Chapter 6 Parental marital dissolution and the intergenerational transmission of homeownership

Children of homeowners are more likely to enter homeownership than are children whose parents rent. We investigate whether this association is dependent on parental divorce, focusing on parental assistance as a conduit of intergenerational transmission. Event history analyses of data for England and Wales from the British Household Panel Survey (BHPS) show that the intergenerational transmission of homeownership is stronger for children of divorced parents compared with children of married parents. Such an eff ect may arise from two channels: (1) children of divorced parents are more in need of parental assistance due to socio-economic disadvantages associated with parental divorce; and (2) compared with married parents, divorced homeowning parents (mothers) rely more on housing wealth, rather than fi nancial wealth, for assisting children. Findings support both explanations. Children of divorced parents are furthermore less likely to co-reside. We fi nd limited evidence that when they do, co-residence is less conductive to homeownership compared with children from married parents

Identification and in vivo characterization of a brain-penetrating nanobody

BACKGROUND: Preclinical models to determine blood to brain transport ability of therapeutics are often ambiguous. In this study a method is developed that relies on CNS target-engagement and is able to rank brain-penetrating capacities. This method led to the discovery of an anti-transferrin receptor nanobody that is able to deliver a biologically active peptide to the brain via receptor-mediated transcytosis. METHODS: Various nanobodies against the mouse transferrin receptor were fused to neurotensin and injected peripherally in mice. Neurotensin is a neuropeptide that causes hypothermia when present in the brain but is unable to reach the brain from the periphery. Continuous body temperature measurements were used as a readout for brain penetration of nanobody-neurotensin fusions after its peripheral administration. Full temperature curves were analyzed using two-way ANOVA with Dunnett multiple comparisons tests. RESULTS: One anti-transferrin receptor nanobody coupled to neurotensin elicited a drop in body temperature following intravenous injection. Epitope binning indicated that this nanobody bound a distinct transferrin receptor epitope compared to the non-crossing nanobodies. This brain-penetrating nanobody was used to characterize the in vivo hypothermia model. The hypothermic effect caused by neurotensin is dose-dependent and could be used to directly compare peripheral administration routes and various nanobodies in terms of brain exposure. CONCLUSION: This method led to the discovery of an anti-transferrin receptor nanobody that can reach the brain via receptor-mediated transcytosis after peripheral administration. This method could be used to assess novel proteins for brain-penetrating capabilities using a target-engaging readout

Mutant and chimeric recobinant plasminogen activatorsproduction in eukaryotic cellsand preliminary characterization

Mutant urokinase-type plasminogen activator (u-PA) genes and hybrid genes between tissue-type plasminogen activator (t-PA) and u-PA have been designed to direct the synthesis of new plasminogen activators and to investigate the structure-function relationship in these molecules. The following classes of constructs were made starting from cDNA encoding human t-PA or u-PA: 1) u-PA mutants in which the Arg156 and Lys158 were substituted with threonine, thus preventing cleavage by thrombin and plasmin; 2) hybrid molecules in which the NH2-terminal regions of t-PA (amino acid residues 1-67, 1-262, or 1-313) were fused with the COOH-terminal region of u-PA (amino acids 136-411, 139-411, or 195-411, respectively); and 3) a hybrid molecule in which the second kringle of t-PA (amino acids 173-262) was inserted between amino acids 130 and 139 of u-PA. In all cases but one, the recombinant proteins, produced by transfected eukaryotic cells, were efficiently secreted in the culture medium. The translation products have been tested for their ability to activate plasminogen after in situ binding to an insolubilized monoclonal antibody directed against urokinase. All recombinant enzymes were shown to be active, except those in which Lys158 of u-PA was substituted with threonine. Recombination of structural regions derived from t-PA, such as the finger, the kringle 2, or most of the A-chain sequences, with the protease part or the complete u-PA molecule did not impair the catalytic activity of the hybrid polypeptides. This observation supports the hypothesis that structural domains in t-PA and u-PA fold independently from one to another

Chapter 6 Parental marital dissolution and the intergenerational transmission of homeownership

Children of homeowners are more likely to enter homeownership than are children whose parents rent. We investigate whether this association is dependent on parental divorce, focusing on parental assistance as a conduit of intergenerational transmission. Event history analyses of data for England and Wales from the British Household Panel Survey (BHPS) show that the intergenerational transmission of homeownership is stronger for children of divorced parents compared with children of married parents. Such an eff ect may arise from two channels: (1) children of divorced parents are more in need of parental assistance due to socio-economic disadvantages associated with parental divorce; and (2) compared with married parents, divorced homeowning parents (mothers) rely more on housing wealth, rather than fi nancial wealth, for assisting children. Findings support both explanations. Children of divorced parents are furthermore less likely to co-reside. We fi nd limited evidence that when they do, co-residence is less conductive to homeownership compared with children from married parents

Quality of chronic disease care for older people in care homes and the community in a primary care pay for performance system: retrospective study

Objective To describe the quality of care for chronic diseases among older people in care homes (nursing and residential) compared with the community in a pay for performance system

Phase Space Reduction for Star-Products: An Explicit Construction for CP^n

We derive a closed formula for a star-product on complex projective space and on the domain $SU(n+1)/S(U(1)\times U(n))$ using a completely elementary construction: Starting from the standard star-product of Wick type on $C^{n+1} \setminus \{ 0 \}$ and performing a quantum analogue of Marsden-Weinstein reduction, we can give an easy algebraic description of this star-product. Moreover, going over to a modified star-product on $C^{n+1} \setminus \{ 0 \}$, obtained by an equivalence transformation, this description can be even further simplified, allowing the explicit computation of a closed formula for the star-product on \CP^n which can easily transferred to the domain $SU(n+1)/S(U(1)\times U(n))$.Comment: LaTeX, 17 page

High resolution crystal structures of the <i>Cerebratulus lacteus</i> mini-Hb in the unligated and carbomonoxy states

The nerve tissue mini-hemoglobin from Cerebratulus lacteus (CerHb) displays an essential globin fold hosting a protein matrix tunnel held to allow traffic of small ligands to and from the heme. CerHb heme pocket hosts the distal TyrB10/GlnE7 pair, normally linked to low rates of O2 dissociation and ultra-high O2 affinity. However, CerHb affinity for O2 is similar to that of mammalian myoglobins, due to a dynamic equilibrium between high and low affinity states driven by the ability of ThrE11 to orient the TyrB10 OH group relative to the heme ligand. We present here the high resolution crystal structures of CerHb in the unligated and carbomonoxy states. Although CO binds to the heme with an orientation different from the O2 ligand, the overall binding schemes for CO and O2 are essentially the same, both ligands being stabilized through a network of hydrogen bonds based on TyrB10, GlnE7, and ThrE11. No dramatic protein structural changes are needed to support binding of the ligands, which can freely reach the heme distal site through the apolar tunnel. A lack of main conformational changes between the heme-unligated and -ligated states grants stability to the folded mini-Hb and is a prerequisite for fast ligand diffusion to/from the heme