Mathematical modeling of diurnal patterns of carbon allocation to shoot and root in Arabidopsis thaliana

We developed a mathematical model to simulate dynamics of central carbon metabolism over complete diurnal cycles for leaves of Arabidopsis thaliana exposed to either normal (120 µmol⋅m-2⋅s-1) or high light intensities (1200 µmol⋅m-2⋅s-1). The main objective was to obtain a high-resolution time series for metabolite dynamics as well as for shoot structural carbon formation (compounds with long residence time) and assimilate export of aerial organs to the sink tissue. Model development comprised a stepwise increment of complexity to finally approach the in vivo situation. The correct allocation of assimilates to either sink export or shoot structural carbon formation was a central goal of model development. Diurnal gain of structural carbon was calculated based on the daily increment in total photosynthetic carbon fixation, and this was the only parameter for structural carbon formation implemented in the model. Simulations of the dynamics of central metabolite pools revealed that shoot structural carbon formation occurred solely during the light phase but not during the night. The model allowed simulation of shoot structural carbon formation as a function of central leaf carbon metabolism under different environmental conditions without structural modifications. Model simulations were performed for the accession Landsberg erecta (Ler) and its hexokinase null-mutant gin2-1. This mutant displays a slow growth phenotype especially at increasing light intensities. Comparison of simulations revealed that the retarded shoot growth in the mutant resulted from an increased assimilate transport to sink organs. Due to its central function in sucrose cycling and sugar signaling, our findings suggest an important role of hexokinase-1 for carbon allocation to either shoot growth or assimilate export

Resolving subcellular plant metabolism

Plant cells are characterized by a high degree of compartmentalization and a diverse proteome and metabolome. Only a very limited number of studies has addressed combined subcellular proteomics and metabolomics which strongly limits biochemical and physiological interpretation of large‐scale ’omics data. Our study presents a methodological combination of nonaqueous fractionation, shotgun proteomics, enzyme activities and metabolomics to reveal subcellular diurnal dynamics of plant metabolism. Subcellular marker protein sets were identified and enzymatically validated to resolve metabolism in a four‐compartment model comprising chloroplasts, cytosol, vacuole and mitochondria. These marker sets are now available for future studies that aim to monitor subcellular metabolome and proteome dynamics. Comparing subcellular dynamics in wild type plants and HXK1‐deficient gin2‐1 mutants revealed a strong impact of HXK1 activity on metabolome dynamics in multiple compartments. Glucose accumulation in the cytosol of gin2‐1 was accompanied by diminished vacuolar glucose levels. Subcellular dynamics of pyruvate, succinate and fumarate amounts were significantly affected in gin2‐1 and coincided with differential mitochondrial proteome dynamics. Lowered mitochondrial glycine and serine amounts in gin2‐1 together with reduced abundance of photorespiratory proteins indicated an effect of the gin2‐1 mutation on photorespiratory capacity. Our findings highlight the necessity to resolve plant metabolism to a subcellular level to provide a causal relationship between metabolites, proteins and metabolic pathway regulation

Evidence of Counter-Streaming Ions near the Inner Pole of the HERMeS Hall Thruster

NASA is continuing the development of a 12.5-kW Hall thruster system to support a phased exploration concept to expand human presence to cis-lunar space and eventually to Mars. The development team is transitioning knowledge gained from the testing of the government-built Technology Development Unit (TDU) to the contractor-built Engineering Test Unit (ETU). A new laser-induced fluorescence diagnostic was developed to obtain data for validating the Hall thruster models and for comparing the behavior of the ETU and TDU. Analysis of TDU LIF data obtained during initial deployment of the diagnostics revealed evidence of two streams of ions moving in opposite directions near the inner front pole. These two streams of ions were found to intersect the downstream surface of the front pole at large oblique angles. This data points to a possible explanation for why the erosion rate of polished pole covers were observed to decrease over the course of several hundred hours of thruster operation

