Equivariant Piecewise-Linear Topology and Combinatorial Applications

For G a finite group, we develop some theory of G-equivariant piecewise-linear topology and prove characterization theorems for G-equivariant regular neighborhoods. We use these results to prove a conjecture of Csorba that the Lovász complex Hom(C5,Kn) of graph multimorphisms from the 5-cycle C5 to the complete graph Kn is equivariantly homeomorphic to the Stiefel manifold, Vn-1,2, the space of (ordered) orthonormal 2-frames in Rn-1 with respect to an action of the cyclic group of order 2

Mechanism of thioamide drug action against tuberculosis and leprosy

Dover developed molecular constructs and the initial in viro data that initiated a structural biology route to the determination of the mode of action of the important anti-TB agent ethionamide used to treat multi-drug resistant infections and its analogue prothionamide used to treat leprosy

Thiacetazone, an Antitubercular Drug that Inhibits Cyclopropanation of Cell Wall Mycolic Acids in Mycobacteria

Background. Mycolic acids are a complex mixture of branched, long-chain fatty acids, representing key components of the highly hydrophobic mycobacterial cell wall. Pathogenic mycobacteria carry mycolic acid sub-types that contain cyclopropane rings. Double bonds at specific sites on mycolic acid precursors are modified by the action of cyclopropane mycolic acid synthases (CMASs). The latter belong to a family of S-adenosyl-methionine-dependent methyl transferases, of which several have been well studied in Mycobacterium tuberculosis, namely, MmaA1 through A4, PcaA and CmaA2. Cyclopropanated mycolic acids are key factors participating in cell envelope permeability, host immunomodulation and persistence of M. tuberculosis. While several antitubercular agents inhibit mycolic acid synthesis, to date, the CMASs have not been shown to be drug targets. Methodology/Principle Findings. We have employed various complementary approaches to show that the antitubercular drug, thiacetazone (TAC), and its chemical analogues, inhibit mycolic acid cyclopropanation. Dramatic changes in the content and ratio of mycolic acids in the vaccine strainMycobacterium bovis BCG, as well as in the related pathogenic speciesMycobacterium marinum were observed after treatment with the drugs. Combination of thin layer chromatography, mass spectrometry and Nuclear Magnetic Resonance (NMR) analyses of mycolic acids purified fromdrug-treated mycobacteria showed a significant loss of cyclopropanation in both the a- and oxygenated mycolate sub-types. Additionally, High-Resolution Magic Angle Spinning (HR-MAS) NMR analyses on whole cells was used to detect cell wall-associated mycolates and to quantify the cyclopropanation status of the cell envelope. Further, overexpression of cmaA2, mmaA2 or pcaA in mycobacteria partially reversed the effects of TAC and its analogue on mycolic acid cyclopropanation, suggesting that the drugs act directly on CMASs. Conclusions/Significance. This is a first report on them echanism of action of TAC, demonstrating the CMASs as its cellular targets in mycobacteria. The implications of this study may be important for the design of alternative strategies for tuberculosis treatment

Forging connections: anthologies, arts collectives, and the politics of inclusion

The changing social and political landscape of twentieth-century Britain catalysed a remarkable rise in collaborative activity by artists and activists of black and Asian heritage. Creative communities began to gather in both local and regional contexts, with the aim of sharing resources and securing an audience. This chapter records some of these many activities, tracing the groups’ genesis, manifest objectives, and key contributions. It argues that anthologising should be understood as a specifically motivated activity. Literary anthologies of poetry and fiction served to showcase the diversity of contemporary writing, while also suggesting its coherence. Drawing on the concept of “strategic essentialism” elucidated by Gayatri Chakravorty Spivak, I show that the anthology acts to ensure the visibility of a group, bannered as a unified and singly-titled selection of texts, while also insisting on the differences within: the heterogeneous multiplicity of black and Asian British experiences and creative practices

'Vernacular Voices: Black British Poetry'

ABSTRACT Black British poetry is the province of experimenting with voice and recording rhythms beyond the iambic pentameter. Not only in performance poetry and through the spoken word, but also on the page, black British poetry constitutes and preserves a sound archive of distinct linguistic varieties. In Slave Song (1984) and Coolie Odyssey (1988), David Dabydeen employs a form of Guyanese Creole in order to linguistically render and thus commemorate the experience of slaves and indentured labourers, respectively, with the earlier collection providing annotated translations into Standard English. James Berry, Louise Bennett, and Valerie Bloom adapt Jamaican Patois to celebrate Jamaican folk culture and at times to represent and record experiences and linguistic interactions in the postcolonial metropolis. Grace Nichols and John Agard use modified forms of Guyanese Creole, with Nichols frequently constructing gendered voices whilst Agard often celebrates linguistic playfulness. The borders between linguistic varieties are by no means absolute or static, as the emergence and marked growth of ‘London Jamaican’ (Mark Sebba) indicates. Asian British writer Daljit Nagra takes liberties with English for different reasons. Rather than having recourse to established Creole languages, and blending them with Standard English, his heteroglot poems frequently emulate ‘Punglish’, the English of migrants whose first language is Punjabi. Whilst it is the language prestige of London Jamaican that has been significantly enhanced since the 1990s, a fact not only confirmed by linguistic research but also by its transethnic uses both in the streets and on the page, Nagra’s substantial success and the mainstream attention he receives also indicate the clout of vernacular voices in poetry. They have the potential to connect with oral traditions and cultural memories, to record linguistic varieties, and to endow ‘street cred’ to authors and texts. In this chapter, these double-voiced poetic languages are also read as signs of resistance against residual monologic ideologies of Englishness. © Book proposal (02/2016): The Cambridge History of Black and Asian British Writing p. 27 of 4

