PAD4 is not essential for disease in the K/BxN murine autoantibody-mediated model of arthritis

INTRODUCTION: Both murine and human genome-wide association studies have implicated peptidyl arginine deiminase (PAD4) as a susceptibility gene in rheumatoid arthritis (RA). In addition, patients with RA commonly have autoantibodies which recognize PAD4 or and/or citrullinated peptides. This study aims to evaluate the role of PAD4 in the effector phase of arthritis. METHODS: PAD4 knock out (KO) and wild type (WT) C57BL/6J mice were injected with K/BxN sera to induce disease. Progression of disease was monitored by measuring paw and ankle swelling and clinical indexes of disease, and pathogenesis was assessed by indexing of clinical progression on paws collected from WT and PAD4 KO mice injected with K/BxN serum. PAD4 activity was determined by visualization of neutrophil extracellular traps (NETs) and immunohistological analysis of histone citrullination. RESULTS: PAD4 activity is readily detectable in the inflamed synovium of WT but not PAD4 deficient animals, as demonstrated by histone citrullination and NET formation. However, PAD4 WT and KO animals develop K/BxN serum transfer disease with comparable severity and kinetics, with no statistically significant differences noted in clinical scores, swelling, joint erosion or joint invasion. CONCLUSIONS: PAD4 WT and KO mice develop disease in the K/BxN serum transfer model of arthritis with similar severity and kinetics, indicating that PAD4 is dispensable in this effector phase model of disease

A Little Blue Bird Told Me: Sentiment Change on Orphanage Tourism

This study examined Twitter conversations to understand the changes in the sentiments related to orphanage tourism between 2009 and 2019. Past research on orphanage tourism mostly took a qualitative approach, which provided profound knowledge but was limited to a single time and those directly involved. This study fills the gap by analyzing the tweets posted by different parties, including the individuals that have participated or are willing to participate in orphanage tourism, institutions that have campaigned against the phenomenon, and organizations that have promoted orphanage volunteering. Analysis of 109,723 tweets using lexicons and supervised learning—Support Vector Machine, Random Forest, Naive Bayes, and Logistic regression—revealed that the year 2014 marked a turning point for orphanage tourism conversations as the number of posts dropped significantly, and the messages against orphanage tourism received attention. However, the positive sentiment still prevailed throughout the decade when all tweets were considered

Tumor Necrosis Factor Receptor–Associated Factor (Traf)2 Represses the T Helper Cell Type 2 Response through Interaction with Nfat-Interacting Protein (Nip45)

Recently we have identified a novel protein NIP45 (nuclear factor of activated T cells [NFAT]-interacting protein) which substantially augments interleukin (IL)-4 gene transcription. The provision of NIP45 together with NFAT and the T helper cell type 2 (Th2)-specific transcription factor c-Maf to cells normally refractory to IL-4 production, such as B cells or Th1 clones, results in substantial IL-4 secretion to levels that approximate those produced by primary Th2 cells. In studies designed to further our understanding of NIP45 activity, we have uncovered a novel facet of IL-4 gene regulation. We present evidence that members of the tumor necrosis factor receptor–associated factor (TRAF) family of proteins, generally known to function as adapter proteins that transduce signals from the tumor necrosis factor receptor superfamily, contribute to the repression of IL-4 gene transcription and that this effect is mediated through their interaction with NIP45

Understanding park visitors’ soundscape perception using subjective and objective measurement

