Cloning and characterisation of a maize carotenoid cleavage dioxygenase (ZmCCD1) and its involvement in the biosynthesis of apocarotenoids with various roles in mutualistic and parasitic interactions

Colonisation of maize roots by arbuscular mycorrhizal (AM) fungi leads to the accumulation of apocarotenoids (cyclohexenone and mycorradicin derivatives). Other root apocarotenoids (strigolactones) are involved in signalling during early steps of the AM symbiosis but also in stimulation of germination of parasitic plant seeds. Both apocarotenoid classes are predicted to originate from cleavage of a carotenoid substrate by a carotenoid cleavage dioxygenase (CCD), but the precursors and cleavage enzymes are unknown. A Zea mays CCD (ZmCCD1) was cloned by RT-PCR and characterised by expression in carotenoid accumulating E. coli strains and analysis of cleavage products using GC¿MS. ZmCCD1 efficiently cleaves carotenoids at the 9, 10 position and displays 78% amino acid identity to Arabidopsis thaliana CCD1 having similar properties. ZmCCD1 transcript levels were shown to be elevated upon root colonisation by AM fungi. Mycorrhization led to a decrease in seed germination of the parasitic plant Striga hermonthica as examined in a bioassay. ZmCCD1 is proposed to be involved in cyclohexenone and mycorradicin formation in mycorrhizal maize roots but not in strigolactone formatio

Damping signatures in future neutrino oscillation experiments

We discuss the phenomenology of damping signatures in the neutrino oscillation probabilities, where either the oscillating terms or the probabilities can be damped. This approach is a possibility for tests of non-oscillation effects in future neutrino oscillation experiments, where we mainly focus on reactor and long-baseline experiments. We extensively motivate different damping signatures due to small corrections by neutrino decoherence, neutrino decay, oscillations into sterile neutrinos, or other mechanisms, and classify these signatures according to their energy (spectral) dependencies. We demonstrate, at the example of short baseline reactor experiments, that damping can severely alter the interpretation of results, e.g., it could fake a value of $\sin(2\theta_{13})$ smaller than the one provided by Nature. In addition, we demonstrate how a neutrino factory could constrain different damping models with emphasis on how these different models could be distinguished, i.e., how easily the actual non-oscillation effects could be identified. We find that the damping models cluster in different categories, which can be much better distinguished from each other than models within the same cluster.Comment: 33 pages, 5 figures, LaTeX. Final version published in JHE

Renormalization group analysis of the 2D Hubbard model

Salmhofer [Commun. Math. Phys. 194, 249 (1998)] has recently developed a new renormalization group method for interacting Fermi systems, where the complete flow from the bare action of a microscopic model to the effective low-energy action, as a function of a continuously decreasing infrared cutoff, is given by a differential flow equation which is local in the flow parameter. We apply this approach to the repulsive two-dimensional Hubbard model with nearest and next-nearest neighbor hopping amplitudes. The flow equation for the effective interaction is evaluated numerically on 1-loop level. The effective interactions diverge at a finite energy scale which is exponentially small for small bare interactions. To analyze the nature of the instabilities signalled by the diverging interactions we extend Salmhofers renormalization group for the calculation of susceptibilities. We compute the singlet superconducting susceptibilities for various pairing symmetries and also charge and spin density susceptibilities. Depending on the choice of the model parameters (hopping amplitudes, interaction strength and band-filling) we find commensurate and incommensurate antiferromagnetic instabilities or d-wave superconductivity as leading instability. We present the resulting phase diagram in the vicinity of half-filling and also results for the density dependence of the critical energy scale.Comment: 16 pages, RevTeX, 16 eps figure

