Challenging Development Concepts

SUMMARY The paper argues that the main need in teaching development in the 1980s is not to overcome academic inertia (using yesterday's theories to think about tomorrow's problems) but to exorcise an ideological concept of ‘development in general’ which remains implicit even in the most fashionably ‘advanced’ theories, and in the currently popular ideal of ‘interdisciplinarity’ in teaching about development. This implies that any course on development, however ‘practical’, must deal systematically with basic theoretical issues, with competing concepts and forms of development, with politics, and with international aspects of development. RESUME Remise en question des concepts de développement Cet article prétend que ce qu'il faut surtout dans l'enseignement du développement dans les années 80, ce n'est pas de combattre l'inertie académique (utiliser les théories d'hier pour penser aux problèmes de demain), mais d'exorciser un concept idéologique de ‘développement en général’ qui demeure implicite même dans les théories ‘avancées’ les plus à la mode, et dans l'‘Interdisciplinarité’, l'idéal actuellement en faveur dans l'enseignement du développement. Cela implique que tout cours sur le développement, aussi ‘pratique’ soit?il, doit systématiquement traiter des problèmes théoriques de base, des concepts et formes de développement rivaux, de la politique et des aspects internationaux du développement. RESUMEN Conceptos del desarrollo puestos en duda En el artículo se alega que la principal necesidad en la enseñanza sobre el desarrollo durante el decenio de 1980 no consistirá en superar la inercia académica (utilizando las teorías de ayer para concebir los problemas del mañana), sino la de depurar un concepto ideológico del ‘desarrollo en general’ que sigue implícito incluso en las teorías más ‘avanzadas’ de acuerdo con la moda, y en el ideal actualmente popular de la ‘interdisciplinaridad’ en la enseñanza sobre el desarrollo. Esto significa que todo curso sobre el desarrollo, por ‘práctico’ que sea debe tratar sistemáticamente los temas teóricos fundamentales con formas y conceptos opuestos de desarrollo y política y con los aspectos internacionales del desarrollo

The Politics of Redistribution with Growth; The ‘target group’ approach

SUMMARY This article challenges the political assumptions which, it argues, characterize Redistribution with Growth: that a large number of Third World countries will continue to be predominantly capitalist, and that poverty relief should be attempted through redistributive policies which will arouse minimum opposition from their ruling classes. The contradictions in these assumptions are reflected in RwG's analysis of the determinants of poverty, which excludes the structural and political forces of capitalist underdevelopment; in its rejection of class analysis and the substitution of arbitrarily defined 'target groups'; in its proposed 'index of performance', intended to replace GNP as a measure; and in the pessimism and indeterminacy of RwG's analysis of the prospects for its actual adoption as a strategy. Finally, the origins and context of RwG must be taken into account in assessing its assumption that radical change is “unlikely” in much of the Third World; it is argued that the nature and approach of RwG are such as to make such change less likely. RESUME La politique de redistribution avec croissance Cet article réfute les hypothèses politiques qui, affirme?t?il, caractérisent Redistribution avec croissance (RAC): aìnsì qu'un grand nomhre de pays du Tiers Monde continueraient à fonctionner de manière prédominante sur le type capitaliste; d'autre part le recul de la pauvreté devrait passer par une politique de redistribution qui aurait I'avantage de provoquer une opposition restreinte de la part des classes dominantes dans ces sociétés. Les contradictions contenues dans ces affirmations sont refletées dans I'analyse faite dans le RAC des origines de la pauvreté; cette analyse exclue les forces structurelles et politiques du sous?développement capitaliste, dans son rejet de I'analyse de classes à laquelle est substitutée celle des groupes arbitrairement qualifiés de groupes è objectif; dans sa proposition de I'indice de rendement conçu pour remplacer le GNP comme élément de mesure; également dans le pessimisme et I'indécision de I'analyse du ‘RwG’ quant aux perspectives desaréelle adoption comme stratégie. En fin de compte, les origines et le contexte du RAC doivent être pris en considération pour évaluer I'affirmation selon laquelle un changement radical est improbable dans la majeure partie du Tiers Monde; on affirme que la nature et I'approche du RAC sont telles qu'elles rendent le changement encore plus improbable. RESUMEN El Modelo Politíco de Redistribuciín con Crecimiento Este artlculo rebate las premisas políticas que, según dice, caracterizan Redistribución con Crecimiento: que un gran número de países del Tercer Mundo continuaá siendo predominantemente capitalista que el alivio de la pobreza debería intentarse a trav?s de políticas de redistribución que despierten un mínimo de oposición por parte de sus clases gobernantes. Las contradicciones de estas premisas se reflejan en el análisis que RCC hace de las determinantes de la pobreza, el cual excluye las fuerzas políticas estructurales del subdesarrollo capitalista; en su rechazo del análisis de clase su substitución por grupos?objetivo' arbitrariamente determinados; en el ‘índice de realizaciones’ que propone para tratar de reemplazar el Producto Nacional Bruto como unidad de medida; en el pesimismo la indeterminación del análisis que RCC hace de sus perspectives de ser efectivamenteadoptado como estrategia. Finalmente, deben tomarseen considereción los orígenes el contexto del libro para evaluar su tesis de que un cambio radical es ‘poco probable’ en la mayor parte del Tercer Mundo. El artlculo exprese que la naturaleza el enfoque de RCC son tales como para hacer menos probable aún un cambio de ese tipo

