Exploring historical ‘frameworks’ as a curriculum goal: a case study examining students’ notions of historical significance when using millennia-wide time scales

History teachers, teacher–researchers, government agencies and history education academics in England often report that students are frequently incapable of producing complex, polythetic or developmental narratives over long time scales. This lack of an overview tends to result in deficiencies in their application of the key concepts of the discipline. Consequently Shemilt has recommended the use of synoptic, millennia-wide ‘frameworks’ of knowledge in order to counteract these issues. With some notable exceptions, however, practising history teachers have appeared sceptical of the benefits of such an approach. I conducted an exploratory case study investigating in what ways a pre-taught framework, in which I had responded to some practitioners’ criticisms, appeared to be manifested in my students’ subsequent thinking regarding historical significance. My goal was to contribute to professional curricular theorising about what constitutes a framework and how it might be expressed as a curricular goal. Themes were derived from pupils’ writing, lesson evaluations, group interviews and observations. Possible curricular goals that were characterised in the students’ work included the pupils producing millennia-wide narratives based on colligatory generalisations and assessments of historical significance incorporating scale-shifting over long time scales

From divergent evolution to witting cross-fertilisation: the need for more awareness of potential inter-discursive communication regarding students' extended historical writing

History education stakeholders in England have consistently judged that some students find formal historical writing prohibitively difficult due to the demands of constructing an extended argument. While policy makers have agreed students need support in their historical writing, recurring themes in centralised resourcing have been wastage, incoordination and replication. Furthermore, two concurrent but largely disconnected discourses have developed and promulgated initiatives relevant to students’ extended historical writing: ‘genre theorists’ and the ‘history teachers’ extended writing movement’. Despite certain goals held in common participants in the two discourses have tended to talk past one another with concomitant issues in resourcing. Unsystematic, cross-fertilisation between the discourses has led to cycles of genre theory being collectively discovered, forgotten, and rediscovered by history teachers with knowledge not being built cumulatively. Furthermore both discourses have independently developed similar initiatives in a form of convergent evolution resulting in duplication of labour. Finally, divergent evolution has occurred where genre theorists have advocated approaches that are increasingly redundant for history teachers’ requirements. A more activist stance is therefore required to ensure meaningful inter-discursive communication between genre theorists and the history teachers’ ‘extended writing movement’ to ensure efficacy in developing approaches to improving students’ extended historical writing

Large-signal dynamic behavior of distributed-feedback lasers including lateral effects

The large-signal behavior of DFB lasers is analyzed, including lateral as well as longitudinal variations in carrier density, photon density, and refractive index. The effective index method and other approximations are used to reduce the complex three-dimensional problem to one dimension. The coupled wave and carrier rate equations are then solved in a self-consistent manner. Lateral spatial carrier hole burning and lateral diffusion are found to affect the relaxation oscillation frequency and damping rate of DFB lasers, depending on their detailed structure. The effective time-averaged linewidth enhancement factor is also affected. In symmetric AR-coated λ/4 phase-shifted lasers the side mode suppression ratio can be deteriorated significantly by lateral spatial hole burning when kL is large.published_or_final_versio

NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I.

Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane, and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms.This work was supported by the Medical Research Council via Intramural Program U105663150 and Program Grant MR/M009858/1 (to J. E. W.)

Persistence of the mitochondrial permeability transition in the absence of subunit c of human ATP synthase.

The permeability transition in human mitochondria refers to the opening of a nonspecific channel, known as the permeability transition pore (PTP), in the inner membrane. Opening can be triggered by calcium ions, leading to swelling of the organelle, disruption of the inner membrane, and ATP synthesis, followed by cell death. Recent proposals suggest that the pore is associated with the ATP synthase complex and specifically with the ring of c-subunits that constitute the membrane domain of the enzyme's rotor. The c-subunit is produced from three nuclear genes, ATP5G1, ATP5G2, and ATP5G3, encoding identical copies of the mature protein with different mitochondrial-targeting sequences that are removed during their import into the organelle. To investigate the involvement of the c-subunit in the PTP, we generated a clonal cell, HAP1-A12, from near-haploid human cells, in which ATP5G1, ATP5G2, and ATP5G3 were disrupted. The HAP1-A12 cells are incapable of producing the c-subunit, but they preserve the characteristic properties of the PTP. Therefore, the c-subunit does not provide the PTP. The mitochondria in HAP1-A12 cells assemble a vestigial ATP synthase, with intact F1-catalytic and peripheral stalk domains and the supernumerary subunits e, f, and g, but lacking membrane subunits ATP6 and ATP8. The same vestigial complex plus associated c-subunits was characterized from human 143B ρ(0) cells, which cannot make the subunits ATP6 and ATP8, but retain the PTP. Therefore, none of the membrane subunits of the ATP synthase that are involved directly in transmembrane proton translocation is involved in forming the PTP.This work was supported by the Medical Research Council (MRC) of the United Kingdom by Grant MC_U1065663150 and by Programme Grant MR/M009858/1 (to J.E.W.). H.C.F. received an MRC PhD studentship

Human METTL20 methylates lysine residues adjacent to the recognition loop of the electron transfer flavoprotein in mitochondria.