Can filesharers be triggered by economic incentives? Results of an experiment

Illegal filesharing on the internet leads to considerable financial losses for artists and copyright owners as well as producers and sellers of music. Thus far, measures to contain this phenomenon have been rather restrictive. However, there are still a considerable number of illegal systems, and users are able to decide quite freely between legal and illegal downloads because the latter are still difficult to sanction. Recent economic approaches account for the improved bargaining position of users. They are based on the idea of revenue-splitting between professional sellers and peers. In order to test such an innovative business model, the study reported in this article carried out an experiment with 100 undergraduate students, forming five small peer-to-peer networks.The networks were confronted with different economic conditions.The results indicate that even experienced filesharers hold favourable attitudes towards revenue-splitting.They seem to be willing to adjust their behaviour to different economic conditions

Modulation of multidrug resistance with dexniguldipine hydrochloride (B8509-035) in the CC531 rot colon carcinoma model

The chemosensitizing potency of dexniguldipine hydrochloride (B8509-035) on epidoxorubicin was assessed in a multidrug-resistant (MDR) tumour model, the intrinsic MDR rat colon carcinoma CC531. In vitro in the sulphorhodamine B cell-viability assay the cytotoxicity of epidoxorubicin was increased approximately 15-fold by co-incubation with 50 ng/ml dexniguldipine. In vivo concentrations of dexniguldipine 5 h after a single oral dose of 30 mg/kg were 72 (± 19 SD) ng/ml in plasma and 925 (± 495 SD) ng/g in tumour tissue. Levels of the metabolite of dexniguldipine, M-1, which has the same chemosensitizing potential, were 26 (± 6 SD) ng/ml and 289 (± 127 SD) ng/g respectively. The efficacy of treatment with 6 mg/kg epidoxorubicin applied intravenously combined with 30 mg kg-1 day-1 dexniguldipine administered orally for 3 days prior to epidoxorubicin injection was evaluated on tumours grown under the renal capsule. Dexniguldipine alone did not show antitumour effects in vivo. Dexniguldipine modestly, but consistently, potentiated the tumour-growth-inhibiting effect of epidoxorubicin, reaching statistical significance in two out of four experiments. In conclusion, these experiments show that dexniguldipine has potency as an MDR reverter in vitro and in vivo in this solid MDR tumour model

Pharmacokinetics of the multidrug-resistance-converting drug dexniguldipine and its pyridine metabolite M-1 in the plasma, tumor, and renal tissue of tumor-bearing Wag/Rij rats

The pharmacokinetics of oral dexniguldipine, a new multidrug-resistance- modifying agent under clinical evaluation, and its pyridine metabolite M-1 were determined in plasma, tumor, and renal tissue in Wag/Rij rats bearing a multidrug-resistant CC531 colon adenocarcinoma tumor under the renal capsule. The pharmacokinetics were studied in four experiments. After a single administration of dexniguldipine (30 mg/kg), tumors and kidneys were collected after 5 (experiment 1), 24 (experiment 2), and 48 h (experiment 3). In the fourth experiment, dexniguldipine was given once daily for 3 consecutive days at a dose of 30 mg/kg. In all experiments, plasma samples were collected at regular intervals. The concentrations of dexniguldipine and M-1 could be determined in plasma in most of the rats at up to 32 h after drug administration. The area under the curve (AUC) of dexniguldipine and M- 1 varied by a factor of 2-6 in the four experiments. High tumor-tissue concentrations of dexniguldipine were observed. The concentrations were highest in the multiple-dose experiment (2014 ± 1005 ng/g tissue). High degrees of correlation (>08) were established between the concentrations of dexniguldipine measured in plasma and tumor as well as renal tissue. Overall, tumor-tissue concentrations of M-1 comprised one-third of the dexniguldipine concentrations measured

MGMT promoter hypermethylation is a frequent, early, and consistent event in astrocytoma progression, and not correlated with TP53 mutation

