Overexpression of mitochondrial sirtuins alters glycolysis and mitochondrial function in HEK293 cells

SIRT3, SIRT4, and SIRT5 are mitochondrial deacylases that impact multiple facets of energy metabolism and mitochondrial function. SIRT3 activates several mitochondrial enzymes, SIRT4 represses its targets, and SIRT5 has been shown to both activate and repress mitochondrial enzymes. To gain insight into the relative effects of the mitochondrial sirtuins in governing mitochondrial energy metabolism, SIRT3, SIRT4, and SIRT5 overexpressing HEK293 cells were directly compared. When grown under standard cell culture conditions (25 mM glucose) all three sirtuins induced increases in mitochondrial respiration, glycolysis, and glucose oxidation, but with no change in growth rate or in steady-state ATP concentration. Increased proton leak, as evidenced by oxygen consumption in the presence of oligomycin, appeared to explain much of the increase in basal oxygen utilization. Growth in 5 mM glucose normalized the elevations in basal oxygen consumption, proton leak, and glycolysis in all sirtuin over-expressing cells. While the above effects were common to all three mitochondrial sirtuins, some differences between the SIRT3, SIRT4, and SIRT5 expressing cells were noted. Only SIRT3 overexpression affected fatty acid metabolism, and only SIRT4 overexpression altered superoxide levels and mitochondrial membrane potential. We conclude that all three mitochondrial sirtuins can promote increased mitochondrial respiration and cellular metabolism. SIRT3, SIRT4, and SIRT5 appear to respond to excess glucose by inducing a coordinated increase of glycolysis and respiration, with the excess energy dissipated via proton leak. © 2014 Barbi de Moura et al

Time of emergence of climate signals

The time at which the signal of climate change emerges from the noise of natural climate variability (Time of Emergence, ToE) is a key variable for climate predictions and risk assessments. Here we present a methodology for estimating ToE for individual climate models, and use it to make maps of ToE for surface air temperature (SAT) based on the CMIP3 global climate models. Consistent with previous studies we show that the median ToE occurs several decades sooner in low latitudes, particularly in boreal summer, than in mid-latitudes. We also show that the median ToE in the Arctic occurs sooner in boreal winter than in boreal summer. A key new aspect of our study is that we quantify the uncertainty in ToE that arises not only from inter-model differences in the magnitude of the climate change signal, but also from large differences in the simulation of natural climate variability. The uncertainty in ToE is at least 30 years in the regions examined, and as much as 60 years in some regions. Alternative emissions scenarios lead to changes in both the median ToE (by a decade or more) and its uncertainty. The SRES B1 scenario is associated with a very large uncertainty in ToE in some regions. Our findings have important implications for climate modelling and climate policy which we discuss

Selecting CMIP5 GCMs for downscaling over multiple regions

The unprecedented availability of 6-hourly data from a multi-model GCM ensemble in the CMIP5 data archive presents the new opportunity to dynamically downscale multiple GCMs to develop high-resolution climate projections relevant to detailed assessment of climate vulnerability and climate change impacts. This enables the development of high resolution projections derived from the same set of models that are used to characterise the range of future climate changes at the global and large-scale, and as assessed in the IPCC AR5. However, the technical and human resource required to dynamically-downscale the full CMIP5 ensemble are significant and not necessary if the aim is to develop scenarios covering a representative range of future climate conditions relevant to a climate change risk assessment. This paper illustrates a methodology for selecting from the available CMIP5 models in order to identify a set of 8–10 GCMs for use in regional climate change assessments. The selection focuses on their suitability across multiple regions—Southeast Asia, Europe and Africa. The selection (a) avoids the inclusion of the least realistic models for each region and (b) simultaneously captures the maximum possible range of changes in surface temperature and precipitation for three continental-scale regions. We find that, of the CMIP5 GCMs with 6-hourly fields available, three simulate the key regional aspects of climate sufficiently poorly that we consider the projections from those models ‘implausible’ (MIROC-ESM, MIROC-ESM-CHEM, and IPSL-CM5B-LR). From the remaining models, we demonstrate a selection methodology which avoids the poorest models by including them in the set only if their exclusion would significantly reduce the range of projections sampled. The result of this process is a set of models suitable for using to generate downscaled climate change information for a consistent multi-regional assessment of climate change impacts and adaptation

