A comprehensive method for determining cellular uptake of purine nucleoside phosphorylase and adenylosuccinate synthetase inhibitors by H. pylori

Due to the growing number of Helicobacter pylori strains resistant to currently available antibiotics, there is an urgent need to design new drugs utilizing different molecular mechanisms than those that have been used up to now. Enzymes of the purine salvage pathway are possible targets of such new antibiotics because H. pylori is not able to synthetize purine nucleotides de novo. The bacterium’s recovery of purines and purine nucleotides from the environment is the only source of these essential DNA and RNA building blocks. We have identified formycins and hadacidin as potent inhibitors of purine nucleoside phosphorylase (PNP) and adenylosuccinate synthetase (AdSS) from H. pylori — two key enzymes of the purine salvage pathway. However, we have found that these compounds are not effective in H. pylori cell cultures. To address this issue, we have developed a universal comprehensive method for assessing H. pylori cell penetration by drug candidates, with three alternative detection assays. These include liquid chromatography tandem mass spectrometry, UV absorption, and inhibition of the target enzyme by the tested compound. Using this approach, we have shown that cellular uptake by H. pylori of formycins and hadacidin is very poor, which reveals why their in vitro inhibition of PNP and AdSS and their effect on H. pylori cell cultures are so different. The cell penetration assessment method developed here will be extremely useful for validating the cellular uptake of other drug candidates, facilitating the design of new potent therapeutic agents against H. pylori. Key points • A method for assessing H. pylori cells penetration by drug candidates is described. • Three alternative detection assays that complement each other can be used. • The method may be adapted for other bacteria as well.

Winning the Battle but Losing the War: Ironic Effects of Training Consumers to Detect Deceptive Advertising Tactics

Misleading information pervades marketing communications, and is a long-standing issue in business ethics. Regulators place a heavy burden on consumers to detect misleading information, and a number of studies have shown training can improve their ability to do so. However, the possible side effects have largely gone unexamined. We provide evidence for one such side-effect, whereby training consumers to detect a specific tactic (illegitimate endorsers), leaves them more vulnerable to a second tactic included in the same ad (a restrictive qualifying footnote), relative to untrained controls. We update standard notions of persuasion knowledge using a goal systems approach that allows for multiple vigilance goals to explain such side-effects in terms of goal shielding, which is a generally adaptive process by which activation and/or fulfillment of a low-level goal inhibits alternative detection goals. Furthermore, the same goal systems logic is used to develop a more general form of training that activates a higher-level goal (general skepticism). This more general training improved detection of a broader set of tactics without the negative goal shielding side effect.

The detection of SARS-CoV-2 using reverse transcription loop-mediated isothermal amplification (RT-LAMP) in developing country

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has infected the human system resulting in Covid-19, and has spread rapidly worldwide. Therefore, a fast, simple, cost-effective, and accurate detecting tool is required. The standard diagnostic tool of the World Health Organization is the reverse transcription-polymerase chain reaction (RT-PCR). This method detects the presence of viral genetic material in the human body with accurate results. However, it has several limitations in terms of equipment, personnel, duration, and cost. Therefore, a fast, simple, and sensitive alternative detection, is required, one of which is the reverse transcription loop-mediated isothermal amplification (RT-LAMP) that functions under isothermal conditions. This method is battery-driven, hence, easy to move closer to the patient. Conclusively, the RT-LAMP test for SARS CoV-2 diagnosis produces comparable sensitivity to a standard RT-PCR and is more suitable for resource-poor settings, such as rural areas of developing countries.

Alternative detection of SARS-CoV-2 RNA by a new assay based on mass spectrometry

Objectives Accurate detection of SARS-CoV-2 RNA is essential to stopping the spread of SARS-CoV-2. The aim of this study was to evaluate the performance of the recently introduced MassARRAY® SARS-CoV-2 Panel and to compare it to the cobas® SARS-CoV-2 Test. Methods The MassARRAY® SARS-CoV-2 Panel consists of five assays targeting different sequences of the SARS-CoV-2 genome. Accuracy was determined using national and international proficiency panels including 27 samples. For clinical evaluation, 101 residual clinical samples were analyzed and results compared. Samples had been tested for SARS-CoV-2 RNA with the cobas® SARS-CoV-2 Test. Results When accuracy was tested with the MassARRAY® SARS-CoV-2 Panel, 25 of 27 (92.6%) samples revealed correct results. When clinical samples were analyzed with the MassARRAY® SARS-CoV-2 Panel and compared to the cobas® SARS-CoV-2 Test, 100 samples showed concordant results. One sample was found to be inconclusive with the MassARRAY® SARS-CoV-2 Panel. When time-to-results were compared, the new assay showed longer total and hands-on times. Conclusions The MassARRAY® SARS-CoV-2 Panel showed a good performance and proved to be suitable for use in the routine diagnostic laboratory. Especially during phases of shortage of reagents and/or disposables, the new test system appears as beneficial alternative to standard assays used for detection of SARS-CoV-2 RNA.

