The School Improvement Partnership Programme: Using Collaboration and Enquiry to tackle Educational Inequity

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Halomethyl-Triazoles for Rapid, Site-Selective Protein Modification

Post-translational modifications (PTMs) are used by organisms to control protein structure and function after protein translation, but their study is complicated and their roles are not often well understood as PTMs are difficult to introduce onto proteins selectively. Designing reagents that are both good mimics of PTMs, but also only modify select amino acid residues in proteins is challenging. Frequently, both a chemical warhead and linker are used, creating a product that is a misrepresentation of the natural modification. We have previously shown that biotin-chloromethyl-triazole is an effective reagent for cysteine modification to give S-Lys derivatives where the triazole is a good mimic of natural lysine acylation. Here, we demonstrate both how the reactivity of the alkylating reagents can be increased and how the range of triazole PTM mimics can be expanded. These new iodomethyl-triazole reagents are able to modify a cysteine residue on a histone protein with excellent selectivity in 30 min to give PTM mimics of acylated lysine side-chains. Studies on the more complicated, folded protein SCP-2L showed promising reactivity, but also suggested the halomethyl-triazoles are potent alkylators of methionine residues

New methods for the synthesis of spirocyclic cephalosporin analogues

Spiro compounds provide attractive targets in drug discovery due to their inherent three-dimensional structures, which enhance protein interactions, aid solubility and facilitate molecular modelling. However, synthetic methodology for the spiro-functionalisation of important classes of penicillin and cephalosporin β-lactam antibiotics is comparatively limited. We report a novel method for the generation of spiro-cephalosporin compounds through a Michael-type addition to the dihydrothiazine ring. Coupling of a range of catechols is achieved under mildly basic conditions (K2CO3, DMF), giving the stereoselective formation of spiro-cephalosporins (d.r. 14:1 to 8:1) in moderate to good yields (28−65%)

The chemical characterisation by HPLC–PDA and HPLC–ESI–MS of unaged and aged fibre samples dyed with sawwort (Serratula tinctoria L.)

The acid-hydrolysed extracts of freshly dyed reference fibres of sawwort harvested from several different geographical locations were characterised by the use of high-performance liquid chromatography with photodiode array detection (HPLC–PDA) and coupled with electrospray ionisation mass spectrometric analysis (HPLC–ESI–MS). A related species, Serratula coronata L. was also characterised. The flavonols quercetin, 3-O-methylquercetin and kaempferol, and the flavones luteolin and apigenin were observed in all samples. Accelerated ageing studies confirmed the sensitivity of the flavonol components to photo-oxidative degradation. The poor lightfastness and small relative proportion of these flavonol components found in the extracts of freshly dyed sawwort limits their use as sawwort ‘markers’ in historical samples

A more representative chamber: representation and the House of Lords

Since 1997 there has been substantive reform of the House of Lords in an effort to make the chamber ‘more democratic and more representative’. Whilst the Labour government failed to press ahead with any of the proposed plans for further reform following the removal of the bulk of the hereditary peers in 1999, it remained committed to the notion that such reform must make the second chamber ‘more representative’. The coalition government's programme advocates a long-term aspiration for a House wholly or mainly elected on the basis of proportional representation, and a short-term approach based on additional appointments to ensure a balance of the parties. What is clear in all of these proposals for reform is a desire for the House of Lords to become more representative than it is at present. However, what is less clear is what is meant by ‘representative’ – who the House of Lords is supposed to represent, and what form representation will take. Moreover, in proposing to make the chamber more representative, either through appointment or election, little attention has been paid to how the current House of Lords provides representation. This article examines these questions in the context of Pitkin's classic conceptions of representation and peers' attitudes towards their own representative rol

Scaling up misoprostol to prevent postpartum hemorrhage at home births in Mozambique: A case study applying the ExpandNet/WHO framework

© Hobday et al. Background: Mozambique has a high maternal mortality ratio, and postpartum hemorrhage (PPH) is a leading cause of maternal deaths. In 2015, the Mozambican Ministry of Health (MOH) commenced a program to distribute misoprostol at the community level in selected districts as a strategy to reduce PPH. This case study uses the ExpandNet/World Health Organization (WHO) scale-up framework to examine the planning, management, and outcomes of the early expansion phase of the scale-up of misoprostol for the prevention of PPH in 2 provinces in Mozambique. Methods: Qualitative semistructured interviews were conducted between February and October 2017 in 5 participating districts in 2 provinces. Participants included program stakeholders, health staff, community health workers (CHWs), and traditional birth attendants (TBAs). Interviews were analyzed using the ExpandNet/WHO framework alongside national policy and planning documents and notes from a 2017 national Ministry of Health maternal, newborn, and child health workshop. Outcomes were estimated using misoprostol coverage and access in 2017 for both provinces. Results: The study revealed a number of barriers and facilitators to scale-up. Facilitators included a supportive political and legal environment; a clear, credible, and relevant innovation; early expansion into some Ministry of Health systems and a strong network of CHWs and TBAs. Barriers included a reduction in reach due to a shift from universal distribution to application of eligibility criteria; fear of misdirecting misoprostol for abortion or labor induction; limited communication and understanding of the national PPH prevention strategy; inadequate monitoring and evaluation; challenges with logistics systems; and the inability to engage remote TBAs. Lower coverage was found in Inhambane province than Nampula province, possibly due to NGO support and political champions. Conclusion: This study identified the need for a formal review of the misoprostol program to identify adaptations and to develop a systematic scale-up strategy to guide national scale-up