The complex behavior of El Niño winter 2015-2016

This paper examines the outstanding characteristics of the strong 2015-2016 El Nino (EN) winter and its impact over the European region through the stratosphere. Despite being classified as a strong eastern Pacific (EP) EN event, our analysis reveals an anomalous behavior, with some signatures that are more typical of central Pacific (CP) EN events instead. They include (i) a record-breaking value of the CP index, (ii) a stronger polar vortex in early and midwinter, due to reduced upward wave activity and a weakened Aleutian low, and (iii) the occurrence of one of the earliest stratospheric final warmings (SFWs) on record, which are more prone to occur during CP-EN. Following the SFW, a stratospheric influence on the Euro-Atlantic sector is reported in spring, with persistent Greenland blocking resulting in extreme precipitation over some southern European regions. Results highlight the importance of considering early SFWs as mediators of El Nino teleconnections

Power allocation strategies for distributed precoded multicell based systems

Multicell cooperation is a promising solution for cellular wireless systems to mitigate intercell interference, improve system fairness, and increase capacity. In this article, we propose power allocation techniques for the downlink of distributed, precoded, multicell cellular-based systems. The precoder is designed in two phases: first the intercell interference is removed by applying a set of distributed precoding vectors; then the system is further optimized through power allocation. Three centralized power allocation algorithms with per-BS power constraint and diferente complexity trade-offs are proposed: one optimal in terms of minimization of the instantaneous average bit error rate (BER), and two suboptimal. In this latter approach, the powers are computed in two phases. First, the powers are derived under total power constraint (TPC) and two criterions are considered, namely, minimization of the instantaneous average BER and minimization of the sum of inverse of signal-to-noise ratio. Then, the final powers are computed to satisfy the individual per-BS power constraint. The performance of the proposed schemes is evaluated, considering typical pedestrian scenarios based on LTE specifications. The numerical results show that the proposed suboptimal schemes achieve a performance very close to the optimal but with lower computational complexity. Moreover, the performance of the proposed per-BS precoding schemes is close to the one obtained considering TPC over a supercell.Portuguese CADWIN - PTDC/ EEA TEL/099241/200

Decadal predictions of the cooling and freshening of the North Atlantic in the 1960s and the role of ocean circulation

In the 1960s North Atlantic sea surface temperatures (SST) cooled rapidly. The magnitude of the cooling was largest in the North Atlantic subpolar gyre (SPG), and was coincident with a rapid freshening of the SPG. Here we analyze hindcasts of the 1960s North Atlantic cooling made with the UK Met Office’s decadal prediction system (DePreSys), which is initialised using observations. It is shown that DePreSys captures—with a lead time of several years—the observed cooling and freshening of the North Atlantic SPG. DePreSys also captures changes in SST over the wider North Atlantic and surface climate impacts over the wider region, such as changes in atmospheric circulation in winter and sea ice extent. We show that initialisation of an anomalously weak Atlantic Meridional Overturning Circulation (AMOC), and hence weak northward heat transport, is crucial for DePreSys to predict the magnitude of the observed cooling. Such an anomalously weak AMOC is not captured when ocean observations are not assimilated (i.e. it is not a forced response in this model). The freshening of the SPG is also dominated by ocean salt transport changes in DePreSys; in particular, the simulation of advective freshwater anomalies analogous to the Great Salinity Anomaly were key. Therefore, DePreSys suggests that ocean dynamics played an important role in the cooling of the North Atlantic in the 1960s, and that this event was predictable

Validation of the present day annual cycle in heavy precipitation over the British Islands simulated by 14 RCMs

The representation of the annual cycle of heavy daily precipitation events across the United Kingdom within 14 regional climate models (RCMs) and the European observation data set (E-OBS) over the 1961-2000 period is investigated. We model extreme precipitation as an inhomogeneous Poisson process with a non-stationary threshold and use a sinusoidal model for the location and scale parameter of the corresponding generalized extreme value distribution and a constant shape parameter. First we fit the statistical model to the UK Met Office 5 km gridded precipitation data set (UKMO). Second the statistical model is fitted to 14 reanalysis driven 25 km resolution RCMs from the ENSEMBLES project and to E-OBS. The resulting characteristics from the RCMs and from E-OBS are compared with those from UKMO. We study the peak time of the annual cycle of the monthly return levels, the relative amplitude of their annual cycle and the relative bias of their absolute values. We show that the performance of the RCMs depends strongly on the region. The RCMs show deficits in modeling the characteristics of the annual cycle, especially in modeling its relative amplitude and mainly in Eastern England. However the peak time of the annual cycle is adequately simulated by most RCMs. E-OBS exhibits considerable biases in the absolute values of all monthly return levels, but the relative amplitude and the phase of the annual cycle of heavy precipitation are well represented. Our results imply that studies which rely on the explicit annual cycle of simulated heavy precipitation should be carefully considered