112 research outputs found

    Barrier Tissue Macrophages: Functional Adaptation to Environmental Challenges

    Get PDF
    Macrophages are found throughout the body, where they have crucial roles in tissue development, homeostasis and remodeling, as well as being sentinels of the innate immune system that can contribute to protective immunity and inflammation. Barrier tissues, such as the intestine, lung, skin and liver, are exposed constantly to the outside world, which places special demands on resident cell populations such as macrophages. Here we review the mounting evidence that although macrophages in different barrier tissues may be derived from distinct progenitors, their highly specific properties are shaped by the local environment, which allows them to adapt precisely to the needs of their anatomical niche. We discuss the properties of macrophages in steady-state barrier tissues, outline the factors that shape their differentiation and behavior and describe how macrophages change during protective immunity and inflammation

    Lipopolysaccharide-induced NF-ÎșB nuclear translocation is primarily dependent on MyD88, but TNFα\alpha expression requires TRIF and MyD88

    Get PDF
    TLR4 signalling through the MyD88 and TRIF-dependent pathways initiates translocation of the transcription factor NF-ÎșB into the nucleus. In cell population studies using mathematical modeling and functional analyses, Cheng et al. suggested that LPS-driven activation of MyD88, in the absence of TRIF, impairs NF-ÎșB translocation. We tested the model proposed by Cheng et al. using real-time single cell analysis in macrophages expressing EGFP-tagged p65 and a TNFα\alpha promoter-driven mCherry. Following LPS stimulation, cells lacking TRIF show a pattern of NF-ÎșB dynamics that is unaltered from wild-type cells, but activation of the TNFα\alpha promoter is impaired. In macrophages lacking MyD88, there is minimal NF-ÎșB translocation to the nucleus in response to LPS stimulation, and there is no activation of the TNFα\alpha promoter. These findings confirm that signalling through MyD88 is the primary driver for LPS-dependent NF-ÎșB translocation to the nucleus. The pattern of NF-ÎșB dynamics in TRIF-deficient cells does not, however, directly reflect the kinetics of TNFα\alpha promoter activation, supporting the concept that TRIF-dependent signalling plays an important role in the transcription of this cytokine.J.S. is supported by the Cambridge Commonwealth, European and International Trust. CEB was supported by a BBSRC fellowship (BB/H021930/1) and a Wellcome Trust Investigator award (WT108045AIA). E.C. and P.C. acknowledge EU-ITN Transpol and EU-ERC Hydrosync. I.D.C.F. is supported by the intramural Research Program of the National Institute of Allergy and Infectious Diseases

    ICAR: endoscopic skull‐base surgery

    Get PDF
    n/

    May measurement month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension (vol 40, pg 2006, 2019)

    Get PDF

    International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

    Get PDF
    Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

    Mitochondrial DNA COI characterization of Helicoverpa armigera (Lepidoptera: Noctuidae) from Paraguay and Uruguay

    No full text
    Since its detection in Brazil in 2013, the Old World cotton bollworm Helicoverpa armigera has been reported in Argentina, Paraguay, and Bolivia. Here we present evidence extending the South American range of H. armigera to Uruguay, using polymerase chain reaction and sequencing of the partial mitochondrial DNA (mtDNA) cytochrome oxidase I region. Molecular characterization of this gene region from individuals from Paraguay also supports previous morphological identification of H. armigera in Paraguay. Shared mtDNA haplotypes in H. armigera from Brazil, Uruguay, and Paraguay were identified. Additional surveying of populations in this region will be imperative to better monitor and understand factors that are underpinning its presence and successful adaptation in these South American regions. We discuss our findings with respect to the development of resistance pest management strategies of this invasive insect pest in a predominantly monoculture soybean crop landscape in the Southern Cone region

    Insect Resistance to Bacillus thuringiensis Toxin Cry2Ab Is Conferred by Mutations in an ABC Transporter Subfamily A Protein

    Get PDF
    The use of conventional chemical insecticides and bacterial toxins to control lepidopteran pests of global agriculture has imposed significant selection pressure leading to the rapid evolution of insecticide resistance. Transgenic crops (e.g., cotton) expressing the Bt Cry toxins are now used world wide to control these pests, including the highly polyphagous and invasive cotton bollworm Helicoverpa armigera. Since 2004, the Cry2Ab toxin has become widely used for controlling H. armigera, often used in combination with Cry1Ac to delay resistance evolution. Isolation of H. armigera and H. punctigera individuals heterozygous for Cry2Ab resistance in 2002 and 2004, respectively, allowed aspects of Cry2Ab resistance (level, fitness costs, genetic dominance, complementation tests) to be characterised in both species. However, the gene identity and genetic changes conferring this resistance were unknown, as was the detailed Cry2Ab mode of action. No cross-resistance to Cry1Ac was observed in mutant lines. Biphasic linkage analysis of a Cry2Ab-resistant H. armigera family followed by exon-primed intron-crossing (EPIC) marker mapping and candidate gene sequencing identified three independent resistance-associated INDEL mutations in an ATP-Binding Cassette (ABC) transporter gene we named HaABCA2. A deletion mutation was also identified in the H. punctigera homolog from the resistant line. All mutations truncate the ABCA2 protein. Isolation of further Cry2Ab resistance alleles in the same gene from field H. armigera populations indicates unequal resistance allele frequencies and the potential for Bt resistance evolution. Identification of the gene involved in resistance as an ABC transporter of the A subfamily adds to the body of evidence on the crucial role this gene family plays in the mode of action of the Bt Cry toxins. The structural differences between the ABCA2, and that of the C subfamily required for Cry1Ac toxicity, indicate differences in the detailed mode-of-action of the two Bt Cry toxins
    • 

    corecore