Biological Insights from a Simulation Model of the Critical FtsZ Accumulation Required for Prokaryotic Cell Division.

A simulation model of prokaryotic Z-ring assembly, based on the observed behavior of FtsZ in vitro as well as on in vivo parameters, is used to integrate critical processes in cell division. According to the model, the cell's ability to divide depends on a "contraction parameter" (χ) that links the force of contraction to the dynamics of FtsZ. This parameter accurately predicts the outcome of division. Evaluating the GTP binding strength, the FtsZ polymerization rate, and the intrinsic GTP hydrolysis/dissociation activity, we find that inhibition of GTP-FtsZ binding is an inefficient antibacterial target. Furthermore, simulations indicate that the temperature sensitivity of the ftsZ84 mutation arises from the conversion of FtsZ to a dual-specificity NTPase. Finally, the sensitivity to temperature of the rate of ATP hydrolysis, over the critical temperature range, leads us to conclude that the ftsZ84 mutation affects the turnover rate of the Z-ring much less strongly than previously reported.

A model of membrane contraction predicting initiation and completion of bacterial cell division.

Bacterial cell division involves a complex and dynamic sequence of events whereby polymers of the protein FtsZ assemble at the division plane and rearrange to achieve the goal of contracting the cell membrane at the site of cell division, thus dividing the parent cell into two daughter cells. We present a mathematical model (which we refer to as CAM-FF: Critical Accumulation of Membrane-bound FtsZ Fibres) of the assembly of the contractile ring in terms of the accumulation of short linear polymers of FtsZ that associate and dissociate from the cell membrane. In prokaryotes, the biochemical function of FtsZ is thought to underpin the assembly and at least the initial kinetic force of ring contraction. Our model extends earlier work of Surovtsev et al. [PLoS Comput. Biol., 2008, 4, e1000102] by adding (i) the kinetics of FtsZ accumulation on cell membrane anchor proteins and (ii) the physical forces required to deform the cell against its surface tension. Moreover, we provide a more rigorous treatment of intracellular diffusion and we revise some of the model parameter values in light of the experimental evidence now available. We derive a critical contraction parameter which links the chemical population dynamics of membrane-bound FtsZ molecules to the force of contraction. Using this parameter as a tool to predict the ability of the cell to initiate division, we are able to predict the division outcome in cells depleted of key FtsZ-binding proteins.

Allopurinol-induced hepatomegaly.

Allopurinol has long been recognised as a cause of hepatotoxicity; however, severe side effects remain rare. We report a case of allopurinol-induced hepatomegaly causing abdominal symptoms in an elderly woman after long-term allopurinol use.

Rapidly growing mass on the tricuspid valve in an elderly woman: a diagnostic dilemma.

BACKGROUND: Papillary fibroelastoma is a rare, benign cardiac valve tumour, which can mimic conditions such as atrial myxoma and infective endocarditis. CASE REPORT: An elderly lady presented with shortness of breath and chest pain and a mass on echocardiogram, which was confirmed on surgical excision to be a papillary fibroelastoma. DISCUSSION: There were aspects of this lady's case that caused confusion over the diagnosis and showed how rare conditions can cause diagnostic problems.