In mammalian mitochondria, protein methylation is a relatively uncommon post-transcriptional modification, and the extent of the mitochondrial protein methylome, the modifying methyltransferases, and their substrates have been little studied. As shown here, the β-subunit of the electron transfer flavoprotein (ETF) is one such methylated protein. The ETF is a heterodimer of α- and β-subunits. Lysine residues 199 and 202 of mature ETFβ are almost completely trimethylated in bovine heart mitochondria, whereas ETFα is not methylated. The enzyme responsible for the modifications was identified as methyltransferase-like protein 20 (METTL20). In human 143B cells, the methylation of ETFβ is less extensive and is diminished further by suppression of METTL20. Tagged METTL20 expressed in HEK293T cells specifically associates with the ETF and promotes the trimethylation of ETFβ lysine residues 199 and 202. ETF serves as a mobile electron carrier linking dehydrogenases involved in fatty acid oxidation and one-carbon metabolism to the membrane-associated ubiquinone pool. The methylated residues in ETFβ are immediately adjacent to a protein loop that recognizes and binds to the dehydrogenases. Suppression of trimethylation of ETFβ in mouse C2C12 cells oxidizing palmitate as an energy source reduced the consumption of oxygen by the cells. These experiments suggest that the oxidation of fatty acids in mitochondria and the passage of electrons via the ETF may be controlled by modulating the protein-protein interactions between the reduced dehydrogenases and the β-subunit of the ETF by trimethylation of lysine residues. METTL20 is the first lysine methyltransferase to be found to be associated with mitochondria.This work was supported by the Medical Research Council (MRC), UK

Classical and Quantum Equations of Motion for a BTZ Black String in AdS Space

We investigate gravitational collapse of a $(3+1)$-dimensional BTZ black string in AdS space in the context of both classical and quantum mechanics. This is done by first deriving the conserved mass per unit length of the cylindrically symmetric domain wall, which is taken as the classical Hamiltonian of the black string. In the quantum mechanical context, we take primary interest in the behavior of the collapse near the horizon and near the origin (classical singularity) from the point of view of an infalling observer. In the absence of radiation, quantum effects near the horizon do not change the classical conclusions for an infalling observer, meaning that the horizon is not an obstacle for him/her. The most interesting quantum mechanical effect comes in when investigating near the origin. First, quantum effects are able to remove the classical singularity at the origin, since the wave function is non-singular at the origin. Second, the Schr\"odinger equation describing the behavior near the origin displays non-local effects, which depend on the energy density of the domain wall. This is manifest in that derivatives of the wavefunction at one point are related to the value of the wavefunction at some other distant point.Comment: 9 pages, 1 figure. Minor Clarification and corrections. Accepted for Publication in JHE

Permeability transition in human mitochondria persists in the absence of peripheral stalk subunits of ATP synthase

The opening of a non-specific channel, known as the permeability transition pore (PTP), in the inner membranes of mitochondria, can be triggered by calcium ions, leading to swelling of the organelle, disruption of the inner membrane and ATP synthesis, and cell death. Pore opening can be inhibited by cyclosporin A mediated via cyclophilin D. It has been proposed that the pore is associated with the dimeric ATP synthase, and that the OSCP (oligomycin sensitivity conferral protein), a component of the enzyme’s peripheral stalk, provides the site where cyclophilin D interacts. Subunit b contributes a central α-helical structure to the peripheral stalk, extending from near the top of the enzyme’s catalytic domain and crossing the membrane domain of the enzyme via two α-helices. We investigated the possible involvement of the subunit b and the OSCP in the PTP by generating clonal cells, HAP1-Δb and HAP1-ΔOSCP, lacking the membrane domain of subunit b or the OSCP, respectively, in which the correponding genes ATP5F1 and ATP5O had been disrupted. Both cell lines preserve the characteristic properties of the PTP. Therefore, the membrane domain of subunit b does not contribute to the PTP, and the OSCP does not provide the site of interaction with cyclophilin D. The membrane subunits ATP6, ATP8 and subunit c have been eliminated previously from possible participation in the PTP. Therefore, the only subunits of ATP synthase that could participate in pore formation are e, f, g, DAPIT (diabetes associated protein in insulin sensitive tissues) and the 6.8 kDa proteolipid.This work was supported by Medical Research Council, United Kingdom Programme Grant MR/M009858/1 (to J.E.W.)

Human METTL12 is a mitochondrial methyltransferase that modifies citrate synthase

The protein methylome in mammalian mitochondria has been little studied until recently. Here, we describe that lysine-368 of human citrate synthase is methylated and that the modifying enzyme, localized in the mitochondrial matrix, is methyltransferase-like protein 12 (METTL12), a member of the family of 7β-strand methyltransferases. Lysine-368 is near the active site of citrate synthase, but removal of methylation has no effect on its activity. In mitochondria, it is possible that some or all of the enzymes of the citric acid cycle, including citrate synthase, are organized in metabolons to facilitate the channelling of substrates between participating enzymes. Thus, possible roles for the methylation of Lys-368 are in controlling substrate channelling itself, or in influencing protein–protein interactions in the metabolon.This work was supported by the Medical Research Council of the United Kingdom by grant MC_U1065663150 and by Programme Grant MR/M009858/1, both to JEW and a Fellowship from the Swiss Novartis Foundation to VFR