The adapter importin-α provides flexible control of nuclear import at the expense of efficiency

Although there exists a large family of nuclear transport receptors (Karyopherins), the majority of known import cargoes use an adapter protein, Importin-α (Impα), which links the cargo to a karyopherin, Importin-β (Impβ). The reason for the existence of transport adapters is unknown. One hypothesis is that, as Impα re-export is coupled to GTP hydrolysis, it can drive a higher concentration of nuclear cargo than could be achieved by direct cargo binding to Importin-β. However, computer simulations predicted the opposite outcome, and showed that direct transport is faster than adapter-mediated transport. These predictions were validated experimentally. The data, together with previous analyses of nuclear protein import, suggest that the use of adapters such as importin-α provides the cell with increased dynamic range for control of nuclear import rates, but at the expense of efficiency

A systems analysis of importin-α–β mediated nuclear protein import

Importin-β (Impβ) is a major transport receptor for Ran-dependent import of nuclear cargo. Impβ can bind cargo directly or through an adaptor such as Importin-α (Impα). Factors involved in nuclear transport have been well studied, but systems analysis can offer further insight into regulatory mechanisms. We used computer simulation and real-time assays in intact cells to examine Impα–β-mediated import. The model reflects experimentally determined rates for cargo import and correctly predicts that import is limited principally by Impα and Ran, but is also sensitive to NTF2. The model predicts that CAS is not limiting for the initial rate of cargo import and, surprisingly, that increased concentrations of Impβ and the exchange factor, RCC1, actually inhibit rather than stimulate import. These unexpected predictions were all validated experimentally. The model revealed that inhibition by RCC1 is caused by sequestration of nuclear Ran. Inhibition by Impβ results from depletion nuclear RanGTP, and, in support of this mechanism, expression of mRFP-Ran reversed the inhibition

Variation in dermcidin expression in a range of primary human tumours and in hypoxic/oxidatively stressed human cell lines.

Dermcidin acts as a survival factor in a variety of cancer cell lines under hypoxia or oxidative stress. The aim of this study was to evaluate dermcidin expression in cell lines following simulation of tumour microenvironmental conditions and in a range of primary tumours. Tumour tissues were collected from patients with oesophageal (28 samples), gastric (20), pancreatic (five), bile duct (one) and prostatic (52) carcinomas as well as 30 benign tissue samples, for assessment of dermcidin mRNA levels using real-time PCR. Dermcidin expression was assessed in prostatic and pancreatic cancer cell lines, with and without induction of hypoxia or oxidative stress. Dermcidin mRNA expression was very low or absent in both unstressed and stressed prostate cell lines. None of the primary prostate tissue, benign or malignant, expressed dermcidin mRNA. Only two (4%) of the gastro-oesophageal cancer samples expressed moderate quantities of dermcidin mRNA. However, three (60%) of the pancreatic cancer samples and the single cholangiocarcinoma specimen had moderate/high levels of dermcidin expression. Of the two pancreatic cancer cell lines, one expressed dermcidin moderately but neither showed a response to hypoxia or oxidative stress. Expression of dermcidin in human primary tumours appears highly variable and is not induced substantially by hypoxia/oxidative stress in cell line model systems. The relationship of these findings to dermcidin protein levels and cell survival remains to be determined

CH4 emission estimates from an active landfill site inferred from a combined approach of CFD modelling and in situ FTIR measurements

Globally, the waste sector contributes to nearly a fifth of anthropogenic methane emitted to the atmosphere and is the second largest source of methane in the UK. In recent years great improvements to reduce those emissions have been achieved by installation of methane recovery systems at landfill sites and subsequently methane emissions reported in national emission inventories have been reduced. Nevertheless, methane emissions of landfills remain uncertain and quantification of emission fluxes is essential to verify reported emission inventories and to monitor changes in emissions. Here we present a new approach for methane emission quantification from a complex source like a landfill site by applying a Computational Fluid Dynamics (CFD) model to calibrated in situ measurements of methane as part of a field campaign at a landfill site near Ipswich, UK, in August 2014. The methane distribution for different meteorological scenarios is calculated with the CFD model and compared to methane mole fractions measured by an in situ Fourier Transform Infrared (FTIR) spectrometer downwind of the prevailing wind direction. Assuming emissions only from the active site, a mean daytime flux of 0.83 mg m−2 s−1, corresponding to 53.26 kg h−1, was estimated. The addition of a secondary source area adjacent to the active site, where some methane hotspots were observed, improved the agreement between the simulated and measured methane distribution. As a result, the flux from the active site was reduced slightly to 0.71 mg m−2 s−1 (45.56 kg h−1), at the same time an additional flux of 0.32 mg m−2 s−1 (30.41 kg h−1) was found from the secondary source area. This highlights the capability of our method to distinguish between different emission areas of the landfill site, which can provide more detailed information about emission source apportionment compared to other methods deriving bulk emissions

