Reaction of the NAD(P)H:flavin oxidoreductase from Escherichia coli with NADPH and riboflavin: identification of intermediates.

International audienceFlavin reductase catalyzes the reduction of free flavins by NAD(P)H. As isolated, Escherichia coli flavin reductase does not contain any flavin prosthetic group but accommodates both the reduced pyridine nucleotide and the flavin substrate in a ternary complex prior to oxidoreduction. The reduction of riboflavin by NADPH catalyzed by flavin reductase has been studied by static and rapid kinetics absorption spectroscopies. Static absorption spectroscopy experiments revealed that, in the presence of riboflavin and reduced pyridine nucleotide, flavin reductase stabilizes, although to a small extent, a charge-transfer complex of NADP+ and reduced riboflavin. In addition, reduction of riboflavin was found to be essentially irreversible. Rapid kinetics absorption spectroscopy studies demonstrated the occurrence of two intermediates with long-wavelength absorption during the catalytic cycle. Such intermediate species exhibit spectroscopic properties similar to those of charge-transfer complexes of oxidized flavin and NAD(P)H, and reduced flavin and NAD(P)+, respectively, which have been identified as intermediates during the reaction of flavoenzymes of the ferredoxin-NADP+ reductase family. Thus, a minimal kinetic scheme for the reaction of flavin reductase with NADPH and riboflavin can be proposed. After formation of the Michaelis complex of flavin reductase with NADPH and riboflavin, a first intermediate, identified as a charge-transfer complex of NADPH and riboflavin, is formed. It is followed by a second charge-transfer intermediate of enzyme-bound NADP+ and reduced riboflavin. The latter decays, yielding the Michaelis complex of flavin reductase with NADP+ and reduced riboflavin, which then dissociates to complete the reaction. These results support the initial hypothesis of a structural similarity between flavin reductase and the enzymes of the ferredoxin-NADP+ reductase family and extend it at a functional level

Bed-load effects on hydrodynamics of rough-bed open-channel flows

Peer reviewedPublisher PD

Interplay between spatially explicit sediment sourcing, hierarchical river-network structure, and in-channel bed material sediment transport and storage dynamics

Understanding how sediment moves along source to sink pathways through watersheds„from hillslopes to channels and in and out of floodplains„is a fundamental problem in geomorphology. We contribute to advancing this understanding by modeling the transport and in-channel storage dynamics of bed material sediment on a river network over a 600æyear time period. Specifically, we present spatiotemporal changes in bed sediment thickness along an entire river network to elucidate how river networks organize and process sediment supply. We apply our model to sand transport in the agricultural Greater Blue Earth River Basin in Minnesota. By casting the arrival of sediment to links of the network as a Poisson process, we derive analytically (under supply-limited conditions) the time-averaged probability distribution function of bed sediment thickness for each link of the river network for any spatial distribution of inputs. Under transport-limited conditions, the analytical assumptions of the Poisson arrival process are violated (due to in-channel storage dynamics) where we find large fluctuations and periodicity in the time series of bed sediment thickness. The time series of bed sediment thickness is the result of dynamics on a network in propagating, altering, and amalgamating sediment inputs in sometimes unexpected ways. One key insight gleaned from the model is that there can be a small fraction of reaches with relatively low-transport capacity within a nonequilibrium river network acting as ñbottlenecksî that control sediment to downstream reaches, whereby fluctuations in bed elevation can dissociate from signals in sediment supply. ©2017. American Geophysical Union. All Rights Reserved

Particle Size Distribution Controls the Threshold Between Net Sediment Erosion and Deposition in Suspended Load Dominated Flows

The central problem of describing most environmental and industrial flows is predicting when material is entrained into, or deposited from, suspension. The threshold between erosional and depositional flow has previously been modeled in terms of the volumetric amount of material transported in suspension. Here a new model of the threshold is proposed, which incorporates (i) volumetric and particle size limits on a flow's ability to transport material in suspension, (ii) particle size distribution effects, and (iii) a new particle entrainment function, where erosion is defined in terms of the power used to lift mass from the bed. While current suspended load transport models commonly use a single characteristic particle size, the model developed herein demonstrates that particle size distribution is a critical control on the threshold between erosional and depositional flow. The new model offers an order of magnitude, or better, improvement in predicting the erosional‐depositional threshold and significantly outperforms existing particle‐laden flow models

An ordinary differential equation for velocity distribution and dip-phenomenon in open channel flows

An ordinary differential equation for velocity distribution in open channel flows is presented based on an analysis of the Reynolds-Averaged Navier-Stokes equations and a log-wake modified eddy viscosity distribution. This proposed equation allows to predict the velocity-dip-phenomenon, i.e. the maximum velocity below the free surface. Two different degrees of approximations are presented, a semi-analytical solution of the proposed ordinary differential equation, i.e. the full dip-modified-log-wake law and a simple dip-modified-log-wake law. Velocity profiles of the two laws and the numerical solution of the ordinary differential equation are compared with experimental data. This study shows that the dip correction is not efficient for a small Coles' parameter, accurate predictions require larger values. The simple dip-modified-log-wake law shows reasonable agreement and seems to be an interesting tool of intermediate accuracy. The full dip-modified-log-wake law, with a parameter for dip-correction obtained from an estimation of dip positions, provides accurate velocity profiles