Microwave Current Imaging in Passive HTS Components by Low-Temperature Laser Scanning Microscopy (LTLSM)

We have used the LTLSM technique for a spatially resolved investigation of the microwave transport properties, nonlinearities and material inhomogeneities in an operating coplanar waveguide YBa_2Cu_3O_{7-\delta} (YBCO) microwave resonator on an LaAlO_3 (LAO) substrate. The influence of twin-domain blocks, in-plane rotated grains, and micro-cracks in the YBCO film on the nonuniform rf current distribution were measured with a micrometer-scale spatial resolution. The impact of the peaked edge currents and rf field penetration into weak links on the linear device performance were studied as well. The LTLSM capabilities and its future potential for non-destructive characterization of the microwave properties of superconducting circuits are discussed.Comment: 8 pages, 9 figures, 2-column format, presented at High Temperature Superconductors in High Frequency Fields 2004, Journal of Superconductivity (in press

Photoelectron circular dichroism of O 1ss-photoelectrons of uniaxially oriented trifluoromethyloxirane: Energy dependence and sensitivity to molecular configuration

The photoelectron circular dichroism (PECD) of the O 1s-photoelectrons of trifluoromethyloxirane(TFMOx) is studied experimentally and theoretically for different photoelectron kinetic energies. The experiments were performed employing circularly polarized synchrotron radiation and coincidentelectron and fragment ion detection using Cold Target Recoil Ion Momentum Spectroscopy. The corresponding calculations were performed by means of the Single Center method within the relaxed-core Hartree-Fock approximation. We concentrate on the energy dependence of the differential PECD of uniaxially oriented TFMOx molecules, which is accessible through the employed coincident detection. We also compare results for differential PECD of TFMOx to those obtained for the equivalent fragmentation channel and similar photoelectron kinetic energy of methyloxirane (MOx), studied in our previous work. Thereby, we investigate the influence of the substitution of the methyl-group by the trifluoromethyl-group at the chiral center on the molecular chiral response. Finally, the presently obtained angular distribution parameters are compared to those available in literature.Comment: 6 fig

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development

"CAN Stop" - Implementation and evaluation of a secondary group prevention for adolescent and young adult cannabis users in various contexts - study protocol

<p>Abstract</p> <p>Background</p> <p>Current research shows that overall numbers for cannabis use among adolescents and young adults dropped in recent years. However, this trend is much less pronounced in continuous cannabis use. With regard to the heightened risk for detrimental health- and development-related outcomes, adolescents and young adults with continuous cannabis use need special attention. The health services structure for adolescents and young adults with substance related problems in Germany, is multifaceted, because different communal, medical and judicial agencies are involved. This results in a rather decentralized organizational structure of the help system. This and further system-inherent characteristics make the threshold for young cannabis users rather high. Because of this, there is a need to establish evidence-based low-threshold help options for young cannabis users, which can be easily disseminated. Therefore, a training programme for young cannabis users (age 14-21) was developed in the "CAN Stop" project. Within the project, we seek to implement and evaluate the training programme within different institutions of the help system. The evaluation is sensitive to the different help systems and their specific prerequisites. Moreover, within this study, we also test the practicability of a training provision through laypersons.</p> <p>Methods/Design</p> <p>The CAN Stop study is a four-armed randomized wait-list controlled trial. The four arms are needed for the different help system settings, in which the CAN Stop training programme is evaluated: (a) the drug addiction aid and youth welfare system, (b) the out-patient medical system, (c) the in-patient medical system and (d) prisons for juvenile offenders. Data are collected at three points, before and after the training or a treatment as usual, and six months after the end of either intervention.</p> <p>Discussion</p> <p>The CAN Stop study is expected to provide an evidence-based programme for young cannabis users seeking to reduce or quit their cannabis use. Moreover, we seek to gain knowledge about the programme's utility within different settings of the German help system for young cannabis users and information about the settings' specific clientele. The study protocol is discussed with regard to potential difficulties within the different settings.</p> <p>Trial registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN57036983">ISRCTN57036983</a></p

