Synergistic effect of imp/ostA and msbA in hydrophobic drug resistance of Helicobacter pylori

<p>Abstract</p> <p>Background</p> <p>Contamination of endoscopy equipment by <it>Helicobacter pylori </it>(<it>H. pylori</it>) frequently occurs after endoscopic examination of <it>H. pylori</it>-infected patients. In the hospital, manual pre-cleaning and soaking in glutaraldehyde is an important process to disinfect endoscopes. However, this might not be sufficient to remove <it>H. pylori </it>completely, and some glutaraldehyde-resistant bacteria might survive and be passed to the next patient undergoing endoscopic examination through unidentified mechanisms. We identified an Imp/OstA protein associated with glutaraldehyde resistance in a clinical strain, NTUH-C1, from our previous study. To better understand and manage the problem of glutaraldehyde resistance, we further investigated its mechanism.</p> <p>Results</p> <p>The minimal inhibitory concentrations (MICs) of glutaraldehyde andexpression of <it>imp/ostA </it>RNA in 11 clinical isolates from the National Taiwan University Hospital were determined. After glutaraldehyde treatment, RNA expression in the strains with the MICs of 4–10 μg/ml was higher than that in strains with the MICs of 1–3 μg/ml. We examined the full-genome expression of strain NTUH-S1 after glutaraldehyde treatment using a microarray and found that 40 genes were upregulated and 31 genes were downregulated. Among the upregulated genes, <it>imp/ostA </it>and <it>msbA</it>, two putative lipopolysaccharide biogenesis genes, were selected for further characterization. The sensitivity to glutaraldehyde or hydrophobic drugs increased in both of <it>imp/ostA </it>and <it>msbA </it>single mutants. The <it>imp/ostA </it>and <it>msbA </it>double mutant was also hypersensitive to these chemicals. The lipopolysaccharide contents decreased in individual <it>imp/ostA </it>and <it>msbA </it>mutants and dramatically reduced in the <it>imp/ostA </it>and <it>msbA </it>double mutant. Outer membrane permeability assay demonstrated that the <it>imp/ostA </it>and <it>msbA </it>double mutation resulted in the increase of outer membrane permeability. Ethidium bromide accumulation assay demonstrated that MsbA was involved in efflux of hydrophobic drugs.</p> <p>Conclusion</p> <p>The expression levels of <it>imp/ostA </it>and <it>msbA </it>were correlated with glutaraldehyde resistance in clinical isolates after glutaraldehyde treatment. Imp/OstA and MsbA play a synergistic role in hydrophobic drugs resistance and lipopolysaccharide biogenesis in <it>H. pylori</it>.</p

A Study of Machine Learning Models in Epidemic Surveillance: Using the Query Logs of Search Engines

Epidemics inevitably result in a large number of deaths and always cause considerable social and economic damage. Epidemic surveillance has thus become an important healthcare research issue. In 2009, Ginsberg et al. observed that the query logs of search engines can be used to estimate the status of epidemics in a timely manner. In this paper, we model epidemic surveillance as a classification problem and employ query statistics from Google to classify the status of a dengue fever epidemic. The query logs of twenty-three dengue-related keywords serve as observations for machine learning and testing, and a number of machine learning models are investigated to evaluate their surveillance performance. Evaluations based on a 5-year real world dataset demonstrate that search engine query logs can be used to construct accurate epidemic status classifiers. Moreover, the learned classifiers generally outperform conventional regression approaches. We also apply various machine learning models, including generative, discriminative, sequential, and non-sequential classification models, to demonstrate their applicability to epidemic surveillance

Developing the Effective Method of Spectral Harmonic Energy Ratio to Analyze the Arterial Pulse Spectrum

