Distinct amino acid compositional requirements for formation and maintenance of the [PSI+] prion in yeast

Multiple yeast prions have been identified that result from the structural conversion of proteins into a self-propagating amyloid form. Amyloid-based prion activity in yeast requires a series of discrete steps. First, the prion protein must form an amyloid nucleus that can recruit and structurally convert additional soluble proteins. Subsequently, maintenance of the prion during cell division requires fragmentation of these aggregates to create new heritable propagons. For the Saccharomyces cerevisiae prion protein Sup35, these different activities are encoded by different regions of the Sup35 prion domain. An N-terminal glutamine/asparagine-rich nucleation domain is required for nucleation and fiber growth, while an adjacent oligopeptide repeat domain is largely dispensable for prion nucleation and fiber growth but is required for chaperone-dependent prion maintenance. Although prion activity of glutamine/asparagine-rich proteins is predominantly determined by amino acid composition, the nucleation and oligopeptide repeat domains of Sup35 have distinct compositional requirements. Here, we quantitatively define these compositional requirements in vivo. We show that aromatic residues strongly promote both prion formation and chaperone-dependent prion maintenance. In contrast, nonaromatic hydrophobic residues strongly promote prion formation but inhibit prion propagation. These results provide insight into why some aggregation-prone proteins are unable to propagate as prions

Rôle d'un intermédiaire lipidique dans le transfert du mannose à des accepteurs glycoprotéiques endogènes chez Aspergillus niger

AbstractPrevious studies from this laboratory have shown that a particulate preparation from Aspergillus niger catalyses the incorporation of mannose, from GDP-mannose, into a lipid fraction which has been identified as polyprenyl phosphate mannose (PPM). The results of kinetic studies presented in this communication suggest that PPM serves as an intermediate in the ensymatic transfer of mannosyl unit from GDP-mannose to endogenous glycoproteins. β-elimination or Pronase treatment and subsequent dialysis result respectively in 70% or 90% release of radioactivity. The absence of passive penetration of GDP-mannose across microsome membranes and the inhibitory effect of palmityl-CoA on mannose transfer are in good agreement with the involvement of PPM in the transport of mannose across membranes

Stochastic analysis of surface roughness

For the characterization of surface height profiles we present a new stochastic approach which is based on the theory of Markov processes. With this analysis we achieve a characterization of the complexity of the surface roughness by means of a Fokker-Planck or Langevin equation, providing the complete stochastic information of multiscale joint probabilities. The method was applied to different road surface profiles which were measured with high resolution. Evidence of Markov properties is shown. Estimations for the parameters of the Fokker-Planck equation are based on pure, parameter free data analysis

Markov Properties of Electrical Discharge Current Fluctuations in Plasma

Using the Markovian method, we study the stochastic nature of electrical discharge current fluctuations in the Helium plasma. Sinusoidal trends are extracted from the data set by the Fourier-Detrended Fluctuation analysis and consequently cleaned data is retrieved. We determine the Markov time scale of the detrended data set by using likelihood analysis. We also estimate the Kramers-Moyal's coefficients of the discharge current fluctuations and derive the corresponding Fokker-Planck equation. In addition, the obtained Langevin equation enables us to reconstruct discharge time series with similar statistical properties compared with the observed in the experiment. We also provide an exact decomposition of temporal correlation function by using Kramers-Moyal's coefficients. We show that for the stationary time series, the two point temporal correlation function has an exponential decaying behavior with a characteristic correlation time scale. Our results confirm that, there is no definite relation between correlation and Markov time scales. However both of them behave as monotonic increasing function of discharge current intensity. Finally to complete our analysis, the multifractal behavior of reconstructed time series using its Keramers-Moyal's coefficients and original data set are investigated. Extended self similarity analysis demonstrates that fluctuations in our experimental setup deviates from Kolmogorov (K41) theory for fully developed turbulence regime.Comment: 25 pages, 9 figures and 4 tables. V3: Added comments, references, figures and major correction

Further functional determinants

Functional determinants for the scalar Laplacian on spherical caps and slices, flat balls, shells and generalised cylinders are evaluated in two, three and four dimensions using conformal techniques. Both Dirichlet and Robin boundary conditions are allowed for. Some effects of non-smooth boundaries are discussed; in particular the 3-hemiball and the 3-hemishell are considered. The edge and vertex contributions to the $C_{3/2}$ coefficient are examined.Comment: 25 p,JyTex,5 figs. on request

Single-Pion Production in pp Collisions at 0.95 GeV/c (II)

The single-pion production reactions $pp\to d\pi^+$, $pp\to np\pi^+$ and $pp\to pp\pi^0$ were measured at a beam momentum of 0.95 GeV/c ($T_p \approx$ 400 MeV) using the short version of the COSY-TOF spectrometer. The central calorimeter provided particle identification, energy determination and neutron detection in addition to time-of-flight and angle measurements from other detector parts. Thus all pion production channels were recorded with 1-4 overconstraints. Main emphasis is put on the presentation and discussion of the $np\pi^+$ channel, since the results on the other channels have already been published previously. The total and differential cross sections obtained are compared to theoretical calculations. In contrast to the $pp\pi^0$ channel we find in the $np\pi^+$ channel a strong influence of the $\Delta$ excitation already at this energy close to threshold. In particular we find a $(3 cos^2\Theta + 1)$ dependence in the pion angular distribution, typical for a pure s-channel $\Delta$ excitation and identical to that observed in the $d\pi^+$ channel. Since the latter is understood by a s-channel resonance in the $^1D_2$ $pn$ partial wave, we discuss an analogous scenario for the $pn\pi^+$ channel

