Assembly of mitochondria

The majority of mitochondrial proteins are synthesized on cytoplasmic ribosomes and transferred to the mitochondria where they are assembled to supramolecular structures. The intracellular transfer of these proteins appears to occur by a post-translational mechanism, i.e., it involves extramitochondrial precursor forms which are translocated in a step independent from translation. The synthesis and transfer of individual proteins was investigated in vivo, or in vitro employing homologous and heterologous cell free systems for protein synthesis. Cytochrome c was initially made as the apoprotein. This precursor protein was converted to the holoprotein on uptake by mitochondria in reconstituted systems. Integrity of mitochondria was essential for the apo to holo conversion. In the case of the ADP/ATP carrier protein, an integral transmembrane protein of the inner mitochondrial membrane, the initial translation product had the same apparent molecular weight as the mature protein. It was found in soluble form in the post-ribosomal supernatant. Citrate synthase, a matrix protein, was synthesized as a precursor with an apparent molecular weight of 47 000. Transfer to the mitochondria was accompanied by cleavage to yield a molecular weight of 45 000. The significance of these results in relation to the mechanisms of intracellular transfer and of assembly of the individual proteins is discussed

Parity to Safety in Polynomial Time for Pushdown and Collapsible Pushdown Systems

We give a direct polynomial-time reduction from parity games played over the configuration graphs of collapsible pushdown systems to safety games played over the same class of graphs. That a polynomial-time reduction would exist was known since both problems are complete for the same complexity class. Coming up with a direct reduction, however, has been an open problem. Our solution to the puzzle brings together a number of techniques for pushdown games and adds three new ones. This work contributes to a recent trend of liveness to safety reductions which allow the advanced state-of-the-art in safety checking to be used for more expressive specifications

Structural Origins of Misfolding Propensity in the Platelet Adhesive Von Willebrand Factor A1 Domain

AbstractThe von Willebrand factor (VWF) A1 and A3 domains are structurally isomorphic yet exhibit distinct mechanisms of unfolding. The A1 domain, responsible for platelet adhesion to VWF in hemostasis, unfolds through a molten globule intermediate in an apparent three-state mechanism, while A3 unfolds by a classical two-state mechanism. Inspection of the sequences or structures alone does not elucidate the source of this thermodynamic conundrum; however, the three-state character of the A1 domain suggests that it has more than one cooperative substructure yielding two separate unfolding transitions not present in A3. We investigate the extent to which structural elements contributing to intermediate conformations can be identified using a residue-specific implementation of the structure-energy-equivalence-of-domains algorithm (SEED), which parses proteins of known structure into their constituent thermodynamically cooperative components using protein-group-specific, transfer free energies. The structural elements computed to contribute to the non-two-state character coincide with regions where Von Willebrand disease mutations induce misfolded molten globule conformations of the A1 domain. This suggests a mechanism for the regulation of rheological platelet adhesion to A1 based on cooperative flexibility of the α2 and α3 helices flanking the platelet GPIbα receptor binding interface

Fossil pollen and spores as a tool for reconstructing ancient solar-ultraviolet irradiance received by plants : an assessment of prospects and challenges using proxy-system modelling

Ultraviolet-B radiation (UV-B, 280-315 nm) constitutes less than 1% of the total solar radiation that reaches the Earth's surface but has a disproportional impact on biological and ecological processes from the individual to the ecosystem level. Absorption of UV-B by ozone is also one of the primary heat sources to the stratosphere, so variations in UV-B have important relationships to the Earth's radiation budget. Yet despite its importance for understanding atmospheric and ecological processes, there is limited understanding about the changes in UV-B radiation in the geological past. This is because systematic measurements of total ozone and surface UV-B only exist since the 1970s, so biological or geochemical proxies from sediment archives are needed to reconstruct UV-B irradiance received at the Earth surface beyond the experimental record. Recent developments have shown that the quantification of UV-B-absorbing compounds in pollen and spores have the potential to provide a continuous record of the solar-ultraviolet radiation received by plants. There is increasing interest in developing this proxy in palaeoclimatic and palaeoecological research. However, differences in interpretation exist between palaeoecologists, who are beginning to apply the proxy under various geological settings, and UV-B ecologists, who question whether a causal dose-response relationship of pollen and spore chemistry to UV-B irradiance has really been established. Here, we use a proxy-system modelling approach to systematically assess components of the pollen-and spore-based UV-B-irradiance proxy to ask how these differences can be resolved. We identify key unknowns and uncertainties in making inferences about past UV-B irradiance, from the pollen sensor, the sedimentary archive, and through the laboratory and experimental procedures in order to target priority areas of future work. We argue that an interdisciplinary approach, modifying methods used by plant ecologists studying contemporary responses to solar-UV-B radiation specifically to suit the needs of palaeoecological analyses, provides a way forward in developing the most reliable reconstructions for the UV-B irradiance received by plants across a range of timescales.Peer reviewe

Nanoelectromechanical control of spin-photon interfaces in a hybrid quantum system on chip

