Heterodimers and family-B GPCRs:RAMPs, CGRP and adrenomedullin

RAMPs (receptor activity-modifying proteins) are single-pass transmembrane proteins that associate with certain family-B GPCRs (G-protein-coupled receptors). Specifically for the CT (calcitonin) receptor-like receptor and the CT receptor, this results in profound changes in ligand binding and receptor pharmacology, allowing the generation of six distinct receptors with preferences for CGRP (CT gene-related peptide) adrenomedullin, amylin and CT. There are three RAMPs: RAMP1-RAMP3. The N-terminus appears to be the main determinant of receptor pharmacology whereas the transmembrane domain contributes to association of the RAMP with the GPCR. The N-terminus of all members of the RAMP family probably contains two disulphide bonds; a potential third disulphide is found in RAMP1 and RAMP3. The N-terminus appears to be in close proximity to the ligand and plays a key role in its binding, either directly or indirectly. BIBN4096BS, a CGRP antagonist, targets RAMP1 and this gives the compound very high selectivity for the human CGRP(1) receptor.

The heteromeric 5-HT3A/B receptor:the effect of 5-HT3B subunits on receptor structure and ligand recognition

The 5-HT3 receptors are members of the cys-loop family of ligand-gated ion channels. Two functional subtypes are known, the homomeric 5HT3A and the heteromeric 5HT3A/B receptors, which exhibit distinct biophysical characteristics but are difficult to differentiate pharmacologically. Atomic force microscopy has been used to determine the stoichiometry and architecture of the heteromeric 5HT3A/B receptor. Each subunit was engineered to express a unique C-terminal epitope tag, together with six sequential histidine residues to facilitate nickel affinity purification. The 5-HT3 receptors, ectopically expressed in HEK293 cells, were solubilised, purified and decorated with antibodies to the subunit specific epitope tags. Imaging of individual receptors by atomic force microscopy revealed a pentameric arrangement of subunits in the order BBABA, reading anti-clockwise when viewed from the extracellular face. Homology models for the heteromeric receptor were then constructed using both the electron microscopic structure of the nicotinic acetylcholine receptor, from Torpedo marmorata, and the X-ray crystallographic structure of the soluble acetylcholine binding protein, from Lymnaea stagnalis, as templates. These homology models were used, together with equivalent models constructed for the homomeric receptor, to interpret mutagenesis experiments designed to explore the minimal recognition differences of both the natural agonist, 5-HT, and the competitive antagonist, granisetron, for the two human receptor subtypes. The results of this work revealed that the 5-HT3B subunit residues within the ligand binding site, for both the agonist and antagonist, are accommodating to conservative mutations. They are consistent with the view that the 5-HT3A subunit provides the principal and the 5-HT38 subunit the complementary recognition interactions at the binding interface.

Impact of suspected food allergy on emotional distress and family life of parents prior to allergy diagnosis

Background: Food allergy is associated with psychological distress in both child and parent. It is unknown whether parental distress is present prior to clinical diagnosis or whether experiences at clinic can reduce any distress present. This study aimed to assess anxiety and depression in parents and the impact of suspected food allergy on the lives of families before and after a visit to an allergy clinic. Methods: One hundred and twenty-four parents visiting an allergy clinic for the first time to have their child assessed for food allergy completed a study-specific questionnaire and the Hospital Anxiety and Depression Scale; 50 parents completed these 4-6 wk later in their own home. Results: Most parents (86.4%) reported suspected food allergy had an impact on their family life prior to clinic attendance; 76% had made changes to their child's diet. 32.5% of parents had mild-to-severe anxiety before their clinic visit; 17.5% had mild-to-moderate depression. Post-clinic, 40% had mild-to-severe anxiety; 13.1% had mild-to-moderate depression. There were no significant differences in anxiety (p = 0.34) or depression scores (p = 0.09) before and after the clinic visit. Conclusions: Anxiety and depression is present in a small proportion of parents prior to diagnosis of food allergy in their child and this does not reduce in the short term after the clinic visit. Identification of parents at risk of suffering from distress is needed and ways in which we communicate allergy information before and at clinic should be investigated to see if we can reduce distress. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bifunctional SO4/ZrO2 catalysts for 5-hydroxymethylfufural (5-HMF) production from glucose

