No abstract

The binding of peripheral proteins to membranes results in different biological effects. The large diversity of membrane lipids is thought to modulate the activity of these proteins. However, information on the selective binding of peripheral proteins to membrane lipids is still largely lacking. Lipid monolayers at the air/water interface are useful model membrane systems for studying the parameters responsible for peripheral protein membrane binding. We have thus measured the maximum insertion pressure (MIP) of two proteins from the photoreceptors, Retinitis pigmentosa 2 (RP2) and recoverin, to estimate their binding to lipid monolayers. Photoreceptor membranes have the unique characteristic that more than 60% of their fatty acids are polyunsaturated, making them the most unsaturated natural membranes known to date. These membranes are also thought to contain significant amounts of saturated phospholipids. MIPs of RP2 and recoverin have thus been measured in the presence of saturated and polyunsaturated phospholipids. MIPs higher than the estimated lateral pressure of biomembranes have been obtained only with a saturated phospholipid for RP2 and with a polyunsaturated phospholipid for recoverin. A new approach was then devised to analyze these data properly. In particular, a parameter called the synergy factor allowed us to highlight the specificity of RP2 for saturated phospholipids and recoverin for polyunsaturated phospholipids as well as to demonstrate clearly the preference of RP2 for saturated phospholipids that are known to be located in microdomains.

Brain injury as a result of hypoxia-ischemia remains a common cause of morbidity and mortality in neonates. No effective therapy is currently available. The hematopoietic cytokine erythropoietin (Epo) provides neuroprotection in many adult models of brain injury and is currently being investigated as a therapeutic agent for human stroke and spinal cord injury. We tested the hypothesis that recombinant Epo (rEpo) would improve neurobehavioral outcomes after neonatal hypoxic-ischemic brain injury. Postnatal day 7 rats underwent right common carotid artery occlusion followed by a 90-min exposure to 8% oxygen. Rats were subsequently treated with rEpo or placebo. Sensory neglect and apomorphine-induced rotation were measured at P27 and P28. Rats were killed at P30, blood was drawn, and the brains were perfusion-fixed for histology and immunohistochemistry. No differences in gross brain injury between rEpo and placebotreated rats were found. Neonatal rEpo treatment protected dopamine neurons as indicated by the preservation of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta and ventral tegmental area. rEpo treatment also improved functional outcomes by reducing sensory neglect and preventing the rotational asymmetry seen in control animals. No differences in hematocrit, white blood cell counts, neutrophil counts, or platelet counts were measured. We observed that rEpo treatment protected mesencephalic dopamine neurons and reduced the degree of behavioral asymmetries at 4 wk of life. On the basis of these findings, we conclude that further studies investigating the safety and efficacy of high-dose rEpo as a neuroprotective strategy are indicated in neonatal models of hypoxic-ischemic brain injury. Abbreviations ADHD, attention-deficit/hyperactivity disorder DA, dopamine Epo, erythropoietin EpoR, erythropoietin receptor HI, hypoxia-ischemia P, postnatal day rEpo, recombinant Epo SNpc, substantia nigra pars compacta TH, tyrosine hydroxylase VTA, ventral tegmental area Perinatal exposure to hypoxia-ischemia (HI) produces brain injury that is a significant source of morbidity and mortality for preterm and term neonates. Neonatal HI exposure initiates a multifactorial cascade that can persist for days, producing injury to multiple brain regions with corresponding motor, behavioral, and cognitive impairments. Although there are currently no effective therapies to ameliorate hypoxic-ischemic brain injury, several useful rodent models of neonatal brain injury are available. Using 7-d-old (P7) rat pups, which are comparable to near-term humans in brain maturity (1), the technique entails unilateral ligation of the common carotid artery and subsequent exposure of the animals to hypoxia (Rice-Vannucci model) (2). This procedure produces permanent unilateral brain injury in multiple regions, with specific impact on the basal ganglia including decreases in striatal dopamine (DA) receptors and increases in striatal DA transporters (3,4). Disruption of dopaminergic neurotransmission is suspect for several de...

Glasses made from compounds of low molecular weight are useful materials with many attractive features, including well-defined compositions. At present, there are no reliable ways to identify molecules that will form long-lived glasses, and efforts to design them have tended to rely on crude principles, such as avoiding small, symmetric, and relatively inflexible molecules that engage in strong intermolecular association. We have found that it is possible to make glasses from such molecules by turning to the dark side of crystal engineering and by making small but carefully selected structural modifications specifically designed to thwart established patterns of crystallization.