Atom-like defects or color centers (CC's) in nanostructured diamond are a leading platform for optically linked quantum technologies, with recent advances including memory-enhanced quantum communication, multi-node quantum networks, and spin-mediated generation of photonic cluster states. Scaling to practically useful applications motivates architectures meeting the following criteria: C1 individual optical addressing of spin qubits; C2 frequency tuning of CC spin-dependent optical transitions; C3 coherent spin control in CC ground states; C4 active photon routing; C5 scalable manufacturability; and C6 low on-chip power dissipation for cryogenic operations. However, no architecture meeting C1-C6 has thus far been demonstrated. Here, we introduce a hybrid quantum system-on-chip (HQ-SoC) architecture that simultaneously achieves C1-C6. Key to this advance is the realization of piezoelectric strain control of diamond waveguide-coupled tin vacancy centers to meet C2 and C3, with ultra-low power dissipation necessary for C6. The DC response of our device allows emitter transition tuning by over 20 GHz, while the large frequency range (exceeding 2 GHz) enables low-power AC control. We show acoustic manipulation of integrated tin vacancy spins and estimate single-phonon coupling rates over 1 kHz in the resolved sideband regime. Combined with high-speed optical routing with negligible static hold power, this HQ-SoC platform opens the path to scalable single-qubit control with optically mediated entangling gates

Comparison of different functions to describe growth from weaning to maturity in crossbred beef cattle

Cow mature weight (MWT) has increased in the past 30 yr. Larger cows cost more to maintain, but their efficiency—and thus profitability— depends on the production environment. Incorporating MWT effectively into selection and mating decisions requires understanding of growth to maturity. The objective of this study was to describe growth to maturity in crossbred beef cattle using Brody, spline, and quadratic functions. Parameter estimates utilized data on crossbred cows from cycle VII and continuous sampling phases of the Germplasm Evaluation Program at the U.S. Meat Animal Research Center. The MWT were estimated at 6 yr from the fitted parameters obtained from the Brody (BMWT), spline (SMWT), and quadratic (QMWT) functions. These were defined as BMWT, SMWT, and QMWT for the Brody, spline, and quadratic functions, respectively. Key parameters from the Brody function were BMWT and maturing constant. The spline was fitted as piecewise linear where the two linear functions joined at a knot. Key parameters were knot position and SMWT. For the quadratic model, the main parameter considered was QMWT. Data were scaled for fitting such that 180 d was the y-intercept with the average weight at 180 d (214.3 kg) subtracted from all weights. Weights were re-expressed by adding 214.3 kg after analysis. Once data were edited, with outliers removed, there were parameter estimates for 5,156, 5,041, and 4,905 cows for the Brody, spline, and quadratic functions, respectively. The average maturing constant (SD) was 0.0023 d−1 (0.0008 d−1). The mean MWT estimates (SD) from the Brody, spline, and quadratic functions were 650.0 kg (64.0 kg), 707.3 kg (79.8 kg), and 597.8 kg (116.7 kg), respectively. The spline function had the highest average R2 value when fit to individual cows’ data. However, the Brody function produced more consistent MWT estimates regardless of the timeframe of data available and produced the fewest extreme MWT. For the spline and quadratic functions, weights through 4 and 5 yr of age, respectively, were needed before consistent estimates of MWT were obtained. Of the three functions fitted, the Brody was best suited for estimating MWT at a later age in crossbred beef cattle

Breed and heterotic effects for mature weight in beef cattle

Cow mature weight (MWT) is heritable and affects the costs and efficiency of a breeding operation. Cow weight is also influenced by the environment, and the relationship between the size and profitability of a cow varies depending on production system. Producers, therefore, need tools to incorporate MWT in their selection of cattle breeds and herd replacements. The objective of this study was to estimate breed and heterotic effects for MWT using weight-age data on crossbred cows. Cow\u27s MWT at 6 yr was predicted from the estimated parameter values-asymptotic weight and maturation constant (k)-from the fit of the Brody function to their individual data. Values were obtained for 5,156 crossbred cows from the U.S. Meat Animal Research Center (USMARC) Germplasm Evaluation Program using 108,957 weight records collected from approximately weaning up to 6 yr of age. The cows were produced from crosses among 18 beef breeds. A bivariate animal model was fitted to the MWT and k obtained for each cow. The fixed effects were birth year-season contemporary group and covariates of direct and maternal breed fractions, direct and maternal heterosis, and age at final weighing. The random effects were direct additive and residual. A maternal additive random effect was also fitted for k. In a separate analysis from that used to estimate breed effects and (co)variances, cow MWT was regressed on sire yearling weight (YWT) Expected Progeny Differences by its addition as a covariate to the animal model fitted for MWT. That regression coefficient was then used to adjust breed solutions for sire selection in the USMARC herd. Direct heterosis was 15.3 ± 2.6 kg for MWT and 0.000118 ± 0.000029 d-1 for k. Maternal heterosis was -5.7 ± 3.0 kg for MWT and 0.000130 ± 0.000035 d-1 for k. Direct additive heritabilities were 0.56 ± 0.03 for MWT and 0.23 ± 0.03 for k. The maternal additive heritability for k was 0.11 ± 0.02. The direct additive correlation between MWT and k was negligible (0.08 ± 0.09). Adjusted for sire sampling, Angus was heaviest at maturity of the breeds compared. Deviations from Angus ranged from -8.9 kg (Charolais) to -136.7 kg (Braunvieh). Ordered by decreasing MWT, the breeds ranked Angus, Charolais, Hereford, Brahman, Salers, Santa Gertrudis, Simmental, Maine Anjou, Limousin, Red Angus, Brangus, Chiangus, Shorthorn, Gelbvieh, Beefmaster, and Braunvieh. These breed effects for MWT can inform breeding programs where cow size is considered a key component of the overall profitability