Publications by authors named "Mark J Miller"

Complications after lung transplantation are largely related to the host immune system responding to the graft. Such immune responses are regulated by crosstalk between donor and recipient cells. A better understanding of these processes relies on the use of preclinical animal models and is aided by an ability to study intra-graft immune cell trafficking in real-time.

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Sterile tissue injury, such as by acute kidney injury, is common in the clinic and frequently associated with respiratory compromise and hypoxemia. We previously described signaling components released by the injured kidney that drive a remote inflammatory response in the lung. How this caused the resultant hypoxemia remained unclear.

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Article Synopsis
  • Venezuelan Equine Encephalitis virus (VEEV) can invade the central nervous system through olfactory sensory neurons (OSN) after intranasal exposure, but its impact on interferon signaling during this process hasn't been extensively studied.
  • Research using a mouse model showed that immature OSNs, which have more VEEV receptors, are initially targeted by the virus; however, the immune response (IFN signaling) is significantly delayed, providing a potential treatment opportunity.
  • Administering intranasal recombinant IFNα during or shortly after VEEV infection not only delayed the disease's onset and prolonged survival but also temporarily suppressed the virus's replication, highlighting its therapeutic potential against alphavirus-induced encephalitis
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The pore-forming S. aureus α-toxin (Hla) contributes to virulence and disease pathogenesis. While high concentrations of toxin induce cell death, neutrophils exhibit relative resistance to lysis, suggesting that the action of Hla may not be solely conferred by lytic susceptibility.

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The endothelium plays a critical role in the host response to infection and has been a focus of investigation in sepsis. While it is appreciated that intravascular thrombus formation, severe inflammation, and loss of endothelial integrity impair tissue oxygenation during sepsis, the precise molecular mechanisms that lead to endothelial injury remain poorly understood. We demonstrate here that endothelial ADAM10 was essential for the pathogenesis of Staphylococcus aureus sepsis, contributing to α-toxin-mediated (Hla-mediated) microvascular thrombus formation and lethality.

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Genomic selection has been utilized for genetic improvement in both plant and animal breeding and is a favorable technique for quantitative trait development. Within this study, genomic selection was evaluated within a breeding program, using novel validation methods in addition to plant materials and data from a commercial soybean (Glycine max) breeding program. A total of 1501 inbred lines were used to test multiple genomic selection models for multiple traits.

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Improving yield is a primary soybean breeding goal, as yield is the main determinant of soybean's profitability. Within the breeding process, selection of cross combinations is one of most important elements. Cross prediction will assist soybean breeders in identifying the best cross combinations among parental genotypes prior to crossing, increasing genetic gain and breeding efficiency.

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Clinical symptoms in many inflammatory diseases of the intestine are directly related to neutrophil (PMN) migration across colonic mucosa and into the intestinal lumen, yet in-vivo studies detailing this process are lacking. Using real-time intravital microscopy and a new distal colon loop model, we report distinct PMN migratory dynamics in response to several models of acute colonic injury. PMNs exhibited rapid swarming responses after mechanically induced intestinal wounds.

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Listeria monocytogenes (Lm) is a food-borne pathogen that causes severe bacterial gastroenteritis, with high rates of hospitalization and mortality. Lm is ubiquitous in soil, water and livestock, and can survive and proliferate at low temperatures. Following oral ingestion of contaminated food, Lm crosses the epithelium through intestinal goblet cells in a mechanism mediated by Lm InlA binding host E-cadherin.

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Article Synopsis
  • Digital technologies and open innovation have led to the creation of virtual organizations, exemplified by the International Natural Product Sciences Taskforce (INPST), established in 2018 for collaboration in natural product research.
  • The INPST utilized Twitter for a week-long networking event in June 2021, using the hashtag #INPST to facilitate interactions among participants.
  • Analysis of the event revealed 6,036 tweets from 686 users, resulting in over 65 million impressions, highlighting Twitter's effectiveness for hosting international biomedical research discussions.
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Ischemia reperfusion injury represents a common pathological condition that is triggered by the release of endogenous ligands. While neutrophils are known to play a critical role in its pathogenesis, the tissue-specific spatiotemporal regulation of ischemia-reperfusion injury is not understood. Here, using oxidative lipidomics and intravital imaging of transplanted mouse lungs that are subjected to severe ischemia reperfusion injury, we discovered that necroptosis, a nonapoptotic form of cell death, triggers the recruitment of neutrophils.

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Enterotoxigenic Escherichia coli (ETEC) isolates are genetically diverse pathological variants of E. coli defined by the production of heat-labile (LT) and/or heat-stable (ST) toxins. ETEC strains are estimated to cause hundreds of millions of cases of diarrheal illness annually.

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Visualization of cell migration via time-lapse microscopy has greatly advanced our understanding of the immune system. However, subtle differences in migration dynamics are easily obscured by biases and imaging artifacts. While several analysis methods have been suggested to address these issues, an integrated tool implementing them is currently lacking.

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Listeria monocytogenes is an intracellular bacterium that elicits robust CD8+ T-cell responses. Despite the ongoing development of L. monocytogenes-based platforms as cancer vaccines, our understanding of how L.

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Soybean [Glycinemax (L.) Merr.] maturity determines the growing region of a given soybean variety and is a primary factor in yield and other agronomic traits.

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Background: Critical advances in the investigation of brain functions and treatment of brain disorders are hindered by our inability to selectively target neurons in a noninvasive manner in the deep brain.

Objective: This study aimed to develop sonothermogenetics for noninvasive, deep-penetrating, and cell-type-specific neuromodulation by combining a thermosensitive ion channel TRPV1 with focused ultrasound (FUS)-induced brief, non-noxious thermal effect.

Methods: The sensitivity of TRPV1 to FUS sonication was evaluated in vitro.

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Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia.

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IL-33 is a key mediator of chronic airway disease driven by type 2 immune pathways, yet the nonclassical secretory mechanism for this cytokine remains undefined. We performed a comprehensive analysis in human airway epithelial cells, which revealed that tonic IL-33 secretion is dependent on the ceramide biosynthetic enzyme neutral sphingomyelinase 2 (nSMase2). IL-33 is cosecreted with exosomes by the nSMase2-regulated multivesicular endosome (MVE) pathway as surface-bound cargo.

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Itch is an evolutionarily conserved sensation that facilitates expulsion of pathogens and noxious stimuli from the skin. However, in organ failure, cancer, and chronic inflammatory disorders such as atopic dermatitis (AD), itch becomes chronic, intractable, and debilitating. In addition to chronic itch, patients often experience intense acute itch exacerbations.

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Herpes simplex virus-2 (HSV-2) and HSV-1 both can cause genital herpes, a chronic infection that establishes a latent reservoir in the nervous system. Clinically, the recurrence frequency of HSV-1 genital herpes is considerably less than HSV-2 genital herpes, which correlates with reduced neuronal infection. The factors dictating the disparate outcomes of HSV-1 and HSV-2 genital herpes are unclear.

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In eukaryotes, Polycomb group (PcG) and trithorax group (trxG) factors oppositely regulate gene transcription during development through histone modifications, with PcG factors repressing and trxG factors activating the expression of their target genes. Although plant trxG factors regulate many developmental and physiological processes, their downstream targets are poorly characterized. Here we use transcriptomics to identify genome-wide targets of the trxG factor ULTRAPETALA1 (ULT1) during vegetative and reproductive development and compare them with those of the PcG factor CURLY LEAF (CLF).

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Neutrophils are essential to the pathogenesis of many inflammatory diseases. In the autoantibody-mediated K/BxN model of inflammatory arthritis, the alternative pathway (AP) of complement and Fc gamma receptors (FcγRs) are required for disease development while the classical pathway is dispensable. The reason for this differential requirement is unknown.

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The protozoan parasite Toxoplasma gondii is thought to exploit monocyte trafficking to facilitate dissemination across endothelial barriers such as the blood-brain barrier. Here, we analysed the migration of parasitized monocytes in model endothelial and interstitial environments. We report that infection enhanced monocyte locomotion on the surface of endothelial cells, but profoundly inhibited monocyte transmigration across endothelial barriers.

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Neutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse-1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2-photon microscopy, we analyzed the effects of DNAse-1 on NETs in mouse orthotopic lung allografts damaged by ischemia-reperfusion injury.

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Background: A direct and independent role of inflammation in atherothrombosis was recently highlighted by the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) trial, showing the benefit of inhibiting signaling molecules, eg, interleukins. Accordingly, we sought to devise a flexible platform for preventing the inflammatory drivers at their source to preserve plaque endothelium and mitigate procoagulant risk.

Methods: p5RHH-siRNA nanoparticles were formulated through self-assembly processes.

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