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

Statistics poster competitions: an opportunity to connect academics and teachers

The Australian Statistics Competition (ASC) was a national statistics poster competition that ran from 2006 to 2016. One of the aims of the ASC was to create connections between academics and teachers. In this paper, we report a study that investigated the experience of the organisers of this competition. We administered a written survey and conducted semistructured interviews with the organisers by a semi-structured protocol, with the aim of exploring the experience of the ASC organisers (the academics) in relation to connecting with teachers. We found geographical, intrinsic, organisational and personnel barriers to continuing connections between academics and teachers. We provide a list of recommendations for those involved in, or planning on starting, a similar competition

Herpetological observations from field expeditions to North Karnataka and Southwest Maharashtra, India

The Western Ghats of India are one of the 34 global hotspots of biodiversity. They are one of the most important large natural areas in the world and are fast becoming recognised for their biological importance. The herpetofauna of the Western Ghats is hugely diverse, with many species exhibiting rare, endemic styles of autecology and niche preference that could equal that of countries such as Borneo and Madagascar. In this report we detail 18 amphibian and 37 reptile species from eight sites following three expeditions to the Western Ghats from 2007-2009. The report details species descriptions, habitat, ecology and conservation to alert the herpetological community to the importance of future research to address the lack of knowledge in species ecology. It also presents newinformation on species distribution and behaviour

Mechanisms of resistance to Hsp90 inhibitor drugs: a complex mosaic emerges

The molecular chaperone Hsp90 holds great promise as a cancer drug target, despite some of the initial clinical trials of Hsp90 inhibitor drugs having not lived up to expectation. Effective use of these drugs will benefit greatly from a much more detailed understanding of the factors that contribute to resistance, whether intrinsic or acquired. We review how cell culture studies have revealed a number of different mechanisms whereby cells can be rendered less susceptible to the effects of Hsp90 inhibitor treatment. A major influence is Hsp90 inhibition causing strong induction of the heat shock response, a stress response that increases cellular levels of prosurvival chaperones such as Hsp27 and Hsp70. Another problem seems to be that these inhibitors do not always access the Hsp90 proteins of the mitochondrion, forms of Hsp90 that-in cancer cells-are operating to suppress apoptosis. It should be possible to overcome these drawbacks through the appropriate drug redesign or with the combinatorial use of an Hsp90 inhibitor with a drug that targets either heat shock factor or the chaperone Hsp70. Still though, cells will often differ in the key antiapoptotic versus proapoptotic activities that are dependent on Hsp90, in the key steps in their apoptotic pathways responsive to Hsp90 inhibition or Hsp70 level, as well as the extents to which their survival is dependent on oncogenic tyrosine kinases that are clients of Hsp90. A systems approach will therefore often be required in order to establish the most prominent effects of Hsp90 inhibition in each type of cancer cell. © 2011 by the authors; licensee MDPI, Basel, Switzerland

The ERATOSTHENES Centre of Excellence (ECoE) as a digital innovation hub for Earth observation

The "EXCELSIOR" H2020 Widespread Teaming Phase 2 Project: ERATOSTHENES: EXcellence Research Centre for Earth SurveiLlance and Space-Based MonItoring Of the EnviRonment is supported from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 857510 for a 7 year project period to establish a Centre of Excellence in Cyprus. As well, the Government of the Republic of Cyprus is providing additional resources to support the establishment of the ERATOSTHENES Centre of Excellence (ECoE) in Cyprus. The ECoE seeks to fill the gap by assisting in the spaceborne Earth Observation activities in the Eastern Mediterranean and become a regional key player in the Earth Observation (EO) sector. There are distinct needs and opportunities that motivate the establishment of an Earth Observation Centre of Excellence in Cyprus, which are primarily related to the geostrategic location of the European Union member state of Cyprus to examine complex scientific problems and address user needs in the Eastern Mediterranean, Middle East and Northern Africa (EMMENA), as well as South-East Europe. An important objective of the ECoE is to be a Digital Innovation Hub and a Research Excellence Centre for EO in the EMMENA region, which will establish an ecosystem where state-of-the-art sensing technology, cutting-edge research, targeted education services, and entrepreneurship come together. It is based on the paradigm of Open Innovation 2.0 (OI2.0), which is founded on the Quadruple Helix Model, where Government, Industry, Academia and Society work together to drive change by taking full advantage of the cross-fertilization of ideas. The ECoE as a Digital Innovation Hub (DIH) adopts a two-axis model, where the vertical axis consists of three Thematic Clusters for sustained excellence in research of the ECoE in the domains of Atmosphere and Climate, Resilient Societies and Big Earth Data Management, while the horizontal axis is built around four functional areas, namely: Infrastructure, Research, Education, and Entrepreneurship. The ECoE will focus on five application areas, which include Climate Change Monitoring, Water Resource Management, Disaster Risk Reduction, Access to Energy and Big EO Data Analytics. This structure is expected to leverage the existing regional capacities and advance the excellence by creating new programs and research, thereby establishing the ECoE as a worldclass centre capable of enabling innovation and research competence in Earth Observation, actively participating in Europe, the EMMENA region and the global Earth Observation arena. The partners of the EXCELSIOR consortium include the Cyprus University of Technology as the Coordinator, the German Aerospace Center (DLR), the Leibniz Institute for Tropospheric Research (TROPOS), the National Observatory of Athens (NOA) and the Department of Electronic Communications, Deputy Ministry of Research, Innovation and Digital Policy

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants

Expression and crystallization of the yeast Hsp82 chaperone, and preliminary X-ray diffraction studies of the amino-terminal domain

Expression of the Saccharomyces cerevisiae Hsp82 chaperone in a pep4-3- and hsc82-deficient strain of S. cerevisiae yielded over 25% of the total cell protein as intact Hsp82. Similarly, the amino-terminal domain (residues 1-220) of Hsp82 was expressed to 18% of the total cell protein. Crystals of the intact Hsp82 were readily obtained. The crystals were very fragile, suggesting a high solvent content, and diffracted to approximately 8 A. Tetragonal bipyrimidal crystals of the amino-terminal domain of Hsp82 were readily obtained under a variety of different conditions. The crystals have primitive tetragonal space group (P422, P4(1)22, or its enantiomorph P4(3)22) with unit cell dimensions of a = 75.1 A and c = 111.3 A, contain 60% by volume solvent, and diffract to 2.5 A resoltuion. Addition of 25% glycerol to the mother liquor gave rise to large rod-shaped crystals. The crystals diffract to 2.8 A resolution, have an orthorhombic space group (P222(1), P2(1)2(1)2, or P2(1)2(1)2(1)) with cell dimensions of a = 45.2 A, b = 115.4 A, and c = 116.9 A, and a solvent content of 58% by volume