The Zeolitoids

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Contributions of Intracellular Ions to Kv Channel Voltage Sensor Dynamics

Voltage-sensing domains (VSDs) of Kv channels control ionic conductance through coupling of the movement of charged residues in the S4 segment to conformational changes at the cytoplasmic region of the pore domain, that allow K+ ions to flow. Conformational transitions within the VSD are induced by changes in the applied voltage across the membrane field. However, several other factors not directly linked to the voltage-dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity, and block of the channel by intracellular ligands. The effect of intracellular ions on voltage sensor dynamics is of importance in the interpretation of gating current measurements and the physiology of pore/voltage sensor coupling. There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization, and relaxation processes of the voltage sensor. Here we separate these factors and focus on the causal role that intracellular ions can play in allosterically modulating the dynamics of Kv voltage sensor deactivation kinetics. These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation

An Outrageous Suggestion

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Human campylobacteriosis related to cross-contamination during handling of raw chicken meat: Application of quantitative risk assessment to guide intervention scenarios analysis in the Australian context

Quantitative Microbiological Risk Assessment (QMRA) is a methodology used to organize and analyze scientific information to both estimate the probability and severity of an adverse event as well as prioritize efforts to reduce the risk of foodborne pathogens. No QMRA efforts have been applied to Campylobacter in the Australian chicken meat sector. Hence, we present a QMRA model of human campylobacteriosis related to the occurrence of cross-contamination while handling raw chicken meat in Western Australia (WA). This work fills a gap in Campylobacter risk characterization in Australia and enables benchmarking against risk assessments undertaken in other countries. The model predicted the average probability of the occurrence of illness per serving of salad that became cross-contaminated from being handled following the handling of fresh chicken meat as 7.0 × 10−4 (90% Confidence Interval [CI] ± 4.7 × 10−5). The risk assessment model was utilized to estimate the likely impact of intervention scenarios on the predicted probability of illness (campylobacteriosis) per serving. Predicted relative risk reductions following changes in the retail prevalence of Campylobacter were proportional to the percentage desired in the reduction scenario; a target that is aiming to reduce the current baseline prevalence of Campylobacter in retail chicken by 30% is predicted to yield approximately 30% relative risk reduction. A simulated one-log reduction in the mean concentration of Campylobacter is anticipated to generate approximately 20% relative risk reductions. Relative risk reduction induced by a one-log decrease in the mean was equally achieved when the tail of the input distribution was affected—that is, by a change (one-log reduction) in the standard deviation of the baseline Campylobacter concentration. A scenario assuming a 5% point decrease in baseline probability of cross-contamination at the consumer phase would yield relative risk reductions of 14%, which is as effective as the impact of a strategic target of 10% reduction in the retail prevalence of Campylobacter. In conclusion, the present model simulates the probability of illness predicted for an average individual who consumes salad that has been cross-contaminated with Campylobacter from retail chicken meat in WA. Despite some uncertainties, this is the first attempt to utilize the QMRA approach as a scientific basis to guide risk managers toward implementing strategies to reduce the risk of human campylobacteriosis in an Australian context

Geological image processing of petrographic thin sections using the rotating polarizer stage

One of the fundamental problems with image processing of petrographic thin sections is that the appearance (colour I intensity) of a mineral grain will vary with the orientation of the crystal lattice to the preferred direction of the polarizing filters on a petrographic microscope. This makes it very difficult to determine grain boundaries, grain orientation and mineral species from a single captured image. To overcome this problem, the Rotating Polarizer Stage was used to replace the fixed polarizer and analyzer on a standard petrographic microscope. The Rotating Polarizer Stage rotates the polarizers while the thin section remains stationary, allowing for better data gathering possibilities. Instead of capturing a single image of a thin section, six composite data sets are created by rotating the polarizers through 900 (or 1800 if quartz c-axes measurements need to be taken) in both plane and cross polarized light. The composite data sets can be viewed as separate images and consist of the average intensity image, the maximum intensity image, the minimum intensity image, the maximum position image, the minimum position image and the gradient image. The overall strategy used by the image processing system is to gather the composite data sets, determine the grain boundaries using the gradient image, classify the different mineral species present using the minimum and maximum intensity images and then perform measurements of grain shape and, where possible, partial crystallographic orientation using the maximum intensity and maximum position images

