Steady state model for evaluation of external and internal mass transfer effects in an immobilized biofilm

A steady model for the evaluation of external liquid film diffusion and internal pore diffusion effects in an immobilized biofilm system under continuous mode of operation was developed. The model takes into account, substrate diffusion through external liquid film and biofilm. Average rate of substrate consumption in the biofilm was considered. The overall efficiency of the biofilm was mathematically represented by considering the combined effects of substrate penetration and substrate utilization in the biofilm. The model was illustrated using a case study of pyridine biodegradation in a rotating biological contactor immobilized with pyridine degrading microbial film. The model is able to effectively predict both internal and external mass transfer effects in an immobilized biofilm system.     

Olfactory coding: non-linear amplification separates smells

How does the nervous system encode complex sensory stimuli? A recent study reveals the fly olfactory system compensates for variability in sensory input as odor representations are restructured for enhanced discriminability and coding efficiency.     

A33 antigen displays persistent surface expression

The A33 antigen is a cell surface glycoprotein of the small intestine and colonic epithelium with homology to tight junction-associated proteins of the immunoglobulin superfamily, including CAR and JAM. Its restricted tissue localization and high level of expression have led to its use as a target in colon cancer immunotherapy. Although the antigen is also present in normal intestine, radiolabeled antibodies against A33 are selectively retained by tumors in the gut as well as in metastatic lesions for as long as 6 weeks. Accordingly, we have studied the trafficking and kinetic properties of the antigen to determine its promise in two-step, pretargeted therapies. The localization, mobility, and persistence of the antigen were investigated, and this work has demonstrated that the antigen is both highly immobile and extremely persistent—retaining its surface localization for a turnover halflife of greater than 2 days. In order to explain these unusual properties, we explored the possibility that A33 is a component of the tight junction. The simple property of surface persistence, described here, may contribute to the prolonged retention of the clinically administered antibodies, and their uncommon ability to penetrate solid tumors.     

Effects of muscle metabolites on responses of muscle sympathetic nerve activity to mechanoreceptor(s) stimulation in healthy humans

Based on animal studies, it has been speculated that muscle metabolites sensitize muscle mechanoreceptors and increase mechanoreceptor-mediated muscle sympathetic nerve activity (MSNA). However, this hypothesis has not been directly tested in humans. In this study, we tested the hypothesis that in healthy individuals passive stretch of forearm muscles would evoke significant increases in mean MSNA when muscle metabolite concentrations were increased. In 12 young healthy subjects, MSNA, ECG, and blood pressure were recorded. Subjects performed static fatiguing isometric handgrip at 30% maximum voluntary contraction followed by 4 min of postexercise muscle ischemia (PEMI). After 2 min of PEMI, wrist extension (i.e., wrist dorsiflexion) was performed. The static stretch protocol was also performed during 1) a freely perfused condition, 2) ischemia alone, and 3) PEMI after nonfatiguing exercise. Finally, repetitive short bouts of wrist extension were also performed under freely perfused conditions. This last paradigm evoked transient increases in MSNA but had no significant effect on mean MSNA over the whole protocol. During the PEMI after fatiguing handgrip, static stretch induced significant increases in MSNA (552 +/- 74 to 673 +/- 90 U/min, P < 0.01) and mean blood pressure (102 +/- 2 to 106 +/- 2 mmHg, P < 0.001). Static stretch performed under the other three conditions had no significant effects on mean MSNA and blood pressure. The present data verified that in healthy humans mechanoreceptor(s) stimulation evokes significant increases in mean MSNA and blood pressure when muscle metabolite concentrations are increased above a certain threshold.     

Cell-permeant NAADP: a novel chemical tool enabling the study of Ca2+ signalling in intact cells

NAADP (nicotinic acid adenine dinucleotide phosphate) is a recently discovered second messenger, and as such, we have much yet to learn about its functions in health and disease. A bottleneck in this basic research is due to NAADP, like all second messengers, being charged to prevent it from leaking out of cells. This makes for effective biology, but imposes difficulties in experiments, as it must be injected, loaded via liposomes, or electroporated, techniques that are highly technically demanding and are possible only in certain single cell preparations. For the better understood second messenger inositol 1,4,5-trisphosphate, great success has been obtained with cell-permeant derivatives where the charged groups are masked through esterification. We now report NAADP-AM as a cell-permeant analogue of NAADP that is taken up into cells and induces NAADP-mediated Ca(2+) signalling. NAADP-AM is a powerful chemical tool that will be of enormous biological utility in a wide range of systems and will greatly facilitate research into the role of NAADP in health and disease.     

Calcium binds to leptospiral immunoglobulin-like protein, LigB, and modulates fibronectin binding

Pathogenic Leptospira spp. express immunoglobulin-like proteins, LigA and LigB, which serve as adhesins to bind to extracellular matrices and mediate their attachment on host cells. However, nothing is known about the mechanism by which these proteins are involved in pathogenesis. We demonstrate that LigBCen2 binds Ca(2+), as evidenced by inductively coupled plasma optical emission spectrometry, energy dispersive spectrometry, (45)Ca overlay, and mass spectrometry, although there is no known motif for Ca(2+) binding. LigBCen2 binds four Ca(2+) as determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The dissociation constant, K(D), for Ca(2+) binding is 7 mum, as measured by isothermal titration calorimetry and calcium competition experiments. The nature of the Ca(2+)-binding site in LigB is possibly similar to that seen in the betagamma-crystallin superfamily, since structurally, both families of proteins possess the Greek key type fold. The conformation of LigBCen2 was significantly influenced by Ca(2+) binding as shown by far- and near-UV CD and by fluorescence spectroscopy. In the apo form, the protein appears to be partially unfolded, as seen in the far-UV CD spectrum, and upon Ca(2+) binding, the protein acquires significant beta-sheet conformation. Ca(2+) binding stabilizes the protein as monitored by thermal unfolding by CD (50.7-54.8 degrees C) and by differential scanning calorimetry (50.0-55.7 degrees C). Ca(2+) significantly assists the binding of LigBCen2 to the N-terminal domain of fibronectin and perturbs the secondary structure, suggesting the involvement of Ca(2+) in adhesion. We demonstrate that LigB is a novel bacterial Ca(2+)-binding protein and suggest that Ca(2+) binding plays a pivotal role in the pathogenesis of leptospirosis.     

Chemicals isolated from Justicia adhatoda Linn reduce fitness of the mosquito,Aedes aegypti L

Extracts from Justicia adhatoda L. (Acanthaceae) strongly reduced the fitness of the mosquito, Aedes aegypti Linn. The methanolic extracts inhibited several enzymes responsible for protecting insects from oxidative and other damage, including glutathione‐S‐transferase, superoxide dismutase, cytochrome P450, and α‐ and β‐esterases. They increased repellency (maximum repellency at 100 ppm) in host‐seeking adult females using the “arm‐in cage assay.” Histopathological examination showed the extracts led to serious midgut cell damage. Justicia adhatoda extracts led to reduced fecundity and oviposition of gravid females compared to controls. The extracts led to substantially reduced A. aegypti survival. We infer that the extracts have potential to reduce pathogen transmission by suppressing population growth of A. aegypti, and possibly other mosquito species.