Quantitative high-throughput screening identifies inhibitors of anthrax-induced cell death

Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a β-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin fusion protein and diphtheria toxin. Further efforts demonstrated that these compounds impaired the PA heptamer pre-pore to pore conversion in cells expressing the CMG2 receptor, but not the related TEM8 receptor, indicating that these compounds likely interfere with toxin internalization.     

Waist Circumference as a Screening Tool for Cardiovascular Risk Factors: Evaluation of Receiver Operating Characteristics (ROC)

To evaluate the receiver operating characteristics (ROC) to determine the cutoffs of waist circumference as a potential population directed screening tool for hypercholesterolaemia (≥6.5 mmol/L), low high density lipoprotein cholesterol (<0.9 mmol/L), and hypertension (treated and/or systolic ≥160 and/or diastolic blood pressure ≥95 mmHg), in 2183 men and 2698 women aged 20 to 59 years selected at random from Dutch civil registries. Main outcome measures: Height, weight, body mass index (BMI), waist circumference, total plasma cholesterol and high density lipoprotein cholesterol concentrations, and blood pressure. Results: ROC curves showed that sensitivity equalled specificity at waist circumferences between 93–95 cm in men and 81–84 cm in women for identifying individual risk factors, and 92 cm in men and 81 cm in women for identifying those with at least one risk factor. Sensitivity and specificity were equal at levels between 61% to 69% for identifying individual risk factors, with positive predictions (56.8% in men and 37.8% in women) within 2% of those using previously defined ‘Action Level 1’ of waist circumference 94 cm in men and 80 cm in women (58.8% in men and 37.4% in women). Risk prediction by anthropometric methods was relatively low: ROC areas for identifying each risk factor by waist varied from 55% to 60%, and reached about 65% for identifying at least one risk factor. Height accounted for less than 03% of variance in waist circumference. Using BMI at 25 kg/m² gave similar prediction to waist, but its combination with waist did not improve predictive values. Conclusions: Measurement of waist circumference ‘Action Level 1’ at 94 cm (37 inches) in men and 80 cm (32 inches) in women could be adopted as a simpler valid alternative to BMI for health promotion, to alert those at risk of cardiovascular disease, and as a guide to risk avoidance by self-weight management     

The Brighton resuscitation ambulances: a continuing experiment in prehospital care by ambulance staff.

Two ambulances from the existing fleet in Brighton and one in Hove are equipped with portable defibrillator-oscilloscope units. Selected attendants have been trained not only to defibrillate patients but also to perform endotracheal intubation and administer intravenous atropine and lignocaine for carefully defined indications. In the two years up to December 1975 the ambulances responded to 2253 calls which were considered possible emergencies. Retrospective analysis showed that half of these had been for patients with myocardial infarction, coronary insufficiency, or angina. The ambulances took a median time of five minutes to reach a patient. Attempts at resuscitation were made in 207 patients with circulatory arrest, of whom 160 had ventricular fibrillation. Coordinated rhythm was restored at least transiently in 66 patients, and 27 of them survived to leave hospital. Sixteen of the survivors had been in ventricular fibrillation before the arrival of the ambulance. The delay before admission to hospital was reduced: over 50% of patients carried in the ambulances were admitted within two hours of the onset of major symptoms. No extra ambulance staff have been employed for the scheme. The increased load on hospital services has been limited by encouraging a rational admission policy and also by early discharge.     

Studies on populations of Folsomia candida (Insecta: Collembola)

Summary Experiments are described that were designed to investigate the effects of food availability and rate of exploitation on the growth and production of populations of Folsomia candida (Willem). In an initial experiment in which there was excess food it was found that increasing the rate of exploitation resulted in increases in both the numerical and biomass productivity of the populations. In a second experiment it was shown that, when there is severe competition for food, the rate of exploitation does not affect either the biomass or the numerical production. It is concluded that the effect of overcrowding, in the form of competition for space, does contribute to the growth in numbers of populations, but that the supply of food plays a more important role in regulating the population. Anomalous results, showing that exploitation has a lesser effect when there is severe competition for food, are discussed.     

Peatland vascular plant functional types affect dissolved organic matter chemistry

Aims

The readily available global rock phosphate (P) reserves may be depleted within the next 50–130 years warranting careful use of this finite resource. We develop a model that allows us to assess a range of P fertiliser and soil management strategies for Barley in order to find which one maximises plant P uptake under certain climate conditions.

Methods

Our model describes the development of the P and water profiles within the soil. Current cultivation techniques such as ploughing and reduced till gradient are simulated along with fertiliser options to feed the top soil or the soil right below the seed.

Results

Our model was able to fit data from two barley field trials, achieving a good fit at early growth stages but a poor fit at late growth stages, where the model underestimated plant P uptake. A well-mixed soil (inverted and 25 cm ploughing) is important for optimal plant P uptake and provides the best environment for the root system.

Conclusions

The model is sensitive to the initial state of P and its distribution within the soil profile; experimental parameters which are sparsely measured. The combination of modelling and experimental data provides useful agricultural predictions for site specific locations.

     

The starch-binding domain from glucoamylase disrupts the structure of starch

The full-length glucoamylase from Aspergillus niger, G1, consists of an N-terminal catalytic domain followed by a semi-rigid linker (which together constitute the G2 form) and a C-terminal starch-binding domain (SBD). G1 and G2 both liberate glucose from insoluble corn starch, although G2 has a rate 80 times slower than G1. Following pre-incubation of the starch with SBD, the activity of G1 is uniformly reduced with increasing concentrations of SBD because of competition for binding sites. However, increasing concentrations of SBD produce an initial increase in the catalytic rate of G2, followed by a decrease at higher SBD concentrations. The results show that SBD has two functions: it binds to the starch, but it also disrupts the surface, thereby enhancing the amylolytic rate.     

The predictive value of transcranial duplex sonography for the clinical diagnosis in undiagnosed parkinsonian syndromes: comparison with SPECT scans

Background  

Transcranial duplex sonography (TCD) of the substantia nigra has emerged as a promising, non-invasive tool to diagnose idiopathic Parkinson's disease (IPD). However, its diagnostic accuracy in patients with undefined parkinsonism remains to be determined.