Staphylococcus aureus DivIB is a peptidoglycan-binding protein that is required for a morphological checkpoint in cell division

Bacterial cell division is a fundamental process that requires the coordinated actions of a number of proteins which form a complex macromolecular machine known as the divisome. The membrane-spanning proteins DivIB and its orthologue FtsQ are crucial divisome components in Gram-positive and Gram-negative bacteria respectively. However, the role of almost all of the integral division proteins, including DivIB, still remains largely unknown. Here we show that the extracellular domain of DivIB is able to bind peptidoglycan and have mapped the binding to its β subdomain. Conditional mutational studies show that divIB is essential for Staphylococcus aureus growth, while phenotypic analyses following depletion of DivIB results in a block in the completion, but not initiation, of septum formation. Localisation studies suggest that DivIB only transiently localises to the division site and may mark previous sites of septation. We propose that DivIB is required for a molecular checkpoint during division to ensure the correct assembly of the divisome at midcell and to prevent hydrolytic growth of the cell in the absence of a completed septum

ROC curve regression analysis: the use of ordinal regression models for diagnostic test assessment.

Diagnostic tests commonly are characterized by their true positive (sensitivity) and true negative (specificity) classification rates, which rely on a single decision threshold to classify a test result as positive. A more complete description of test accuracy is given by the receiver operating characteristic (ROC) curve, a graph of the false positive and true positive rates obtained as the decision threshold is varied. A generalized regression methodology, which uses a class of ordinal regression models to estimate smoothed ROC curves has been described. Data from a multi-institutional study comparing the accuracy of magnetic resonance (MR) imaging with computed tomography (CT) in detecting liver metastases, which are ideally suited for ROC regression analysis, are described. The general regression model is introduced and an estimate for the area under the ROC curve and its standard error using parameters of the ordinal regression model is given. An analysis of the liver data that highlights the utility of the methodology in parsimoniously adjusting comparisons for covariates is presented

Use of ERTS-1 data in identification, classification, and mapping of salt-affected soils in California

There are no author-identified significant results in this report

Gait training with real-time augmented toe-ground clearance information decreases tripping risk in older adults and a person with chronic stroke

Falls risk increases with ageing but is substantially higher in people with stroke. Tripping-related balance loss is the primary cause of falls, and Minimum Toe Clearance (MTC) during walking is closely linked to tripping risk. The aim of this study was to determine whether real-time augmented information of toe-ground clearance at MTC can increase toe clearance, and reduce tripping risk. Nine healthy older adults (76 ± 9 years) and one 71 year old female stroke patient participated. Vertical toe displacement was displayed in real-time such that participants could adjust their toe clearance during treadmill walking. Participants undertook a session of unconstrained walking (no-feedback baseline) and, in a subsequent Feedback condition, were asked to modify their swing phase trajectory to match a "target" increased MTC. Tripping probability (PT) pre- and post-training was calculated by modeling MTC distributions. Older adults showed significantly higher mean MTC for the post-training retention session (27.7 ± 3.79 mm) compared to the normal walking trial (14.1 ± 8.3 mm). The PT on a 1 cm obstacle for the older adults reduced from 1 in 578 strides to 1 in 105,988 strides. With gait training the stroke patient increased MTC and reduced variability (baseline 16 ± 12 mm, post-training 24 ± 8 mm) which reduced obstacle contact probability from 1 in 3 strides in baseline to 1 in 161 strides post-training. The findings confirm that concurrent visual feedback of a lower limb kinematic gait parameter is effective in changing foot trajectory control and reducing tripping probability in older adults. There is potential for further investigation of augmented feedback training across a range of gait-impaired populations, such as stroke

Individual differences in anchoring: Numerical ability, education and experience

Anchoring is a well-known effect leading to bias in estimation in various decision-making contexts. A question, however, is whether individuals with greater numerical and academic ability would be less prone to this effect than others because of greater ability to discern the value being estimated. In light of growing interest in the role of individual differences in bias susceptibility, anchoring was examined in a simulated poker-like card game, using people with varying levels of academic achievement and psychometric reasoning scores. The results showed that anchoring susceptibility was unrelated to education levels, but negatively associated with numerical reasoning and cognitive reflection scores. This result, however, was mediated by task expertise because participants with higher cognitive abilities were those more likely to display improvements in anchoring performance over the course of the experiment.Matthew B. Welsh, Paul Delfabbro, Nicholas R. Burns and Steve H. Beg

The Broad-Spectrum Antimicrobial Potential of [Mn(CO)(4)(S2CNMe(CH2CO2H))], a Water-Soluble CO-Releasing Molecule (CORM-401): Intracellular Accumulation, Transcriptomic and Statistical Analyses, and Membrane Polarization

Aims: Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM. Results: [Mn(CO)(4)S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. CORM-401 releases CO that binds oxidases in vivo, but is an ineffective respiratory inhibitor. Extensive CORM accumulation (assayed as intracellular manganese) accompanies antimicrobial activity. CORM-401 stimulates respiration, polarizes the cytoplasmic membrane in an uncoupler-like manner, and elicits loss of intracellular potassium and zinc. Transcriptomics and mathematical modeling of transcription factor activities reveal a multifaceted response characterized by elevated expression of genes encoding potassium uptake, efflux pumps, and envelope stress responses. Regulators implicated in stress responses (CpxR), respiration (Arc, Fnr), methionine biosynthesis (MetJ), and iron homeostasis (Fur) are significantly disturbed. Although CORM-401 reduces bacterial growth in combination with cefotaxime and trimethoprim, fractional inhibition studies reveal no interaction. Innovation: We present the most detailed microbiological analysis yet of a CORM that is not a ruthenium carbonyl. We demonstrate CO-independent striking effects on the bacterial membrane and global transcriptomic responses. Conclusions: CORM-401, contrary to our expectations of a CO delivery vehicle, does not inhibit respiration. It accumulates in the cytoplasm, acts like an uncoupler in disrupting cytoplasmic ion balance, and triggers multiple effects, including osmotic stress and futile respiration

Reproducibility of measurements of potential doubling time of tumour cells in the multicentre National Cancer Institute protocol T92-0045

We compared the flow cytometric measurement and analysis of the potential doubling time (Tpot) between three centres involved in the National Cancer Institute (NCI) protocol T92-0045. The primary purpose was to understand and minimize the variation within the measurement. A total of 102 specimens were selected at random from patients entered into the trial. Samples were prepared, stained, run and analysed in each centre and a single set of data analysed by all three centres. Analysis of the disc data set revealed that the measurement of labelling index (LI) was robust and reproducible. The estimation of duration of S-phase (Ts) was subject to errors of profile interpretation, particularly DNA ploidy status, and analysis. The LI dominated the variation in Tpot such that the level of final agreement, after removal of outliers and ploidy agreement, reached correlation coefficients of 0.9. The sample data showed poor agreement within each of the components of the measurement. There was some improvement when ploidy was in agreement, but correlation coefficients failed to exceed values of 0.5 for Tpot. The data suggest that observer-associated analysis of Ts and tissue processing and tumour heterogeneity were the major causes of variability in the Tpot measurement. The first two aspects can be standardized and minimized, but heterogeneity will remain a problem with biopsy techniques. © 1999 Cancer Research Campaig