Trained Immunity Confers Prolonged Protection From Listeriosis.

Trained immunity refers to the ability of the innate immune system exposed to a first challenge to provide an enhanced response to a secondary homologous or heterologous challenge. We reported that training induced with β-glucan one week before infection confers protection against a broad-spectrum of lethal bacterial infections. Whether this protection persists over time is unknown. To tackle this question, we analyzed the immune status and the response to Listeria monocytogenes (L. monocytogenes) of mice trained 9 weeks before analysis. The induction of trained immunity increased bone marrow myelopoiesis and blood counts of Ly6C <sup>high</sup> inflammatory monocytes and polymorphonuclear neutrophils (PMNs). Ex vivo, whole blood, PMNs and monocytes from trained mice produced increased levels of cytokines in response to microbial products and limited the growth of L. monocytogenes. In vivo, following challenge with L. monocytogenes, peripheral blood leukocytes were massively depleted in control mice but largely preserved in trained mice. PMNs were reduced also in the spleen from control mice, and increased in the spleen of trained mice. In transwell experiments, PMNs from trained mice showed increased spontaneous migration and CXCL2/MIP2α-induced chemotaxis, suggesting that training promotes the migration of PMNs in peripheral organs targeted by L. monocytogenes. Trained PMNs and monocytes had higher glycolytic activity and mitochondrial respiration than control cells when exposed to L. monocytogenes. Bacterial burden and dissemination in blood, spleen and liver as well as systemic cytokines and inflammation (multiplex bead assay and bioluminescence imaging) were reduced in trained mice. In full agreement with these results, mice trained 9 weeks before infection were powerfully protected from lethal listeriosis. Altogether, these data suggest that training increases the generation and the antimicrobial activity of PMNs and monocytes, which may confer prolonged protection from lethal bacterial infection

Explicit Evidence Systems with Common Knowledge

Justification logics are epistemic logics that explicitly include justifications for the agents' knowledge. We develop a multi-agent justification logic with evidence terms for individual agents as well as for common knowledge. We define a Kripke-style semantics that is similar to Fitting's semantics for the Logic of Proofs LP. We show the soundness, completeness, and finite model property of our multi-agent justification logic with respect to this Kripke-style semantics. We demonstrate that our logic is a conservative extension of Yavorskaya's minimal bimodal explicit evidence logic, which is a two-agent version of LP. We discuss the relationship of our logic to the multi-agent modal logic S4 with common knowledge. Finally, we give a brief analysis of the coordinated attack problem in the newly developed language of our logic

COVID-19 rapidly increases MDSCs and prolongs innate immune dysfunctions.

We used unsupervised immunophenotyping of blood leukocytes and measured cytokine production by innate immune cell exposed to LPS and R848. We show that COVID-19 induces a rapid, transient upregulation of myeloid-derived suppressor cells (MDSCs) accompanied by a rapid, sustained (up to 3 months) hyporesponsiveness of dendritic cells and monocytes. Blood MDSCs may represent biomarkers and targets for intervention strategies in COVID-19 patients

Long-range transfer of electron-phonon coupling in oxide superlattices

The electron-phonon interaction is of central importance for the electrical and thermal properties of solids, and its influence on superconductivity, colossal magnetoresistance, and other many-body phenomena in correlated-electron materials is currently the subject of intense research. However, the non-local nature of the interactions between valence electrons and lattice ions, often compounded by a plethora of vibrational modes, present formidable challenges for attempts to experimentally control and theoretically describe the physical properties of complex materials. Here we report a Raman scattering study of the lattice dynamics in superlattices of the high-temperature superconductor $\bf YBa_2 Cu_3 O_7$ and the colossal-magnetoresistance compound $\bf La_{2/3}Ca_{1/3}MnO_{3}$ that suggests a new approach to this problem. We find that a rotational mode of the MnO$_6$ octahedra in $\bf La_{2/3}Ca_{1/3}MnO_{3}$ experiences pronounced superconductivity-induced lineshape anomalies, which scale linearly with the thickness of the $\bf YBa_2 Cu_3 O_7$ layers over a remarkably long range of several tens of nanometers. The transfer of the electron-phonon coupling between superlattice layers can be understood as a consequence of long-range Coulomb forces in conjunction with an orbital reconstruction at the interface. The superlattice geometry thus provides new opportunities for controlled modification of the electron-phonon interaction in complex materials.Comment: 13 pages, 4 figures. Revised version to be published in Nature Material

Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

BACKGROUND: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. METHODS: In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. RESULTS: Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. CONCLUSIONS: Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity

Change of annexin binding of monocytes as an expression of cellular response to Candida albicans: down-regulation in severe sepsis

To study the differences of monocyte activation by albicans and non-albicans species of Candida and its change in sepsis, peripheral blood mononuclear cells were isolated from 17 healthy volunteers and 26 patients with severe sepsis/shock, and incubated in the absence/presence of heat-killed (HK) isolates of four different Candida species and purified β-D-glucan from C.albicans. Experiments were repeated in the presence and absence of inhibitors of intracellular activation pathways. Expression of annexin V on cells membranes of monocytes and lymphocytes, cytoplasmic activity of caspase-3, and DNA fragmentation of monocytes were studied. Membrane expression of annexin V on viable monocytes of healthy volunteers decreased significantly after incubation with C.albicans but not with non-albicans species. The decrease was dose-dependent from the Candida inoculum and by the concentration of β-D-glucan. A relationship with inhibition of apoptosis was found as the activity of caspase-3 activity, and the level of DNA fragmentation were also decreased. Incubation in the absence/presence of inhibitors showed that the decrease by annexin V expression resulted by activation of the dectin-1 pathway and Raf-1 by β-D glucan. The decrease of annexin V(+)/PI(−) expression was not shown on monocytes of patients with severe sepsis/shock, where no effect of inhibitors was found. Decrease of annexin V binding on monocytes can be viewed as a selective response to C.albicans partly effected through activation of dectin-1. This response is down-regulated after a septic insult. © 2016, Springer-Verlag Berlin Heidelberg

