Money is not enough: exploring the impact of social and cultural resources on youth health

Findings on socioeconomic health differentials in youth remain fragmented with the role of cumulative and interaction effects of different forms of health resources not well understood.

Characterization of Molecular Determinants of the Conformational Stability of Macrophage Migration Inhibitory Factor: Leucine 46 Hydrophobic Pocket

Macrophage Migration Inhibitory Factor (MIF) is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the β-strand β3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF’s trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G), alanine (L46A) and phenylalanine (L46F), and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state.

Bleeding on probing and pocket probing depth in relation to probing pressure and mucosal health around oral implants

OBJECTIVES: To assess the bleeding on probing (BOP) tendency and periodontal probe penetration when applying various probing forces at implant sites in patients with a high standard of oral hygiene with well-maintained peri-implant tissues. MATERIAL AND METHODS: Seventeen healthy patients with excellent oral hygiene in a maintenance program after having been treated for periodontitis or gingivitis were recruited. Missing teeth had been replaced using oral implants. The BOP and probing depth (PPD) were assessed at the mid-buccal, mid-oral, mesial and distal aspects of the buccal surfaces of each implant. Moreover, contralateral teeth were designated and assessed for BOP and PPD in the same locations and at the same observation visits. At each visit, implants and contralateral teeth were randomly assigned to one of the standardized probing forces (0.15 or 0.25 N). The second probing force was applied at the repetition of the examination 7 days later. RESULTS: Increasing the probing pressure by 0.1 N from 0.15 N resulted in an increase of BOP percentage by 13.7% and 6.6% for implants and contralateral teeth, respectively. There appeared to be a significant difference of the mean BOP percentage at implant and tooth sites when a probing pressure of 0.25 N was applied. A significantly deeper mean PPD at implant sites compared with tooth sites was found irrespective of the probing pressure applied. CONCLUSIONS: The results of the present study demonstrated that 0.15 N might represent the threshold pressure to be applied to avoid false positive BOP readings around oral implants. Hence, probing around implants demonstrated a higher sensitivity compared with probing around teeth.

Relative positioning of diazepam in the benzodiazepine-binding-pocket of GABA receptors

GABA(A) receptors are the major inhibitory neurotransmitter receptors in the brain. Some of them are targets of benzodiazepines that are widely used in clinical practice for their sedative/hypnotic, anxiolytic, muscle relaxant and anticonvulsant effects. In order to rationally separate these different drug actions, we need to understand the interaction of such compounds with the benzodiazepine-binding pocket. With this aim, we mutated residues located in the benzodiazepine-binding site individually to cysteine. These mutated receptors were combined with benzodiazepine site ligands carrying a cysteine reactive group in a defined position. Proximal apposition of reaction partners will lead to a covalent reaction. We describe here such proximity-accelerated chemical coupling reactions of alpha(1)S205C and alpha(1)T206C with a diazepam derivative modified at the C-3 position with a reactive isothiocyanate group (-NCS). We also provide new data that identify alpha(1)H101C and alpha(1)N102C as exclusive sites of the reaction of a diazepam derivative where the -Cl atom is replaced by a -NCS group. Based on these observations we propose a relative positioning of diazepam within the benzodiazepine-binding site of alpha(1)beta(2)gamma(2) receptors.