SUMO chain formation is required for response to replication arrest in S. pombe

SUMO is a ubiquitin-like protein that is post-translationally attached to one or more lysine residues on target proteins. Despite having only 18% sequence identity with ubiquitin, SUMO contains the conserved betabetaalphabetabetaalphabeta fold present in ubiquitin. However, SUMO differs from ubiquitin in having an extended N-terminus. In S. pombe the N-terminus of SUMO/Pmt3 is significantly longer than those of SUMO in S. cerevisiae, human and Drosophila. Here we investigate the role of this N-terminal region. We have used two dimensional gel electrophoresis to demonstrate that S. pombe SUMO/Pmt3 is phosphorylated, and that this occurs on serine residues at the extreme N-terminus of the protein. Mutation of these residues (in pmt3-1) results in a dramatic reduction in both the levels of high Mr SUMO-containing species and of total SUMO/Pmt3, indicating that phosphorylation of SUMO/Pmt3 is required for its stability. Despite the significant reduction in high Mr SUMO-containing species, pmt3-1 cells do not display an aberrant cell morphology or sensitivity to genotoxins or stress. Additionally, we demonstrate that two lysine residues in the N-terminus of S. pombe SUMO/Pmt3 (K14 and K30) can act as acceptor sites for SUMO chain formation in vitro. Inability to form SUMO chains results in aberrant cell and nuclear morphologies, including stretched and fragmented chromatin. SUMO chain mutants are sensitive to the DNA synthesis inhibitor, hydroxyurea (HU), but not to other genotoxins, such as UV, MMS or CPT. This implies a role for SUMO chains in the response to replication arrest in S. pomb

Quantum jumps of light recording the birth and death of a photon in a cavity

A microscopic system under continuous observation exhibits at random times sudden jumps between its states. The detection of this essential quantum feature requires a quantum non-demolition (QND) measurement repeated many times during the system evolution. Quantum jumps of trapped massive particles (electrons, ions or molecules) have been observed, which is not the case of the jumps of light quanta. Usual photodetectors absorb light and are thus unable to detect the same photon twice. They must be replaced by a transparent counter 'seeing' photons without destroying them3. Moreover, the light has to be stored over a duration much longer than the QND detection time. We have fulfilled these challenging conditions and observed photon number quantum jumps. Microwave photons are stored in a superconducting cavity for times in the second range. They are repeatedly probed by a stream of non-absorbing atoms. An atom interferometer measures the atomic dipole phase shift induced by the non-resonant cavity field, so that the final atom state reveals directly the presence of a single photon in the cavity. Sequences of hundreds of atoms highly correlated in the same state, are interrupted by sudden state-switchings. These telegraphic signals record, for the first time, the birth, life and death of individual photons. Applying a similar QND procedure to mesoscopic fields with tens of photons opens new perspectives for the exploration of the quantum to classical boundary

Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules

THE α1 and α2 domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire. Although the α3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CDS. CDS is important in the selection of T cells as anti-CDS antibody injected into perinatal mice interfers with this process. We previously used a hybrid class I molecule with the α1/α2 domains from L^d and the α3 domain from Q7^b and showed that this molecule binds an L^d-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes. Expression of this molecule in transgenic mice fails to negatively select a subpopulation of anti-L^d cytotoxic T lymphocytes. In addition, positive selection of virus-specific L^d-restricted cytotoxic T lymphocytes does not occur. We conclude that besides the α1/α2 domains of class I, the α3 domain plays an important part in both positive and negative selection of antigen-specific cells

Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base

Nesting Biology and Fungiculture of the Fungus-Growing Ant, Mycetagroicus cerradensis: New Light on the Origin of Higher Attine Agriculture

The genus Mycetagroicus is perhaps the least known of all fungus-growing ant genera, having been first described in 2001 from museum specimens. A recent molecular phylogenetic analysis of the fungus-growing ants demonstrated that Mycetagroicus is the sister to all higher attine ants (Trachymyrmex, Sericomyrmex, Acromyrmex, Pseudoatta, and Atta), making it of extreme importance for understanding the transition between lower and higher attine agriculture. Four nests of Mycetagroicus cerradensis near Uberlândia, Minas Gerais, Brazil were excavated, and fungus chambers for one were located at a depth of 3.5 meters. Based on its lack of gongylidia (hyphal-tip swellings typical of higher attine cultivars), and a phylogenetic analysis of the ITS rDNA gene region, M. cerradensis cultivates a lower attine fungus in Clade 2 of lower attine (G3) fungi. This finding refines a previous estimate for the origin of higher attine agriculture, an event that can now be dated at approximately 21–25 mya in the ancestor of extant species of Trachymyrmex and Sericomyrmex