The laurentian record of neoproterozoic glaciation, tectonism, and eukaryotic evolution in Death Vally, California

Neoproterozoic strata in Death Valley, California contain eukaryotic microfossils and glacial deposits that have been used to assess the severity of putative Snowball Earth events and the biological response to extreme environmental change. These successions also contain evidence for syn-sedimentary faulting that has been related to the rifting of Rodinia, and in turn the tectonic context of the onset of Snowball Earth. These interpretations hinge on local geological relationships and both regional and global stratigraphic correlations. Here we present new geological mapping, measured stratigraphic sections, carbon and strontium isotope chemostratigraphy, and micropaleontology from the Neoproterozoic glacial deposits and bounding strata in Death Valley. These new data enable us to refine regional correlations both across Death Valley and throughout Laurentia, and construct a new age model for glaciogenic strata and microfossil assemblages. Particularly, our remapping of the Kingston Peak Formation in the Saddle Peak Hills and near the type locality shows for the first time that glacial deposits of both the Marinoan and Sturtian glaciations can be distinguished in southeastern Death Valley, and that beds containing vase-shaped microfossils are slump blocks derived from the underlying strata. These slump blocks are associated with multiple overlapping unconformities that developed during syn-sedimentary faulting, which is a common feature of Cyrogenian strata along the margin of Laurentia from California to Alaska. With these data, we conclude that all of the microfossils that have been described to date in Neoproterozoic strata of Death Valley predate the glaciations and do not bear on the severity, extent or duration of Neoproterozoic Snowball Earth events

Markedly Divergent Tree Assemblage Responses to Tropical Forest Loss and Fragmentation across a Strong Seasonality Gradient

We examine the effects of forest fragmentation on the structure and composition of tree assemblages within three seasonal and aseasonal forest types of southern Brazil, including evergreen, Araucaria, and deciduous forests. We sampled three southernmost Atlantic Forest landscapes, including the largest continuous forest protected areas within each forest type. Tree assemblages in each forest type were sampled within 10 plots of 0.1 ha in both continuous forests and 10 adjacent forest fragments. All trees within each plot were assigned to trait categories describing their regeneration strategy, vertical stratification, seed-dispersal mode, seed size, and wood density. We detected differences among both forest types and landscape contexts in terms of overall tree species richness, and the density and species richness of different functional groups in terms of regeneration strategy, seed dispersal mode and woody density. Overall, evergreen forest fragments exhibited the largest deviations from continuous forest plots in assemblage structure. Evergreen, Araucaria and deciduous forests diverge in the functional composition of tree floras, particularly in relation to regeneration strategy and stress tolerance. By supporting a more diversified light-demanding and stress-tolerant flora with reduced richness and abundance of shade-tolerant, old-growth species, both deciduous and Araucaria forest tree assemblages are more intrinsically resilient to contemporary human-disturbances, including fragmentation-induced edge effects, in terms of species erosion and functional shifts. We suggest that these intrinsic differences in the direction and magnitude of responses to changes in landscape structure between forest types should guide a wide range of conservation strategies in restoring fragmented tropical forest landscapes worldwide

Geranylgeraniol overcomes the block of cell proliferation by lovastatin in C6 glioma cells

It is well documented that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors prevent cultured mammalian cells from progressing through the cell cycle, suggesting a critical role for a mevalonate-derived product. Recently, it has been shown that free geranylgeraniol (GG-OH) and farnesol (F-OH) can be utilized by C6 glioma cells for protein isoprenylation. The ability of CC-OH and F-OH to restore protein geranylgeranylation or farnesylation selectively has enabled us to examine the possibility that mevalonate is essential for cell proliferation because it is a precursor of farnesyl pyrophosphate or geranylgeranyl pyrophosphate, the isoprenyl donors involved in the posttranslational modification of key regulatory proteins. In this study we report that CC-OH, as well as mevalonate, overcomes the arrest of cell proliferation of C6 glioma cells treated with lovastatin, as assessed by increased cell numbers and a stimulation in [H-3]thymidine incorporation. The increase in cell number and [H-3]thymidine incorporation were significantly lower when F-OH was added. Under these conditions [H-3]mevalonate and [H-3]GG-OH are actively incorporated into a set of isoprenylated proteins in the size range of small, GTP-binding proteins (19-27 kDa) and a polypeptide with the molecular size (46 kDa) of the smaller isoform of 2',3'-cyclic nucleotide 3'-phosphodiesterase. Analysis of the proteins metabolically labeled by [H-3]mevalonate and [H-3]GG-OH reveals the presence of labeled proteins containing geranylgeranylated cysteinyl residues. Consistent with geranylgeranylated proteins playing a critical role in the entry of C6 cells into the cell cycle, a (phosphonoacetamido) oxy derivative of GG-OH, a drug previously shown to interfere with protein geranylgeranylation, prevented the increase in cell number when mevalonate or GG-OH was added to lovastatin-treated cells. These results strongly suggest that geranylgeranylated proteins are essential for progression of C6 cells into the S phase of the cell cycle and provide the first evidence that the "salvage" pathway for the utilization of the free isoprenols is physiologically significant in the CNS