Nucleocytoplasmic transport: a thermodynamic mechanism

The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include

Methane emissions from oil and gas platforms in the North Sea

Since 1850 the concentration of atmospheric methane (CH4), a potent greenhouse gas, has more than doubled. Recent studies suggest that emission inventories may be missing sources and underestimating emissions. To investigate whether offshore oil and gas platforms leak CH4 during normal operation, we measured CH4 mole fractions around eight oil and gas production platforms in the North Sea which were neither flaring gas nor offloading oil. We use the measurements from summer 2017, along with meteorological data, in a Gaussian plume model to estimate CH4 emissions from each platform. We find CH4 mole fractions of between 11 and 370 ppb above background concentrations downwind of the platforms measured, corresponding to a median CH4 emission of 6.8 g CH4 s−1 for each platform, with a range of 2.9 to 22.3 g CH4 s−1. When matched to production records, during our measurements individual platforms lost between 0.04 % and 1.4 % of gas produced with a median loss of 0.23 %. When the measured platforms are considered collectively (i.e. the sum of platforms' emission fluxes weighted by the sum of the platforms' production), we estimate the CH4 loss to be 0.19 % of gas production. These estimates are substantially higher than the emissions most recently reported to the National Atmospheric Emission Inventory (NAEI) for total CH4 loss from United Kingdom platforms in the North Sea. The NAEI reports CH4 losses from the offshore oil and gas platforms we measured to be 0.13 % of gas production, with most of their emissions coming from gas flaring and offshore oil loading, neither of which was taking place at the time of our measurements. All oil and gas platforms we observed were found to leak CH4 during normal operation, and much of this leakage has not been included in UK emission inventories. Further research is required to accurately determine total CH4 leakage from all offshore oil and gas operations and to properly include the leakage in national and international emission inventories

Observation of Exclusive Gamma Gamma Production in p pbar Collisions at sqrt{s}=1.96 TeV

We have observed exclusive \gamma\gamma production in proton-antiproton collisions at \sqrt{s}=1.96 TeV, using data from 1.11 \pm 0.07 fb^{-1} integrated luminosity taken by the Run II Collider Detector at Fermilab. We selected events with two electromagnetic showers, each with transverse energy E_T > 2.5 GeV and pseudorapidity |\eta| < 1.0, with no other particles detected in -7.4 < \eta < +7.4. The two showers have similar E_T and azimuthal angle separation \Delta\phi \sim \pi; 34 events have two charged particle tracks, consistent with the QED process p \bar{p} to p + e^+e^- + \bar{p} by two-photon exchange, while 43 events have no charged tracks. The number of these events that are exclusive \pi^0\pi^0 is consistent with zero and is < 15 at 95% C.L. The cross section for p\bar{p} to p+\gamma\gamma+\bar{p} with |\eta(\gamma)| < 1.0 and E_T(\gamma) > 2.5$ GeV is 2.48^{+0.40}_{-0.35}(stat)^{+0.40}_{-0.51}(syst) pb.Comment: 7 pages, 4 figure

Measurements of branching fraction ratios and CP-asymmetries in suppressed B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^- decays

We report the first reconstruction in hadron collisions of the suppressed decays B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^-, sensitive to the CKM phase gamma, using data from 7 fb^-1 of integrated luminosity collected by the CDF II detector at the Tevatron collider. We reconstruct a signal for the B^- -> D(-> K^+ pi^-)K^- suppressed mode with a significance of 3.2 standard deviations, and measure the ratios of the suppressed to favored branching fractions R(K) = [22.0 \pm 8.6(stat)\pm 2.6(syst)]\times 10^-3, R^+(K) = [42.6\pm 13.7(stat)\pm 2.8(syst)]\times 10^-3, R^-(K)= [3.8\pm 10.3(stat)\pm 2.7(syst]\times 10^-3, as well as the direct CP-violating asymmetry A(K) = -0.82\pm 0.44(stat)\pm 0.09(syst) of this mode. Corresponding quantities for B^- -> D(-> K^+ pi^-)pi^- decay are also reported.Comment: 8 pages, 1 figure, accepted by Phys.Rev.D Rapid Communications for Publicatio