Deficiency of the Cyclin Kinase Inhibitor p21(WAF-1/CIP-1) Promotes Apoptosis of Activated/Memory T Cells and Inhibits Spontaneous Systemic Autoimmunity

A characteristic feature of systemic lupus erythematosus is the accumulation of activated/memory T and B cells. These G0/G1-arrested cells express high levels of cyclin-dependent kinase inhibitors such as p21, are resistant to proliferation and apoptosis, and produce large amounts of proinflammatory cytokines. Herein, we show that ablation of p21 in lupus-prone mice allows these cells to reenter the cell cycle and undergo apoptosis, leading to autoimmune disease reduction. Absence of p21 resulted in enhanced Fas/FasL-mediated activation-induced T cell death, increased activation of procaspases 8 and 3, and loss of mitochondrial transmembrane potential. Increased apoptosis was also associated with p53 up-regulation and a modest shift in the ratio of Bax/Bcl-2 toward the proapoptotic Bax. Proliferation and apoptosis of B cells were also increased in p21−/− lupus mice. Thus, modulation of the cell cycle pathway may be a novel approach to reduce apoptosis-resistant pathogenic lymphocytes and to ameliorate systemic autoimmunity

Systemic Autoimmunity and Lymphoproliferation Are Associated with Excess IL-7 and Inhibited by IL-7Rα Blockade

Lupus is characterized by disturbances in lymphocyte homeostasis, as demonstrated by the marked accumulation of activated/memory T cells. Here, we provide evidence that proliferation of the CD8+ precursors for the accumulating CD4–CD8– T cells in MRL-Faslpr lupus-predisposed mice is, in part, driven by commensal antigens. The ensuing lymphadenopathy is associated with increased production of IL-7 due to expansion of fibroblastic reticular cells, the primary source of this cytokine. The excess IL-7 is not, however, consumed by CD4–CD8– T cells due to permanent down-regulation of IL-7Rα (CD127), but instead supports proliferation of autoreactive T cells and progression of autoimmunity. Accordingly, IL-7R blockade reduced T cell activation and autoimmune manifestations even when applied at advanced disease stage. These findings indicate that an imbalance favoring production over consumption of IL-7 may contribute to systemic autoimmunity, and correction of this imbalance may be a novel therapeutic approach in lymphoproliferative and autoimmune syndromes

Gray space \u3ci\u3eand\u3c/i\u3e green space proximity associated with higher anxiety in youth with autism

This study used ZIP code level data on children\u27s health (National Survey of Children\u27s Health, 2012) and land cover (National Land Cover Database, 2011) from across the United States to investigate connections between proximity to green space (tree canopy), gray space (impervious surfaces), and expression of a critical co-morbid condition, anxiety, in three groups of youth: children diagnosed with autism spectrum disorder (ASD, n=1501), non-ASD children with special healthcare needs (CSHCN, n=15,776), and typically developing children (n=53,650). Both impervious surface coverage and tree canopy coverage increased the risk of severe anxiety in youth with autism, but not CSHCN or typical children. Children with ASD might experience the stress-reducing benefits of nature differently than their typically developing peers. More research using objective diagnostic metrics at finer spatial scales would help to illuminate complex relationships between green space, anxiety, and other co-morbid conditions in youth with ASD

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes

Where's all the 'good' sports journalism? Sports media research, the sociology of sport, and the question of quality sports reporting

Across newsrooms and journalism schools, questions as to what constitutes or ‘counts’ as excellent reporting are currently inciting much debate. Among the various frameworks being put forward to describe and encourage ‘excellent’ journalism in its various forms, sport is seldom mentioned – a legacy perhaps of its perennial dismissal as trivial subject matter. This essay grew from our curiosity as to whether the reverse was also true: that is, whether and what those who study sports journalism and sports media – in particular sociologists of sport – have contributed to understandings of ‘best’ and even excellent journalistic practice. We identified and analysed 376 articles from eight leading scholarly journals that feature sports media research with the aim of examining instances where ‘excellent’ sports reporting was either highlighted, described or advocated. After outlining the major themes that emerged from this analysis, we reflect on why so few of the sampled articles explicitly advise on what best practice sports journalism might look like – especially when it comes to coverage of the sport-related social issues that sociologists of sport tend to focus on – and why so little theoretical attention has been afforded to the question of excellent sports journalism more generally. While there are good sociological reasons for focusing on problematic sports reporting, on structural and systemic issues in which media are implicated, and on producing alternatives to hegemonic sports media, we conclude that it is high time for instances of excellent sports journalism to be afforded the theoretical and empirical attention long granted to their ‘bad’ journalistic counterparts