Agonist and antagonist properties of an insect GABA-gated chloride channel (RDL) are influenced by heterologous expression conditions

Pentameric ligand-gated ion channels (pLGICs) activated by the inhibitory neurotransmitter γ-aminobutyric acid (GABA) are expressed widely in both vertebrate and invertebrate species. One of the best characterised insect GABA-gated chloride channels is RDL, an abbreviation of 'resistance to dieldrin', that was originally identified by genetic screening in Drosophila melanogaster. Here we have cloned the analogous gene from the bumblebee Bombus terrestris audax (BtRDL) and examined its pharmacological properties by functional expression in Xenopus oocytes. Somewhat unexpectedly, the sensitivity of BtRDL to GABA, as measured by its apparent affinity (EC50), was influenced by heterologous expression conditions. This phenomenon was observed in response to alterations in the amount of cRNA injected; the length of time that oocytes were incubated before functional analysis; and by the presence or absence of a 3' untranslated region. In contrast, similar changes in expression conditions were not associated with changes in apparent affinity with RDL cloned from D. melanogaster (DmRDL). Changes in apparent affinity with BtRDL were also observed following co-expression of a chaperone protein (NACHO). Similar changes in apparent affinity were observed with an allosteric agonist (propofol) and a non-competitive antagonist (picrotoxinin), indicating that expression-depended changes are not restricted to the orthosteric agonist binding site. Interestingly, instances of expression-dependent changes in apparent affinity have been reported previously for vertebrate glycine receptors, which are also members of the pLGIC super-family. Our observations with BtRDL are consistent with previous data obtained with vertebrate glycine receptors and indicates that agonist and antagonist apparent affinity can be influenced by the level of functional expression in a variety of pLGICs

Assessing the effects of the first 2 years of industry-led badger culling in England on the incidence of bovine tuberculosis in cattle in 2013–2015

Culling badgers to control the transmission of bovine tuberculosis (TB) between this wildlife reservoir and cattle has been widely debated. Industry-led culling began in Somerset and Gloucestershire between August and November 2013 to reduce local badger populations. Industry-led culling is not designed to be a randomised and controlled trial of the impact of culling on cattle incidence. Nevertheless, it is important to monitor the effects of the culling and, taking the study limitations into account, perform a cautious evaluation of the impacts. A standardised method for selecting areas matched to culling areas in factors found to affect cattle TB risk has been developed to evaluate the impact of badger culling on cattle TB incidence. The association between cattle TB incidence and badger culling in the first two years has been assessed. Descriptive analyses without controlling for confounding showed no association between culling and TB incidence for Somerset, or for either of the buffer areas for the first two years since culling began. A weak association was observed in Gloucestershire for Year 1 only. Multivariable analysis adjusting for confounding factors showed that reductions in TB incidence were associated with culling in the first two years in both the Somerset and Gloucestershire intervention areas when compared to areas with no culling (IRR: 0.79, 95%CI: 0.72-0.87, p<0.001 and IRR: 0.42, 95%CI: 0.34-0.51, p<0.001 respectively). An increase in incidence was associated with culling in the 2 km buffer surrounding the Somerset intervention area (IRR: 1.38, 95%CI: 1.09-1.75, p=0.008), but not in Gloucestershire (IRR: 0.91, 95%CI: 0.77-1.07, p=0.243). As only two intervention areas with two years’ of data are available for analysis, and the biological cause-effect relationship behind the statistical associations is difficult to determine, it would be unwise to use these findings to develop generalisable inferences about the effectiveness of the policy at present