An Investigation of Atomic Structures Derived from X-ray Crystallography and Cryo-Electron Microscopy Using Distal Blocks of Side-Chains

Cryo-electron microscopy (cryo-EM) is a structure determination method for large molecular complexes. As more and more atomic structures are determined using this technique, it is becoming possible to perform statistical characterization of side-chain conformations. Two data sets were involved to characterize block lengths for each of the 18 types of amino acids. One set contains 9131 structures resolved using X-ray crystallography from density maps with better than or equal to 1.5 Å resolutions, and the other contains 237 protein structures derived from cryo-EM density maps with 2-4 Å resolutions. The results show that the normalized probability density function of block lengths is similar between the X-ray data set and the cryo-EM data set for most of the residue types, but differences were observed for ARG, GLU, ILE, LYS, PHE, TRP, and TYR for which conformations with certain shorter block lengths are more likely to be observed in the cryo-EM set with 2-4 Å resolutions

The distributional consequences of tax reforms under capital-skill complementarity

This paper analyses wage inequality and the welfare effects of changes in capital and labour income tax rates for different types of agents. To achieve this, we develop a model that allows for capital–skill complementarity given non-uniform distributions of asset holdings and labour skills. We find that capital tax reductions lead to the highest aggregate welfare gains but are skill-biased and thus increase inequality. However, our analysis also shows that the inequality effects of capital tax reductions are lower over the transition period compared with the long run

Experimental investigation of ventilation efficiency in a dentistry surgical room

As a response to the need to provide an acceptable thermal comfort and air quality in indoor environments, various ventilation performance indicators were developed over the years. These metrics are mainly geared towards air distribution, heat and pollutant removals. Evidence exists of influencing factors on these indicators as centered on ventilation design and operations. Unlike other indoor environments, health care environment requires better performance of ventilation system to prevent an incidence of nosocomial and other hospital acquired illnesses. This study investigates, using in-situ experiments, the ventilation efficiency in a dentistry surgical room. Thermal and hygric parameters were monitored on the air terminal devices and occupied zone over a period of one week covering both occupied and unoccupied hours. The resulting time-series parameters were used to evaluate the room's ventilation effectiveness. Also, the obtained parameters were benchmarked against ASHRAE 170 (2013) and MS1525 (2014) requirements for ventilation in health care environment and building energy efficiency respectively. The results show that the mean daily operative conditions failed to satisfy the provisions of both standards. Regarding effectiveness, the findings reveal that the surgical room ventilation is ineffective with ventilation efficiency values ranging between 0 and 0.5 indicating air distribution short-circuiting. These results suggest further investigations, through numerical simulation, on the effect of this short-circuiting on thermal comfort, infection risk assessments and possible design improvements, an endeavour that forms our next line of research inquiries

Human METTL20 methylates lysine residues adjacent to the recognition loop of the electron transfer flavoprotein in mitochondria.

In mammalian mitochondria, protein methylation is a relatively uncommon post-transcriptional modification, and the extent of the mitochondrial protein methylome, the modifying methyltransferases, and their substrates have been little studied. As shown here, the β-subunit of the electron transfer flavoprotein (ETF) is one such methylated protein. The ETF is a heterodimer of α- and β-subunits. Lysine residues 199 and 202 of mature ETFβ are almost completely trimethylated in bovine heart mitochondria, whereas ETFα is not methylated. The enzyme responsible for the modifications was identified as methyltransferase-like protein 20 (METTL20). In human 143B cells, the methylation of ETFβ is less extensive and is diminished further by suppression of METTL20. Tagged METTL20 expressed in HEK293T cells specifically associates with the ETF and promotes the trimethylation of ETFβ lysine residues 199 and 202. ETF serves as a mobile electron carrier linking dehydrogenases involved in fatty acid oxidation and one-carbon metabolism to the membrane-associated ubiquinone pool. The methylated residues in ETFβ are immediately adjacent to a protein loop that recognizes and binds to the dehydrogenases. Suppression of trimethylation of ETFβ in mouse C2C12 cells oxidizing palmitate as an energy source reduced the consumption of oxygen by the cells. These experiments suggest that the oxidation of fatty acids in mitochondria and the passage of electrons via the ETF may be controlled by modulating the protein-protein interactions between the reduced dehydrogenases and the β-subunit of the ETF by trimethylation of lysine residues. METTL20 is the first lysine methyltransferase to be found to be associated with mitochondria.This work was supported by the Medical Research Council (MRC), UK

