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Connecting fluctuation measurements in heavy-ion collisions with the grand-canonical susceptibilities
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Stochiometric quantification of the thiol redox proteome of macrophages reveals subcellular compartmentalization and susceptibility to oxidative perturbations
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Transcriptome-wide association analysis identifies candidate susceptibility genes for prostate-specific antigen levels in men without prostate cancer
Deciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility for prostate cancer (PCa) screening. Using genome-wide association study (GWAS) summary statistics from 95,768 PCa-free men, we conducted a transcriptome-wide association study (TWAS) to examine impacts of genetically predicted gene expression on PSA. Analyses identified 41 statistically significant (p < 0.05/12,192 = 4.10 × 10 –6 ) associations in whole blood and 39 statistically significant (p < 0.05/13,844 = 3.61 × 10 –6 ) associations in prostate tissue, with 18 genes associated in both tissues. Cross-tissue analyses identified 155 statistically significantly (p < 0.05/22,249 = 2.25 × 10 –6 ) genes. Out of 173 unique PSA-associated genes across analyses, we replicated 151 (87.3%) in a TWAS of 209,318 PCa-free individuals from the Million Veteran Program. Based on conditional analyses, we found 20 genes (11 single tissue, nine cross-tissue) that were associated with PSA levels in the discovery TWAS that were not attributable to a lead variant from a GWAS. Ten of these 20 genes replicated, and two of the replicated genes had colocalization probability of >0.5: CCNA2 and HIST1H2BN. Six of the 20 identified genes are not known to impact PCa risk. Fine-mapping based on whole blood and prostate tissue revealed five protein-coding genes with evidence of causal relationships with PSA levels. Of these five genes, four exhibited evidence of colocalization and one was conditionally independent of previous GWAS findings. These results yield hypotheses that should be further explored to improve understanding of genetic factors underlying PSA levels.
Corrosion Susceptibility of Cr–Mo Steels and Ferritic Stainless Steels in Biomass-Derived Pyrolysis Oil Constituents
In this work, to better understand and evaluate the corrosion performance of candidate structural steels and ferritic stainless steels for production, transport, and storage of biomass pyrolysis oils, corrosion studies were conducted in selected organic constituents of bio-oils, including catechol, formic acid, and their mixtures as well as lactobionic acid, using electrochemical impedance spectroscopy. R 2 , the resistance against corrosion reaction, was obtained by fitting measured impedance spectra into an equivalent circuit. The values of R 2 were then used to assess corrosion resistance of the steels in each organic constituent and mixture. Type 410 and 430 stainless steels were resistant to corrosion in all tested organic constituents, while 2.25Cr-1Mo steel was not. 9Cr-1Mo steel was corrosion resistant in catechol but not in the other mixtures that contained organic acids. On the basis of the results of this work, it is suggested that the corrosion resistance against organic acids is attributed to formation of a Cr-rich passive film that requires stainless steels with critical Cr levels in excess of approximately 11 wt %. In catechol-only solution, lower levels of Cr intermediate between that of 2.25Cr-1Mo steel and 9Cr-1Mo steel appeared sufficient.
Evaluating the Role of Macrocycles in the Susceptibility of Hepatitis C Virus NS3/4A Protease Inhibitors to Drug Resistance
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Simulating toxicokinetic variability to identify susceptible and highly exposed populations
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A planar defect spin sensor in a two-dimensional material susceptible to strain and electric fields
Abstract The boron-vacancy spin defect ( $${\,{{\mbox{V}}}}_{{{\mbox{B}}}\,}^{-}$$ V B − ) in hexagonal boron nitride (hBN) has a great potential as a quantum sensor in a two-dimensional material that can directly probe various external perturbations in atomic-scale proximity to the quantum sensing layer. Here, we apply first-principles calculations to determine the coupling of the $${\,{{\mbox{V}}}}_{{{\mbox{B}}}\,}^{-}$$ V B − electronic spin to strain and electric fields. Our work unravels the interplay between local piezoelectric and elastic effects contributing to the final response to the electric fields. The theoretical predictions are then used to analyse optically detected magnetic resonance (ODMR) spectra recorded on hBN crystals containing different densities of $${\,{{\mbox{V}}}}_{{{\mbox{B}}}\,}^{-}$$ V B − centres. We prove that the orthorhombic zero-field splitting parameter results from local electric fields produced by surrounding charge defects. This work paves the way towards applications of $${\,{{\mbox{V}}}}_{{{\mbox{B}}}\,}^{-}$$ V B − centres for quantitative electric field imaging and quantum sensing under pressure.
The cardiac molecular setting of metabolic syndrome in pigs reveals disease susceptibility and suggests mechanisms that exacerbate COVID-19 outcomes in patients
Abstract Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes compared to their non MetS peers. Here, we use obese Yorkshire pigs as a highly relevant animal model of human MetS, where pigs develop the hallmarks of human MetS and reproducibly mimics the myocardial pathophysiology in patients. Myocardium-specific mass spectroscopy-derived metabolomics, proteomics, and transcriptomics enabled the identity and quality of proteins and metabolites to be investigated in the myocardium to greater depth. Myocardium-specific deregulation of pro-inflammatory markers, propensity for arterial thrombosis, and platelet aggregation was revealed by computational analysis of differentially enriched pathways between MetS and control animals. While key components of the complement pathway and the immune response to viruses are under expressed, key N6-methyladenosin RNA methylation enzymes are largely overexpressed in MetS. Blood tests do not capture the entirety of metabolic changes that the myocardium undergoes, making this analysis of greater value than blood component analysis alone. Our findings create data associations to further characterize the MetS myocardium and disease vulnerability, emphasize the need for a multimodal therapeutic approach, and suggests a mechanism for observed worse outcomes in MetS patients with COVID-19 comorbidity.