Environmental noise knows no boundaries, affecting even protected areas. Noise pollution, originating from both external and internal sources, imposes costs on these areas. It is associated with adverse health effects, while natural sounds contribute to cognitive and emotional improvements as ecosystem services. When it comes to parks, individual visitors hold unique perceptions of soundscapes, which can be shaped by various factors such as their motivations for visiting, personal norms, attitudes towards specific sounds, and expectations. In this study, we utilized linear models and geospatial data to evaluate how visitors’ personal norms and attitudes, the park’s acoustic environment, visitor counts, and the acoustic environment of visitors’ neighborhoods influenced their perception of soundscapes at Muir Woods National Monument. Our findings indicate that visitors’ subjective experiences had a greater impact on their perception of the park’s soundscape compared to purely acoustic factors like sound level of the park itself. Specifically, we found that motivations to hear natural sounds, interference caused by noise, sensitivity to noise, and the sound levels of visitors’ home neighborhoods influenced visitors’ perception of the park’s soundscape. Understanding how personal factors shape visitors’ soundscape perception can assist urban and non-urban park planners in effectively managing visitor experiences and expectations

An extension of the benefit segmentation base for the consumption of organic foods : a time perspective

Benefit segmentation is a long-standing marketing approach that emphasises the ‘what’ and ‘how’ dimensions of consumer benefits; that is, what benefits consumers perceive in product/service consumption, and how such benefits are perceived. This research proposes a fresh time-based approach to benefit segmentation – namely, focusing on the ‘when’ element or when in time benefits take effect. Drawing upon a survey of UK consumers, it explains and discusses consumption motivations through examining antecedents of temporally dominated benefits in application to organic food. Specifically, the study investigates why some consumers predominantly seek present-based benefits vis-à-vis future-based benefits or vice versa in organic food purchase and consumption behaviour. Using correlation and regression analyses, the research findings establish significant associations of level of involvement, prior knowledge level, and product usage level, and some association of time orientation with the temporally emphasised consumption benefits consumers ultimately pursue. Overall, the research highlights the added contribution of a time perspective in a benefit segmentation approach which can assist marketers in understanding better and communicating more effectively with consumers through drawing up consumer profiles based on when in time their dominantly pursued benefit for an offering is perceived to take effect

Television viewing and consumer behaviour

Looks at the influence of television on children’s development as consumers,beginning with a literature review of consumer socialisation which establishes the importance of television as an influential model for children’s expressions of nonverbal behaviour and emotion.Explains the results of a survey of Malaysian schoolchildren which considers demographic variables such as gender and family income, and also personality traits, in relation to television viewing habits and consumer behaviour, including propensity to buy, time spent watching television, preferred type of programme etc.Discusses the results, which indicate the importance of family income as a predictor of differences in socialisation; gender is less influential, and of the six personality traits studied, the aggressive - passive is the most influential on socialisation

Methylthioadenosine reverses brain autoimmune disease

OBJECTIVE: To assess the immunomodulatory activity of methylthioadenosine (MTA) in rodent experimental autoimmune encephalomyelitis (EAE) and in patients with multiple sclerosis. METHODS: We studied the effect of intraperitoneal MTA in the acute and chronic EAE model by quantifying clinical and histological scores and by performing immunohistochemistry stains of the brain. We studied the immunomodulatory effect of MTA in lymphocytes from EAE animals and in peripheral blood mononuclear cells from healthy control subjects and multiple sclerosis patients by assessing cell proliferation and cytokine gene expression, by real-time polymerase chain reaction, and by nuclear factor-kappaB modulation by Western blot. RESULTS: We found that MTA prevents acute EAE and, more importantly, reverses chronic-relapsing EAE. MTA treatment markedly inhibited brain inflammation and reduced brain damage. Administration of MTA suppressed T-cell activation in vivo and in vitro, likely through a blockade in T-cell signaling resulting in the prevention of inhibitor of kappa B (IkappaB-alpha) degradation and in the impaired activation transcription factor nuclear factor-kappaB. Indeed, MTA suppressed the production of proinflammatory genes and cytokines (interferon-gamma, tumor necrosis factor-alpha, and inducible nitric oxide synthase) and increased the production of antiinflammatory cytokines (interleukin-10). INTERPRETATION: MTA has a remarkable immunomodulatory activity and may be beneficial for multiple sclerosis and other autoimmune diseases