Metabolic response to low-level toxicant exposure in a novel renal tubule epithelial cell system

Toxicity testing is vital to protect human health from exposure to toxic chemicals in the environment. Furthermore, combining novel cellular models with molecular profiling technologies, such as metabolomics can add new insight into the molecular basis of toxicity and provide a rich source of biomarkers that are urgently required in a 21st Century approach to toxicology. We have used an NMR-based metabolic profiling approach to characterise for the first time the metabolome of the RPTEC/TERT1 cell line, an immortalised non-tumour human renal epithelial cell line that recapitulates phenotypic characteristics that are absent in other in vitro renal cell models. RPTEC/TERT1 cells were cultured with either the dosing vehicle (DMSO) or with exposure to one of six compounds (nifedipine, potassium bromate, monuron, D-mannitol, ochratoxin A and sodium diclofenac), several of which are known to cause renal effects. Aqueous intracellular and culture media metabolites were profiled by (1)H NMR spectroscopy at 6, 24 and 72 hours of exposure to a low effect dose (IC(10)). We defined the metabolome of the RPTEC/TERT1 cell line and used a principal component analysis approach to derive a panel of key metabolites, which were altered by chemical exposure. By considering only major changes (±1.5 fold change from control) across this metabolite panel we were able to show specific alterations to cellular processes associated with chemical treatment. Our findings suggest that metabolic profiling of RPTEC/TERT1 cells can report on the effect of chemical exposure on multiple cellular pathways at low-level exposure, producing different response profiles for the different compounds tested with a greater number of major metabolic effects observed in the toxin treated cells. Importantly, compounds with established links to chronic renal toxicity produced more diverse and severe perturbations to the cellular metabolome than non-toxic compounds in this model. As these changes can be rationalised with the different pharmacological and toxicity profiles of the chemicals it is suggested that metabolic profiling in the RPTEC/TERT1 model would be useful in investigating the mechanism of action of toxins at a low dose.     

Trunk muscle activity during stability ball and free weight exercises

The purpose of this investigation was to compare trunk muscle activity during stability ball and free weight exercises. Nine resistance-trained men participated in one testing session in which squats (SQ) and deadlifts (DL) were completed with loads of approximately 50, 70, 90, and 100% of one-repetition maximum (1RM). Isometric contractions during 3 stability ball exercises (quadruped (QP), pelvic thrust (PT), ball back extension (BE)) were also completed. During all exercises, average integrated electromyography (IEMG) from the rectus abdominus (RA), external oblique (EO), longissimus (L1) and multifidus (L5) was collected and analyzed. Results demonstrate that when expressed relative to 100% DL 1RM, muscle activity was 19.5 +/- 14.8% for L1 and 30.2 +/- 19.3% for L5 during QP, 31.4 +/- 13.4% for L1 and 37.6 +/- 12.4% for L5 during PT, and 44.2 +/- 22.8% for L1 and 45.5 +/- 21.6% for L5 during BE. IEMG of L1 during SQ and DL at 90 and 100% 1RM, and relative muscle activity of L5 during SQ and DL at 100% 1RM was significantly greater (P < or = 0.05) than in the stability ball exercises. Furthermore, relative muscle activity of L1 during DL at 50 and 70% 1RM was significantly greater than in QP and PT. No significant differences were observed in RA and EO during any of the exercises. In conclusion, activity of the trunk muscles during SQs and DLs is greater or equal to that which is produced during the stability ball exercises. It appears that stability ball exercises may not provide a sufficient stimulus for increasing muscular strength or hypertrophy; consequently, the role of stability ball exercises in strength and conditioning programs is questioned. SQs and DLs are recommended for increasing strength and hypertrophy of the back extensors.     

Electron microscope study of the effect of benzalkonium, chlorhexidine and polymyxin on Pseudomonas cepacia

Electron micrographs of Pseudomonas cepacia cell grown in nutrient broth show an external membrane which is distinctly wavy, when compared with similar preparations of Pseudomonas aeruginosa, and which is not affected by growing in the presence of broth containing benzalkonium (10 microgram/ml), chlorhexidine (10 microgram/ml) or polymyxin (25 units/ml). Both benzalkonium (10 microgram/ml) and chlorhexidine (10 microgram/ml) damage the cytoplasmic membrane of P. cepacia cell grown in the presence of the chemicals. Contrasts are shown between the effect of polymyxin (chlorhexidine and benzalkonium) on the outer membrane of P. cepacia and P. aeruginosa.     

Direct explanations for the development and use of a multi-layer perceptron network that classifies low-back-pain patients.

Using a new method published by the first author, this article shows how direct explanations can be provided to interpret the classification of any input case by a standard multilayer perceptron (MLP) network. The method is demonstrated for a real-world MLP that classifies low-back-pain patients into three diagnostic classes. The application of the method leads to the discovery of a number of mis-diagnosed training and test cases and to the development of a more optimal low-back-pain MLP network.     

Venom and Dufour's gland secretions in an Australian species of Camponotus

Constituents of the venom (1) and Dufour's gland (25) have been characterized in an Australian representative of the highly evolved ant subfamily Formicinae. The venom reservoir of this ant, Camponotus intrepidus, contains formic acid, identified as the benzyl ester. The Dufour's gland contains a major hydrocarbon and a minor fatty acid fraction. Hydrocarbons include the normal alkanes, C₁₀ to C₁₇ (82 per cent); two series of monomethylalkanes, C₁₂, C₁₃, C₁₄, C₁₆, and C₁₇, the 3-methyl derivatives comprise approximately 16 per cent, and the 5-methylalkanes 2 per cent of the total; there are trace proportions of the n-alkenes, C₁₂, C₁₃, and C₁₅. The minor fatty acids, myristic, pentadecanoic, palmitic, and stearic are present in the ratio 2 : 2 : 12 : 11.