The telescopic conversion of glucose to fructose and then 5-hydroxymethylfurfural (5-HMF), the latter a potential, bio-derived platform chemical feedstock, has been explored over a family of bifunctional sulfated zirconia catalysts possessing tuneable acid-base properties. Characterisation by acid-base titration, XPS, XRD and Raman reveal that submonolayer SO4 coverages offer the ideal balance of basic and Lewis-Brønsted acid sites required to respectively isomerise glucose to fructose, and subsequently dehydrate fructose to 5-HMF. A constant acid site normalised turnover frequency is observed for fructose dehydration to 5-HMF, confirming a common Brønsted acid site is responsible for this transformation. This journal is © The Royal Society of Chemistry.

Bifunctional SO4/ZrO2 catalysts for 5-hydroxymethylfufural (5-HMF) production from glucose

The telescopic conversion of glucose to fructose and then 5-hydroxymethylfurfural (5-HMF), the latter a potential, bio-derived platform chemical feedstock, has been explored over a family of bifunctional sulfated zirconia catalysts possessing tuneable acid-base properties. Characterisation by acid-base titration, XPS, XRD and Raman reveal that submonolayer SO4 coverages offer the ideal balance of basic and Lewis-Brønsted acid sites required to respectively isomerise glucose to fructose, and subsequently dehydrate fructose to 5-HMF. A constant acid site normalised turnover frequency is observed for fructose dehydration to 5-HMF, confirming a common Brønsted acid site is responsible for this transformation. This journal is © The Royal Society of Chemistry.

The roles of family history of dyslexia, language, speech production and phonological processing in predicting literacy progress

It is well established that speech, language and phonological skills are closely associated with literacy, and that children with a family risk of dyslexia (FRD) tend to show deficits in each of these areas in the preschool years. This paper examines what the relationships are between FRD and these skills, and whether deficits in speech, language and phonological processing fully account for the increased risk of dyslexia in children with FRD. One hundred and fifty-three 4-6-year-old children, 44 of whom had FRD, completed a battery of speech, language, phonology and literacy tasks. Word reading and spelling were retested 6 months later, and text reading accuracy and reading comprehension were tested 3 years later. The children with FRD were at increased risk of developing difficulties in reading accuracy, but not reading comprehension. Four groups were compared: good and poor readers with and without FRD. In most cases good readers outperformed poor readers regardless of family history, but there was an effect of family history on naming and nonword repetition regardless of literacy outcome, suggesting a role for speech production skills as an endophenotype of dyslexia. Phonological processing predicted spelling, while language predicted text reading accuracy and comprehension. FRD was a significant additional predictor of reading and spelling after controlling for speech production, language and phonological processing, suggesting that children with FRD show additional difficulties in literacy that cannot be fully explained in terms of their language and phonological skills. It is well established that speech, language and phonological skills are closely associated with literacy, and that children with a family risk of dyslexia (FRD) tend to show deficits in each of these areas in the preschool years. This paper examines what the relationships are between FRD and these skills, and whether deficits in speech, language and phonological processing fully account for the increased risk of dyslexia in children with FRD. One hundred and fifty-three 4-6-year-old children, 44 of whom had FRD, completed a battery of speech, language, phonology and literacy tasks. © 2014 John Wiley & Sons Ltd.

