Compartment-Specific and Sequential Role of MyD88 and CARD9 in Chemokine Induction and Innate Defense during Respiratory Fungal Infection

Aspergillus fumigatus forms ubiquitous airborne conidia that humans inhale on a daily basis. Although respiratory fungal infection activates the adaptor proteins CARD9 and MyD88 via C-type lectin, Toll-like, and interleukin-1 family receptor signals, defining the temporal and spatial pattern of MyD88- and CARD9-coupled signals in immune activation and fungal clearance has been difficult to achieve. Herein, we demonstrate that MyD88 and CARD9 act in two discrete phases and in two cellular compartments to direct chemokine- and neutrophil-dependent host defense. The first phase depends on MyD88 signaling because genetic deletion of MyD88 leads to delayed induction of the neutrophil chemokines CXCL1 and CXCL5, delayed neutrophil lung trafficking, and fatal pulmonary damage at the onset of respiratory fungal infection. MyD88 expression in lung epithelial cells restores rapid chemokine induction and neutrophil recruitment via interleukin-1 receptor signaling. Exogenous CXCL1 administration reverses murine mortality in MyD88-deficient mice. The second phase depends predominately on CARD9 signaling because genetic deletion of CARD9 in radiosensitive hematopoietic cells interrupts CXCL1 and CXCL2 production and lung neutrophil recruitment beyond the initial MyD88-dependent phase. Using a CXCL2 reporter mouse, we show that lung-infiltrating neutrophils represent the major cellular source of CXCL2 during CARD9-dependent recruitment. Although neutrophil-intrinsic MyD88 and CARD9 function are dispensable for neutrophil conidial uptake and killing in the lung, global deletion of both adaptor proteins triggers rapidly progressive invasive disease when mice are challenged with an inoculum that is sub-lethal for single adapter protein knockout mice. Our findings demonstrate that distinct signal transduction pathways in the respiratory epithelium and hematopoietic compartment partially overlap to ensure optimal chemokine induction, neutrophil recruitment, and fungal clearance within the respiratory tract

Promoting dental care to children using traditional and interactive media following threat appeals

In recent years, computer games have become an important part of children’s lives. Gaming is not only one of their favorite pastime activities, but games are also increasingly used by marketers in an attempt to influence children’s purchase behavior. Today, almost every food and beverage brand targeting children has an advergame on its website. Advergames are “computer games specifically created to function as advertisements to promote brands”, containing brand identifiers such as logos and brand characters (Kretchmer, 2005: 7). Games can also be powerful learning tools. Several authors (e.g., Gee, 2003; Prensky, 2001) argue that computer games can be more enjoyable, more interesting and thus more effective than traditional learning modes to increase children’s knowledge. Empirical studies that evaluated the impact of the use of games within disciplines such as mathematics, science, language, geography and computer science show positive outcomes in terms of learning effectiveness in relation to curricular objectives (e.g., Papastergiou, 2009; Rosas et al., 2003). However, these authors mainly focus on the learning ability of games rather than their persuasive impact for social marketing purposes. In the area of health education, playing computer games has often been seen with skepticism (e.g., Bale, 1994; Funk and Buchman, 1995)

Infection-mediated priming of phagocytes protects against lethal secondary Aspergillus fumigatus challenge

Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection

Factors Affecting the Quality of Texas Butter as Revealed by a Statewide Survey.

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Improving the Quality of Veteran Health Care by Optimizing VA Integrated Primary Care: 20 Years and Beyond of the Center for Integrated Healthcare