Quantification of temporal fault trees based on fuzzy set theory

© Springer International Publishing Switzerland 2014. Fault tree analysis (FTA) has been modified in different ways to make it capable of performing quantitative and qualitative safety analysis with temporal gates, thereby overcoming its limitation in capturing sequential failure behaviour. However, for many systems, it is often very difficult to have exact failure rates of components due to increased complexity of systems, scarcity of necessary statistical data etc. To overcome this problem, this paper presents a methodology based on fuzzy set theory to quantify temporal fault trees. This makes the imprecision in available failure data more explicit and helps to obtain a range of most probable values for the top event probability

Persistence of the mitochondrial permeability transition in the absence of subunit c of human ATP synthase.

The permeability transition in human mitochondria refers to the opening of a nonspecific channel, known as the permeability transition pore (PTP), in the inner membrane. Opening can be triggered by calcium ions, leading to swelling of the organelle, disruption of the inner membrane, and ATP synthesis, followed by cell death. Recent proposals suggest that the pore is associated with the ATP synthase complex and specifically with the ring of c-subunits that constitute the membrane domain of the enzyme's rotor. The c-subunit is produced from three nuclear genes, ATP5G1, ATP5G2, and ATP5G3, encoding identical copies of the mature protein with different mitochondrial-targeting sequences that are removed during their import into the organelle. To investigate the involvement of the c-subunit in the PTP, we generated a clonal cell, HAP1-A12, from near-haploid human cells, in which ATP5G1, ATP5G2, and ATP5G3 were disrupted. The HAP1-A12 cells are incapable of producing the c-subunit, but they preserve the characteristic properties of the PTP. Therefore, the c-subunit does not provide the PTP. The mitochondria in HAP1-A12 cells assemble a vestigial ATP synthase, with intact F1-catalytic and peripheral stalk domains and the supernumerary subunits e, f, and g, but lacking membrane subunits ATP6 and ATP8. The same vestigial complex plus associated c-subunits was characterized from human 143B ρ(0) cells, which cannot make the subunits ATP6 and ATP8, but retain the PTP. Therefore, none of the membrane subunits of the ATP synthase that are involved directly in transmembrane proton translocation is involved in forming the PTP.This work was supported by the Medical Research Council (MRC) of the United Kingdom by Grant MC_U1065663150 and by Programme Grant MR/M009858/1 (to J.E.W.). H.C.F. received an MRC PhD studentship

Prediction of Three-body B0→ρ−pnˉ,π−pnˉB^0\to \rho^-p\bar{n}, \pi^-p\bar{n} Decay Rates

We predict the rates of the charmless three-body $B^0\to \rho^-p\bar{n}$ and $\pi^-p\bar{n}$ modes due to weak vector current contributions to be $\sim 4\times 10^{-6}$ and $2\times 10^{-6}$, respectively. The basis is a factorization approach of current produced nucleon pairs, together with an isospin transformation that relates nucleon weak vector form factors to electromagnetic form factors. Adding the axial vector current contribution, we find $B^0\to \rho^-p\bar{n}$ and $B^+\to \rho^0p\bar{n}$ to be at $10^{-5}$ order. The three-body modes appear to dominate over the two-body modes such as $B\to p\bar{p}$, $p\bar \Lambda$.Comment: 5 pages, 4 figures. Version to appear in Phys. Lett.

