins to cover tumor motion resulting from respiration. This may avoid underdosage but increases toxicity risks. To maximize healthy tissue sparing, we previously developed MRI-guided MLC tumor tracking for the 1.5 T Unity MR-linac (Elekta AB, Stockholm, SE) in combination with IMRT. Recently, we also piloted VMAT deliveries on Unity to further maximize plan conformality and delivery efficiency. In this study, we demonstrate the feasibility of a first experimental setup on an MR-linac that combines VMAT with MLC-tracking for a range of lung SBRT indications. Materials and Methods All experiments were performed on a 1.5 T Unity MR-linac in research mode. A Quasar MRI4D phantom (ModusQA, London, CA) was used to generate: no motion (static reference), Lujan motion (cos4, peak-to-peak amplitude A = 20 mm, f = 0.25 Hz), and subject-derived real respiratory motion (average A = 11 mm, average f = 0.33 Hz) with an average baseline drift of 0.6 mm/min. The phantom contained a film insert with a 3 cm spherical target (GTV) that could be positioned centrally or 10 cm off-center (peripheral) in a water-filled body oval. Target positions were continuously estimated from 2D cine-MR (4 Hz). A linear regression prediction filter compensated for system latency. Predicted positions were used continuously to realign the MLC with the target position. We created three VMAT treatment plans with 3 mm GTV-to-PTV margins following the clinical planning template for lung SBRT: a central plan (8x7.5 Gy) and two peripheral plans (3x18 Gy and 1x34 Gy).EBT3 or EBTXD films were used to measure the delivered dose. A 1%/1mm local Gamma-analysis quantified dose differences between the static reference and tracking cases. Additionally, the dose area histogram (DAH) was determined for the target. Results The VMAT plans had a conformity index (prescribed isodose volume/ PTV) of 1.4-1.5 and an MU-weighted mean-field area of 13-16 cm2. Treatment delivery times were: 6.7 min, 13.1 min, and 24.2 min, for the 8x7.5 Gy, 3x18 Gy, 1x34 Gy lung SBRT plans respectively. The plans required an RMS leaf speed of 0.5-0.7 cm/s. Tracking required a maximal additional 2.4 cm/s leaf speed. Each plan was delivered in respectively 2, 4, and 6 arcs. The local gamma analysis for the central delivery shows that MLC-tracking improved the gamma pass-rate from 67.5% to 98.3% for Lujan motion and to 94.2% for the real respiratory trace. For peripheral deliveries with real respiratory motion, the 3x18 Gy delivery had a 97.3% pass-rate and the 1x34 Gy delivery had a 96.8% pass-rate (Fig.1). The DAH (Fig.2) shows that the target dose agrees well between static and tracking deliveries with real respiratory motion. The figure also shows that the minimum dose in the target is well above the prescribed dose. Conclusion We provided a first experimental demonstration of the technical feasibility of VMAT combined with MR-guided MLC-tracking for central and peripheral lung SBRT