In this article, we analyze the arterial pulse in the spectral domain. A parameter, the spectral harmonic energy ratio (SHER), is developed to assess the features of the overly decreased spectral energy in the fourth to sixth harmonic for palpitation patients. Compared with normal subjects, the statistical results reveal that the mean value of SHER in the patient group (57.7 ± 27.9) is significantly higher than that of the normal group (39.7 ± 20.9) (P-value = .0066 < .01). This means that the total energy in the fourth to sixth harmonic of palpitation patients is significantly less than it is in normal subjects. In other words, the spectral distribution of the arterial pulse gradually decreases for normal subjects while it decreases abruptly in higher-order harmonics (the fourth, fifth and sixth harmonics) for palpitation patients. Hence, SHER is an effective method to distinguish the two groups in the spectral domain. Also, we can thus know that a “gradual decrease” might mean a “balanced” state, whereas an “abrupt decrease” might mean an “unbalanced” state in blood circulation and pulse diagnosis. By SHER, we can determine the ratio of energy distribution in different harmonic bands, and this method gives us a novel viewpoint from which to comprehend and quantify the spectral harmonic distribution of circulation information conveyed by the arterial pulse. These concepts can be further applied to improve the clinical diagnosis not only in Western medicine but also in traditional Chinese medicine (TCM)

Impact of Lidocaine on Pain-Related Grooming in Cuttlefish

Nociception is the neural process of encoding noxious stimuli and is typically accompanied by a reflex withdrawal response away from the potentially injurious stimulus. Studies on nociception in cephalopods have so far focused on octopus and squid, with no investigations to our knowledge on cuttlefish. Yet, these are an important species both in scientific and commercial use. Therefore, the present study demonstrated that a standard pain stimulus, acetic acid, induced grooming behaviour directed towards the injection site in cuttlefish and that the injection of lidocaine reduces grooming behaviours in acetic-acid-injected cuttlefish. Wound-directed behaviour demonstrates that the animal is aware of the damage; thus, when subjecting these animals to any painful treatments in the laboratory, researchers should consider alleviating pain by the administration of pain-relieving drugs

The Arabidopsis Malectin-Like/LRR-RLK IOS1 is Critical for BAK1-Dependent and BAK1-Independent Pattern-Triggered Immunity

Plasma membrane-localized pattern recognition receptors (PRRs) such as FLAGELLIN SENSING2 (FLS2), EF-TU RECEPTOR (EFR) and CHITIN ELICITOR RECEPTOR KINASE 1 (CERK1) recognize microbe-associated molecular patterns (MAMPs) to activate pattern-triggered immunity (PTI). A reverse genetics approach on genes responsive to the priming agent beta-aminobutyric acid (BABA) revealed IMPAIRED OOMYCETE SUSCEPTIBILITY1 (IOS1) as a critical PTI player. Arabidopsis thaliana ios1 mutants were hyper-susceptible to Pseudomonas syringae bacteria. Accordingly, ios1 mutants showed defective PTI responses, notably delayed up-regulation of the PTI-marker gene FLG22-INDUCED RECEPTOR-LIKE KINASE1 (FRK1), reduced callose deposition and mitogen-activated protein kinase activation upon MAMP treatment. Moreover, Arabidopsis lines over-expressing IOS1 were more resistant to bacteria and showed a primed PTI response. In vitro pull-down, bimolecular fluorescence complementation, co-immunoprecipitation, and mass spectrometry analyses supported the existence of complexes between the membrane-localized IOS1 and BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1 (BAK1)-dependent PRRs FLS2 and EFR, as well as with the BAK1-independent PRR CERK1. IOS1 also associated with BAK1 in a ligand-independent manner, and positively regulated FLS2-BAK1 complex formation upon MAMP treatment. In addition, IOS1 was critical for chitin-mediated PTI. Finally, ios1 mutants were defective in BABA-induced resistance and priming. This work reveals IOS1 as a novel regulatory protein of FLS2-, EFR- and CERK1-mediated signaling pathways that primes PTI activation

Radial Pressure Pulse and Heart Rate Variability in Heat- and Cold-Stressed Humans

