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"Young, John R"
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Evolution of an Expanded Mannose Receptor Gene Family
Sequences of peptides from a protein specifically immunoprecipitated by an antibody, KUL01, that recognises chicken macrophages, identified a homologue of the mammalian mannose receptor, MRC1, which we called MRC1L-B. Inspection of the genomic environment of the chicken gene revealed an array of five paralogous genes, MRC1L-A to MRC1L-E, located between conserved flanking genes found either side of the single MRC1 gene in mammals. Transcripts of all five genes were detected in RNA from a macrophage cell line and other RNAs, whose sequences allowed the precise definition of spliced exons, confirming or correcting existing bioinformatic annotation. The confirmed gene structures were used to locate orthologues of all five genes in the genomes of two other avian species and of the painted turtle, all with intact coding sequences. The lizard genome had only three genes, one orthologue of MRC1L-A and two orthologues of the MRC1L-B antigen gene resulting from a recent duplication. The Xenopus genome, like that of most mammals, had only a single MRC1-like gene at the corresponding locus. MRC1L-A and MRC1L-B genes had similar cytoplasmic regions that may be indicative of similar subcellular migration and functions. Cytoplasmic regions of the other three genes were very divergent, possibly indicating the evolution of a new functional repertoire for this family of molecules, which might include novel interactions with pathogens.
Journal Article
A Critical Role for MAPK Signalling Pathways in the Transcriptional Regulation of Toll Like Receptors
Toll-like Receptors (TLR) are phylogenetically conserved transmembrane proteins responsible for detection of pathogens and activation of immune responses in diverse animal species. The stimulation of TLR by pathogen-derived molecules leads to the production of pro-inflammatory mediators including cytokines and nitric oxide. Although TLR-induced events are critical for immune induction, uncontrolled inflammation can be life threatening and regulation is a critical feature of TLR biology. We used an avian macrophage cell line (HD11) to determine the relationship between TLR agonist-induced activation of inflammatory responses and the transcriptional regulation of TLR. Exposure of macrophages to specific TLR agonists induced upregulation of cytokine and nitric oxide pathways that were inhibited by blocking various components of the TLR signalling pathways. TLR activation also led to changes in the levels of mRNA encoding the TLR responsible for recognising the inducing agonist (cognate regulation) and cross-regulation of other TLR (non-cognate regulation). Interestingly, in most cases, regulation of TLR mRNA was independent of NFκB activity but dependent on one or more of the MAPK pathway components. Moreover, the relative importance of ERK, JNK and p38 was dependent upon both the stimulating agonist and the target TLR. These results provide a framework for understanding the complex pathways involved in transcriptional regulation of TLR, immune induction and inflammation. Manipulation of these pathways during vaccination or management of acute inflammatory disease may lead to improved clinical outcome or enhanced vaccine efficacy.
Journal Article
Expression of Chicken DEC205 Reflects the Unique Structure and Function of the Avian Immune System
The generation of appropriate adaptive immune responses relies critically on dendritic cells, about which relatively little is known in chickens, a vital livestock species, in comparison with man and mouse. We cloned and sequenced chicken DEC205 cDNA and used this knowledge to produce quantitative PCR assays and monoclonal antibodies to study expression of DEC205 as well as CD83. The gene structure of DEC205 was identical to those of other species. Transcripts of both genes were found at higher levels in lymphoid tissues and the expression of DEC205 in normal birds had a characteristic distribution in the primary lymphoid organs. In spleen, DEC205 was seen on cells ideally located to trap antigen. In thymus it was found on cells thought to participate in the education of T cells, and in the bursa on cells that may be involved in presentation of antigen to B cells and regulation of B cell migration. The expression of DEC205 on cells other than antigen presenting cells (APC) is also described. Isolated splenocytes strongly expressing DEC205 but not the KUL01 antigen have morphology similar to mammalian dendritic cells and the distinct expression of DEC205 within the avian-specific Bursa of Fabricius alludes to a unique function in this organ of B cell diversification.
Journal Article
Forever Young : a life of adventure in air and space
The autobiography of astronaut John Young.
Book
Core competencies for dermatology physician assistants: knowledge recommendations from a national survey of dermatologists and physician assistants
Methods An electronic survey protocol was approved by the institutional review board at Kaiser Permanente in Sacramento, CA. Supplementary Fig. 1e shows responses to the remaining 35 conditions; Supplementary Table 3e shows groups of diagnoses eliciting noteworthy discrepancies between cohorts’ answers [See PDF for image] Fig. 2 Dermatologist and PA responses regarding systemic medications, ranked by percent of dermatologists recommending “start for some cases” and “comprehensively manage most” Discussion This study asked dermatologists and PAs what depth of knowledge should be expected of PAs upon accruing 2 years of dermatology experience, and showed that both expect strong understanding for 67 diagnoses and 32 medications. Declarations Conflict of interest PAY and AN have received honoraria from the National Commission for Certification of Physician Assistants.
Journal Article
الدين والتعليم والعلم في العصر العباسي
يضم هذا الكتاب الذي أصدرته جامعة كمبريدج تسع وعشرين دراسة قام بها عدد من أهم المتخصصين في تراث الحضارة العربية الإسلامية في مجالات الدراسات الدينية والتعليم والعلم وقد تنوعت موضوعات هذا التاب الفريد الممتع ما بين العلوم الإسلامية : كالتفسير وعلم الكلام والفقه، والعلوم العربية مثل اللغة والنحو وتصنيف المعاجم والقوامييس والشعر التعليمي وإسهامات المسلمين في الطب والفلك والكمياء والرياضيات والتنجيم. تناولت هذه الدراسات الأدب الصوفي والشعر التعليمي ورصدت موجزا لحركة الترجمة عن اللغة اليونانية في بداية عصور الثقافة العربية.
Book
A Versatile Panel of Reference Gene Assays for the Measurement of Chicken mRNA by Quantitative PCR
Quantitative real-time PCR assays are widely used for the quantification of mRNA within avian experimental samples. Multiple stably-expressed reference genes, selected for the lowest variation in representative samples, can be used to control random technical variation. Reference gene assays must be reliable, have high amplification specificity and efficiency, and not produce signals from contaminating DNA. Whilst recent research papers identify specific genes that are stable in particular tissues and experimental treatments, here we describe a panel of ten avian gene primer and probe sets that can be used to identify suitable reference genes in many experimental contexts. The panel was tested with TaqMan and SYBR Green systems in two experimental scenarios: a tissue collection and virus infection of cultured fibroblasts. GeNorm and NormFinder algorithms were able to select appropriate reference gene sets in each case. We show the effects of using the selected genes on the detection of statistically significant differences in expression. The results are compared with those obtained using 28s ribosomal RNA, the present most widely accepted reference gene in chicken work, identifying circumstances where its use might provide misleading results. Methods for eliminating DNA contamination of RNA reduced, but did not completely remove, detectable DNA. We therefore attached special importance to testing each qPCR assay for absence of signal using DNA template. The assays and analyses developed here provide a useful resource for selecting reference genes for investigations of avian biology.
Journal Article