Primary care patients often present with mental and behavioral health concerns, such as depression or insomnia, leaving medical teams scrambling. To help fill this gap and increase access to care while aligning with patient preferences, a new service delivery model of integrated care, characterized by embedding behavioral health providers within medical teams, was embraced in a grassroots effort, with the VA being one of the first healthcare systems to implement it throughout all primary care settings. A common challenge to grassroot efforts is the lack of research establishing effectiveness and identifying ways to optimize the innovation’s impact. Innovative VA leaders and Congress recognized integrated care’s promise but also realized the importance of and need for research, training, and implementation support to optimize its success resulting in the creation of the VA Center for Integrated Healthcare (CIH) in 2004. To assist in overcoming the known lengthy timeline of translating research into practice and vice versa, CIH integrated research with training and implementation support through a purposeful and highly collaborative approach impacting both the CIH structure and processes, which contributed to a high level of productivity over the past 20 years helping to optimize evidence-based mental and behavioral health care for Veterans. This article will describe CIH’s successes in bringing evidence-based integrated care practices to over 450,000 Veterans annually and how this novel approach contributed. Exemplars are provided on how internal synergies created more empirical evidence for integrated care and greater utilization of evidence-based practices within integrated care settings

Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

The Vehicle, November 1960, Vol. 3 no. 1

CONTENTS To the ReaderStaffpage 2 N’ = N : 1Donald C. Blairpage 3 ConsistencyDonald C. Blairpage 3 Unto MeLinda Kay Campbellpage 4 The Meek Shall InheritE. J. B. page 5 The Infinite QuestLarry W. Dudleypage 6 Dreamer’s DawnMike Hindmanpage 7 BirthNancy Coepage 7 The Lost DutchmanDonald C. Blairpage 8 W. E. Noonan IRobert S. Hodgepage 8 A Soldier’s OrdealDonald E. Shephardsonpage 9 Personal PossessionMary Beilpage 11 Thine The GloryDonald C. Blairpage 12 The ThornJan Holstlawpage 13 A Lord’s Day MorningLinda Campbellpage 14 Observations of a 6-Year-OldTom McPeakpage 15 Jewels of TimeJudith Jerintspage 16 LavenderE. J. B. page 16https://thekeep.eiu.edu/vehicle/1008/thumbnail.jp

Factors Affecting the Quality of Southern Short Cure Cheddar Cheese.

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Structural and functional analysis of the finished genome of the recently isolated toxic Anabaena sp WA102

Background: Very few closed genomes of the cyanobacteria that commonly produce toxic blooms in lakes and reservoirs are available, limiting our understanding of the properties of these organisms. A new anatoxin-a-producing member of the Nostocaceae, Anabaena sp. WA102, was isolated from a freshwater lake in Washington State, USA, in 2013 and maintained in non-axenic culture. Results: The Anabaena sp. WA102 5.7 Mbp genome assembly has been closed with long-read, single-molecule sequencing and separately a draft genome assembly has been produced with short-read sequencing technology. The closed and draft genome assemblies are compared, showing a correlation between long repeats in the genome and the many gaps in the short-read assembly. Anabaena sp. WA102 encodes anatoxin-a biosynthetic genes, as does its close relative Anabaena sp. AL93 (also introduced in this study). These strains are distinguished by differences in the genes for light-harvesting phycobilins, with Anabaena sp. AL93 possessing a phycoerythrocyanin operon. Biologically relevant structural variants in the Anabaena sp. WA102 genome were detected only by long-read sequencing: a tandem triplication of the anaBCD promoter region in the anatoxin-a synthase gene cluster (not triplicated in Anabaena sp. AL93) and a 5-kbp deletion variant present in two-thirds of the population. The genome has a large number of mobile elements (160). Strikingly, there was no synteny with the genome of its nearest fully assembled relative, Anabaena sp. 90. Conclusion: Structural and functional genome analyses indicate that Anabaena sp. WA102 has a flexible genome. Genome closure, which can be readily achieved with long-read sequencing, reveals large scale (e.g., gene order) and local structural features that should be considered in understanding genome evolution and functioKeywords: PacBio, Illumina, Mobilome, Cyanobacteria, Anabaena, Long-read sequencing, Structural variation, Anatoxin-a, Synteny, Tandem repeatKeywords: PacBio, Illumina, Mobilome, Cyanobacteria, Anabaena, Long-read sequencing, Structural variation, Anatoxin-a, Synteny, Tandem repea