Suicidality in primary care patients who present with sadness and anhedonia: a prospective European study

Background: Sadness and anhedonia (loss of interest in activities) are central symptoms of major depression. However, not all people with these symptoms meet diagnostic criteria for major depression. We aimed to assess the importance of suicidality in the outcomes for primary care patients who present with sadness and anhedonia. Method: Cohort study of 2,599 unselected primary care attenders in six European countries followed up at 6 and 12 months. Results: 1) In patients with sadness and/or anhedonia who were not depressed at entry to the study, suicide plans (OR = 3.05; 95 % CI = 1.50–6.24; p = 0.0022) and suicide attempts (OR = 9.08; 95 % CI = 2.57–32.03; p = 0.0006) were significant predictors of developing new onset depression at 6 or 12 months. 2) In patients with sadness and/or anhedonia who met CIDI criteria for major depression at entry, suicidal ideation (OR = 2.93; 95 % CI = 1.70–5.07; p = 0.0001), suicide plans (OR = 3.70; 95 % CI = 2.08–6.57; p < 0.0001), and suicide attempts (OR = 3.33; 95 % CI = 1.47–7.54; p = 0.0040) were significant predictors of persistent depression at 6 or 12 months. Conclusions: Three questions on suicidality could help primary care professionals to assess such patients more closely without necessarily establishing whether they meet criteria for major depression.This research was funded by a grant from The European Commission, referencePREDICT-QL4-CT2002-00683. We are also grateful for part support in Europe from: the Estonian Scientific Foundation (grant number 5696); the Slovenian Ministry for Research (grant No.4369-1027); the Spanish Ministry of Health (grant FIS references: PI041980, PI041771, PI042450) and the Spanish Network of Primary Care Research, redIAPP (ISCIII-RETICS RD06/0018) and SAMSERAP group; and the UK NHS Research and Development office for providing service support costs in the UK. We are also grateful for the support from the University of Malaga (Spain) and to Carlos García from Loyola Andalucía University (Spain)

Predicting the onset and persistence of episodes of depression in primary health care. The predictD-Spain study: Methodology

Background: The effects of putative risk factors on the onset and/or persistence of depression remain unclear. We aim to develop comprehensive models to predict the onset and persistence of episodes of depression in primary care. Here we explain the general methodology of the predictD-Spain study and evaluate the reliability of the questionnaires used. Methods: This is a prospective cohort study. A systematic random sample of general practice attendees aged 18 to 75 has been recruited in seven Spanish provinces. Depression is being measured with the CIDI at baseline, and at 6, 12, 24 and 36 months. A set of individual, environmental, genetic, professional and organizational risk factors are to be assessed at each follow-up point. In a separate reliability study, a proportional random sample of 401 participants completed the test-retest (251 researcher-administered and 150 self-administered) between October 2005 and February 2006. We have also checked 118,398 items for data entry from a random sample of 480 patients stratified by province. Results: All items and questionnaires had good test-retest reliability for both methods of administration, except for the use of recreational drugs over the previous six months. Cronbach's alphas were good and their factorial analyses coherent for the three scales evaluated (social support from family and friends, dissatisfaction with paid work, and dissatisfaction with unpaid work). There were 191 (0.16%) data entry errors. Conclusion: The items and questionnaires were reliable and data quality control was excellent. When we eventually obtain our risk index for the onset and persistence of depression, we will be able to determine the individual risk of each patient evaluated in primary health care.The research in Spain was funded by grants from the Spanish Ministry of Health (grant FIS references: PI04/1980, PI0/41771, PI04/2450, and PI06/1442), Andalusian Council of Health (grant references: 05/403, 06/278 and 08/0194), and the Spanish Ministry of Education and Science (grant reference SAF 2006/07192). The Malaga sample, as part of the predictD-International study, was also funded by a grant from The European Commission (reference QL4-CT2002-00683)