The private provision of NHS clinical services: how is the NHS handling the contracts?

How well are GP-led Clinical Commissioning Groups equipped to handle contracts with private providers of NHS clinical services? In this article, Colin Leys finds that the case for outsourcing clinical work to private providers continues to lack evidential support, and that there should be an independent enquiry into the capacity of CCGs to handle major new contracts before they are allowed to be made

In the dedicated pursuit of dedicated capital: restoring an indigenous investment ethic to British capitalism

Tony Blair’s landslide electoral victory on May 1 (New Labour Day?) presents the party in power with a rare, perhaps even unprecedented, opportunity to revitalise and modernise Britain’s ailing and antiquated manufacturing economy.* If it is to do so, it must remain true to its long-standing (indeed, historic) commitment to restore an indigenous investment ethic to British capitalism. In this paper we argue that this in turn requires that the party reject the very neo-liberal orthodoxies which it offered to the electorate as evidence of its competence, moderation and ‘modernisation’, which is has internalised, and which it apparently now views as circumscribing the parameters of the politically and economically possible

Structural characterization of CYP144A1 - a cytochrome P450 enzyme expressed from alternative transcripts in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) causes the disease tuberculosis (TB). The virulent Mtb H37Rv strain encodes 20 cytochrome P450 (CYP) enzymes, many of which are implicated in Mtb survival and pathogenicity in the human host. Bioinformatics analysis revealed that CYP144A1 is retained exclusively within the Mycobacterium genus, particularly in species causing human and animal disease. Transcriptomic annotation revealed two possible CYP144A1 start codons, leading to expression of (i) a "full-length" 434 amino acid version (CYP144A1-FLV) and (ii) a "truncated" 404 amino acid version (CYP144A1-TRV). Computational analysis predicted that the extended N-terminal region of CYP144A1-FLV is largely unstructured. CYP144A1 FLV and TRV forms were purified in heme-bound states. Mass spectrometry confirmed production of intact, His6-tagged forms of CYP144A1-FLV and -TRV, with EPR demonstrating cysteine thiolate coordination of heme iron in both cases. Hydrodynamic analysis indicated that both CYP144A1 forms are monomeric. CYP144A1-TRV was crystallized and the first structure of a CYP144 family P450 protein determined. CYP144A1-TRV has an open structure primed for substrate binding, with a large active site cavity. Our data provide the first evidence that Mtb produces two different forms of CYP144A1 from alternative transcripts, with CYP144A1-TRV generated from a leaderless transcript lacking a 5'-untranslated region and Shine-Dalgarno ribosome binding site

