Cell Therapy for Type 1 Diabetes

Acknowledgements The work described in this review was supported by a grant from the MRC. K.R.M. is supported by a fellowship from the Scottish Translational Medicines and Therapeutics Initiative through the Wellcome Trust.Peer reviewedPublisher PD

Cobalt‐Catalysed, Ligand‐Controlled Regiodivergent Alkene Hydrosilylation

Alkene hydrosilylation is amongst the largest industrial homogenous catalysis processes. Cobalt catalysis offers a sustainable alternative to commonly used platinum catalysts to achieve this transformation. Using two bisiminopyridine cobalt(II) catalysts the regiodivergent hydrosilylation of alkenes has been developed. Variation of pre-catalyst activator and ligand substituents were investigated to enable the controlled, regiodivergent hydrosilylation of both aryl- and alkyl-substituted alkenes with phenylsilane. In contrast to other regiodivergence strategies, excellent regioselectivity for either isomer was achieved using the same ligand class but differing by a single methyl group (ethyl vs isopropyl)

Nucleophile induced ligand rearrangement reactions of alkoxy- and arylsilanes

The ligand-redistribution reactions of aryl- and alkoxy-hydrosilanes can potentially cause the formation of gaseous hydrosilanes, which are flammable and pyrophoric. The ability of generic nucleophiles to initiate the ligand-redistribution reaction of commonly used hydrosilane reagents was investigated, alongside methods to hinder and halt the formation of hazardous hydrosilanes. Our results show that the ligand-redistribution reaction can be completely inhibited by common electrophiles and first-row transition metal pre-catalysts

Simplified access to low oxidation-state earth-abundant metals for catalytic application

A sustainable future lies in the use of first row, low cost, low toxicity, Earth-abundant metals. Despite this, the metals that are most abundant have yet to be widely adopted by the global community. The overarching aim at the outset of the project was to ask the question: Why is this? Why do expensive metals such as; platinum, palladium and rhodium dominate? Why does the synthetic chemist not instinctively use iron, manganese or cobalt? The simple answer: The non-expert chemist is simply not equipped to try. Many modern synthetic methods for the reductive functionalisation of alkenes and alkynes rely on the use of air- and moisture-sensitive pre-catalysts or reagents, which are challenging to handle, store and transport. In the ideal scenario, all reagents and pre-catalysts would be air- and moisture-stable solids that are easily handled, and applicable in large-scale processes with minimal associated hazards. This project entailed the development of a simple pre-catalyst activation protocol using a safe and easily handled reagent (NaOtBu) with wide commercial availability. This has allowed generic access to sustainable first-row transition metal (Fe, Co, Mn, Ni) low oxidation-state catalysis across a wide range of reductive alkene and alkyne functionlisation reactions (hydroboration, hydrosilylation, hydrogenation, hydrovinylation and [2π+2π] cyclisation reactions). Using this straightforward catalyst activation strategy a new regiodivergent cobalt-catalyst alkene hydrosilylation manifold was discovered and mechanistically explored. Taken together, all results are suggestive of a new and unique catalyst activation mechanism that is primed for future reaction, catalyst and mechanistic development

Knowledge and information needs of informal caregivers in palliative care : a qualitative systematic review

Objectives: To review current understanding of the knowledge and information needs of informal caregivers in palliative settings. Data sources: Seven electronic databases were searched for the period January 1994–November 2006: Medline, CINAHL, PsychINFO, Embase, Ovid, Zetoc and Pubmed using a meta-search engine (Metalib®). Key journals and reference lists of selected papers were hand searched. Review methods: Included studies were peer-reviewed journal articles presenting original research. Given a variety of approaches to palliative care research, a validated systematic review methodology for assessing disparate evidence was used in order to assign scores to different aspects of each study (introduction and aims, method and data, sampling, data analysis, ethics and bias, findings/results, transferability/generalizability, implications and usefulness). Analysis was assisted by abstraction of key details of study into a table. Results: Thirty-four studies were included from eight different countries. The evidence was strongest in relation to pain management, where inadequacies in caregiver knowledge and the importance of education were emphasized. The significance of effective communication and information sharing between patient, caregiver and service provider was also emphasized. The evidence for other caregiver knowledge and information needs, for example in relation to welfare and social support was weaker. There was limited literature on non-cancer conditions and the care-giving information needs of black and minority ethnic populations. Overall, the evidence base was predominantly descriptive and dominated by small-scale studies, limiting generalizability. Conclusions: As palliative care shifts into patients’ homes, a more rigorously researched evidence base devoted to understanding caregivers knowledge and information needs is required. Research design needs to move beyond the current focus on dyads to incorporate the complex, three-way interactions between patients, service providers and caregivers in end-of-life care setting

