Ongoing exposure to peritoneal dialysis fluid alters resident peritoneal macrophage phenotype and activation propensity

Peritoneal dialysis (PD) is a more continuous alternative to haemodialysis, for patients with chronic kidney disease, with considerable initial benefits for survival, patient independence and healthcare costs. However, long-term PD is associated with significant pathology, negating the positive effects over haemodialysis. Importantly, peritonitis and activation of macrophages is closely associated with disease progression and treatment failure. However, recent advances in macrophage biology suggest opposite functions for macrophages of different cellular origins. While monocyte-derived macrophages promote disease progression in some models of fibrosis, tissue resident macrophages have rather been associated with protective roles. Thus, we aimed to identify the relative contribution of tissue resident macrophages to PD induced inflammation in mice. Unexpectedly, we found an incremental loss of homeostatic characteristics, anti-inflammatory and efferocytic functionality in peritoneal resident macrophages, accompanied by enhanced inflammatory responses to external stimuli. Moreover, presence of glucose degradation products within the dialysis fluid led to markedly enhanced inflammation and almost complete disappearance of tissue resident cells. Thus, alterations in tissue resident macrophages may render long-term PD patients sensitive to developing peritonitis and consequently fibrosis/sclerosis

Taming the neutrophil : Balance between anti‐parasite defence and pathogenesis

Non peer reviewedPublisher PD

The extracellular matrix and the immune system : A mutually dependent relationship

Acknowledgments: We are very grateful to our colleagues at the Wellcome Centre for Cell-Matrix Research and the Lydia Becker Institute for Immunology and Inflammation for many stimulating discussions. We would especially like to thank A. Day, D. Thornton, R. Lennon, A. MacDonald, and T. Hardingham and the anonymous referees for critical review of the manuscript. Figures have been drawn in BioRender. Funding: This work was supported by MRC-UK grant MR/V011235/1 (J.E.A.) and Wellcome Trust grants 106898/A/15/Z (J.E.A.), 218570/Z/19/Z (D.P.D.), and 203128/A/16/Z (T.E.S., D.P.D., and J.E.A.).Peer reviewedPostprin

Developing motivated adolescent readers and enhancing student voice, using action research in disadvantaged contexts

This action research study, drawing on participatory frameworks, investigated whether a Year 10 English class (15–16-year-olds), including struggling readers, could develop their reading self-concept and ‘voice’. The research aimed to extend findings from a larger, mixed-method study, developing reading comprehension and motivation with younger adolescents, conducted in the south-east of England. Set in an urban state school in a deprived area, the present 12-week study aimed to explore, first, the impact on students of an evolving reading model, emphasizing motivation, extended reading, peer talk and use of metacognitive, multiple strategies. Second, it explored the effects of students engaging, loosely, as ‘co-researchers’, co-constructing knowledge with their teacher and reflecting on reading and pedagogy, in terms of ‘voice’ and agency. The primarily qualitative study combined open-response, student questionnaires, semi-structured interviews, written reflections on reading, and a teacher/ researcher journal. Using the ‘constant comparative’ data-analysis method, the study found that students enhanced their reading self-concept, and developed their ‘voice’. However, unpredictably, reading confidence was threatened by students’ internalized discourses about performativity and feelings of anxiety and lack of agency, attributed to ‘high-stakes’ public examinations nearly two years away

Magnitude effects for experienced rewards at short delays in the escalating interest task

A first-person shooter video game was adapted for the study of choice between smaller sooner and larger later rewards. Participants chose when to fire a weapon that increased in damage potential over a short interval. When the delay to maximum damage was shorter (5 – 8 s), people showed greater sensitivity to the consequences of their choices than when the delay was longer (17 – 20 s). Participants also evidenced a magnitude effect by waiting proportionally longer when the damage magnitudes were doubled for all rewards. The experiment replicated the standard magnitude effect with this new video game preparation over time scales similar to those typically used in nonhuman animal studies and without complications due to satiation or cost

Silk from Crickets: A New Twist on Spinning

Raspy crickets (Orthoptera: Gryllacrididae) are unique among the orthopterans in producing silk, which is used to build shelters. This work studied the material composition and the fabrication of cricket silk for the first time. We examined silk-webs produced in captivity, which comprised cylindrical fibers and flat films. Spectra obtained from micro-Raman experiments indicated that the silk is composed of protein, primarily in a beta-sheet conformation, and that fibers and films are almost identical in terms of amino acid composition and secondary structure. The primary sequences of four silk proteins were identified through a mass spectrometry/cDNA library approach. The most abundant silk protein was large in size (300 and 220 kDa variants), rich in alanine, glycine and serine, and contained repetitive sequence motifs; these are features which are shared with several known beta-sheet forming silk proteins. Convergent evolution at the molecular level contrasts with development by crickets of a novel mechanism for silk fabrication. After secretion of cricket silk proteins by the labial glands they are fabricated into mature silk by the labium-hypopharynx, which is modified to allow the controlled formation of either fibers or films. Protein folding into beta-sheet structure during silk fabrication is not driven by shear forces, as is reported for other silks

IL-17A both initiates, via IFNγ suppression, and limits the pulmonary type 2 immune response to nematode infection

Peer reviewedPublisher PD

The magnitude of airway remodeling is not altered by distinct allergic inflammatory responses in BALB/c versus C57BL/6 mice but matrix composition differs

From Wiley via Jisc Publications RouterHistory: received 2020-10-20, rev-recd 2021-01-23, accepted 2021-02-11, pub-electronic 2021-03-19, pub-print 2021-07Article version: VoRPublication status: PublishedFunder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/K01207X/1, MR/P02615X/1Funder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100010269; Grant(s): 106898/A/15/ZFunder: Asthma UK; Id: http://dx.doi.org/10.13039/501100000362; Grant(s): MRFAUK‐2015‐302Funder: Medical Research Foundation UK; Grant(s): MRFAUK‐2015‐302Abstract: Allergic airway inflammation is heterogeneous with variability in immune phenotypes observed across asthmatic patients. Inflammation has been thought to directly contribute to airway remodeling in asthma, but clinical data suggest that neutralizing type 2 cytokines does not necessarily alter disease pathogenesis. Here, we utilized C57BL/6 and BALB/c mice to investigate the development of allergic airway inflammation and remodeling. Exposure to an allergen cocktail for up to 8 weeks led to type 2 and type 17 inflammation, characterized by airway eosinophilia and neutrophilia and increased expression of chitinase‐like proteins in both C57BL/6 and BALB/c mice. However, BALB/c mice developed much greater inflammatory responses than C57BL/6 mice, effects possibly explained by a failure to induce pathways that regulate and maintain T‐cell activation in C57BL/6 mice, as shown by whole lung RNA transcript analysis. Allergen administration resulted in a similar degree of airway remodeling between mouse strains but with differences in collagen subtype composition. Increased collagen III was observed around the airways of C57BL/6 but not BALB/c mice while allergen‐induced loss of basement membrane collagen IV was only observed in BALB/c mice. This study highlights a model of type 2/type 17 airway inflammation in mice whereby development of airway remodeling can occur in both BALB/c and C57BL/6 mice despite differences in immune response dynamics between strains. Importantly, compositional changes in the extracellular matrix between genetic strains of mice may help us better understand the relationships between lung function, remodeling and airway inflammation