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In particular, the application of denoising and the motion correction were the most crucial improvement steps. In vitro experiments verified the preservation of specificity of the dualCEST signal to proteins. Good-to-excellent intra-session and good inter-session repeatability was achieved, allowing reliable detection of relative signal differences of about 16% or higher. Applicability in a clinical setting was demonstrated by examining a patient with glioblastoma. The optimized acquisition protocol for dualCEST-MRI at 3 T enables selective imaging of endogenous bulk mobile proteins under clinically relevant conditions. © 2020 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.Vancomycin is a first-line treatment for invasive infections caused by multidrug-resistant gram-positive bacteria. However, vancomycin-induced nephrotoxicity is an increasing burden, particularly in patients with complex life-threatening conditions. Vancomycin-induced nephrotoxicity associated with clinically relevant exposure on the target site has not been well defined. This study aimed to acquire the concentration of vancomycin in the renal tubules and kidneys in humans using physiologically based pharmacokinetic (PBPK) modeling and simulation. Based upon the exposure of vancomycin in the renal tubule, the toxicity of vancomycin in human renal proximal tubular epithelial cells was examined with the XTT assay and in vitro metabolomics analysis. A rat PBPK model predicting plasma and kidney concentration-time profiles of vancomycin matched the observed behavior after a single administration of 10 mg/kg. The concentration of vancomycin in renal tubules was about 40-50 times higher than that in plasma. The human PBPK model transferred from the rat model predicted renal tubule concentrations of vancomycin as 316.1-2136.6 μg/mL at 500 mg every 6 hours, and 199.0-3932.5 μg/mL at 1000 mg every 12 hours. Vancomycin showed significant nephrotoxicity at 4 mg/mL in XTT assessment. In total, 11 lysophosphatidylcholines and one lysophosphatidylethanolamine were identified by metabolomics analysis. The concentration-dependent increase was evident in the release of lysophospholipids after vancomycin treatment (0.125-4 mg/mL) for 24 hours. CQ inhibitor in vivo Our study revealed the relationship between the exposure of vancomycin in the kidney and toxicity of vancomycin at clinically relevant concentrations achieved from a mechanical PBPK model. A series of lysophospholipids as potential metabolic markers of renal toxicity were identified. © 2020 John Wiley & Sons, Ltd.The use of paper-based devices in combination with noninstrumental detection systems is becoming increasingly important in the analytical field due to its simplicity, rapidity, and low cost. However, their use for determination of volatile analyte derivatives is still relatively scarce. The present work reports on the assessment of a paper-based gas-sensing approach for the simultaneous noninstrumental colorimetric detection of nitrite and sulfide. Colorimetric systems based on the Griess and methylene blue assays, formation of colored metallic sulfides, and interaction/reaction with in situ generated metallic nanoparticles were preliminary evaluated. Then, the effect of experimental variables affecting the analytical performance of the paper-based gas sensor was studied with two digitization systems, namely a scanner and a smartphone. Under optimal conditions, the developed system yielded limits of detection of 0.055 and 0.005 mg/L for nitrite and sulfide, respectively. The repeatability, expressed as relative standard deviation, was found to be 5.9 and 6.7% for nitrite and sulfide, respectively. The proposed method was finally applied to the analysis of water samples, showing recoveries in the range of 95-105%. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.AIM Mammary serine protease inhibitor (maspin) acts as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. link2 Paradoxically, maspin levels are increased in some types of malignant cells. The aim of this study was to investigate the maspin expression in cervical dysplasia and cervical cancer, and to analyze its' relation with survival. METHODS Maspin expression was detected by immunohistochemistry using labeled streptavidin biotin method to determine cytoplasmic and nuclear maspin expressions in cervical intraepithelial neoplasia grade 1 (CIN1), cervical intraepithelial neoplasia grade 2 (CIN2), cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer. RESULTS A total of 89 patients with CIN (29 cases of CIN1, 30 cases of CIN2 and 30 cases of CIN3), and 27 patients with cervical cancer were included to the study. 7.8% of the patients with CIN had maspin staining positivity. On the other hand maspin staining was positive in 20 of 27 patients (74.1%) with cervical carcinoma (P = 0.001). Of these patients 20 (100%) had cytoplasmic, and 8 (40%) had nuclear maspin staining positivity. Cytoplasmic maspin immunoreactive scores were found to be significantly higher in carcinoma group when compared to the patients with CIN1/3 (respectively; P = 0.01, P = 0.02). No difference was noted for nuclear maspin expression. Significant overall survival advantage was detected for patients with nuclear maspin staining (P = 0.03). CONCLUSION The current study shows that nuclear maspin expression is related with better overall survival in cervical cancer. Maspin staining can be a useful diagnostic marker to discriminate cervical intraepithelial neoplasia from cervical carcinoma. © 2020 Japan Society of Obstetrics and Gynecology.The magnetotactic lifestyle represents one of the most complex traits found in many