Distinct Recognition of Non-Clade B Human Immunodeficiency Virus Type 1 Epitopes by Cytotoxic T Lymphocytes Generated from Donors Infected in Africa

We present detailed studies of human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte (CTL) responses to clade A or C HIV type 1 in three donors infected in East Africa. We define several novel non-clade B CTL epitopes, including some restricted by HLA alleles common in Africans. Although cross-clade CTL recognition of these epitopes does occur, recognition can also be highly clade specific.     

CoQ10: could it have a role in cancer management?

Coenzyme Q10 or ubiquinone has been shown to have both anti-cancer and immune system enhancing properties when tested in animals. Preliminary results reported here suggest that it might inhibit tumour-associated cytokines. Clinical studies conducted with combination therapies of CoQ10 and other antioxidants are ongoing, but the results are difficult evaluate owing to the lack of proper control groups and of initial randomisation. Also on the basis of some anti-cancer effects of antioxidants reported in literature, further animal studies and a proper clinical trial of coenzyme Q10 in cancer patients are needed.     

Genome-wide association mapping in Arabidopsis identifies previously known flowering time and pathogen resistance genes

There is currently tremendous interest in the possibility of using genome-wide association mapping to identify genes responsible for natural variation, particularly for human disease susceptibility. The model plant Arabidopsis thaliana is in many ways an ideal candidate for such studies, because it is a highly selfing hermaphrodite. As a result, the species largely exists as a collection of naturally occurring inbred lines, or accessions, which can be genotyped once and phenotyped repeatedly. Furthermore, linkage disequilibrium in such a species will be much more extensive than in a comparable outcrossing species. We tested the feasibility of genome-wide association mapping in A. thaliana by searching for associations with flowering time and pathogen resistance in a sample of 95 accessions for which genome-wide polymorphism data were available. In spite of an extremely high rate of false positives due to population structure, we were able to identify known major genes for all phenotypes tested, thus demonstrating the potential of genome-wide association mapping in A. thaliana and other species with similar patterns of variation. The rate of false positives differed strongly between traits, with more clinal traits showing the highest rate. However, the false positive rates were always substantial regardless of the trait, highlighting the necessity of an appropriate genomic control in association studies.     

Myosin VI: cellular functions and motor properties

Myosin VI has been localized in membrane ruffles at the leading edge of cells, at the trans-Golgi network compartment of the Golgi complex and in clathrin-coated pits or vesicles, indicating that it functions in a wide variety of intracellular processes. Myosin VI moves along actin filaments towards their minus end, which is the opposite direction to all of the other myosins so far studied (to our knowledge), and is therefore thought to have unique properties and functions. To investigate the cellular roles of myosin VI, we identified various myosin VI binding partners and are currently characterizing their interactions within the cell. As an alternative approach, we have expressed and purified full-length myosin VI and studied its in vitro properties. Previous studies assumed that myosin VI was a dimer, but our biochemical, biophysical and electron microscopic studies reveal that myosin VI can exist as a stable monomer. We observed, using an optical tweezers force transducer, that monomeric myosin VI is a non-processive motor which, despite a relatively short lever arm, generates a large working stroke of 18 nm. Whether monomer and/or dimer forms of myosin VI exist in cells and their possible functions will be discussed.     

Localisation of the Vacuolar Proton Pump (V-H+-ATPase) and Carbonic Anhydrase II in the Human Eccrine Sweat Gland

The localisation of the vacuolar proton pump (V-H+ -ATPase) and the enzyme carbonic anhydrase II (CAII) was investigated in the human eccrine sweat gland employing standard immunohistochemical techniques after antigen retrieval using microwave heat treatment and high pressure. The high-pressure antigen retrieval unmasked the presence of V-H+ -ATPase in the clear cells of the secretory coil, with a distribution similar to that previously observed for CAII. However, the dark cells were unreactive to both antibodies. In addition, heat and high-pressure antigen retrieval demonstrated the presence of CAII in the apical zone of luminal cells of the reabsorptive duct, a location not previously reported. The localisation of V-H+ -ATPase and CAII in the secretory coil clear cells suggests that the formation of HCO3- and H+ by carbonic anhydrase II and the transport of H+ by V-H+ -ATPase may play an role in sweat fluid secretion. Their presence at the apex of the duct cells indicates involvement in ductal ion reabsorption.     

Ibuprofen reduces zebrafish PGE2 levels but steroid hormone levels and reproductive parameters are not affected

Prostaglandins are important regulators of reproductive function in fish. Analgesics like aspirin and ibuprofen are prostaglandin inhibitors and have been detected in freshwater systems at ng/L–μg/L levels. We investigated whether ibuprofen would affect prostaglandin and sex steroid hormone levels in adult zebrafish (Danio rerio) and if expression levels of genes involved in steroidogenesis and prostaglandin synthesis were affected. Zebrafish were exposed to moderate concentrations of ibuprofen (21, 201 or 506 μg/L) for 7 days in a semi-static test system. Ibuprofen concentrations were close to nominal levels and decreased by a maximum of 12–13% over 24 h. Prostaglandin E₂ (PGE₂) levels in whole body homogenates of males and ovaries of females decreased in a monotonic dose–response relationship whereas male 11-ketotestosterone levels and ovarian 17β-estradiol levels remained unchanged. Ibuprofen did not have an influence on vitellogenin levels, female gonadosomatic index or cumulative egg production and no dose–response relationship in ovarian and testicular expression levels of the investigated genes was observed. This study shows that ibuprofen reduces PGE₂ levels in male and female zebrafish but has no consistent effects on other investigated reproductive parameters.