Cobalt-catalysed Markovnikov selective hydroboration of vinylarenes

A bipyridiyl-oxazoline cobalt catalyst tBuBPOCoCl2 has been developed for the Markovnikov selective hydroboration of alkenes using pinacolborane and NaOtBu as the in situ activator with up to >98 : 2 branched : linear selectivity (24 examples, 45-92% isolated yield)

Testicular somatic cell-like cells derived from embryonic stem cells induce differentiation of epiblasts into germ cells

Regeneration of the testis from pluripotent stem cells is a real challenge, reflecting the complexity of the interaction of germ cells and somatic cells. Here we report the generation of testicular somatic cell-like cells (TesLCs) including Sertoli cell-like cells (SCLCs) from mouse embryonic stem cells (ESCs) in xeno-free culture. We find that Nr5a1/SF1 is critical for interaction between SCLCs and PGCLCs. Intriguingly, co-culture of TesLCs with epiblast-like cells (EpiLCs), rather than PGCLCs, results in self-organised aggregates, or testicular organoids. In the organoid, EpiLCs differentiate into PGCLCs or gonocyte-like cells that are enclosed within a seminiferous tubule-like structure composed of SCLCs. Furthermore, conditioned medium prepared from TesLCs has a robust inducible activity to differentiate EpiLCs into PGCLCs. Our results demonstrate conditions for in vitro reconstitution of a testicular environment from ESCs and provide further insights into the generation of sperm entirely in xeno-free culture

Iron-catalysed C(sp²)-H borylation enabled by carboxylate activation

Arene C(sp2)-H bond borylation reactions provide rapid and efficient routes to synthetically versatile boronic esters. While iridium catalysts are well established for this reaction, the discovery and development of methods using Earth-abundant alternatives is limited to just a few examples. Applying an in situ catalyst activation method using air-stable and easily handed reagents, the iron-catalysed C(sp2)-H borylation reactions of furans and thiophenes under blue light irradiation have been developed. Key reaction intermediates have been prepared and characterised, and suggest two mechanistic pathways are in action involving both C-H metallation and the formation of an iron boryl species

A Boron–Boron Double Transborylation Strategy for the Synthesis of gem-Diborylalkanes

Olefin hydroboration reactions provide efficient access to synthetically versatile and easily handled organoboronic esters. In this study, we demonstrate that the commercially available organoborane reagent 9-borabicyclo[3.3.1]nonane (H-B-9-BBN) can serve as a catalyst for the sequential double hydroboration of alkynes using pinacolborane (HBpin). This strategy, which is effective for a wide range of terminal alkynes, is predicated upon a key C(sp3)-B/B-H transborylation reaction. Transition-state thermodynamic parameters and 10-boron-isotopic labeling experiments are indicative of a σ-bond metathesis exchange pathway

WHOOPING CRANE TITERS TO EASTERN EQUINE ENCEPHALITIS VACCINATIONS

In 1984 an epizootic of eastern equine encephalitis (EEE) virus killed 7 of 39 (18%) whooping cranes in captivity at the Patuxent Wildlife Research Center in Laurel, Maryland, USA. Since that time whooping cranes have been vaccinated with a human EEE vaccine. This vaccine was unavailable for several years, necessitating use of an equine vaccine in the cranes. This study compared the antibody titers measured for three years using the human vaccine with those measured for two years using the equine form. Whooping cranes developed similarly elevated titers in one year using the human vaccine and both years using the equine vaccine. However, in two years where the human vaccine was used, the whooping cranes developed significantly lower titers compared to other years