Hoffmcgarry2052

© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Hot carriers (HCs) and thermal effects, stemming from plasmon decays, are crucial for most plasmonic applications. However, quantifying these two effects remains extremely challenging due to the experimental difficulty in accurately measuring the temperature at reaction sites. Herein, we provide a novel strategy to disentangle HCs from photothermal effects based on the different traits of heat dissipation (long range) and HCs transport (short range), and quantitatively uncover the dominant and potential-dependent role of photothermal effect by investigating the rapid- and slow-response currents in plasmon-mediated electrochemistry at nanostructured Ag electrode. Furthermore, the plasmoelectric surface potential is found to contribute to the rapid-response currents, which is absent in the previous studies. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Cell image classification methods are currently being used in numerous applications in cell biology and medicine. Applications include understanding the effects of genes and drugs in screening experiments, understanding the role and subcellular localization of different proteins, as well as diagnosis and prognosis of cancer from images acquired using cytological and histological techniques. The article also reviews three main approaches for cell image classification most often used numerical feature extraction, end-to-end classification with neural networks (NNs), and transport-based morphometry (TBM). In addition, we provide comparisons on four different cell imaging datasets to highlight the relative strength of each method. The results computed using four publicly available datasets show that numerical features tend to carry the best discriminative information for most of the classification tasks. Results also show that NN-based methods produce state-of-the-art results in the dataset that contains a relatively large number of training samples. Data augmentation or the choice of a more recently reported architecture does not necessarily improve the classification performance of NNs in the datasets with limited number of training samples. If understanding and visualization are desired aspects, TBM methods can offer the ability to invert classification functions, and thus can aid in the interpretation of results. These and other comparison outcomes are discussed with the aim of clarifying the advantages and disadvantages of each method. © 2020 International Society for Advancement of Cytometry.Cardiac ischaemia-reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re-perfused post-ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post-anoxic heart mitochondria. However, post-ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up-regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro-fibrotic and pro-apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label-free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC-derived signals during cardiac adaptive remodelling and identified ROS as a possible effector. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.PURPOSE Time is the key criterion in the management of non-arteritic central retinal artery occlusion (NA-CRAO). However, the precise onset of vision loss is often difficult to determine. This study aimed to evaluate the temporal changes of retinal thickness in acute NA-CRAO and the potential of this parameter to be used as a surrogate marker to estimate the onset of retinal ischaemia. METHODS Optical coherence tomography was used to continuously assess retinal thickness and oedema progression rate in six porcine eyes. Additionally, a retrospective analysis of 12 patients with acute NA-CRAO was performed to determine association strength and progression rate between retinal thickness and onset of ischaemia. All Optical coherence tomography (OCT) scans (pigs and NA-CRAO patients) were performed within an ischaemic time frame of up to 9 hr. AZD1775 RESULTS Retinal oedema progression rate in pigs was 25.32 µm/hr [CI 95% 24.24-26.40 µm/hr]. Retrospective analysis of the patients revealed a strong correlation between retinal oedema and duration of ischaemia (Spearman's rho = 0.77, p = 0.004) with an estimated progression rate of 10.02 µm/hr [CI 95% 3.30-16.74 µm/hr]. CONCLUSION Retinal thickness increases with oedema formation, and ischaemia onset is strongly correlated with this structural biomarker in both, pigs and NA-CRAO patients. Prospective clinical trials will have to determine the clinical feasibility of retinal thickness measurements as a biomarker to support clinical management of NA-CRAO. © 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.This article describes a procedure for isolating T cell subpopulations using various methods including indirect panning and immunopanning by microarray. In these methods, cells are selected by their capacity to bind to antibody-coated plates (or slides) on the basis of particular cell-surface markers. Such methods can be superior to the antibody/complement lysis method (Alternate Protocol), as they can select additional cell population for analysis. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1 Isolation of T cell populations by indirect panning Basic Protocol 2 Immunopanning with microarray Alternate Protocol Isolation of T cell populations by antibody/complement-mediated cytotoxicity.INTRODUCTION Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease often managed with Nintedanib, a tyrosine kinase inhibitor targeting several profibrotic pathways. link2 Although clotting processes are involved in wound healing and repair in the lung, there is no data on the role of antithrombin III on in IPF patients treated with Nintedanib. A previous proteomic analysis of serum of IPF patients before and after one year of Nintedanib treatment showed differential protein expression of antithrombin III. AIMS Here we used quantitative methods to evaluate differential ATIII concentrations in IPF patients before and after one year of Nintedanib treatment and to assess the potential of ATIII as a prognostic biomarker in IPF patients. METHODS Serum levels of ATIII were measured by ELISA in 14 IPF patients before and after one year of Nintedanib treatment. RESULTS A statistically significant inverse correlation was found between serum ATIII concentrations and PFT s parameters in all patients at baseline and follow up. Baseline serum ATIII and BAL neutrophils proved to be reliable predictors of poor prognosis. A baseline ATIII threshold of 126.5 μg/mL discriminated survivors from non-survivors. CONCLUSIONS After 12 months of antifibrotic treatment, IPF patients with high serum ATIII concentrations and high BAL neutrophil percentages had a poor prognosis and increased survival risk. link3 The results of this preliminary study suggest, that ATIII has potential as a biomarker of IPF severity and in predicting answer to Nintedanib therapy. As a marker, ATIII showed several advantages over BAL neutrophil percentage. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Bacterial  trans -acyltransferase polyketide synthases ( trans -AT PKSs) are multimodular megaenzymes that biosynthesize many bioactive natural products. They contain a remarkable range of domains and module types that introduce different substituents into growing polyketide chains. As one such modification, we recently reported Baeyer-Villiger-type oxygen insertion into nascent  polyketide backbones, generating malonyl thioester intermediates. In this work, genome mining focusing on architecturally diverse oxidation modules in  trans -AT PKSs led us to the culturable plant symbiont  Gynuella sunshinyii  that harbors two distinct modules in one orphan PKS. The PKS product was revealed to be lobatamide A, a potent cytotoxin previously only known from a marine tunicate. Biochemical studies show that one module generates glycolyl thioester intermediates, while the other is proposed to be involved in oxime formation. The data suggest varied roles of oxygenation modules in the biosynthesis of polyketide scaffolds and support the importance of  trans -AT PKSs in the specialized metabolism of symbiotic bacteria. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The promise of cell and gene therapies is being realized as new products emerge to treat diseases once considered intractable. These treatments are emerging amidst reports of patients being injured by unproven "stem cell" interventions. At this juncture, it is vital to be supporting the continued development of promising regenerative medicine products while protecting patients from the risks posed by unproven interventions. Various stakeholders including governments, patient groups, medical societies, and the media are committed to this outcome. In this perspective, we draw on our experience gained from partnerships in developing regenerative medicine products to identify technical, organizational, and ethical benchmarks for the responsible delivery of regenerative medicine treatments. These benchmarks may serve as the basis for policy interventions intended to drive the responsible delivery of stem cell and regenerative medicine products. Our particular focus is California-based policy, but the suggested benchmarks are broadly applicable to national and international jurisdictions. © 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.A spider-transmitted fungus ( Rhizopus microsporus ) that was isolated from necrotic human tissue was found to harbor endofungal bacteria ( Burkholderia sp.). Metabolic profiling of the symbionts revealed a complex of cytotoxic agents (necroximes). Their structures were fully characterized as oxime-substituted benzolactone enamides equipped with a peptidic side chain. Necroximes are potent cytotoxic agents that are also formed in symbiosis with the fungal host and could have contributed to the necrosis. Genome sequencing and in silico analyses revealed a novel modular PKS/NRPS assembly line equipped with several non-canonical domains. Based on gene deletion mutants, we propose the first biosynthetic model for bacterial benzolactones. We identified specific traits that serve as genetic handles to identify related salicylate macrolide pathways in various other bacterial genera (lobatamide, oximidine, apicularen and cruentaren). Our work sets an unusual example of hypothesis-based drug discovery in the context of human disease.