Structure and RNA binding of the third KH domain of poly(C)-binding protein 1

Poly(C)-binding proteins (CPs) are important regulators of mRNA stability and translational regulation. They recognize C-rich RNA through their triple KH (hn RNP K homology) domain structures and are thought to carry out their function though direct protection of mRNA sites as well as through interactions with other RNA-binding proteins. We report the crystallographically derived structure of the third domain of αCP1 to 2.1 Å resolution. αCP1-KH3 assumes a classical type I KH domain fold with a triple-stranded β-sheet held against a three-helix cluster in a βααββα configuration. Its binding affinity to an RNA sequence from the 3′-untranslated region (3′-UTR) of androgen receptor mRNA was determined using surface plasmon resonance, giving a K(d) of 4.37 μM, which is indicative of intermediate binding. A model of αCP1-KH3 with poly(C)-RNA was generated by homology to a recently reported RNA-bound KH domain structure and suggests the molecular basis for oligonucleotide binding and poly(C)-RNA specificity

Three-dimensionality of space and the quantum bit: an information-theoretic approach

It is sometimes pointed out as a curiosity that the state space of quantum two-level systems, i.e. the qubit, and actual physical space are both three-dimensional and Euclidean. In this paper, we suggest an information-theoretic analysis of this relationship, by proving a particular mathematical result: suppose that physics takes place in d spatial dimensions, and that some events happen probabilistically (not assuming quantum theory in any way). Furthermore, suppose there are systems that carry "minimal amounts of direction information", interacting via some continuous reversible time evolution. We prove that this uniquely determines spatial dimension d=3 and quantum theory on two qubits (including entanglement and unitary time evolution), and that it allows observers to infer local spatial geometry from probability measurements.Comment: 13 + 22 pages, 9 figures. v4: some clarifications, in particular in Section V / Appendix C (added Example 39

Grb7 SH2 domain structure and interactions with a cyclic peptide inhibitor of cancer cell migration and proliferation

<p>Abstract</p> <p>Background</p> <p>Human growth factor receptor bound protein 7 (Grb7) is an adapter protein that mediates the coupling of tyrosine kinases with their downstream signaling pathways. Grb7 is frequently overexpressed in invasive and metastatic human cancers and is implicated in cancer progression via its interaction with the ErbB2 receptor and focal adhesion kinase (FAK) that play critical roles in cell proliferation and migration. It is thus a prime target for the development of novel anti-cancer therapies. Recently, an inhibitory peptide (G7-18NATE) has been developed which binds specifically to the Grb7 SH2 domain and is able to attenuate cancer cell proliferation and migration in various cancer cell lines.</p> <p>Results</p> <p>As a first step towards understanding how Grb7 may be inhibited by G7-18NATE, we solved the crystal structure of the Grb7 SH2 domain to 2.1 Å resolution. We describe the details of the peptide binding site underlying target specificity, as well as the dimer interface of Grb 7 SH2. Dimer formation of Grb7 was determined to be in the μM range using analytical ultracentrifugation for both full-length Grb7 and the SH2 domain alone, suggesting the SH2 domain forms the basis of a physiological dimer. ITC measurements of the interaction of the G7-18NATE peptide with the Grb7 SH2 domain revealed that it binds with a binding affinity of K_d= ~35.7 μM and NMR spectroscopy titration experiments revealed that peptide binding causes perturbations to both the ligand binding surface of the Grb7 SH2 domain as well as to the dimer interface, suggesting that dimerisation of Grb7 is impacted on by peptide binding.</p> <p>Conclusion</p> <p>Together the data allow us to propose a model of the Grb7 SH2 domain/G7-18NATE interaction and to rationalize the basis for the observed binding specificity and affinity. We propose that the current study will assist with the development of second generation Grb7 SH2 domain inhibitors, potentially leading to novel inhibitors of cancer cell migration and invasion.</p

Social trajectories or disrupted identities? : Changing and competing models of teacher professionalism under New Labour

Since the 1988 Education Reform Act, the teacher’s role in England has changed in many ways, a process which intensified under New Labour after 1997. Conceptions of teacher professionalism have become more structured and formalized, often heavily influenced by government policy objectives. Career paths have become more diverse and specialised. In this article, three post-1997 professional roles are given consideration as examples of these new specialised career paths: Higher Level Teaching Assistants, Teach First trainees and Advanced Skills Teachers. The article goes on to examine such developments within teaching, using Bourdieu’s concept of habitus to inform the analysis, as well as Bernstein’s theories of knowledge and identity. The article concludes that there has been considerable specialization and subsequent fragmentation of roles within the teaching profession, as part of workforce remodelling initiatives. However, there is still further scope for developing a greater sense of professional cohesion through social activism initiatives, such as the children's agenda. This may produce more stable professional identities in the future as the role of teachers within the wider children’s workforce is clarified

Generalization of entanglement to convex operational theories: Entanglement relative to a subspace of observables

We define what it means for a state in a convex cone of states on a space of observables to be generalized-entangled relative to a subspace of the observables, in a general ordered linear spaces framework for operational theories. This extends the notion of ordinary entanglement in quantum information theory to a much more general framework. Some important special cases are described, in which the distinguished observables are subspaces of the observables of a quantum system, leading to results like the identification of generalized unentangled states with Lie-group-theoretic coherent states when the special observables form an irreducibly represented Lie algebra. Some open problems, including that of generalizing the semigroup of local operations with classical communication to the convex cones setting, are discussed.Comment: 19 pages, to appear in proceedings of Quantum Structures VII, Int. J. Theor. Phy

A derivation of quantum theory from physical requirements

Quantum theory is usually formulated in terms of abstract mathematical postulates, involving Hilbert spaces, state vectors, and unitary operators. In this work, we show that the full formalism of quantum theory can instead be derived from five simple physical requirements, based on elementary assumptions about preparation, transformations and measurements. This is more similar to the usual formulation of special relativity, where two simple physical requirements -- the principles of relativity and light speed invariance -- are used to derive the mathematical structure of Minkowski space-time. Our derivation provides insights into the physical origin of the structure of quantum state spaces (including a group-theoretic explanation of the Bloch ball and its three-dimensionality), and it suggests several natural possibilities to construct consistent modifications of quantum theory.Comment: 16 pages, 2 figures. V3: added alternative formulation of Requirement 5, extended abstract, some minor modification