bacteria from aquatic environments and depends on magnetic organelles, the magnetosomes. link3 Genetic transfer of magnetosome biosynthesis operons to a non-magnetotactic bacterium has only been reported once so far, but it is unclear whether this may also occur in other recipients. Besides magnetotactic species from freshwater, the genus Magnetospirillum of the Alphaproteobacteria also comprises a number of strains lacking magnetosomes, which are abundant in diverse microbial communities. Their close phylogenetic interrelationships raise the question whether the non-magnetotactic magnetospirilla may have the potential to (re)gain a magnetotactic lifestyle upon acquisition of magnetosome gene clusters. Here, we studied the transfer of magnetosome gene operons into several non-magnetotactic environmental magnetospirilla. Single-step transfer of a compact vector harbouring >30 major magnetosome genes from M. gryphiswaldense induced magnetosome biosynthesis in a Magnetospirillum strain from a constructed wetland. However, the resulting magnetic cellular alignment was insufficient for efficient magnetotaxis under conditions mimicking the weak geomagnetic field. Our work provides insights into possible evolutionary scenarios and potential limitations for the dissemination of magnetotaxis by horizontal gene transfer and expands the range of foreign recipients that can be genetically magnetized. © 2020 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.Phosphorus is a macronutrient that is essential for plant survival. Most land plants have evolved the ability to form a mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi, which enhances phosphate (Pi) acquisition. Modulation of Pi transporter systems is the master strategy used by mycorrhizal plants to adapt to ambient Pi concentrations. However, the specific functions of PHOSPHATE TRANSPORTER 1 (PHT1) genes, which are Pi transporters that are responsive to high Pi availability, are largely unknown. Here, we report that AsPT5, an Astragalus sinicus (Chinese milk vetch) member of the PHT1 gene family, is conserved across dicotyledons and is constitutively expressed in a broad range of tissues independently of Pi supply, but is remarkably induced by indole-3-acetic acid (auxin) treatment under moderately high Pi conditions. Subcellular localization experiments indicated that AsPT5 localizes to the plasma membrane of plant cells. Using reverse genetics, we showed that AsPT5 not only mediates Pi transport and remodels root system architecture but is also essential for arbuscule formation in A. sinicus under moderately high Pi concentrations. Overall, our study provides insight into the function of AsPT5 in Pi transport, AM development and the cross-talk between Pi nutrition and auxin signalling in mycorrhizal plants. © 2020 Society for Applied Microbiology and John Wiley & Sons Ltd.During recent decades, survey studies have documented the widespread presence of oocytes in the testes of male Smallmouth Bass Micropterus dolomieu collected from surface waters throughout the United States. There are few published reports of testicular oocytes (TO) in Smallmouth Bass before the 1990s, so it is difficult to know how long this has been occurring. Consequently, this study was conducted to evaluate the prevalence and severity of TO occurrence in whole fish specimens from two archival collections-the Smithsonian Institution's National Museum of Natural History in Suitland, Maryland, and Cornell University's Museum of Vertebrates in Ithaca, New York. Gonads were excised from 167 preserved male Smallmouth Bass that were originally collected between 1875 and 2004, and routine histologic sections were prepared and examined. The severity of TO was determined using a semiquantitative scoring system. Overall, 52.1% of male Smallmouth Bass were found to have TO. Affected fish had been collected in 11 of the 18 represented states, and TO were found in specimens harvested during decades as early as the 1880s and 1900s. Unfortunately, the small number of samples acquired at the earliest time periods precluded analyses of prevalence and severity trends over time. The results of this study demonstrated that the phenomenon of TO in male Smallmouth Bass is at least a century old and confirmed the widespread nature of this finding throughout the species' historic range. Further research efforts should focus on determining the baseline prevalence of TO in laboratory-reared male Smallmouth Bass that have not been exposed to endocrine active substances or the effects of experimental estrogen exposure on such fish. © 2020 American Fisheries Society.The opportunistic human pathogen Acinetobacter baumannii is one of the leading causes of nosocomial infections. The high prevalence of multidrug-resistant strains, a high adaptability to changing environments and an overall pronounced stress resistance contribute to persistence and spread of the bacteria in hospitals and thereby promote repeated outbreaks. Altogether, the success of A. baumannii is mainly built on adaptation and stress resistance mechanisms, rather than relying on 'true' virulence factors. One of the stress factors that pathogens must cope with is osmolarity, which can differ between the external environment and different body parts of the human host. A. baumannii ATCC 19606T accumulates the compatible solutes glutamate, mannitol and trehalose in response to high salinities. In this work, it was found that most of the solutes vanish immediately after reaching stationary phase, a very unusual phenomenon. While glutamate can be metabolized, mannitol produced by MtlD is excreted to the medium in high amounts.

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