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Many helminth life cycles, including hookworm, involve a mandatory lung phase, where myeloid and granulocyte subsets interact with the helminth and respond to infection-induced lung injury. To evaluate these innate subsets in Nippostrongylus brasiliensis infection, reporter mice for myeloid cells (CX3CR1GFP ) and granulocytes (PGRPdsRED ) are employed. Nippostrongylus infection induces lung infiltration of reporter cells, including CX3CR1+ myeloid cells and PGRP+ eosinophils. Strikingly, CX3CR1GFP/GFP mice, which are deficient in CX3CR1, are protected from Nippostrongylus infection with reduced weight loss, lung leukocyte infiltration, and worm burden compared to CX3CR1+/+ mice. This protective effect is specific for CX3CR1 as CCR2-deficient mice do not exhibit reduced worm burdens. Nippostrongylus co-culture with lung Ly6C+ monocytes or CD11c+ cells demonstrates that CX3CR1GFP/GFP monocytes secrete more pro-inflammatory cytokines and actively bind the parasites causing reduced motility. RNA sequencing of Ly6C+ or CD11c+ cells shows Nippostrongylus-induced gene expression changes, particularly in monocytes, associated with inflammation, chemotaxis, and extracellular matrix remodeling pathways. Analysis reveals cytotoxic and adhesion molecules as potential effectors against the parasite, such as Gzma and Gzmb, which are elevated in CX3CR1GFP/GFP monocytes. These studies validate a dual innate cell reporter for lung helminth infection and demonstrate that CX3CR1 impairs monocyte-helminth interaction.

Macrophages are critically involved in wound healing, from dampening inflammation to clearing cell debris and coordinating tissue repair. Within the wound, the complexity of macrophage function is increasingly recognized, with adverse outcomes when macrophages are inappropriately activated, such as in fibrosis or chronic non-healing wounds. Recent advances in in vivo and translational wound models, macrophage-specific deletions and new technologies to distinguish macrophage subsets, have uncovered the vast spectrum of macrophage activation and effector functions. Here, we summarize the main players in wound-healing macrophage activation and function, including cytokines, apoptotic cells, nucleotides and mechanical stimuli. We highlight recent studies demonstrating cooperation between these factors for optimal wound healing. Next, we describe recent technologies such as cell tracking and single-cell RNA-seq, which have uncovered remarkable plasticity and heterogeneity in blood-derived or tissue-resident macrophages and discuss the implications for wound healing. Lastly, we evaluate macrophage dysfunction in aberrant wound healing that occurs in aging, diabetes and fibrosis. A better understanding of the longevity and plasticity of wound-healing macrophages, and identification of unique macrophage subsets or specific effector molecules in wound healing, would shed light on the therapeutic potential of manipulating macrophage function for optimal wound healing.

This dissertation details the synthesis and properties of Ca-doped BiFeO3 thin films. The phase diagram was established as a function of the Ca doping concentration and temperature through structural analysis to study the effect of divalent-ion-calcium doping on BiFeO3 films. A ferroelectric-paraelectric boundary exists around at 10% Ca doping ratio. For this doping concentration, the largest transition of conduction states was observed. The mechanisms for the observed effects are discussed on the basis of the interplay of ionic and electronic conduction through the redistribution of oxygen vacancies by application of electric fields. Application of electric fields enables to control and manipulate this electronic transition to the extent that a p-n junction can be created, erased and inverted in this material. Beside this conduction transition, the visible shading effect was observed with application of electric fields. Based on these reversible transitions of the electrical and optical characteristics of Ca-doped BiFeO3, electrical and optical memory devices are proposed in this dissertation. The memory device built with a hetero-junction presented a nonvolatile conduction modulation with a rectified current behavior, which is essential for realizing random access memory devices. The switching mechanism is elucidated by junction property modification ascribed to the change of local oxygen vacancy concentration. In addition, the optical characteristics of Ca-doped BiFeO3 films for potential electro-optic memory devices were measured and evaluated. Detailed discussion about the origin of the shading effect is given based on the change of a polar order parameter and an oxygen vacancy ordered state.

ARKIVOC: vol. 2010, no. 7, (issn) 1551-7012, (dlps) 5550190.0011.709, This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 License. Please contact mpub-help@umich.edu to use this work in a way not covered by the license.