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

.Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

Long-range transfer of electron-phonon coupling in oxide superlattices

The electron-phonon interaction is of central importance for the electrical and thermal properties of solids, and its influence on superconductivity, colossal magnetoresistance, and other many-body phenomena in correlated-electron materials is currently the subject of intense research. However, the non-local nature of the interactions between valence electrons and lattice ions, often compounded by a plethora of vibrational modes, present formidable challenges for attempts to experimentally control and theoretically describe the physical properties of complex materials. Here we report a Raman scattering study of the lattice dynamics in superlattices of the high-temperature superconductor $\bf YBa_2 Cu_3 O_7$ and the colossal-magnetoresistance compound $\bf La_{2/3}Ca_{1/3}MnO_{3}$ that suggests a new approach to this problem. We find that a rotational mode of the MnO$_6$ octahedra in $\bf La_{2/3}Ca_{1/3}MnO_{3}$ experiences pronounced superconductivity-induced lineshape anomalies, which scale linearly with the thickness of the $\bf YBa_2 Cu_3 O_7$ layers over a remarkably long range of several tens of nanometers. The transfer of the electron-phonon coupling between superlattice layers can be understood as a consequence of long-range Coulomb forces in conjunction with an orbital reconstruction at the interface. The superlattice geometry thus provides new opportunities for controlled modification of the electron-phonon interaction in complex materials.Comment: 13 pages, 4 figures. Revised version to be published in Nature Material

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

Organisational learning - a critical systems thinking discipline

Original Paper European Journal of Information Systems (2001) 10, 135–146; doi:10.1057/palgrave.ejis.3000394 Organisational learning—a critical systems thinking discipline P Panagiotidis1,3 and J S Edwards2,4 1Deloitte and Touche, Athens, Greece 2Aston Business School, Aston University, Aston Triangle, Birmingham, B4 7ET, UK Correspondence: Dr J S Edwards, Aston Business School, Aston University, Aston Triangle, Birmingham, B4 7ET, UK. E-mail: [email protected] 3Petros Panagiotidis is Manager responsible for the Process and Systems Integrity Services of Deloitte and Touche in Athens, Greece. He has a BSc in Business Administration and an MSc in Management Information Systems from Western International University, Phoenix, Arizona, USA; an MSc in Business Systems Analysis and Design from City University, London, UK; and a PhD degree from Aston University, Birmingham, UK. His doctorate was in Business Systems Analysis and Design. His principal interests now are in the ERP/DSS field, where he serves as project leader and project risk managment leader in the implementation of SAP and JD Edwards/Cognos in various major clients in the telecommunications and manufacturing sectors. In addition, he is responsible for the development and application of knowledge management systems and activity-based costing systems. 4John S Edwards is Senior Lecturer in Operational Research and Systems at Aston Business School, Birmingham, UK. He holds MA and PhD degrees (in mathematics and operational research respectively) from Cambridge University. His principal research interests are in knowledge management and decision support, especially methods and processes for system development. He has written more than 30 research papers on these topics, and two books, Building Knowledge-based Systems and Decision Making with Computers, both published by Pitman. Current research work includes the effect of scale of operations on knowledge management, interfacing expert systems with simulation models, process modelling in law and legal services, and a study of the use of artifical intelligence techniques in management accounting. Top of pageAbstract This paper deals with the application of critical systems thinking in the domain of organisational learning and knowledge management. Its viewpoint is that deep organisational learning only takes place when the business systems' stakeholders reflect on their actions and thus inquire about their purpose(s) in relation to the business system and the other stakeholders they perceive to exist. This is done by reflecting both on the sources of motivation and/or deception that are contained in their purpose, and also on the sources of collective motivation and/or deception that are contained in the business system's purpose. The development of an organisational information system that captures, manages and institutionalises meaningful information—a knowledge management system—cannot be separated from organisational learning practices, since it should be the result of these very practices. Although Senge's five disciplines provide a useful starting-point in looking at organisational learning, we argue for a critical systems approach, instead of an uncritical Systems Dynamics one that concentrates only on the organisational learning practices. We proceed to outline a methodology called Business Systems Purpose Analysis (BSPA) that offers a participatory structure for team and organisational learning, upon which the stakeholders can take legitimate action that is based on the force of the better argument. In addition, the organisational learning process in BSPA leads to the development of an intrinsically motivated information organisational system that allows for the institutionalisation of the learning process itself in the form of an organisational knowledge management system. This could be a specific application, or something as wide-ranging as an Enterprise Resource Planning (ERP) implementation. Examples of the use of BSPA in two ERP implementations are presented