Apolipoprotein A-I: the dual face of a protein

Conformational plasticity and flexibility are key structural features of ApoAI in lipid metabolism. Amyloidogenic single point mutations, associated with incurable familial amyloidosis with fibril deposition in peripheral organs, may have a dramatic impact on the structural and functional features of ApoAI. Here, the consistent body of data on ApoAI variants has been reviewed, with the aim of highlighting the hallmarks of the pathology. In accordance with our observations, as well as that of others, we propose a model that accounts for the alteration of the delicate balance between lipid-free/lipid-bound dynamic states which is based on monomer-to-dimer interconversion via domain swapping

Increased risk of atherosclerosis by elevated plasma levels of phospholipid transfer protein.

Plasma phospholipid transfer protein (PLTP) is thought to be involved in the remodeling of high density lipoproteins (HDL), which are atheroprotective. It is also involved in the metabolism of very low density lipoproteins (VLDL). Hence, PLTP is thought to be an important factor in lipoprotein metabolism and the development of atherosclerosis. We have overexpressed PLTP in mice heterozygous for the low density lipoprotein (LDL) receptor, a model for atherosclerosis. We show that increased PLTP activity results in a dose-dependent decrease in HDL, and a moderate stimulation of VLDL secretion (</=1.5-fold). The mice were given a high fat, high cholesterol diet, which resulted in hypercholesterolemia in all animals. HDL concentrations were dramatically reduced in PLTP-overexpressing animals when compared with LDL receptor controls, whereas VLDL + LDL cholesterol levels were identical. Susceptibility to atherosclerosis was increased in a PLTP dose-responsive manner. We conclude that PLTP increases susceptibility to atherosclerosis by lowering HDL concentrations, and therefore we suggest that an increase in PLTP is a novel, long term risk factor for atherosclerosis in humans

Neurobiology of rodent self-grooming and its value for translational neuroscience

Self-grooming is a complex innate behaviour with an evolutionarily conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders-including models of autism spectrum disorder and obsessive compulsive disorder-that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action.National Institutes of Health (U.S.) (Grant NS025529)National Institutes of Health (U.S.) (Grant HD028341)National Institutes of Health (U.S.) (Grant MH060379

Sex determines which section of the SLC6A4 gene is linked to obsessive–compulsive symptoms in normal Chinese college students

Previous case-control and family-based association studies have implicated the SLC6A4 gene in obsessive-compulsive disorder (OCD). Little research, however, has examined this gene's role in obsessive-compulsive symptoms (OCS) in community samples. The present study genotyped seven tag SNPs and two common functional tandem repeat polymorphisms (5-HTTLPR and STin2), which together cover the whole SLC6A4 gene, and investigated their associations with OCS in normal Chinese college students (N&nbsp;=&nbsp;572). The results revealed a significant gender main effect and gender-specific genetic effects of the SLC6A4 gene on OCS. Males scored significantly higher on total OCS and its three dimensions than did females (ps&nbsp;&lt;&nbsp;.01). The 5-HTTLPR in the promoter region showed a female-specific genetic effect, with the l/l and l/s genotypes linked to higher OCS scores than the s/s genotype (ps&nbsp;&lt;&nbsp;.05). In contrast, a conserved haplotype polymorphism (rs1042173| rs4325622| rs3794808| rs140701| rs4583306| rs2020942) covering from intron 3 to the 3' UTR of the SLC6A4 gene showed male-specific genetic effects, with the CGAAGG/CGAAGG genotype associated with lower OCS scores than the other genotypes (ps&nbsp;&lt;&nbsp;.05). These effects remained significant after controlling for OCS-related factors including participants' depressive and anxiety symptoms as well as stressful life events, and correction for multiple tests. These results are discussed in terms of their implications for our understanding of the sex-specific role of the different sections of the SLC6A4 gene in OCD