Modulation of sterol homeostasis by the Cdc42p effectors Cla4p and Ste20p in the yeast Saccharomyces cerevisiae

This article is available open access through the publisher’s website at the link below. Copyright @ 2009 The Authors.The conserved Rho-type GTPase Cdc42p is a key regulator of signal transduction and polarity in eukaryotic cells. In the yeast Saccharomyces cerevisiae, Cdc42p promotes polarized growth through the p21-activated kinases Ste20p and Cla4p. Previously, we demonstrated that Ste20p forms a complex with Erg4p, Cbr1p and Ncp1p, which all catalyze important steps in sterol biosynthesis. CLA4 interacts genetically with ERG4 and NCP1. Furthermore, Erg4p, Ncp1p and Cbr1p play important roles in cell polarization during vegetative growth, mating and filamentation. As Ste20p and Cla4p are involved in these processes it seems likely that sterol biosynthetic enzymes and p21-activated kinases act in related pathways. Here, we demonstrate that the deletion of either STE20 or CLA4 results in increased levels of sterols. In addition, higher concentrations of steryl esters, the storage form of sterols, were observed in cla4Δ cells. CLA4 expression from a multicopy plasmid reduces enzyme activity of Are2p, the major steryl ester synthase, under aerobic conditions. Altogether, our data suggest that Ste20p and Cla4p may function as negative modulators of sterol biosynthesis. Moreover, Cla4p has a negative effect on steryl ester formation. As sterol homeostasis is crucial for cell polarization, Ste20p and Cla4p may regulate cell polarity in part through the modulation of sterol homeostasis.Deutsche Forschungsgemeinschaft and the Austrian FWF

Non-perturbative QEG Corrections to the Yang-Mills Beta Function

We discuss the non-perturbative renormalization group evolution of the gauge coupling constant by using a truncated form of the functional flow equation for the effective average action of the Yang-Mills-gravity system. Our result is consistent with the conjecture that Quantum Einstein Gravity (QEG) is asymptotically safe and has a vanishing gauge coupling constant at the non-trivial fixed point.Comment: To appear in the proceedings of CORFU 200

Prognostic impact of Claudin 18.2 in gastric and esophageal adenocarcinomas

INTRODUCTION: The tight junction molecule Claudin 18.2 is selectively expressed in healthy and malignant gastric epithelial tissue and is a promising therapy target for high Claudin 18.2 expressing adenocarcinomas of the esophagogastric junction and stomach (AEG/S). METHODS: This study analyzed the prevalence, characteristics and prognostic impact of Claudin 18.2 expression in primary tumor, lymph node and distant metastasis in a large Caucasian AGE/S cohort with 414 patients. RESULTS: Claudin 18.2 was highly expressed in 17.1% of primary tumors, 26.7% of lymph node metastasis and 16.7% of distant metastasis. High Claudin 18.2 expression in lymph node metastasis and primary tumors correlated significantly (p < 0.001). High expression of Claudin 18.2 was neither associated with histomorphogical subtype, or tumor state, nor with overall survival. CONCLUSION: In Caucasian AEG/S patients, 17.1% appeared to be eligible for an anti-Claudin 18.2 therapy. Claudin 18.2 expression itself has no impact on prognosis and is not related to any tumor subtype

SeeBridge Next Generation Bridge Inspection: Overview, Information Delivery Manual and Model View Definition

Innovative solutions for rapid and intelligent survey and assessment methods are required in maintenance, repair, retrofit and rebuild of enormous numbers of bridges in service throughout the world. Motivated by this need, a next-generation integrated bridge inspection system, called SeeBridge, has been proposed. An Information Delivery Manual (IDM) was compiled to specify the technical components, activities and information exchanges in the SeeBridge process, and a Model View Definition (MVD) was prepared to specify the data exchange schema to serve the IDM. The MVD was bound to the IFC4 Add2 data schema standard. The IDM and MVD support research and development of the system by rigorously defining the information and data that structure bridge engineers' knowledge. The SeeBridge process is mapped, parts of the data repositories are presented, and the future use of the IDM is discussed. The development underlines the real potential for automated inspection of infrastructure at large, because it demonstrates that the hurdles in the way of automated acquisition of detailed and semantically rich models of existing infrastructure are computational in nature, not instrumental, and are surmountable with existing technologies

Low-energy pions in nuclear matter and 2pi photoproduction within a BUU transport model

