Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated with HIV-1-Associated Dementia

BACKGROUND: Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. METHODS: We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. RESULTS: The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2 × 10(-5)). Prep1 has recently been identified as a transcription factor preferentially binding the -2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. CONCLUSION: These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders

Surface reactivity of Pd nanoparticles supported on polycrystalline substrates as compared to thin film model catalysts: Infrared study of CO adsorption

To identify the nature and the local structure of the surface of supported catalyst nanoparticles, we have performed a detailed comparative study of CO adsorption on two categories of oxide-supported Palladium catalysts: (1) polycrystalline MgO and -Al2O3 supported Pd metal catalysts prepared by impregnation techniques and characterized by different degrees of regularity and perfection and (2) single-crystal based Pd model catalysts prepared under ultrahigh vacuum (UHV) conditions. The assignment of the CO vibrational frequencies to different types of sites on these systems has allowed a detailed structural characterization. For the Pd model catalyst, at low CO coverage, the infrared (IR) reflection absorption spectra closely resemble the expected behavior for terminations by a majority of (111) facets and a minority of (100) facets. The spectral features are indicative of defect sites such as particle steps and edges. Occupation of the defect sites can be affected by surface contaminations such as atomic carbon. Thus the CO spectra at high coverage can be used as both a structural and chemical probe under reaction conditions, provided that complementary information on the particle morphology is available. For the MgO and -Al2O3 supported Pd systems, two distinct narrow bands ( 2070 and 1970 cm-1) have been assigned to linearly bonded and bridge-bonded CO species, on Pd (100)/(111) edges or facets, in agreement with the previous results obtained on model catalysts. The broad character of the 2070 cm-1 feature indicates the simultaneous presence of (100) and (111) faces, with edge and corner sites present at their intersection. The high intensity and the small half-width (fwhm) of the band at 1970 cm-1 on a Pd/MgO sample treated at high temperature, assigned to bridge-bonded CO species, suggests that the metal particles expose faces with a high level of regularity. Further spectroscopic features (ny ~ 1920-1800 cm-1), are ascribed to the presence of different types of 3-fold hollow sites on (111) faces