Swine acute diarrhea syndrome coronavirus replication in primary human cells reveals potential susceptibility to infection
Zoonotic coronaviruses represent an ongoing threat, yet the myriads of circulating animal viruses complicate the identification of higher-risk isolates that threaten human health. Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered, highly pathogenic virus that likely evolved from closely related HKU2 bat coronaviruses, circulating in Rhinolophus spp. bats in China and elsewhere. As coronaviruses cause severe economic losses in the pork industry and swine are key intermediate hosts of human disease outbreaks, we synthetically resurrected a recombinant virus (rSADS-CoV) as well as a derivative encoding tomato red fluorescent protein (tRFP) in place of ORF3. rSADS-CoV replicated efficiently in a variety of continuous animal and primate cell lines, including human liver and rectal carcinoma cell lines. Of concern, rSADS-CoV also replicated efficiently in several different primary human lung cell types, as well as primary human intestinal cells. rSADS-CoV did not use human coronavirus ACE-2, DPP4, or CD13 receptors for docking and entry. Contemporary human donor sera neutralized the group I human coronavirus NL63, but not rSADS-CoV, suggesting limited human group I coronavirus cross protective herd immunity. Importantly, remdesivir, a broad-spectrum nucleoside analog that is effective against other group 1 and 2 coronaviruses, efficiently blocked rSADS-CoV replication in vitro. rSADS-CoV demonstrated little, if any, replicative capacity in either immune-competent or immunodeficient mice, indicating a critical need for improved animal models. Efficient growth in primary human lung and intestinal cells implicate SADS-CoV as a potential higher-risk emerging coronavirus pathogen that could negatively impact the global economy and human health.
Dietary modulation of gut microbiota affects susceptibility to drug-induced liver injury
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The ability of Salmonella enterica subsp. enterica strains to form biofilms on abiotic surfaces and their susceptibility to selected essential oil components
Abstract The ability of Salmonella enterica subsp. enterica to persist and form biofilms on different surfaces can constitute a source of food contamination, being an issue of global concern. The objective of this study was to understand the biofilm formation profile of 14 S. enterica strains among different serovars and sources and to evaluate the ability of essential oil (EO) components (carveol, citronellol, and citronellal) to disinfect the biofilms formed on stainless steel and polypropylene surfaces. All the strains were able to form biofilms with counts between 5.34 to 6.78 log CFU cm−2. Then, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EO components were evaluated on two selected strains. All compounds inhibited the growth of Salmonella Typhimurium (strain 1; MIC = 800–1000 µg ml−1) and Salmonella Enteritidis (strain 5; MIC = 400–1000 µg ml−1) and only carveol showed bactericidal activity against strains 1 and 5 (MBC = 1200 µg ml−1). Biofilms were exposed to the EO components at 10 × MIC for 30 min and polypropylene surfaces were more difficult to disinfect showing reductions between 0.9 and <1.2 log CFU cm−2. In general, the S. enterica biofilms demonstrated a significant tolerance to disinfection, demonstrating their high degree of recalcitrance on food processing surfaces.
Arabidopsis bZIP11 Is a Susceptibility Factor During Pseudomonas syringae Infection
The induction of plant nutrient secretion systems is critical for successful pathogen infection. Some bacterial pathogens (e.g., Xanthomonas spp.) use transcription activator-like (TAL) effectors to induce transcription of SWEET sucrose efflux transporters. Pseudomonas syringae pv. tomato strain DC3000 lacks TAL effectors yet is able to induce multiple SWEETs in Arabidopsis thaliana by unknown mechanisms. Because bacteria require other nutrients in addition to sugars for efficient reproduction, we hypothesized that Pseudomonas spp. may depend on host transcription factors involved in secretory programs to increase access to essential nutrients. Bioinformatic analyses identified the Arabidopsis basic-leucine zipper transcription factor bZIP11 as a potential regulator of nutrient transporters, including SWEETs and UmamiT amino acid transporters. Inducible downregulation of bZIP11 expression in Arabidopsis resulted in reduced growth of P. syringae pv. tomato strain DC3000, whereas inducible overexpression of bZIP11 resulted in increased bacterial growth, supporting the hypothesis that bZIP11-regulated transcription programs are essential for maximal pathogen titer in leaves. Our data are consistent with a model in which a pathogen alters host transcription factor expression upstream of secretory transcription networks to promote nutrient efflux from host cells. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The genetic basis of phage susceptibility, cross-resistance and host-range in Salmonella
Though bacteriophages (phages) are known to play a crucial role in bacterial fitness and virulence, our knowledge about the genetic basis of their interaction, cross-resistance and host-range is sparse. Here, we employed genome-wide screens in Salmonella enterica serovar Typhimurium to discover host determinants involved in resistance to eleven diverse lytic phages including four new phages isolated from a therapeutic phage cocktail. We uncovered 301 diverse host factors essential in phage infection, many of which are shared between multiple phages demonstrating potential cross-resistance mechanisms. We validate many of these novel findings and uncover the intricate interplay between RpoS, the virulence-associated general stress response sigma factor and RpoN, the nitrogen starvation sigma factor in phage cross-resistance. Finally, the infectivity pattern of eleven phages across a panel of 23 genome sequenced Salmonella strains indicates that additional constraints and interactions beyond the host factors uncovered here define the phage host range.
Collective magnetic dynamics in artificial spin ice probed by ac susceptibility
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