UbiD domain dynamics underpins aromatic decarboxylation

From Springer Nature via Jisc Publications RouterHistory: received 2020-12-03, accepted 2021-07-20, registration 2021-08-03, pub-electronic 2021-08-20, online 2021-08-20, collection 2021-12Publication status: PublishedFunder: EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council); doi: https://doi.org/10.13039/100010663; Grant(s): 695013Funder: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC); doi: https://doi.org/10.13039/501100000268; Grant(s): BB/P000622/1Abstract: The widespread UbiD enzyme family utilises the prFMN cofactor to achieve reversible decarboxylation of acrylic and (hetero)aromatic compounds. The reaction with acrylic compounds based on reversible 1,3-dipolar cycloaddition between substrate and prFMN occurs within the confines of the active site. In contrast, during aromatic acid decarboxylation, substantial rearrangement of the substrate aromatic moiety associated with covalent catalysis presents a molecular dynamic challenge. Here we determine the crystal structures of the multi-subunit vanillic acid decarboxylase VdcCD. We demonstrate that the small VdcD subunit acts as an allosteric activator of the UbiD-like VdcC. Comparison of distinct VdcCD structures reveals domain motion of the prFMN-binding domain directly affects active site architecture. Docking of substrate and prFMN-adduct species reveals active site reorganisation coupled to domain motion supports rearrangement of the substrate aromatic moiety. Together with kinetic solvent viscosity effects, this establishes prFMN covalent catalysis of aromatic (de)carboxylation is afforded by UbiD dynamics

Thinking like a man? The cultures of science

Culture includes science and science includes culture, but conflicts between the two traditions persist, often seen as clashes between interpretation and knowledge. One way of highlighting this false polarity has been to explore the gendered symbolism of science. Feminism has contributed to science studies and the critical interrogation of knowledge, aware that practical knowledge and scientific understanding have never been synonymous. Persisting notions of an underlying unity to scientific endeavour have often impeded rather than fostered the useful application of knowledge. This has been particularly evident in the recent rise of molecular biology, with its delusory dream of the total conquest of disease. It is equally prominent in evolutionary psychology, with its renewed attempts to depict the fundamental basis of sex differences. Wars over science have continued to intensify over the last decade, even as our knowledge of the political, economic and ideological significance of science funding and research has become ever more apparent

Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors.

The essential enzyme CYP121 is a target for drug development against antibiotic resistant strains of Mycobacterium tuberculosis. A triazol-1-yl phenol fragment 1 was identified to bind to CYP121 using a cascade of biophysical assays. Synthetic merging and optimization of 1 produced a 100-fold improvement in binding affinity, yielding lead compound 2 (KD = 15 μM). Deconstruction of 2 into its component retrofragments allowed the group efficiency of structural motifs to be assessed, the identification of more LE scaffolds for optimization and highlighted binding affinity hotspots. Structure-guided addition of a metal-binding pharmacophore onto LE retrofragment scaffolds produced low nanomolar (KD = 15 nM) CYP121 ligands. Elaboration of these compounds to target binding hotspots in the distal active site afforded compounds with excellent selectivity against human drug-metabolizing P450s. Analysis of the factors governing ligand potency and selectivity using X-ray crystallography, UV-vis spectroscopy, and native mass spectrometry provides insight for subsequent drug development.MEK was supported by a Commonwealth (University of Cambridge) Scholarship awarded in conjunction with the Cambridge Commonwealth Trust and Cambridge Overseas Trust. AGC and KJM were supported by grants from the BBSRC (Grant No: BB/I019669/1 and BB/I019227/1). GGJ received funding from the Ogden Trust and the Isaac Newton Trust administered through the University of Cambridge Bursary Scheme. DSCH was supported by a Croucher Cambridge International Scholarship awarded in conjunction between the Croucher Foundation and the Cambridge Overseas Trust. SAH was supported by an Oliphant Cambridge Australia Scholarship (App No: 10132070) awarded by the Cambridge Commonwealth Trust. The contributions of LBM and LPSC were supported by funds from the Francis Crick Institute, which receives its core funding principally from Wellcome Trust, Cancer Research UK, and the UK Medical Research Council (to LPSC - MC_UP_A253_1111) and funds from FAPESP, CNPq and CAPES-PDSE (to LBM - 2011/21232-1, 140079/2013-0, 99999.003125/2014-09).This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/acs.jmedchem.6b0000