Ferredoxin:NADP(H) Oxidoreductase Abundance and Location Influences Redox Poise and Stress Tolerance

In linear photosynthetic electron transport, ferredoxin:NADP(H) oxidoreductase (FNR) transfers electrons from ferredoxin (Fd) to NADP(+). Both NADPH and reduced Fd (Fd(red)) are required for reductive assimilation and light/dark activation/deactivation of enzymes. FNR is therefore a hub, connecting photosynthetic electron transport to chloroplast redox metabolism. A correlation between FNR content and tolerance to oxidative stress is well established, although the precise mechanism remains unclear. We investigated the impact of altered FNR content and localization on electron transport and superoxide radical evolution in isolated thylakoids, and probed resulting changes in redox homeostasis, expression of oxidative stress markers, and tolerance to high light in planta. Our data indicate that the ratio of Fd(red) to FNR is critical, with either too much or too little FNR potentially leading to increased superoxide production, and perception of oxidative stress at the level of gene transcription. In FNR overexpressing plants, which show more NADP(H) and glutathione pools, improved tolerance to high-light stress indicates that disturbance of chloroplast redox poise and increased free radical generation may help “prime” the plant and induce protective mechanisms. In fnr1 knock-outs, the NADP(H) and glutathione pools are more oxidized relative to the wild type, and the photoprotective effect is absent despite perception of oxidative stress at the level of gene transcription

Gravity duals of supersymmetric gauge theories on three-manifolds

We study gravity duals to a broad class of N=2 supersymmetric gauge theories defined on a general class of three-manifold geometries. The gravity backgrounds are based on Euclidean self-dual solutions to four-dimensional gauged supergravity. As well as constructing new examples, we prove in general that for solutions defined on the four-ball the gravitational free energy depends only on the supersymmetric Killing vector, finding a simple closed formula when the solution has U(1) x U(1) symmetry. Our result agrees with the large N limit of the free energy of the dual gauge theory, computed using localization. This constitutes an exact check of the gauge/gravity correspondence for a very broad class of gauge theories with a large N limit, defined on a general class of background three-manifold geometries.Comment: 74 pages, 2 figures; v2: minor change

All solutions of the localization equations for N=2 quantum black hole entropy

We find the most general bosonic solution to the localization equations describing the contributions to the quantum entropy of supersymmetric black holes in four-dimensional N=2 supergravity coupled to n_v vector multiplets. This requires the analysis of the BPS equations of the corresponding off-shell supergravity (including fluctuations of the auxiliary fields) with AdS2 \times S2 attractor boundary conditions. Our work completes and extends the results of arXiv:1012.0265 that were obtained for the vector multiplet sector, to include the fluctuations of all the fields of the off-shell supergravity. We find that, when the auxiliary SU(2) gauge field strength vanishes, the most general supersymmetric configuration preserving four supercharges is labelled by n_v+1 real parameters corresponding to the excitations of the conformal mode of the graviton and the scalars of the n_v vector multiplets. In the general case, the localization manifold is labelled by an additional SU(2) triplet of one-forms and a scalar function.Comment: 27 page

Holographic renormalization and supersymmetry

Holographic renormalization is a systematic procedure for regulating divergences in observables in asymptotically locally AdS spacetimes. For dual boundary field theories which are supersymmetric it is natural to ask whether this defines a supersymmetric renormalization scheme. Recent results in localization have brought this question into sharp focus: rigid supersymmetry on a curved boundary requires specific geometric structures, and general arguments imply that BPS observables, such as the partition function, are invariant under certain deformations of these structures. One can then ask if the dual holographic observables are similarly invariant. We study this question in minimal N = 2 gauged supergravity in four and five dimensions. In four dimensions we show that holographic renormalization precisely reproduces the expected field theory results. In five dimensions we find that no choice of standard holographic counterterms is compatible with supersymmetry, which leads us to introduce novel finite boundary terms. For a class of solutions satisfying certain topological assumptions we provide some independent tests of these new boundary terms, in particular showing that they reproduce the expected VEVs of conserved charges.Comment: 70 pages; corrected typo

Rigid Supersymmetric Backgrounds of Minimal Off-Shell Supergravity

We discuss various aspects of rigid supersymmetry within minimal N=1 off-shell supergravity using the old and new minimal formulations both in Lorentzian and Euclidean signatures. In particular, we construct all rigid supersymmetry backgrounds with a hypersurface orthogonal Killing vector. In the Lorentzian signature we show that AdS_4 provides a rigid supersymmetric background in both formulations albeit with different amounts of preserved supersymmetry. In the Euclidean signature we find new backgrounds of the old-minimal supergravity, including squashed four-spheres and a half-BPS version of flat space.Comment: 40 pages: v2 References added, typos correcte

Simulation vs. Reality: A Comparison of In Silico Distance Predictions with DEER and FRET Measurements

Site specific incorporation of molecular probes such as fluorescent- and nitroxide spin-labels into biomolecules, and subsequent analysis by Förster resonance energy transfer (FRET) and double electron-electron resonance (DEER) can elucidate the distance and distance-changes between the probes. However, the probes have an intrinsic conformational flexibility due to the linker by which they are conjugated to the biomolecule. This property minimizes the influence of the label side chain on the structure of the target molecule, but complicates the direct correlation of the experimental inter-label distances with the macromolecular structure or changes thereof. Simulation methods that account for the conformational flexibility and orientation of the probe(s) can be helpful in overcoming this problem. We performed distance measurements using FRET and DEER and explored different simulation techniques to predict inter-label distances using the Rpo4/7 stalk module of the M. jannaschii RNA polymerase. This is a suitable model system because it is rigid and a high-resolution X-ray structure is available. The conformations of the fluorescent labels and nitroxide spin labels on Rpo4/7 were modeled using in vacuo molecular dynamics simulations (MD) and a stochastic Monte Carlo sampling approach. For the nitroxide probes we also performed MD simulations with explicit water and carried out a rotamer library analysis. Our results show that the Monte Carlo simulations are in better agreement with experiments than the MD simulations and the rotamer library approach results in plausible distance predictions. Because the latter is the least computationally demanding of the methods we have explored, and is readily available to many researchers, it prevails as the method of choice for the interpretation of DEER distance distributions

Antibiotic resistance determinants in the interplay between food and gut microbiota

A complex and heterogeneous microflora performs sugar and lactic acid fermentations in food products. Depending on the fermentable food matrix (dairy, meat, vegetable etc.) as well as on the species composition of the microbiota, specific combinations of molecules are produced that confer unique flavor, texture, and taste to each product. Bacterial populations within such “fermented food microbiota” are often of environmental origin, they persist alive in foods ready for consumption, eventually reaching the gastro-intestinal tract where they can interact with the resident gut microbiota of the host. Although this interaction is mostly of transient nature, it can greatly contribute to human health, as several species within the food microbiota also display probiotic properties. Such an interplay between food and gut microbiota underlines the importance of the microbiological quality of fermented foods, as the crowded environment of the gut is also an ideal site for genetic exchanges among bacteria. Selection and spreading of antibiotic resistance genes in foodborne bacteria has gained increasing interest in the past decade, especially in light of the potential transferability of antibiotic resistance determinants to opportunistic pathogens, natural inhabitants of the human gut but capable of acquiring virulence in immunocompromised individuals. This review aims at describing major findings and future prospects in the field, especially after the use of antibiotics as growth promoters was totally banned in Europe, with special emphasis on the application of genomic technologies to improve quality and safety of fermented foods

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences