Cholesterol efflux pathways, inflammation, and atherosclerosis

Plasma levels of high-density lipoprotein (HDL) inversely correlate with the incidence of cardiovascular diseases (CVD). The causal relationship between plasma HDL-cholesterol levels and CVD has been called into question by Mendelian randomization studies and the majority of clinical trials not showing any benefit of plasma HDL-cholesterol raising drugs on CVD. Nonetheless, recent Mendelian randomization studies including an increased number of CVD cases compared to earlier studies have confirmed that HDL-cholesterol levels and CVD are causally linked. Moreover, several studies in large population cohorts have shown that the cholesterol efflux capacity of HDL inversely correlates with CVD. Cholesterol efflux pathways exert anti-inflammatory and antiatherogenic effects by suppressing proliferation of hematopoietic stem and progenitor cells, and inflammation and inflammasome activation in macrophages. Cholesterol efflux pathways also suppress the accumulation of cholesteryl esters in macrophages, i.e. macrophage foam cell formation. Recent single-cell RNASeq studies on atherosclerotic plaques have suggested that macrophage foam cells have lower expression of inflammatory genes than non-foam cells, probably reflecting liver X receptor activation, upregulation of ATP Binding Cassette A1 and G1 cholesterol transporters and suppression of inflammation. However, when these pathways are defective lesional foam cells may become pro-inflammatory

Plasma oxidation as key mechanism for stoichiometry in Pulsed Laser Deposition grown oxide films

We present a unique overview on the influence of growth parameters on the characteristics of the PLD plasma plume using Optical Self-Emission (OSE) imaging and spectroscopy, supported with Laser Induced Fluorescence (LIF) measurements. It is shown that in a relatively small background gas pressure regime, from 10-2 mbar to 10-1 mbar oxygen pressure, a transition from nonstoichiometric to stoichiometric growth of SrTiO3 films occurs as measured with X-ray Diffraction (XRD). In this pressure regime, OSE spectroscopy and LIF measurements also show a transition from incomplete to full oxidation of species in the plasma plume. This suggests that the oxidation of species in the plasma is a crucial mechanism for the stoichiometric reconstruction of the synthesized oxide thin films

Research Report 2004–2005

The National Health and Medical Research Council Clinical Trials Centre has the purpose of improving outcomes in health through clinical trials research. It was established by the National Health and Medical Research Council in 1988 as a research centre at the University of Sydney. The CTC provides the knowledge and infrastructure to ensure the quality, timely completion and reporting of clinical trials. It has vast expertise in the design, conduct and analysis of randomised controlled trials, particularly in cancer and cardiovascular disease. Over 100 staff have specialised skills, taking in clinical trials design, biostatistics, database design, randomisation and drug distribution, outcome assessment, quality assurance, and regulatory and ethical issues. In the past 16 years, the CTC has participated in more than 50 investigatorinitiated, collaborative-group clinical trials and coordinated some of the largest randomised trials initiated by Australian investigators (LIPID and FIELD studies, each with over 9000 patients). Over 40 000 patients have been randomised to these trials. All clinical trials undertaken through the CTC are conducted strictly according to guidelines for clinical trials research and conduct, and are audited by sponsors, the CTC itself and regulatory authorities. The CTC has a history of working collaboratively with cooperative groups, clinical trial networks and other organisations, and has played a central role in establishing some of these groups. These activities have been recognised in increased grant funding to enable further collaboration and to increase the number of investigator-initiated trials in Australia. In its research, the CTC has prospered: it has developed strategies for patient recruitment, trial and data management, study coordination, information systems and randomisation in an environment of academic excellence. In addition to trials management, the CTC is a leader in biostatistical methodology and analysis and in systematic review of health evidence. The integrated expertise of the CTC staff is turned to good use in frequent educational activities in Australia and elsewhere. This report covers the CTC’s achievements for the biennium, 2004–2005

Partial duplication of the PRLR and SPEF2 genes at the late feathering locus in chicken

Background One of the loci responsible for feather development in chickens is K. The K allele is partially dominant to the k+ allele and causes a retard in the emergence of flight feathers at hatch. The K locus is sex linked and located on the Z chromosome. Therefore, the locus can be utilized to produce phenotypes that identify the sexes of chicks at hatch. Previous studies on the organization of the K allele concluded the integration of endogenous retrovirus 21 (ev21) into one of two large homologous segments located on the Z chromosome of late feathering chickens. In this study, a detailed molecular analysis of the K locus and a DNA test to distinguish between homozygous and heterozygous late feathering males are presented. Results The K locus was investigated with quantitative PCR by examining copy number variations in a total of fourteen markers surrounding the ev21 integration site. The results showed a duplication at the K allele and sequence analysis of the breakpoint junction indicated a tandem duplication of 176,324 basepairs. The tandem duplication of this region results in the partial duplication of two genes; the prolactin receptor and the gene encoding sperm flagellar protein 2. Sequence analysis revealed that the duplication is similar in Broiler and White Leghorn. In addition, twelve late feathering animals, including Broiler, White Leghorn, and Brown Layer lines, contained a 78 bp breakpoint junction fragment, indicating that the duplication is similar in all breeds. The breakpoint junction was used to develop a TaqMan-based quantitative PCR test to allow distinction between homozygous and heterozygous late feathering males. In total, 85.3% of the animals tested were correctly assigned, 14.7% were unassigned and no animals were incorrectly assigned. Conclusion The detailed molecular analysis presented in this study revealed the presence of a tandem duplication in the K allele. The duplication resulted in the partial duplication of two genes; the prolactin receptor and the gene encoding sperm flagellar protein 2. Furthermore, a DNA test was developed to distinguish between homozygous and heterozygous late feathering males

A comparison of electrochemical degradation of phenol on boron doped diamond and lead dioxide anodes

This work compares two electrode materials used to mineralize phenol contained in waste waters. Two disks covered with either boron doped diamond (BDD) or PbO2 were used as anodes in a one compartment flow cell under the same hydrodynamic conditions. Efficiencies of galvanostatic electrolyses are compared on the basis of measurements of Total Organic Carbon (TOC) and Chemical Oxygen Demand (COD). Galvanostatic electrolyses were monitored by analysis of phenol and of its oxidation derivatives to evaluate the operating time needed for complete elimination of toxic aromatics. The experimental current efficiency is close to the theoretical value for the BDD electrode. Other parameters being equal, phenol species disappeared at the same rate using the two electrode materials but the BDD anode showed better efficiency to eliminate TOC and COD. Moreover, during the electrolysis less intermediates are formed with BDD compared to PbO2 whatever the current density. A comparison of energy consumption is given based on the criterion of 99% removal of aromatic compounds