EVALUATION OF CANINE DETECTION OF COVID-19 INFECTED INDIVIDUALS UNDER CONTROLLED SETTINGS

RT-PCR is currently the standard diagnostic method to detect symptomatic and asymptomatic individuals infected with SARS-CoV-2. However, RT-PCR results are not immediate and may falsely be negative before an infected individual sheds viral particle in the upper airway where swabs are collected. Infected individuals emit volatile organic compounds (VOCs) in their breath and sweat that are detectable by trained dogs. Here we evaluate the diagnostic accuracy of dog detection against SARS-CoV-2 infection. Fifteen dogs previously trained at two centres in Australia were presented to axillary sweat specimens collected from known SARS-CoV-2 human cases and non-cases. The true infection status of the cases and non-cases were confirmed based on RT-PCR results as well as clinical presentation. Across dogs, the overall diagnostic sensitivity (DSe) was 95.6% (95%CI: 93.6%-97.6%) and diagnostic specificity (DSp) was 98.1% (95%CI: 96.3%-100.0%). The DSp decreased significantly with non-case specimens sourced from UAE ( P-value < 0.001). The location of evaluation did not impact the detection performances. The accuracy of detection varied across dogs and experienced dogs revealed a marginally better DSp ( P-value = 0.003). The potential and limitations of this alternative detection tool are discussed.

A Bispectral Analysis of the Radio Emissions of Pulsar J0437-4715

A combination of the very low signal-to-noise ratio and the very large parameter space spanned by pulsar emissions makes pulsar detection a challenging task. Currently, brute force parameter searches are often used for pulsar detection and a cyclostationary Gaussian model is assumed for pulsar emissions. Higher-Order spectra offer high signal-to-noise ratio domains in problems where the desired signal is polluted by Gaussian noise. The presence of nonzero higher-order spectral components in pulsar bursts may offer alternative detection methods. This work presents a review of higher-order statistics and offers a motivation for their use in the characterization of pulsar bursts. A dish from the MeerKAT telescope was used to acquire recorded radio bursts from pulsar J0437-4715. These bursts were found to contain nonzero bispectral components that were dispersed in the same way as the components of the power spectrum.

Alternative Detection of n = 1 Modes Slowing Down on ASDEX Upgrade

Disruptions in tokamaks are very often associated with the slowing down of magneto-hydrodynamic (MHD) instabilities and their subsequent locking to the wall. To improve the understanding of the chain of events ending with a disruption, a statistically robust and physically based criterion has been devised to track the slowing down of modes with toroidal mode numbers n = 1 and mostly poloidal mode number m = 2, providing an alternative and earlier detection tool compared to simple threshold based indicators. A database of 370 discharges of axially symmetric divertor experiment—upgrade (AUG) has been studied and results compared with other indicators used in real time. The estimator is based on a weighted average value of the fast Fourier transform of the perturbed radial n = 1 magnetic field, caused by the rotation of the modes. The use of a carrier sinusoidal wave helps alleviating the spurious influence of non-sinusoidal magnetic perturbations induced by other instabilities like Edge localized modes (ELMs). The indicator constitutes a good candidate for further studies including machine learning approaches for mitigation and avoidance since, by deploying it systematically to evaluate the time instance for the expected locking, multi-machine databases can be populated. Furthermore, it can be thought as a contribution to a wider approach to dynamically tracking the chain of events leading to disruptions.

svpluscnv: analysis and visualization of complex structural variation data

Motivation Despite widespread prevalence of somatic structural variations (SVs) across most tumor types, understanding of their molecular implications often remains poor. SVs are extremely heterogeneous in size and complexity, hindering the interpretation of their pathogenic role. Tools integrating large SV datasets across platforms are required to fully characterize the cancer’s somatic landscape. Results svpluscnv R package is a swiss army knife for the integration and interpretation of orthogonal datasets including copy number variant segmentation profiles and sequencing-based structural variant calls. The package implements analysis and visualization tools to evaluate chromosomal instability and ploidy, identify genes harboring recurrent SVs and detects complex rearrangements such as chromothripsis and chromoplexia. Further, it allows systematic identification of hot-spot shattered genomic regions, showing reproducibility across alternative detection methods and datasets. Availability and implementation https://github.com/ccbiolab/svpluscnv. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.