Molecular diagnosis of cystic fibrosis in South African populations

Cystic fibrosis (CF) is present in all South African population groups. In a significant proportion of patients a diagnosis of CF can be confirmed by DNAanalysis and the detection of two CF transmembrane conductance regulator (CFTR) mutations, using the panels of mutations developed in this study. The index of suspicion will also be raised in patients with a single CFTR mutation. DNAtesting is important, especially in region s without access to reliable sweat tests, and should be considered an aid to diagnosis. In addition to receiving appropriate treatment, patients and their families can receive more accurate genetic counselling, CF carrier testing and prenatal diagnosis

Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe

Determination of the lateral size and thickness of solution-processed graphene flakes

We present a method to determine the lateral size distribution of solution–processed graphene via direct image analysis techniques. Initially transmission electron microscopy (TEM) and optical microscopy (OM) were correlated and used to provide a reliable benchmark. A rapid, automated OM method was then developed to obtain the distribution from thousands of flakes, avoiding statistical uncertainties and providing high accuracy. Dynamic light scattering (DLS) was further employed to develop an in-situ method to derive the number particle size distribution (PSD) for a dispersion, with a deviation lower than 22% in the sub-micron regime. Methods for determining flake thickness are also discussed

Atomistic modelling of large-scale metal film growth fronts

We present simulations of metallization morphologies under ionized sputter deposition conditions, obtained by a new theoretical approach. By means of molecular dynamics simulations using a carefully designed interaction potential, we analyze the surface adsorption, reflection, and etching reactions taking place during Al physical vapor deposition, and calculate their relative probability. These probabilities are then employed in a feature-scale cellular-automaton simulator, which produces calculated film morphologies in excellent agreement with scanning-electron-microscopy data on ionized sputter deposition.Comment: RevTeX 4 pages, 2 figure

Citrullination facilitates cross-reactivity of rheumatoid factor with non-IgG1 Fc epitopes in rheumatoid arthritis

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the two most prevalent autoantibodies in rheumatoid arthritis (RA), and are thought to have distinct autoantigen targets. Whilst RF targets the Fc region of antibodies, ACPAs target a far broader spectrum of citrullinated peptides. Here we demonstrate significant sequence and structural homology between proposed RF target epitopes in IgG1 Fc and the ACPA target fibrinogen. Two of the three homologous sequences were susceptible to citrullination, and this modification, which occurs extensively in RA, permitted significant cross-reactivity of RF+ patient sera with fibrinogen in both western blots and ELISAs. Crucially, this reactivity was specific to RF as it was absent in RF− patient and healthy control sera, and could be inhibited by pre-incubation with IgG1 Fc. These studies establish fibrinogen as a common target for both RF and ACPAs, and suggest a new mechanism in RF-mediated autoimmune diseases wherein RF may act as a precursor from which the ACPA response evolves