A description of low-energy scattering of pions and nuclei within a BUU transport model is presented. Implementing different scenarios of medium modifications, the mean free path of pions in nuclear matter at low momenta and pion absorption reactions on nuclei have been studied and compared to data and to results obtained via quantum mechanical scattering theory. We show that even in a regime of a long pionic wave length the semi-classical transport model is still a reliable framework for pion kinetic energies greater than ~20-30 MeV. Results are presented on pion-absorption cross sections in the regime of 10 MeV < E(kin) < 130 MeV and on photon-induced double-pion production at incident beam energies of 400-500 MeV.Comment: 22 pages, 20 figures Replaced with a revised version. Accepted for publication in EPJ A. Added a short section on pion reaction and charge exchange cross-section

Mitochondrial precursor proteins are imported through a hydrophilic membrane environment

We have analyzed how translocation intermediates of imported mitochondrial precursor proteins, which span contact sites, interact with the mitochondrial membranes. F1-ATPase subunit β(F1β) was trapped at contact sites by importing it into Neurospora mitochondria in the presence of low levels of nucleoside triphosphates. This F1β translocation intermediate could be extracted from the membranes by treatment with protein denaturants such as alkaline pH or urea. By performing import at low temperatures, the ADP/ATP carrier was accumulated in contact sites of Neurospora mitochondria and cytochrome b2 in contact sites of yeast mitochondria. These translocation intermediates were also extractable from the membranes at alkaline pH. Thus, translocation of precursor proteins across mitochondrial membranes seems to occur through an environment which is accessible to aqueous perturbants. We propose that proteinaceous structures are essential components of a translocation apparatus present in contact sites

Towards a field theoretic understanding of NN->NNpi

We study the production amplitude for the reaction NN->NNpi up to next--to--leading order in chiral perturbation theory using a counting scheme that takes into account the large scale introduced by the initial momentum. In particular we investigate a subtlety that arises once the leading loop contributions are convoluted with the NN wavefunctions as demanded by the non--perturbative nature of the NN interaction. We show how to properly identify the irreducible contribution of loop diagrams in such type of reaction. The net effect of the inclusion of all next-to-leading order loops is to enhance the leading rescattering amplitude by a factor of 4/3, bringing its contribution to the cross section for pp->dpi+ close to the experimental value.Comment: 15 Pages, 5 Figure

Quantum Einstein Gravity

We give a pedagogical introduction to the basic ideas and concepts of the Asymptotic Safety program in Quantum Einstein Gravity. Using the continuum approach based upon the effective average action, we summarize the state of the art of the field with a particular focus on the evidence supporting the existence of the non-trivial renormalization group fixed point at the heart of the construction. As an application, the multifractal structure of the emerging space-times is discussed in detail. In particular, we compare the continuum prediction for their spectral dimension with Monte Carlo data from the Causal Dynamical Triangulation approach.Comment: 87 pages, 13 figures, review article prepared for the New Journal of Physics focus issue on Quantum Einstein Gravit

Neutron velocity distribution from a superthermal solid 2H2 ultracold neutron source

We have determined for the first time the velocity distribution of neutrons from a solid 2H2 ultracold neutron (UCN) source. The spectrum rises sharply above 4.5m/s and has a maximum around 7m/s after transport in an 8m long guide. The number of neutrons in the UCN velocity range (< 7m/s) may be increased by a factor of two by placing the experiment 1m above the UCN source leve

Renormalization Group Flow in Scalar-Tensor Theories. II

We study the UV behaviour of actions including integer powers of scalar curvature and even powers of scalar fields with Functional Renormalization Group techniques. We find UV fixed points where the gravitational couplings have non-trivial values while the matter ones are Gaussian. We prove several properties of the linearized flow at such a fixed point in arbitrary dimensions in the one-loop approximation and find recursive relations among the critical exponents. We illustrate these results in explicit calculations in $d=4$ for actions including up to four powers of scalar curvature and two powers of the scalar field. In this setting we notice that the same recursive properties among the critical exponents, which were proven at one-loop order, still hold, in such a way that the UV critical surface is found to be five dimensional. We then search for the same type of fixed point in a scalar theory with minimal coupling to gravity in $d=4$ including up to eight powers of scalar curvature. Assuming that the recursive properties of the critical exponents still hold, one would conclude that the UV critical surface of these theories is five dimensional.Comment: 14 pages. v.2: Minor changes, some references adde