Eurasian Arctic greening reveals teleconnections and the potential for novel ecosystems

Arctic warming has been linked to observed increases in tundra shrub cover and growth in recent decades on the basis of significant relationships between deciduous shrub growth/biomass and temperature. These vegetation trends have been linked to Arctic sea ice decline and thus to the sea ice/albedo feedback known as Arctic amplification. However, the interactions between climate, sea ice and tundra vegetation remain poorly understood. Here we reveal a 50- year growth response over a >100,000 km2 area to a rise in summer temperature for alder (Alnus) and willow (Salix), the most abundant shrub genera respectively at and north of the continental treeline. We demonstrate that whereas plant productivity is related to sea ice in late spring, the growing season peak responds to persistent synoptic-scale air masses over West Siberia associated with Fennoscandian weather systems through the Rossby wave train. Substrate is important for biomass accumulation, yet a strong correlation between growth and temperature encompasses all observed soil types. Vegetation is especially responsive to temperature in early summer. These results have significant implications for modelling present and future Low Arctic vegetation responses to climate change, and emphasize the potential for structurally novel ecosystems to emerge fromwithin the tundra zone.Vertaisarviointia edeltävä käsikirjoitu

Coherent versus Incoherent Light Scattering from a Quantum Dot

We analyze the light scattered by a single InAs quantum dot interacting with a resonant continuous-wave laser. High resolution spectra reveal clear distinctions between coherent and incoherent scattering, with the laser intensity spanning over four orders of magnitude. We find that the fraction of coherently scattered photons can approach unity under sufficiently weak or detuned excitation, ruling out pure dephasing as a relevant decoherence mechanism. We show how spectral diffusion shapes spectra, correlation functions, and phase-coherence, concealing the ideal radiatively-broadened two-level system described by Mollow.Comment: to appear in PRB 85, 23531

Evidence of association with type 1 diabetes in the SLC11A1 gene region

BackgroundLinkage and congenic strain analyses using the nonobese diabetic (NOD) mouse as a model for human type 1 autoimmune diabetes (T1D) have identified several NOD mouse Idd (insulin dependent diabetes) loci, including Slc11a1 (formerly known as Nramp1). Genetic variants in the orthologous region encompassing SLC11A1 in human chromosome 2q35 have been reported to be associated with various immune-related diseases including T1D. Here, we have conducted association analysis of this candidate gene region, and then investigated potential correlations between the most T1D-associated variant and RNA expression of the SLC11A1 gene and its splice isoform.MethodsNine SNPs (rs2276631, rs2279015, rs1809231, rs1059823, rs17235409 (D543N), rs17235416 (3'UTR), rs3731865 (INT4), rs7573065 (-237 C → T) and rs4674297) were genotyped using TaqMan genotyping assays and the polymorphic promoter microsatellite (GT)n was genotyped using PCR and fragment length analysis. A maximum of 8,863 T1D British cases and 10,841 British controls, all of white European descent, were used to test association using logistic regression. A maximum of 5,696 T1D families were also tested for association using the transmission/disequilibrium test (TDT). We considered P ≤ 0.005 as evidence of association given that we tested nine variants in total. Upon identification of the most T1D-associated variant, we investigated the correlation between its genotype and SLC11A1 expression overall or with splice isoform ratio using 42 PAXgene whole blood samples from healthy donors by quantitative PCR (qPCR).ResultsUsing the case-control collection, rs3731865 (INT4) was identified to be the variant most associated with T1D (P = 1.55 × 10-6). There was also some evidence of association at rs4674297 (P = 1.57 × 10-4). No evidence of disease association was obtained at any of the loci using the family collections (PTDT ≥ 0.13). We also did not observe a correlation between rs3731865 genotypes and SLC11A1 expression overall or with splice isoform expression.ConclusionWe conclude that rs3731685 (INT4) in the SLC11A1 gene may be associated with T1D susceptibility in the European ancestry population studied. We did not observe a difference in SLC11A1 expression at the RNA level based on the genotypes of rs3731865 in whole blood samples. However, a potential correlation cannot be ruled out in purified cell subsets especially monocytes or macrophages