Corrigendum: A Real-World, Multicenter, Observational Retrospective Study of Durvalumab After Concomitant or Sequential Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer (Front. Oncol., (2021), 11, (744956), 10.3389/fonc.2021.744956)

In the original article there was an error. The survival numbers were incorrect. A correction has been made to Abstract: “1-year PFS and OS were 83.5% (95%CI: 77.6-89.7) and 97.2% (95%CI: 94.6-99.9), respectively.” “1-year PFS and OS were 65.5% (95%CI: 57.6-74.4) and 87.9% (95%CI: 82.26.6-93.9), respectively” In the original article, there was an error. The survival numbers were incorrect. A correction has been made to Results, Survival: “PFS at 12, 18, and 24 months was 83.5% (95%CI: 77.6– 89.7), 65.5 (95%CI: 57.6–74.4), and 53.1% (95%CI: 43.8–64.3), respectively. (Figure 1). OS at 12, 18, and 24 months was 97.2% (95%CI: 94.6– 99.9), 87.9% (95%CI: 82.26–93.9), and 79.3% (95%CI: 71.1–88.4), respectively (Figure 1).” “PFS at 6, 12, and 18 months was 83.5% (95%CI: 77.6– 89.7), 65.5% (95%CI: 57.6–74.4), and 53.1% (95%CI: 43.8– 64.3), respectively. (Figure 1). OS at 6, 12, and 18 months was 97.2% (95%CI: 94.6– 99.9), 87.9% (95%CI: 82.26–93.9), and 79.3% (95%CI: 71.1–88.4), respectively (Figure 1)” In the original article, there was an error. The survival numbers were incorrect. A correction has been made to Discussion: “12-month PFS was 83.5%, and OS 97.2%” “12-month PFS was 65.5%, and OS 87.9%” The authors apologize for these errors and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

Transcriptomics and metabolomics integration reveals redox-dependent metabolic rewiring in breast cancer cells

Rewiring glucose metabolism toward aerobic glycolysis provides cancer cells with a rapid generation of pyruvate, ATP, and NADH, while pyruvate oxidation to lactate guarantees refueling of oxidized NAD+ to sustain glycolysis. CtPB2, an NADH-dependent transcriptional co-regulator, has been proposed to work as an NADH sensor, linking metabolism to epigenetic transcriptional reprogramming. By integrating metabolomics and transcriptomics in a triple-negative human breast cancer cell line, we show that genetic and pharmacological down-regulation of CtBP2 strongly reduces cell proliferation by modulating the redox balance, nucleotide synthesis, ROS generation, and scavenging. Our data highlight the critical role of NADH in controlling the oncogene-dependent crosstalk between metabolism and the epigenetically mediated transcriptional program that sustains energetic and anabolic demands in cancer cells

Numerical simulation of turbulent sediment transport, from bed load to saltation

Sediment transport is studied as a function of the grain to fluid density ratio using two phase numerical sim- ulations based on a discrete element method (DEM) for particles coupled to a continuum Reynolds averaged description of hydrodynamics. At a density ratio close to unity (typically under water), vertical velocities are so small that sediment transport occurs in a thin layer at the surface of the static bed, and is called bed load. Steady, or 'saturated' transport is reached when the fluid borne shear stress at the interface between the mobile grains and the static grains is reduced to its threshold value. The number of grains transported per unit surface is therefore limited by the flux of horizontal momentum towards the surface. However, the fluid velocity in the transport layer remains almost undisturbed so that the mean grain velocity scales with the shear velocity u\ast. At large density ratio (typically in air), the vertical velocities are large enough to make the transport layer wide and dilute. Sediment transport is then called saltation. In this case, particles are able to eject others when they collide with the granular bed, a process called splash. The number of grains transported per unit surface is selected by the balance between erosion and deposition and saturation is reached when one grain is statistically replaced by exactly one grain after a collision, which has the consequence that the mean grain velocity remains independent of u\ast. The influence of the density ratio is systematically studied to reveal the transition between these two transport regimes. Based on the mechanisms identified in the steady case, we discuss the transient of saturation of sediment transport and in particular the saturation time and length. Finally, we investigate the exchange of particles between the mobile and static phases and we determine the exchange time of particles.Comment: 17 pages, 14 figures, submitted to Physics of Fluid

Drag Reduction in Open Channel Flow by Aeration and Suspended Load

In supercritical open channel flows air is entrained at the free surface. Such air-water flows, called self-aerated flows, exhibit smaller friction losses than non-aerated flows. New data on drag reduction in self-aerated flows are presented. It is shown that the drag reduction process is linked with the presence of an air concentration boundary layer next to the channel bottom. An analogy with dilute polymer solutions and micro bubble modified boundary layers is developed and it is suggested that the presence of air next to the bottom increases the effective viscosity of the mixture and the sublayer thickness. A parallel with sediment laden flows is also developed. Although the distribution of suspended sediments differs from the distribution of air bubbles, it is suggested that the mechanisms of drag reduction observed in suspended sediment flows are similar to those in self-aerated flows