Difference in membrane repair capacity between cancer cell lines and a normal cell line

Electroporation-based treatments and other therapies that permeabilize the plasma membrane have been shown to be more devastating to malignant cells than to normal cells. In this study, we asked if a difference in repair capacity could explain this observed difference in sensitivity. Membrane repair was investigated by disrupting the plasma membrane using laser followed by monitoring fluorescent dye entry over time in seven cancer cell lines, an immortalized cell line, and a normal primary cell line. The kinetics of repair in living cells can be directly recorded using this technique, providing a sensitive index of repair capacity. The normal primary cell line of all tested cell lines exhibited the slowest rate of dye entry after laser disruption and lowest level of dye uptake. Significantly, more rapid dye uptake and a higher total level of dye uptake occurred in six of the seven tested cancer cell lines (p < 0.05) as well as the immortalized cell line (p < 0.001). This difference in sensitivity was also observed when a viability assay was performed one day after plasma membrane permeabilization by electroporation. Viability in the primary normal cell line (98 % viable cells) was higher than in the three tested cancer cell lines (81–88 % viable cells). These data suggest more effective membrane repair in normal, primary cells and supplement previous explanations why electroporation-based therapies and other therapies permeabilizing the plasma membrane are more effective on malignant cells compared to normal cells in cancer treatment

Toward one‐pot olefin/thiophene block copolymers using an in situ ligand exchange

Block copolymers containing both conducting and insulating segments are of interest due to their enhanced electrical properties arising from their increased crystallization. Yet few methods exist for generating these copolymers, because the reaction conditions for synthesizing each block are often incompatible. Herein, efforts toward identifying a one‐pot, living polymerization method for synthesizing block copolymers of 1‐pentene and 3‐hexylthiophene is described. An in situ ligand exchange enables the optimal catalyst to be utilized for synthesizing each block. Even under these conditions, however, only homopolymers are observed. Computational studies modeling the ligand exchange reveal that the added stabilizing ligands likely inhibit propagation of the second block. These results suggest an ancillary ligand‐based “goldilocks” effect wherein catalysts that are stable yet still reactive are required. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1601–1605Combined experimental and computational studies revealed unexpected challenges in applying sequential catalysis for the streamlined synthesis of insulating/conducting block copolymers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150553/1/pola29426_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150553/2/pola29426.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150553/3/pola29426-sup-0001-AppendixS1.pd

Lectin-Based Food Poisoning: A New Mechanism of Protein Toxicity

BACKGROUND: Ingestion of the lectins present in certain improperly cooked vegetables can result in acute GI tract distress, but the mechanism of toxicity is unknown. In vivo, gut epithelial cells are constantly exposed to mechanical and other stresses and consequently individual cells frequently experience plasma membrane disruptions. Repair of these cell surface disruptions allows the wounded cell to survive: failure results in necrotic cell death. Plasma membrane repair is mediated, in part, by an exocytotic event that adds a patch of internal membrane to the defect site. Lectins are known to inhibit exocytosis. We therefore tested the novel hypothesis that lectin toxicity is due to an inhibitory effect on plasma membrane repair. METHODS AND FINDINGS: Repair of plasma membrane disruptions and exocytosis of mucus was assessed after treatment of cultured cell models and excised segments of the GI tract with lectins. Plasma membrane disruptions were produced by focal irradiation of individual cells, using a microscope-based laser, or by mechanical abrasion of multiple cells, using a syringe needle. Repair was then assessed by monitoring the cytosolic penetration of dyes incapable of crossing the intact plasma membrane. We found that cell surface-bound lectins potently inhibited plasma membrane repair, and the exocytosis of mucus that normally accompanies the repair response. CONCLUSIONS: Lectins potently inhibit plasma membrane repair, and hence are toxic to wounded cells. This represents a novel form of protein-based toxicity, one that, we propose, is the basis of plant lectin food poisoning

Dendritic silver self-assembly in molten-carbonate membranes for efficient carbon dioxide capture

Membranes for CO2 capture should offer high permeant fluxes to keep membrane surface area small and material requirements low. Ag-supported, dual-phase, molten-carbonate membranes routinely demonstrate the highest CO2 fluxes in this class of membrane. However, using Ag as a support incurs high cost. Here, the non-equilibrium conditions of permeation were exploited to stimulate the self-assembly of a percolating, dendritic network of Ag from the molten carbonate. Multiple membrane support geometries and Ag incorporation methods were employed, demonstrating the generality of the approach, while X-ray micro-computed tomography confirmed that CO2 and O2 permeation stimulated self-assembly. We report the highest flux of Ag-supported molten-salt membranes to date (1.25 ml min−1 cm−2 at 650 °C) and ultrahigh permeability (9.4 × 10−11 mol m−1 s−1 Pa−1), surpassing the permeability requirement for economically-competitive post-combustion CO2 capture, all whilst reducing the membrane-volume-normalised demand for Ag by one order of magnitude

A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence

A bivariate copula mixed model has been recently proposed to synthesize diagnostic test accuracy studies and it has been shown that it is superior to the standard generalized linear mixed model in this context. Here, we call trivariate vine copulas to extend the bivariate meta-analysis of diagnostic test accuracy studies by accounting for disease prevalence. Our vine copula mixed model includes the trivariate generalized linear mixed model as a special case and can also operate on the original scale of sensitivity, specificity, and disease prevalence. Our general methodology is illustrated by re-analyzing the data of two published meta-analyses. Our study suggests that there can be an improvement on trivariate generalized linear mixed model in fit to data and makes the argument for moving to vine copula random effects models especially because of their richness, including reflection asymmetric tail dependence, and computational feasibility despite their three dimensionality

Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.

MotivationMultiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.ResultsWe performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementationDatasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary informationSupplementary data are available at Bioinformatics online

Trends in seasonal influenza vaccine uptake during pregnancy in Western Australia: Implications for midwives

Background: Antenatal influenza vaccination is an important public health intervention for preventing serious illness in mothers and newborns, yet uptake remains low. Aim: To evaluate trends in seasonal influenza vaccine coverage and identify determinants for vaccination among pregnant women in Western Australia. Methods: We conducted an annual telephone survey in a random sample of post-partum women who delivered a baby in Western Australia between 2012 and 2014. Women were asked whether influenza vaccination was recommended and/or received during their most recent pregnancy; women were also asked why or why they were not immunised. Findings: Between 2012 and 2014, influenza vaccine coverage increased from 22.9% to 41.4%. Women who reported receiving the majority of their antenatal care from a private obstetrician were significantly more likely to have influenza vaccination recommended to them than those receiving the majority of their care from a public antenatal hospital or general practitioner (p \u3c 0.001). In 2014, the most common reason women reported for accepting influenza vaccination was to protect the baby (92.8%) and the most common reason for being unimmunised was lack of a healthcare provider recommendation (48.5%). Discussion: Antenatal influenza vaccination uptake is increasing, but coverage remains below 50%. A recommendation from the principal care provider is an important predictor of maternal influenza vaccination. Conclusion: Antenatal care providers, including midwives, have a key role in providing appropriate information and evidence-based recommendations to pregnant women to ensure they are making informed decisions. Consistent recommendations from antenatal care providers are critical to improving influenza vaccine coverage in pregnant women