This study aims to explore the effects of heat and cold stress on the radial pressure pulse (RPP) and heart rate variability (HRV). The subjects immersed their left hand into 45°C and 7°C water for 2 minutes. Sixty healthy subjects (age 25 ± 4 yr; 29 men and 31 women) were enrolled in this study. All subjects underwent the supine temperature measurements of the bilateral forearms, brachial arterial blood pressure, HRV and RPP with a pulse analyzer in normothermic conditions, and thermal stresses. The power spectral low-frequency (LF) and high-frequency (HF) components of HRV decreased in the heat test and increased in the cold test. The heat stress significantly reduced radial augmentation index (AIr) (P < .05), but the cold stress significantly increased AIr (P < .01). The spectral energy of RPP did not show any statistical difference in 0 ~ 10 Hz region under both conditions, but in the region of 10 ~ 50 Hz, there was a significant increase (P < .01) in the heat test and a significant decrease in the cold test (P < .01). The changes in AIr induced by heat and cold stress were significantly negatively correlated with the spectral energy in the region of 10 ~ 50 Hz (SE10−50 Hz) but not in the region of 0 ~ 10 Hz (SE0−10 Hz). The results demonstrated that the SE10−50 Hz, which only possessed a small percentage in total pulse energy, presented more physiological characteristics than the SE0−10 Hz under the thermal stresses

Tau PET With 18F-THK-5351 Taiwan Patients With Familial Alzheimer's Disease With the APP p.D678H Mutation

Background: Brain 18F-AV-45 amyloid positron emission tomography (PET) in Taiwanese patients with familial Alzheimer's disease with the amyloid precursor protein (APP) p.D678H mutation tends to involve occipital and cerebellar cortical areas. However, tau pathology in patients with this specific Taiwan mutation remains unknown. In this study, we aimed to study the Tau PET images in these patients.Methods: Clinical features, brain magnetic resonance imaging/computed tomography (MRI/CT), and brain 18F-THK-5351 PET were recorded in five patients with the APP p.D678H mutation and correlated with brain 18F-AV-45 PET images. We also compared the tau deposition patterns among five patients with familial mild cognitive impairment (fMCI), six patients with sporadic amnestic mild cognitive impairment (sMCI), nine patients with mild to moderate dementia due to Alzheimer's disease (AD), and 12 healthy controls (HCs). All of the subjects also received brain 18F-AV-45 PET.Results: The nine patients with sAD and six patients with sMCI had a positive brain AV-45 PET scans, while the 12 HCs had negative brain AV-45 PET scans. All five patients with fMCI received a tau PET scan with the age at onset ranging from 46 to 53 years, in whom increased standard uptake value ratio (SUVR) of 18F-THK-5351 was noted in all seven brain cortical areas compared with the HCs. In addition, the SUVRs of 18F-THK-5351 were increased in the frontal, medial parietal, lateral parietal, lateral temporal, and occipital areas (P &lt; 0.001) in the patients with sAD compared with the HCs. The patients with fMCI had a significant higher SUVR of 18F-THK-5351 in the cerebellar cortex compared to the patients with sMCI. The correlations between regional SUVR and Mini-Mental State Examination score and between regional SUVR and clinical dementia rating (sum box) scores within volumes of interest of Braak stage were statistically significant.Conclusion: Tau deposition was increased in the patients with fMCI compared to the HCs. Increased regional SUVR in the cerebellar cortical area was a characteristic finding in the patients with fMCI. As compared between amyloid and tau PET, the amyloid deposition is diffuse, but tau deposition is limited to the temporal lobe in the patients with fMCI

A QoS-Guaranteed Coverage Precedence Routing Algorithm for Wireless Sensor Networks

For mission-critical applications of wireless sensor networks (WSNs) involving extensive battlefield surveillance, medical healthcare, etc., it is crucial to have low-power, new protocols, methodologies and structures for transferring data and information in a network with full sensing coverage capability for an extended working period. The upmost mission is to ensure that the network is fully functional providing reliable transmission of the sensed data without the risk of data loss. WSNs have been applied to various types of mission-critical applications. Coverage preservation is one of the most essential functions to guarantee quality of service (QoS) in WSNs. However, a tradeoff exists between sensing coverage and network lifetime due to the limited energy supplies of sensor nodes. In this study, we propose a routing protocol to accommodate both energy-balance and coverage-preservation for sensor nodes in WSNs. The energy consumption for radio transmissions and the residual energy over the network are taken into account when the proposed protocol determines an energy-efficient route for a packet. The simulation results demonstrate that the proposed protocol is able to increase the duration of the on-duty network and provide up to 98.3% and 85.7% of extra service time with 100% sensing coverage ratio comparing with LEACH and the LEACH-Coverage-U protocols, respectively

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects