Personalized 3D-printed anthropomorphic whole-body phantom irradiated by protons, photons, and neutrons.

The objective of this study was to confirm the feasibility of three-dimensionally-printed (3D-printed), personalized whole-body anthropomorphic phantoms for radiation dose measurements in a variety of charged and uncharged particle radiation fields. We 3D-printed a personalized whole-body phantom of an adult female with a height of 154.8 cm, mass of 90.

Macrophage-derived netrin-1 drives adrenergic nerve-associated lung fibrosis.

Fibrosis is a macrophage-driven process of uncontrolled extracellular matrix accumulation. Neuronal guidance proteins such as netrin-1 promote inflammatory scarring. We found that macrophage-derived netrin-1 stimulates fibrosis through its neuronal guidance functions.

Aldosterone Mediated Regulation of Epithelial Sodium Channel (ENaC) Subunits in the Rat Hypothalamus.

Current evidence suggests that the epithelial Na channel (ENaC) in the brain plays a significant role in the development of hypertension. ENaC is present in vasopressin (VP) neurons in the hypothalamus, suggesting that ENaC in VP neurons is involved in the regulation of blood pressure. Our recent study demonstrated that high dietary salt intake caused an increase in the expression and activity of ENaC that were responsible for the more depolarized basal membrane potential in VP neurons.

Antifibrotic role of vascular endothelial growth factor in pulmonary fibrosis.

The chronic progressive decline in lung function observed in idiopathic pulmonary fibrosis (IPF) appears to result from persistent nonresolving injury to the epithelium, impaired restitution of the epithelial barrier in the lung, and enhanced fibroblast activation. Thus, understanding these key mechanisms and pathways modulating both is essential to greater understanding of IPF pathogenesis. We examined the association of VEGF with the IPF disease state and preclinical models in vivo and in vitro.

Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and enhances mammalian lung fibrosis.

Pulmonary fibrosis is a progressive and often fatal condition that is believed to be partially orchestrated by macrophages. Mechanisms that control migration of these cells into and within the lung remain undefined. We evaluated the contributions of the semaphorin receptor, plexin C1 (PLXNC1), and the exocytic calcium sensor, synaptotagmin 7 (Syt7), in these processes.

Regulatory T Cells in Idiopathic Pulmonary Fibrosis: Too Much of a Good Thing?

This commentary highlights the article by Birjandi et al showing that alterations in regulatory T cells can exacerbate lung fibrosis.

RIG-like Helicase Regulation of Chitinase 3-like 1 Axis and Pulmonary Metastasis.

Chi3l1 is induced by a variety of cancers where it portends a poor prognosis and plays a key role in the generation of metastasis. However, the mechanisms that Chi3l1 uses to mediate these responses and the pathways that control Chi3l1-induced tumor responses are poorly understood. We characterized the mechanisms that Chi3l1 uses to foster tumor progression and the ability of the RIG-like helicase (RLH) innate immune response to control Chi3l1 elaboration and pulmonary metastasis.

Mitral Valve Replacement After Failed Mitral Ring Insertion With or Without Leaflet/Chordal Repair for Pure Mitral Regurgitation.

Mitral repair operations for correction of pure mitral regurgitation (MR) are generally quite successful. Occasionally, however, the reparative procedure incompletely corrects the MR or the MR recurs. From March 1993 to January 2016, twenty nine patients had mitral valve replacement after the initial mitral repair operation, and observations in them were analyzed.

Netrin-1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin-Induced Pulmonary Fibrosis.

Objective: Fibrocytes are collagen-producing leukocytes that accumulate in patients with systemic sclerosis (SSc; scleroderma)-related interstitial lung disease (ILD) via unknown mechanisms that have been associated with altered expression of neuroimmune proteins. The extracellular matrix (ECM) influences cellular phenotypes. However, a relationship between the lung ECM and fibrocytes in SSc has not been explored.

Chitinase 3-like 1 suppresses injury and promotes fibroproliferative responses in Mammalian lung fibrosis.

Epithelial injury, alternative macrophage accumulation, and fibroproliferation coexist in the lungs of patients with idiopathic pulmonary fibrosis (IPF). Chitinase 3-like 1 (CHI3L1) is a prototypic chitinase-like protein that has been retained over species and evolutionary time. However, the regulation of CHI3L1 in IPF and its ability to regulate injury and/or fibroproliferative repair have not been fully defined.

CD4+CD25+FoxP3+ Regulatory Tregs inhibit fibrocyte recruitment and fibrosis via suppression of FGF-9 production in the TGF-β1 exposed murine lung.

Pulmonary fibrosis is a difficult to treat, often fatal disease whose pathogenesis involves dysregulated TGF-β1 signaling. CD4+CD25+FoxP3+ Regulatory T cells ("Tregs") exert important effects on host tolerance and arise from naïve CD4+ lymphocytes in response to TGF-β1. However, the precise contribution of Tregs to experimentally induced murine lung fibrosis remains unclear.

Regulation and Relevance of Myofibroblast Responses in Idiopathic Pulmonary Fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, incurable lung disease of unknown etiology with only limited treatment options. Current paradigms of disease pathogenesis feature recurrent or prolonged epithelial injury and an ensuing inflammatory response that culminates in the appearance of activated myofibroblasts. These cells are believed central to the excessive deposition of extracellular matrix that eventually obliterates the alveolar space to cause respiratory failure.

Air quality impact and physicochemical aging of biomass burning aerosols during the 2007 San Diego wildfires.

Intense wildfires burning >360000 acres in San Diego during October, 2007 provided a unique opportunity to study the impact of wildfires on local air quality and biomass burning aerosol (BBA) aging. The size-resolved mixing state of individual particles was measured in real-time with an aerosol time-of-flight mass spectrometer (ATOFMS) for 10 days after the fires commenced. Particle concentrations were high county-wide due to the wildfires; 84% of 120-400 nm particles by number were identified as BBA, with particles <400 nm contributing to mass concentrations dangerous to public health, up to 148 μg/m(3).

Approach for measuring the chemistry of individual particles in the size range critical for cloud formation.

Aerosol particles, especially those ranging from 50 to 200 nm, strongly impact climate by serving as nuclei upon which water condenses and cloud droplets form. However, the small number of analytical methods capable of measuring the composition of particles in this size range, particularly at the individual particle level, has limited our knowledge of cloud condensation nuclei (CCN) composition and hence our understanding of aerosols effect on climate. To obtain more insight into particles in this size range, we developed a method which couples a growth tube (GT) to an ultrafine aerosol time-of-flight mass spectrometer (UF-ATOFMS), a combination that allows in situ measurements of the composition of individual particles as small as 38 nm.

Timescale for hygroscopic conversion of calcite mineral particles through heterogeneous reaction with nitric acid.

Atmospheric heterogeneous reactions can potentially change the hygroscopicity of atmospheric aerosols as they undergo chemical aging processes in the atmosphere. A particle's hygroscopicity influences its cloud condensation nuclei (CCN) properties with potential impacts on cloud formation and climate. In this study, size-selected calcite mineral particles were reacted with controlled amounts of nitric acid vapour over a wide range of relative humidities in an aerosol flow tube to study the conversion of insoluble and thus apparently non-hygroscopic calcium carbonate into soluble and hygroscopic calcium nitrate.

Impact of emissions from the Los Angeles port region on San Diego air quality during regional transport events.

Oceangoing ships emit an estimated 1.2-1.6 million metric tons (Tg) of PM10 per year and represent a significant source of air pollution to coastal communities.

Activation of human monocytes by live Borrelia burgdorferi generates TLR2-dependent and -independent responses which include induction of IFN-beta.

It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion by demonstrating that phagocytosis of live Bb by peripheral blood mononuclear cells (PBMCs) elicited greater production of proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared to lysates, live spirochetes elicited a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-beta and a number of interferon-stimulated genes (ISGs), which are not known to result from TLR2 signaling.

Phagocytosis of Borrelia burgdorferi, the Lyme disease spirochete, potentiates innate immune activation and induces apoptosis in human monocytes.

We have previously demonstrated that phagocytosed Borrelia burgdorferi induces activation programs in human peripheral blood mononuclear cells that differ qualitatively and quantitatively from those evoked by equivalent lipoprotein-rich lysates. Here we report that ingested B. burgdorferi induces significantly greater transcription of proinflammatory cytokine genes than do lysates and that live B.

Phagocytosis of Borrelia burgdorferi and Treponema pallidum potentiates innate immune activation and induces gamma interferon production.

We examined the interactions of live and lysed spirochetes with innate immune cells. THP-1 monocytoid cells were activated to comparable extents by live Borrelia burgdorferi and by B. burgdorferi and Treponema pallidum lysates but were poorly activated by live T.

Lipoprotein-dependent and -independent immune responses to spirochetal infection.

In this study, we used the epidermal suction blister technique, in conjunction with multiparameter flow cytometry, to analyze the cellular and cytokine responses elicited by intradermal injection of human volunteers with synthetic analogs for spirochetal lipoproteins and compared the responses to findings previously reported from patients with erythema migrans (EM). Compared with peripheral blood (PB), lipopeptides derived from the N termini of the Borrelia burgdorferi outer surface protein C and the 17-kDa lipoprotein of Treponema pallidum (OspC-L and 17-L, respectively) elicited infiltrates enriched in monocytes/macrophages and dendritic cells (DCs) but also containing substantial percentages of neutrophils and T cells. Monocytoid (CD11c(+)) and plasmacytoid (CD11c(-)) DCs were selectively recruited to the skin in ratios similar to those in PB, but only the former expressed the activation/maturation surface markers CD80, CD83, and DC-SIGN.

Fully functional memory CD8 T cells in the absence of CD4 T cells.

The role of CD4 T cells in providing help to CD8 T cells in primary and secondary responses to infection remains controversial. Using recombinant strains of virus and bacteria expressing the same Ag, we determined the requirement for CD4 T cells in endogenous CD8 T cell responses to infection with vesicular stomatitis virus and Listeria monocytogenes (LM). Depletion of CD4 T cells had no effect on the frequency of primary or secondary vesicular stomatitis virus-specific CD8 T cells in either lymphoid or nonlymphoid tissues.

Coevolution of markers of innate and adaptive immunity in skin and peripheral blood of patients with erythema migrans.

We used multiparameter flow cytometry to characterize leukocyte immunophenotypes and cytokines in skin and peripheral blood of patients with erythema migrans (EM). Dermal leukocytes and cytokines were assessed in fluids aspirated from epidermal suction blisters raised over EM lesions and skin of uninfected controls. Compared with corresponding peripheral blood, EM infiltrates were enriched for T cells, monocytes/macrophages, and dendritic cells (DCs), contained lower proportions of neutrophils, and were virtually devoid of B cells.

Expression of Streptococcus mutans fimA is iron-responsive and regulated by a DtxR homologue.

Iron uptake, transport and storage in Streptococcus mutans, the principal causative agent of human dental cavities, is unexplored despite early reports in the literature which predict a role for this trace metal in cariogenesis. Experiments in the authors' laboratory revealed several iron-responsive proteins in S. mutans, one of which reacted with a polyclonal antiserum directed against the FimA fimbrial adhesin from Streptococcus parasanguis on Western blots.