Micro-Raman depth profiling of silicon amorphization induced by high-energy ion channeling implantation

In this work, we study the silicon amorphization dependence on the crystal depth induced by 6-MeV Al2+ ions implanted in the LT 110 GT and randomly oriented silicon crystal channels, which was not directly experimentally accessible in the previous similar high-energy ioncrystal implantation cases. Accordingly, the micro-Raman spectroscopy scanning measurements along the crystal transversal cross section of the ion implanted region were performed. The ion fluence was 10(17) particles/cm(2). The scanning steps were 0.2 and 0.3 mu m, for the channeling and random ion implantations, respectively. The obtained results are compared with the corresponding Rutherford backscattering spectra of 1.2-MeV protons in the random and channeling orientations measured during the channeling implantation. Additionally, scanning electron microscope picture was taken on the transversal cross section of the implanted region in the channeling implantation case. We show here that the obtained silicon amorphization maxima are in excellent agreement with the corresponding estimated maxima of the aluminum concentration in silicon. This clearly indicates that the used specific micro-Raman spectroscopy scanning technique can be successfully applied for the depth profiling of the crystal amorphization induced by high-energy ion implantation. Copyright (c) 2013 John Wiley and Sons, Ltd

Impact of comorbidities on the performance of interferon-gamma release assay in an elderly Greek population without overt immunodeficiency

Background The prevalence of latent tuberculosis infection (LTBI) increases with age. Interferon-gamma release assay (IGRA) is a T-cell based assay widely used for the detection of LTBI. Objectives To identify the prevalence of LTBI among an elderly Greek population using IGRA and to evaluate comorbidities associated with LTBI. Methods Individuals aged at least 65 years who were non-immunocompromised and had no history of active tuberculosis infection (TBI) underwent IGRA to identify LTBI. Participant characteristics were compared between the LTBI and non-LTBI groups. Interferon-gamma (INFγ) levels were analysed in each group. Results A total of 130 (38.7%) participants with LTBI and 206 (61.3%) participants without LTBI were included. Multivariate logistic regression analysis identified the following features that were independently associated with a positive IGRA result: female sex (odds ratio [OR]: 0.45; 95% confidence interval [CI]: 0.28-0.72; P=0.001), chronic heart failure (OR: 0.41; 95% CI: 0.22-0.77; P=0.005), history of major surgery (OR: 0.55; 95% CI: 0.33-0.92; P=0.022) and Charlson Comorbidity Index >3 (OR: 3.06; 95% CI: 1.46-6.40; P=0.003). Production of stimulated INFγ was significantly lower in the non-LTBI group. Conclusions Female sex, history of chronic heart failure and history of any surgical intervention were independently associated with a negative IGRA result, and CCI >3 was associated with a positive IGRA result. These results indicate careful interpretation of IGRA is required among elderly individuals with these characteristics. © 2020 Elsevier Lt

Virtual audits of the urban streetscape: comparing the inter-rater reliability of GigaPan® to Google Street View

Abstract Background Although previous research has highlighted the association between the built environment and individual health, methodological challenges in assessing the built environment remain. In particular, many researchers have demonstrated the high inter-rater reliability of assessing large or objective built environment features and the low inter-rater reliability of assessing small or subjective built environment features using Google Street View. New methods for auditing the built environment must be evaluated to understand if there are alternative tools through which researchers can assess all types of built environment features with high agreement. This paper investigates measures of inter-rater reliability of GigaPan®, a tool that assists with capturing high-definition panoramic images, relative to Google Street View. Methods Street segments (n = 614) in Pittsburgh, Pennsylvania in the United States were randomly selected to audit using GigaPan® and Google Street View. Each audit assessed features related to land use, traffic and safety, and public amenities. Inter-rater reliability statistics, including percent agreement, Cohen’s kappa, and the prevalence-adjusted bias-adjusted kappa (PABAK) were calculated for 106 street segments that were coded by two, different, human auditors. Results Most large-scale, objective features (e.g. bus stop presence or stop sign presence) demonstrated at least substantial inter-rater reliability for both methods, but significant differences emerged across finely detailed features (e.g. trash) and features at segment endpoints (e.g. sidewalk continuity). After adjusting for the effects of bias and prevalence, the inter-rater reliability estimates were consistently higher for almost all built environment features across GigaPan® and Google Street View. Conclusion GigaPan® is a reliable, alternative audit tool to Google Street View for studying the built environment. GigaPan® may be particularly well-suited for built environment projects with study settings in areas where Google Street View imagery is nonexistent or updated infrequently. The potential for enhanced, detailed imagery using GigaPan® will be most beneficial in studies in which current, time sensitive data are needed or microscale built environment features would be challenging to see in Google Street View. Furthermore, to better understand the effects of prevalence and bias in future reliability studies, researchers should consider using PABAK to supplement or expand upon Cohen’s kappa findings.http://deepblue.lib.umich.edu/bitstream/2027.42/173713/1/12942_2020_Article_226.pd