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The colonic human MUC2 mucin forms a polymeric gel by covalent disulfide bonds in its N- and C-termini. The middle part of MUC2 is largely composed of two highly O-glycosylated mucin domains that are interrupted by a CysD domain of unknown function. We studied its function as recombinant proteins fused to a removable immunoglobulin Fc domain. Analysis of affinity-purified fusion proteins by native gel electrophoresis and gel filtration showed that they formed oligomeric complexes. Analysis of the individual isolated CysD parts showed that they formed dimers both when flanked by two MUC2 tandem repeats and without these. Cleavages of the two non-reduced CysD fusion proteins and analysis by MS revealed the localization of all five CysD disulfide bonds and that the predicted C-mannosylated site was not glycosylated. All disulfide bonds were within individual peptides showing that the domain was stabilized by intramolecular disulfide bonds and that CysD dimers were of non-covalent nature. These observations suggest that CysD domains act as non-covalent cross-links in the MUC2 gel, thereby determining the pore sizes of the mucus.

Plants produce a unique peroxisomal short chain-specific acyl-CoA oxidase (ACX4) for β-oxidation of lipids. The short chain-specific oxidase has little resemblance to other peroxisomal acyl-CoA oxidases but has an ∼30% sequence identity to mitochondrial acyl-CoA dehydrogenases. Two biochemical features have been linked to structural properties by comparing the structures of short chain-specific Arabidopsis thaliana ACX4 with and without a substrate analogue bound in the active site to known acyl-CoA oxidases and dehydrogenase structures: (i) a solvent-accessible acyl binding pocket is not required for oxygen reactivity, and (ii) the oligomeric state plays a role in substrate pocket architecture but is not linked to oxygen reactivity. The structures indicate that the acyl-CoA oxidases may encapsulate the electrons for transfer to molecular oxygen by blocking the dehydrogenase substrate interaction site with structural extensions. A small binding pocket observed adjoining the flavin adenine dinucleotide N5 and C4a atoms could increase the number of productive encounters between flavin adenine dinucleotide and O2.

This article draws on findings from a three-year project to develop and deliver culturally appropriate support group materials for South Asian and Eastern European family carers of relatives with dementia living in the UK. Analysis of interview and field note data revealed insights into how understandings of dementia in different cultural contexts can become operationalized through stigma processes and in turn influence the ways in which people with dementia and their family carers engage with formal and informal support.

Lesbian, gay, and bisexual youth are at increased risk for a variety of poor health outcomes, relative to their heterosexual counterparts, and recent research implicates family responses to a child’s sexual orientation as an important predictor of these health difficulties. Lead with Love is a 35-min documentary-style preventive intervention created to improve parents’ behaviors toward their lesbian, gay, and bisexual (LGB) children, by providing parents with support, information, and concrete behavioral guidance. The film was made available free online, and was promoted widely with a multi-media marketing campaign. In this paper we describe the theoretical and empirical rationale for the intervention, and report findings from pilot data collected in the first year after the film’s release. Specifically, we gathered data to examine the feasibility of reaching parents of LGB youth with this intervention, to determine whether it was acceptable, and to provide preliminary indicators of its potential efficacy. In the first 12 months after launch, 10,949 individuals viewed the film online. The film successfully reached parents of LGB youth (n = 1,865), including the hardest to reach parents: 21 % had only learned about their child’s sexual orientation in the past month, 36 % reported having an LGB child was “very” or “extremely” hard for them, and 86 % had never obtained any other formal support for having an LGB child. Parents who completed a follow-up assessment immediately after the film reported significant pre- to post-film increases in self-efficacy for parenting an LGB child.

The EGF receptor is an important target of cancer immunotherapies. The 7A7 monoclonal antibody has been raised against the murine EGFR, but it cross-reacts with the human receptor. The results from experiments using immune-competent mice can therefore, in principle, be extrapolated to the corresponding scenario in humans. In this work we report the crystal structure of the 7A7 Fab at an effective resolution of 1.4A. The antibody binding site comprises a deep pocket, located at the interface between the light and heavy chains, with major contributions from CDR loops H1, H2, H3 and L1. Binding experiments show that 7A7 recognizes a site on the EGFR extracellular domain that is not accessible in its most stable conformations, but that becomes exposed upon treatment with a tyrosine kinase inhibitor. This suggests a recognition mechanism similar to that proposed for mAb 806.

An in-service training programme was developed to meet the needs of an NHS palliative care service for children and young people, specifically focused on bereavement work. A training day was held every six months that allowed staff to share and support each other's practice and to consider how best practice could be promoted. Each training day was evaluated by attendees, who were asked to rate the usefulness of the day and give qualitative feedback. After four training days had been completed, staff views on the impact and benefits of the programme were sought using a questionnaire that incorporated a set of statements highlighting factors important to good bereavement care. Participant evaluations indicated that the aims of the training days were being met. Responses to the questionnaire were positive, both in terms of improvement and positive outcomes in the workplace. Ongoing training and support as well as clinical supervision are essential to maintain good practice in palliative and bereavement care.

List of Illustrations Preface Part 1. The Harp in the Ancient World 1. The Beginning 2. Beyond the Earliest Sources Part 2. The Non-Pedal Harp in Western Europe and North America 3. Early Representations 4. The Harp in Art, 12001665 5. The Harp in Literature and Music 6. Concerning Non-pedal Harps and Harpists Part 3. The Pedal Harp in Western Europe and North America 7. Some Early Harps, Harpists, and Music 8. From Single to Double Action 9. The Colonies and the United States 10. The Harp International Part 4. Retrospection and the Future 11. Some Notable Events 12. Four Essays by the Author Appendix Notes Selected Bibliography Index