Expressed in the yeast Saccharomyces cerevisiae, human ERK5 is a client of the Hsp90 chaperone that complements loss of the Slt2p (Mpk1p) cell integrity stress-activated protein kinase

ERK5 is a mitogen-activated protein (MAP) kinase regulated in human cells by diverse mitogens and stresses but also suspected of mediating the effects of a number of oncogenes. Its expression in the slt2Delta Saccharomyces cerevisiae mutant rescued several of the phenotypes caused by the lack of Slt2p (Mpk1p) cell integrity MAP kinase. ERK5 is able to provide this cell integrity MAP kinase function in yeast, as it is activated by the cell integrity signaling cascade that normally activates Slt2p and, in its active form, able to stimulate at least one key Slt2p target (Rlm1p, the major transcriptional regulator of cell wall genes). In vitro ERK5 kinase activity was abolished by Hsp90 inhibition. ERK5 activity in vivo was also lost in a strain that expresses a mutant Hsp90 chaperone. Therefore, human ERK5 expressed in yeast is an Hsp90 client, despite the widely held belief that the protein kinases of the MAP kinase class are non-Hsp90-dependent activities. Two-hybrid and protein binding studies revealed that strong association of Hsp90 with ERK5 requires the dual phosphorylation of the TEY motif in the MAP kinase activation loop. These phosphorylations, at positions adjacent to the Hsp90-binding surface recently identified for a number of protein kinases, may cause a localized rearrangement of this MAP kinase region that leads to creation of the Hsp90-binding surface. Complementation of the slt2Delta yeast defect by ERK5 expression establishes a new tool with which to screen for novel agonists and antagonists of ERK5 signaling as well as for isolating mutant forms of ERK5

Geometric construction of cohomology for arithmetic groups I

This article does not have an abstract

A new method for testing polymer gear wear rate and performance

This paper provides details of a new test rig design and methodology intended for, and successfully applied to, measuring the gear wear rate and performance of polymer composite gears under both dry and lubricated conditions. One of its unique contributions is that it continuously measures the gear wear rate, a feature essential for understanding polymer gear behaviour. While sharing some concepts with the traditional back-to-back test configuration used for steel gears, the new method introduces a rotary freedom to the block supporting the polymer gears under test. This block rotates if the gear tooth thickness is reduced, which aids control of the test load. The gear surface wear rate is recorded continuously by using a capacitance transducer to measure the pivot block motion. A second unique contribution of the new test method involves splitting the support block so that controlled misaligned gear engagements (not reported in other designs) can be introduced and subsequent changes to wear behaviour studied. The paper first outlines the test rig concepts and design before discussing in more detail the gear wear rate measuring principles, the methods of centre distance adjustment and the achievement of virtually constant gear loading. Finally, a selection test results are presented in summary to further validate the new test method and illustrate potential applications

Gaudin Models and Bending Flows: a Geometrical Point of View

In this paper we discuss the bihamiltonian formulation of the (rational XXX) Gaudin models of spin-spin interaction, generalized to the case of sl(r)-valued spins. In particular, we focus on the homogeneous models. We find a pencil of Poisson brackets that recursively define a complete set of integrals of the motion, alternative to the set of integrals associated with the 'standard' Lax representation of the Gaudin model. These integrals, in the case of su(2), coincide wih the Hamiltonians of the 'bending flows' in the moduli space of polygons in Euclidean space introduced by Kapovich and Millson. We finally address the problem of separability of these flows and explicitly find separation coordinates and separation relations for the r=2 case.Comment: 27 pages, LaTeX with amsmath and amssym

UCS protein function is partially restored in the Saccharomyces cerevisiae she4 mutant with expression of the human UNC45-GC, but not UNC45-SM

A dedicated UNC45, Cro1, She4 (UCS) domain-containing protein assists in the Hsp90-mediated folding of the myosin head. Only weak sequence conservation exists between the single UCS protein of simple eukaryotes (She4 in budding yeast) and the two UCS proteins of higher organisms (the general cell and striated muscle UNC45s; UNC45-GC and UNC45-SM, respectively). In vertebrates, UNC45-GC facilitates cytoskeletal functions, whereas the 55% identical UNC45-SM assists assembly of the contractile apparatus of cardiac and skeletal muscles. A Saccharomyces cerevisiae she4Δ mutant, totally lacking any UCS protein, was engineered to express as its sole Hsp90 either the Hsp90α or the Hsp90β isoforms of human cytosolic Hsp90. A transient induction of the human UNC45-GC, but not UNC45-SM, could rescue the defective endocytosis in these she4Δ cells at 39 °C, irrespective of whether they possessed Hsp90α or Hsp90β. UNC45-GC-mediated rescue of the localisation of a Myo5-green fluorescent protein (GFP) fusion to cortical patches at 39 °C was more efficient in the yeast containing Hsp90α, though this may relate to more efficient functioning of Hsp90α as compared to Hsp90β in these strains. Furthermore, inducible expression of UNC45-GC, but not UNC45-SM, could partially rescue survival at a more extreme temperature (45 °C) that normally causes she4Δ mutant yeast cells to lyse. The results indicate that UCS protein function has been most conserved-yeast to man-in the UNC45-GC, not UNC45-SM. This may reflect UNC45-GC being the vertebrate UCS protein that assists formation of the actomyosin complexes needed for cytokinesis, cell morphological change, and organelle trafficking-events also facilitated by the myosins in yeast

Global Health Governance and the Commercial Sector: A Documentary Analysis of Tobacco Company Strategies to Influence the WHO Framework Convention on Tobacco Control

Heide Weishaar and colleagues did an analysis of internal tobacco industry documents together with other data and describe the industry's strategic response to the proposed World Health Organization Framework Convention on Tobacco Control