The Vehicle, Fall 1984

Vol. 26, No. 1 Table of Contents Thoughts on I-57Jim Caldwellpage 3 A Night Between Lonely and BlindJennifer K. Soulepage 4 What is Unnatural is Sometimes MagicAngelique Jenningspage 4 Cutting ClosenessBecky Lawsonpage 5 PhotoBrian Ormistonpage 6 The Sensuality of Corn One Week in AugustMichelle Mitchellpage 7 American MusicJim Caldwellpage 7 Water is WaitingMichael Kuopage 8 WhereJennifer K. Soulepage 8 The Fishing HoleJan Kowalskipage 9 Miller\u27s PondSue Gradypage 9 PhotoCathy Stonerpage 11 Young Man Reading To His LoverMaggie Kennedypage 11 ShellsChristopher R. Albinpage 12 In The ShadeJohn Fehrmannpage 12 FallLynanne Feilenpage 13 IndecisionDave L. Brydenpage 13 Dark Falls SoftlyAngelique Jenningspage 14 Not a Parked \u2757 Chevy in the Summer in the CountryMichelle Mitchellpage 20 BirdAnnie Heisepage 20 Clouds Created Only For Poets And Certain WomenJennifer K. Soulepage 21 SandGraham Lewispage 22 PhotoFred Zwickypage 23 Judgment CallCathy Moepage 23 I was hip that night Dan Hintzpage 24 A Sight Of WindDan Von Holtenpage 25 Tillard Isabel M. Parrottpage 26 The WidowMaggie Kennedypage 27 The SeparationMichelle Mitchellpage 27 The Garden Hose TrialMaggie Kennedypage 28 InterruptionsJennifer K. Soulepage 28 On Happening Across Jesus While Cleaning the BasementMaggie Kennedypage 29 GileonMichelle Mitchellpage 30 If My Father Were A Writer, He Would Still BuildAngelique Jenningspage 36 A Visit to Grandpa Gib\u27s HouseTammy Veachpage 37 For Having SeenAngelique Jenningspage 38 PhotoJudy Klancicpage 39 The Earth in BlueSusan J. Bielskypage 39 Things I Could Have SaidAngelique Jenningspage 40 AcrosticsAnnie Heisepage 40https://thekeep.eiu.edu/vehicle/1044/thumbnail.jp

The Vehicle, Fall 1984

Vol. 26, No. 1 Table of Contents Thoughts on I-57Jim Caldwellpage 3 A Night Between Lonely and BlindJennifer K. Soulepage 4 What is Unnatural is Sometimes MagicAngelique Jenningspage 4 Cutting ClosenessBecky Lawsonpage 5 PhotoBrian Ormistonpage 6 The Sensuality of Corn One Week in AugustMichelle Mitchellpage 7 American MusicJim Caldwellpage 7 Water is WaitingMichael Kuopage 8 WhereJennifer K. Soulepage 8 The Fishing HoleJan Kowalskipage 9 Miller\u27s PondSue Gradypage 9 PhotoCathy Stonerpage 11 Young Man Reading To His LoverMaggie Kennedypage 11 ShellsChristopher R. Albinpage 12 In The ShadeJohn Fehrmannpage 12 FallLynanne Feilenpage 13 IndecisionDave L. Brydenpage 13 Dark Falls SoftlyAngelique Jenningspage 14 Not a Parked \u2757 Chevy in the Summer in the CountryMichelle Mitchellpage 20 BirdAnnie Heisepage 20 Clouds Created Only For Poets And Certain WomenJennifer K. Soulepage 21 SandGraham Lewispage 22 PhotoFred Zwickypage 23 Judgment CallCathy Moepage 23 I was hip that night Dan Hintzpage 24 A Sight Of WindDan Von Holtenpage 25 Tillard Isabel M. Parrottpage 26 The WidowMaggie Kennedypage 27 The SeparationMichelle Mitchellpage 27 The Garden Hose TrialMaggie Kennedypage 28 InterruptionsJennifer K. Soulepage 28 On Happening Across Jesus While Cleaning the BasementMaggie Kennedypage 29 GileonMichelle Mitchellpage 30 If My Father Were A Writer, He Would Still BuildAngelique Jenningspage 36 A Visit to Grandpa Gib\u27s HouseTammy Veachpage 37 For Having SeenAngelique Jenningspage 38 PhotoJudy Klancicpage 39 The Earth in BlueSusan J. Bielskypage 39 Things I Could Have SaidAngelique Jenningspage 40 AcrosticsAnnie Heisepage 40https://thekeep.eiu.edu/vehicle/1044/thumbnail.jp