On the importance of discharge variability in the morphodynamic modeling of rivers

River morphodynamics and sediment transportRiver morphology and morphodynamic

Анализ составляющих теплового баланса системы "прокатный стан - прокатываемая полоса" и пути снижения энергозатрат в процессе сортовой прокатки

Выполнен анализ составляющих теплового баланса системы «прокатный стан – прокатываемая полоса». Рассмотрены основные направления решения температурной задачи сортовой прокатки. Предложен ряд мероприятий, позволяющих снизить расход энергоресурсов на прокатку и уменьшить расходную часть теплового баланса системы «прокатный стан – прокатываемая полоса»

Rationalisation of the Differences between APOBEC3G Structures from Crystallography and NMR Studies by Molecular Dynamics Simulations

The human APOBEC3G (A3G) protein is a cellular polynucleotide cytidine deaminase that acts as a host restriction factor of retroviruses, including HIV-1 and various transposable elements. Recently, three NMR and two crystal structures of the catalytic deaminase domain of A3G have been reported, but these are in disagreement over the conformation of a terminal β-strand, β2, as well as the identification of a putative DNA binding site. We here report molecular dynamics simulations with all of the solved A3G catalytic domain structures, taking into account solubility enhancing mutations that were introduced during derivation of three out of the five structures. In the course of these simulations, we observed a general trend towards increased definition of the β2 strand for those structures that have a distorted starting conformation of β2. Solvent density maps around the protein as calculated from MD simulations indicated that this distortion is dependent on preferential hydration of residues within the β2 strand. We also demonstrate that the identification of a pre-defined DNA binding site is prevented by the inherent flexibility of loops that determine access to the deaminase catalytic core. We discuss the implications of our analyses for the as yet unresolved structure of the full-length A3G protein and its biological functions with regard to hypermutation of DNA

Encapsidation of APOBEC3G into HIV-1 virions involves lipid raft association and does not correlate with APOBEC3G oligomerization

<p>Abstract</p> <p>Background</p> <p>The cellular cytidine deaminase APOBEC3G (A3G), when incorporated into the human immunodeficiency virus type 1 (HIV-1), renders viral particles non-infectious. We previously observed that mutation of a single cysteine residue of A3G (C100S) inhibited A3G packaging. In addition, several recent studies showed that mutation of tryptophan 127 (W127) and tyrosine 124 (Y124) inhibited A3G encapsidation suggesting that the N-terminal CDA constitutes a viral packaging signal in A3G. It was also reported that W127 and Y124 affect A3G oligomerization.</p> <p>Results</p> <p>Here we studied the mechanistic basis of the packaging defect of A3G W127A and Y124A mutants. Interestingly, cell fractionation studies revealed a strong correlation between encapsidation, lipid raft association, and genomic RNA binding of A3G. Surprisingly, the presence of a C-terminal epitope tag affected lipid raft association and encapsidation of the A3G W127A mutant but had no effect on wt A3G encapsidation, lipid raft association, and interaction with viral genomic RNA. Mutation of Y124 abolished A3G encapsidation irrespective of the presence or absence of an epitope tag. Contrasting a recent report, our co-immunoprecipitation studies failed to reveal a correlation between A3G oligomerization and A3G encapsidation. In fact, our W127A and Y124A mutants both retained the ability to oligomerize.</p> <p>Conclusion</p> <p>Our results confirm that W127 and Y124 residues in A3G are important for encapsidation into HIV-1 virions and our data establish a novel correlation between genomic RNA binding, lipid raft association, and viral packaging of A3G. In contrast, we were unable to confirm a role of W127 and Y124 in A3G oligomerization and we thus failed to confirm a correlation between A3G oligomerization and virus encapsidation.</p

Model Structure of Human APOBEC3G

BACKGROUND: APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) has antiretroviral activity associated with the hypermutation of viral DNA through cytosine deamination. APOBEC3G has two cytosine deaminase (CDA) domains; the catalytically inactive amino-terminal domain of APOBEC3G (N-CDA) carries the Vif interaction domain. There is no 3-D structure of APOBEC3G solved by X-ray or nuclear magnetic resonance. METHODOLOGY/PRINCIPAL FINDINGS: We predicted the structure of human APOBEC3G based on the crystal structure of APOBEC2. To assess the model structure, we evaluated 48 mutants of APOBEC3G N-CDA that identify novel variants altering ΔVif HIV-1 infectivity and packaging of APOBEC3G. Results indicated that the key residue D128 is exposed at the surface of the model, with a negative local electrostatic potential. Mutation D128K changes the sign of that local potential. In addition, two novel functionally relevant residues that result in defective APOBEC3G encapsidation, R122 and W127, cluster at the surface. CONCLUSIONS/SIGNIFICANCE: The structure model identifies a cluster of residues important for packaging of APOBEC3G into virions, and may serve to guide functional analysis of APOBEC3G

Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity

TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations

The VLT-FLAMES Tarantula Survey IV: Candidates for isolated high-mass star formation in 30 Doradus

Whether massive stars can occasionally form in relative isolation or if they require a large cluster of lower-mass stars around them is a key test in the differentiation of star formation theories as well as how the initial mass function of stars is sampled. Previous attempts to find O-type stars that formed in isolation were hindered by the possibility that such stars are merely runaways from clusters, i.e., their current isolation does not reflect their birth conditions. We introduce a new method to find O-type stars that are not affected by such a degeneracy. Using the VLT-FLAMES Tarantula Survey and additional high resolution imaging we have identified stars that satisfy the following constraints: 1) they are O-type stars that are not detected to be part of a binary system based on RV time series analysis; 2) they are designated spectral type O7 or earlier ; 3) their velocities are within 1\sigma of the mean of OB-type stars in the 30 Doradus region, i.e. they are not runaways along our line-of-sight; 4) the projected surface density of stars does not increase within 3 pc towards the O-star (no evidence for clusters); 5) their sight lines are associated with gaseous and/or dusty filaments in the ISM, and 6) if a second candidate is found in the direction of the same filament with which the target is associated, both are required to have similar velocities. With these criteria, we have identified 15 stars in the 30 Doradus region, which are strong candidates for being high-mass stars that have formed in isolation. Additionally, we employed extensive MC stellar cluster simulations to confirm that our results rule out the presence of clusters around the candidates. Eleven of these are classified as Vz stars, possibly associated with the zero-age main sequence. We include a newly discovered W-R star as a candidate, although it does not meet all of the above criteria.Comment: 14 pages, 13 figures, 5 tables; Accepted for publication by A&