The beta subunit of the signal recognition particle receptor is a transmembrane GTPase that anchors the alpha subunit, a peripheral membrane GTPase, to the endoplasmic reticulum membrane.

The signal recognition particle receptor (SR) is required for the cotranslational targeting of both secretory and membrane proteins to the endoplasmic reticulum (ER) membrane. During targeting, the SR interacts with the signal recognition particle (SRP) which is bound to the signal sequence of the nascent protein chain. This interaction catalyzes the GTP-dependent transfer of the nascent chain from SRP to the protein translocation apparatus in the ER membrane. The SR is a heterodimeric protein comprised of a 69-kD subunit (SR alpha) and a 30-kD subunit (SR beta) which are associated with the ER membrane in an unknown manner. SR alpha and the 54-kD subunits of SRP (SRP54) each contain related GTPase domains which are required for SR and SRP function. Molecular cloning and sequencing of a cDNA encoding SR beta revealed that SR beta is a transmembrane protein and, like SR alpha and SRP54, is a member of the GTPase superfamily. Although SR beta defines its own GTPase subfamily, it is distantly related to ARF and Sar1. Using UV cross-linking, we confirm that SR beta binds GTP specifically. Proteolytic digestion experiments show that SR alpha is required for the interaction of SRP with SR. SR alpha appears to be peripherally associated with the ER membrane, and we suggest that SR beta, as an integral membrane protein, mediates the membrane association of SR alpha. The discovery of its guanine nucleotide-binding domain, however, makes it likely that its role is more complex than that of a passive anchor for SR alpha. These findings suggest that a cascade of three directly interacting GTPases functions during protein targeting to the ER membrane

Repeat exercise normalizes the gas-exchange impairment induced by a previous exercise bout in asthmatic subjects

Twenty-one subjects with asthma underwent treadmill exercise to exhaustion at a workload that elicited approximately 90% of each subject's maximal O2 uptake (EX1). After EX1, 12 subjects experienced significant exercise-induced bronchospasm [(EIB+), %decrease in forced expiratory volume in 1.0 s = -24.0 +/- 11.5%; pulmonary resistance at rest vs. postexercise = 3.2 +/- 1.5 vs. 8.1 +/- 4.5 cmH2O.l(-1).s(-1)] and nine did not (EIB-). The alveolar-to-arterial Po2 difference (A-aDo2) was widened from rest (9.1 +/- 6.7 Torr) to 23.1 +/- 10.4 and 18.1 +/- 9.1 Torr at 35 min after EX1 in subjects with and without EIB, respectively (P < 0.05). Arterial Po2 (PaO2) was reduced in both groups during recovery (EIB+, -16.0 +/- -13.0 Torr vs. baseline; EIB-, -11.0 +/- 9.4 Torr vs. baseline, P < or = 0.05). Forty minutes after EX1, a second exercise bout was completed at maximal O2 uptake. During the second exercise bout, pulmonary resistance decreased to baseline levels in the EIB+ group and the A-aDo2 and PaO2 returned to match the values seen during EX1 in both groups. Sputum histamine (34.6 +/- 25.9 vs. 61.2 +/- 42.0 ng/ml, pre- vs. postexercise) and urinary 9alpha,11beta-prostaglandin F2 (74.5 +/- 38.6 vs. 164.6 +/- 84.2 ng/mmol creatinine, pre- vs. postexercise) were increased after exercise only in the EIB+ group (P < 0.05), and postexercise sputum histamine was significantly correlated with the exercise PaO2 and A-aDo2 in the EIB+ subjects. Thus exercise causes gas-exchange impairment during the postexercise period in asthmatic subjects independent of decreases in forced expiratory flow rates after the exercise; however, a subsequent exercise bout normalizes this impairment secondary in part to a fast acting, robust exercise-induced bronchodilatory response

Toarcian oceanic anoxic event: An assessment of global causes using belemnite C isotope records

Two hypotheses have been proposed to explain simultaneous large negative excursions (up to 7% PeeDee belemnite) in bulk carbonate (delta(13)C(carb)) and organic carbon isotope records (delta(13)C(org)) from black shales marking the Toarcian oceanic anoxic event (T-OAE). The first explanation envisions recycling of dissolved inorganic carbon (DIC) with a light isotopic signature into the photic zone from the lower levels of a salinity-stratified water mass, essentially requiring a regional paleoceanographic driver of the carbon cycle. The second involves the rapid and massive dissociation of methane from gas hydrates that effectively renders the T-OAE a global perturbation of the carbon cycle. We present C isotope records from belemnites (delta(13)C(bel)) sampled from two localities, calibrated with high-resolution ammonite biostratigraphy and Sr isotope stratigraphy, in Yorkshire (England) and Dotternhausen (Germany), that can be used to assess which model best explains the observed changes in carbon isotopes. Our records of the delta(13)C composition of belemnite calcite do not show the large negative C isotope excursions shown by coeval records of delta(13)C in sedimentary organic matter or bulk sedimentary carbonate. It follows that isotopically light carbon cannot have dominated the ocean-atmosphere carbon reservoir during the Toarcian OAE, as would be required were the methane release hypothesis correct. On the basis of an evaluation of available carbon isotope records we discuss a model in which the recycling of DIC from the deeper levels of a stratified water body, and shallowing of anoxic conditions into the photic zone, can explain all isotopic profiles. In particular, the model accounts for the higher C isotope values of belemnites that are characteristic of open ocean, well-mixed conditions, and the lower C isotope values of neritic phytoplankton communities that recorded the degree of density stratification and shallowing of anoxia in the photic zone