Discriminant Sets of Families of Hyperbolic Polynomials of Degree 4 and 5

∗ Research partially supported by INTAS grant 97-1644

APP controls the formation of PI(3,5)P2 vesicles through its binding of the PIKfyve complex

Phosphoinositides are signalling lipids that are crucial for major signalling events as well as established regulators of membrane trafficking. Control of endosomal sorting and endosomal homeostasis requires phosphatidylinositol-3-phosphate (PI(3)P) and phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), the latter a lipid of low abundance but significant physiological relevance. PI(3,5)P2 is formed by phosphorylation of PI(3)P by the PIKfyve complex which is crucial for maintaining endosomal homeostasis. Interestingly, loss of PIKfyve function results in dramatic neurodegeneration. Despite the significance of PIKfyve, its regulation is still poorly understood. Here we show that the Amyloid Precursor Protein (APP), a central molecule in Alzheimer’s disease, associates with the PIKfyve complex (consisting of Vac14, PIKfyve and Fig4) and that the APP intracellular domain directly binds purified Vac14. We also show that the closely related APP paralogues, APLP1 and 2 associate with the PIKfyve complex. Whether APP family proteins can additionally form direct protein–protein interaction with PIKfyve or Fig4 remains to be explored. We show that APP binding to the PIKfyve complex drives formation of PI(3,5)P2 positive vesicles and that APP gene family members are required for supporting PIKfyve function. Interestingly, the PIKfyve complex is required for APP trafficking, suggesting a feedback loop in which APP, by binding to and stimulating PI(3,5)P2 vesicle formation may control its own trafficking. These data suggest that altered APP processing, as observed in Alzheimer’s disease, may disrupt PI(3,5)P2 metabolism, endosomal sorting and homeostasis with important implications for our understanding of the mechanism of neurodegeneration in Alzheimer’s disease.

The impact of family forms on interpersonal influence between single parent and full families

The relationship between individual thoughts and the social environment has been widely studied in sociology (Weber, 1968), psychology (Lewin, 1951) and social psychology. The influence of reference groups on individual behaviour is often manifested in the decisions made by consumers while members of these reference groups are often the individual’s friends and acquaintances. Their decisions, their values and norms serve as an example for the individual. In this study the influences of reference groups are examined within the context of the family form in Hungary. The paper focuses on the nature of peer influence in single parent households and full families, to analyse the normative and informational dimensions of peer pressure and communication patterns within the family.

“Like a Family”: Perspectives of Doctoral Students from Traditionally Under-represented Populations on Cohorts

This study examined the experiences of special education doctoral students from minority populations and investigated the perceptions of students in the cohort experience. Three themes emerged: The cohort was a (a) family for bonding and support, (b) motivator for academic success and retention, and an (c) inhibitor of educational growth.

The impact of migration and intergenerational changes on the Cuban family in the United States

This study examines changes in the Cuban family in the United States produced by time, migration, and the rise of new generations. The thesis will use a data set extracted from the 5% Public Use Microdata Series (PUMS) of the U.S. Decennial Census of Population for the years 1970, 1980 and 1990. Contingency table analysis and comparison of means were used to examine various family-related variables. The analysis points to changes in the traditional Cuban family towards less traditional family arrangements. The multigenerational feature of the Cuban household has diminished as the elderly have become independent and are more likely to be living on their own. Although female labor participation remains high, the occupational patterns of the first generation of Cuban women have diversified and a new trend has emerged for the second generation. The second generation of Cuban women demonstrates a strong inclination for white-collar occupations. Fertility rates remain low.

Macrophage migration inhibitory factor (MIF) family in arthropods : cloning and expression analysis of two MIF and one D-dopachrome tautomerase (DDT) homologues in Mud crabs, Scylla paramamosain

5. Acknowledgements This research was supported by grants from the National Natural Science Foundation of China (Nos. 31172438 and U1205123), the Natural Science Foundation of Fujian Province (No. 2012J06008 and 201311180002) and the projects-sponsored by SRF. TW received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland) funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions.

68-year-old Esther Balfour in family marathon

General note: Title and date provided by Bettye Lane.

Jane Kaatz at Lesbian Mothers demonstration at family court

General note: Title and date provided by Bettye Lane.

Family packing car for camping trip

Inscriptions: Verso: [stamped] Photograph by Freda Leinwand. [463 West Street, Studio 229G, New York, NY 10014].