Superconductivity at 60 K in La2-XSrxCaCu2o6the Simplest Double-Layer Cuprate

STARTING with the pioneering work of Bednorz and Müller1, many copper-oxide-based superconductors with high transition temperatures (T c) have been discovered. All contain layers of copper-oxygen squares, pyramids or octahedra as their electronically active structural components2,3. One structure type, first reported for La2SrCu2O6 and La2CaCu2O6 (ref. 4), has stood as an enigma since the beginning of high-T c research. This crystal structure4-7 (Fig. 1) is the least complex of all the structures with the double layers of copper oxide pyramids common to the compounds with highest T c, yet despite considerable effort, both published8,9 and unpublished, it has not until now been made superconducting. Here we report the successful synthesis and preliminary physical characterization of superconducting (La, Sr)2CaCu2O6. The highest transition temperature observed is 60 K at the composition La1.6Sr0.4CaCu2O6. This is a uniquely simple double-layer superconductor, which, like its single-layer analogue (La, Sr)2CuO4, becomes superconducting through the introduction of carriers in an unambiguous manner-by straightforward atomic substitution without the intervention of charge reservoir layers with flexible valence states

Inhibition of mycolic acid biosynthesis in <i>M. bovis</i> BCG by treatment with TAC or its analogue SRI-224.

<p>Exponentially-growing cultures were treated with the drugs for 18 h and labeled by adding ¹⁴C-acetate for another 8 h. Fatty acid methyl esters (FAMEs) and mycolic acid methyl esters (MAMEs) were then extracted and separated by TLC on 10% silver nitrate-impregnated plates prior to exposure to a film overnight. All extracts were loaded equally for 100,000 cpm on silica plates impregnated with 10% silver nitrate. The autoradiographs show FAMEs, MAMES, oleic acid methyl esters (OAMEs), α- and keto-mycolates (k) and the lipids X and Y as indicated by arrowheads. (A) 1D TLC analysis using petroleum ether and diethyl ether (17∶3, v/v) as solvents. Drug concentrations employed are indicated in µg/ml. (B) 1D TLC profile of MAMEs extracted from cells treated with low concentrations of SRI-224 for either 1 day or over a period of 5 days, as indicated. (C) Extracts prepared after delipidation of the cells to remove the free and loosely bound lipids, while retaining the covalently bound mycolates. Extract from cells treated with SRI-224 but not subjected to delipidation is included to identify the lipids X and Y by comparison with extracts from delipidated cells that were either untreated (c) or treated with 5 µg/ml of the indicated drug for 24 h. (D) 2D TLC analysis on silica plates impregnated with 10% silver nitrate. Extracts were separated in the first direction by using two developments with hexane/ethyl acetate (19∶1, v/v) and in the second direction by using a triple development with petroleum ether/diethylether (17∶3, v/v). (E) Extracts from cells radiolabeled with [<i>methyl</i>-¹⁴C]-methionine are compared with those from cells radiolabeled with ¹⁴C-acetate.</p

Proposed mechanism for generation of mycolic acid sub-types by the action of CMAS enzymes (A) and inhibition by TAC/SRI-224 (B).

<p>The generation of α- and the oxygenated mycolic acids is considered to follow to two independent pathways. A common, di-unsaturated precursor, Y, is envisaged for the two pathways. Y is subsequently transformed into α-mycolic acids by the action of the MmaA2 and PcaA that modify the distal or proximal double bond, respectively. Action of MmaA4 commits Y to the pathway for the oxygenated mycolic acids, by producing the precursor X. MmaA3, which is required for generation of methoxy-mycolic acids in <i>M. tb</i> is inactive in <i>M. bovis</i> BCG Pasteur due to the presence of a point mutation <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001343#pone.0001343-Behr1" target="_blank">[50]</a>. The proximal double bond is modified by the CmaA2 (and MmaA2) or PcaA to generate <i>trans</i>- or <i>cis</i>-cyclopropanated derivatives, respectively. In the presence of TAC, all the CMASs mentioned above are inhibited, except for MmaA4. Due to inhibition of MmaA2, excess of Y is diverted to MmaA4 leading to generation of X, which accumulates due to lack of activities of CmaA2 and MmaA2. SRI-224 appears to affect MmaA4 to a certain degree, leading to accumulation Y in addition to X. (For simplicity, only the meromycolyl moiety of mycolates has been depicted).</p