Gas exchange during exercise in habitually active asthmatic subjects

We determined the relations among gas exchange, breathing mechanics, and airway inflammation during moderate- to maximum-intensity exercise in asthmatic subjects. Twenty-one habitually active (48.2 +/- 7.0 ml.kg(-1).min(-1) maximal O2 uptake) mildly to moderately asthmatic subjects (94 +/- 13% predicted forced expiratory volume in 1.0 s) performed treadmill exercise to exhaustion (11.2 +/- 0.15 min) at approximately 90% of maximal O2 uptake. Arterial O2 saturation decreased to < or =94% during the exercise in 8 of 21 subjects, in large part as a result of a decrease in arterial Po2 (PaO2): from 93.0 +/- 7.7 to 79.7 +/- 4.0 Torr. A widened alveolar-to-arterial Po2 difference and the magnitude of the ventilatory response contributed approximately equally to the decrease in PaO2 during exercise. Airflow limitation and airway inflammation at baseline did not correlate with exercise gas exchange, but an exercise-induced increase in sputum histamine levels correlated with exercise Pa(O2) (negatively) and alveolar-to-arterial Po2 difference (positively). Mean pulmonary resistance was high during exercise (3.4 +/- 1.2 cmH2O.l(-1).s) and did not increase throughout exercise. Expiratory flow limitation occurred in 19 of 21 subjects, averaging 43 +/- 35% of tidal volume near end exercise, and end-expiratory lung volume rose progressively to 0.25 +/- 0.47 liter greater than resting end-expiratory lung volume at exhaustion. These mechanical constraints to ventilation contributed to a heterogeneous and frequently insufficient ventilatory response; arterial Pco2 was 30-47 Torr at end exercise. Thus pulmonary gas exchange is impaired during high-intensity exercise in a significant number of habitually active asthmatic subjects because of high airway resistance and, possibly, a deleterious effect of exercise-induced airway inflammation on gas exchange efficiency

The impact of combustor turbulence on turbine loss mechanisms

Abstract A blade row which is located downstream of a combustor has an extremely high turbulence intensity at inlet, typically above 10%. The peak turbulent length scale is also high, at around 20% of the chord of the downstream blade row. In a combustor, the turbulence is created by impinging jets in cross flow. This may result in the turbulence being anisotropic in nature. The aim of this paper is to investigate the effect of combustor turbulence on the loss mechanisms which occur in a turbine blade row. The paper has a number of important findings. The combustor turbulence is characterized and is shown to be isotropic in nature. It shows that, when no pressure gradient is present, combustor turbulence increases the loss of a turbulent boundary layer by 22%. The mechanism responsible for this change is shown to be a deep penetration of the turbulence into the boundary layer. It shows that the presence of combustor turbulence increases the profile loss and endwall loss in the turbine cascade studied by 37% and 47%, respectively. The presence of combustor turbulence also introduces a freestream loss resulting in the total loss of the turbine cascade rising by 47%. When these loss mechanisms were applied to the vane alone, of an engine representative high pressure turbine, it was found to result in a 1.3% reduction in stage efficiency.Rolls-Royce and EPSRC Cenre for Doctoral Training in Gas Turbine Aerodynamic

Age-specific mortality during the 1918 influenza pandemic: unravelling the mystery of high young adult mortality.

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889-90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics

Estimation of Ocean Surface Currents from Maximum Cross Correlation applied to GOCI geostationary satellite remote sensing data over the Tsushima (Korea) Straits

Attempts to automatically estimate surface current velocities from satellite-derived thermal or visible imagery face the limitations of data occlusion due to cloud cover, the complex evolution of features and the degradation of their surface signature. The Geostationary Ocean Color Imager (GOCI) provides a chance to reappraise such techniques due to its multi-year record of hourly high-resolution visible spectrum data. Here we present the results of applying a Maximum Cross Correlation (MCC) technique to GOCI data. Using a combination of simulated and real data we derive suitable processing parameters and examine the robustness of different satellite products, those being water-leaving radiance and chlorophyll concentration. These estimates of surface currents are evaluated using High Frequency (HF) radar systems located in the Tsushima (Korea) Strait. We show the performance of the MCC approach varies depending on the amount of missing data and the presence of strong optical contrasts. Using simulated data it was found that patchy cloud cover occupying 25% of the image pair reduces the number of vectors by 20% compared to using perfect images. Root mean square errors between the MCC and HF radar velocities are of the order of 20 cm s−1. Performance varies depending on the wavelength of the data with the blue-green products out-performing the red and near infra-red products. Application of MCC to GOCI chlorophyll data results in similar performance to radiances in the blue-green bands. The technique has been demonstrated using specific examples of an eddy feature and tidal induced features in the region. This article is protected by copyright. All rights reserved