Hypermethylation of the MGMT gene promoter and mutation of the TP53 tumor-suppressor gene are frequently present in diffuse astrocytomas. However, there is only anecdotal information about MGMT methylation status and TP53 mutations during progression of low-grade diffuse astrocytoma (AII) to anaplastic astrocytoma (AIII) and secondary glioblastoma (sGB). In this study biopsy specimens from 51 patients with astrocytic tumors with radiologically proved progression from low to high-grade malignancy were investigated for the presence and consistency of MGMT promoter hypermethylation and TP53 mutations. For 27 patients biopsy samples both of primary tumors and their recurrences were available. For the other 24 patients histology of either the low-grade lesion or the high-grade recurrence was available. It was found that MGMT promoter hypermethylation and TP53 mutations are both frequent and early events in the progression of astrocytomas and that their status is consistent over time. No correlation was found between MGMT methylation status and the presence of TP53 mutations. In addition, no correlation was found between MGMT promoter hypermethylation and the type of TP53 mutations. These results argue against the putative TP53 G:C>A:T transition mutations suggested to occur preferentially in MGMT hypermethylated tumors

Ab initio Calculations of Multilayer Relaxations of Stepped Cu Surfaces

We present trends in the multilayer relaxations of several vicinals of Cu(100) and Cu(111) of varying terrace widths and geometry. The electronic structure calculations are based on density functional theory in the local density approximation with norm-conserving, non-local pseudopotentials in the mixed basis representation. While relaxations continue for several layers, the major effect concentrates near the step and corner atoms. On all surfaces the step atoms contract inwards, in agreement with experimental findings. Additionally, the corner atoms move outwards and the atoms in the adjacent chain undergo large inward relaxation. Correspondingly, the largest contraction (4%) is in the bond length between the step atom and its bulk nearest neighbor (BNN), while that between the corner atom and BNN is somewhat enlarged. The surface atoms also display changes in registry of upto 1.5%. Our results are in general in good agreement with LEED data including the controversial case of Cu(511). Subtle differences are found with results obtained from semi-empirical potentials.Comment: 21 pages and 3 figure

Evaluating a computer aid for assessing stomach symptoms (ECASS): study protocol for a randomised controlled trial

Background: For most cancers, only a minority of patients have symptoms meeting the National Institute for Health and Clinical Excellence guidance for urgent referral. For gastro-oesophageal cancers, the ‘alarm’ symptoms of dysphagia and weight loss are reported by only 32 and 8 % of patients, respectively, and their presence correlates with advanced-stage disease. Electronic clinical decision-support tools that integrate with clinical computer systems have been developed for general practice, although uncertainty remains concerning their effectiveness. The objectives of this trial are to optimise the intervention and establish the acceptability of both the intervention and randomisation, confirm the suitability and selection of outcome measures, finalise the design for the phase III definitive trial, and obtain preliminary estimates of the intervention effect. Methods/design: This is a two-arm, multi-centre, cluster-randomised, controlled phase II trial design, which will extend over a 16-month period, across 60 general practices within the North East and North Cumbria and the Eastern Local Clinical Research Network areas. Practices will be randomised to receive either the intervention (the electronic clinical decision-support tool) or to act as a control (usual care). From these practices, we will recruit 3000 adults who meet the trial eligibility criteria and present to their GP with symptoms suggestive of gastro-oesophageal cancer. The main measures are the process data, which include the practitioner outcomes, service outcomes, diagnostic intervals, health economic outcomes, and patient outcomes. One-on-one interviews in a sub-sample of 30 patient-GP dyads will be undertaken to understand the impact of the use or non-use of the electronic clinical decision-support tool in the consultation. A further 10–15 GPs will be interviewed to identify and gain an understanding of the facilitators and constraints influencing implementation of the electronic clinical decision-support tool in practice. Discussion: We aim to generate new knowledge on the process measures regarding the use of electronic clinical decision-support tools in primary care in general and to inform a subsequent definitive phase III trial. Preliminary data on the impact of the support tool on resource utilisation and health care costs will also be collected. Trial registration: ISRCTN Registry, ISRCTN12595588