Rejection is at the heart of anti-consumption and is therefore key to some of the central relationships in symbolic consumption. However, researchers find rejection difficult to study because of the lack of material traces. This article draws on earlier frameworks to develop a new integrated and expanded conceptualization in order to achieve a more nuanced view of how rejection operates within symbolic consumption; and also to initiate research directions for investigating and theorizing rejection in anti-consumption. The focus on anti-consumption incorporates the interaction between avoidance, aversion and abandonment, and the relationship between distastes and the undesired self (mediated by the marketing, social and individual environments). A series of interrelationships and illustrations suggest how the expanded conceptualization is useful for theorizing and investigating anti-consumption. Crown
Marfan syndrome (MFS) is a heritable disorder of connective tissue, caused by mutations in the fibrillin-1 gene. Pulmonary functional abnormalities, such as emphysema and restrictive lung diseases, are frequently observed in patients with MFS. However, the pathogenesis and molecular mechanism of pulmonary involvement in MFS patients are underexplored. Notch signaling is essential for lung development and the airway epithelium regeneration and repair. Therefore, we investigated whether Notch3 signaling plays a role in pulmonary emphysema in MFS. By using a murine model of MFS, fibrillin-1 hypomorphic mgR mice, we found pulmonary emphysematousappearing alveolar patterns in the lungs of mgR mice. The septation in terminal alveoli of lungs in mgR mice was reduced compared to wild type controls in the early lung development. These changes were associated with increased Notch3 activation. To confirm that the increased Notch3 signaling in mgR mice was responsible for structure alterations in the lungs, mice were treated with N-[N-(3,5difluorophenacetyl)-l-alanyl]-S-phenylglucine t-butyl ester (DAPT), a γ-secretase inhibitor, which inhibits Notch signaling. DAPT treatment reduced lung cell apoptosis and attenuated pulmonary alteration in mice with MFS. This study indicates that Notch3 signaling contributes to pulmonary emphysema in mgR mice. Our results may have the potential to lead to novel strategies to prevent and treat pulmonary manifestations in patients with MFS. Marfan syndrome (MFS) is an autosomal dominant inherited disorder of connective tissue that exhibits variable expressivity among affected individuals 1,2. It is a systemic disorder with increased early morbidity and mortality related to aortic pathology. It is reported that 63% of MFS patients have an alteration in lung function 3. Pulmonary emphysema appears to be a significant problem in those affected with neonatal MFS, the most severe form of MFS 4-6. MFS is primarily caused by mutations in the FBN1 gene, which encodes the extracellular matrix (ECM) protein fibrillin-1 7,8. Fibrillin-1 is the main component of elastic tissue microfibrils, which form a scaffolding network for tropoelastin deposition but also interact with Notch, Notch ligands, and transforming growth factor β (TGF-β) 9,10. Previous studies have shown histological and mechanical impairment of lungs in murine models of MFS, Fbn1 mgΔ/mgΔ , Fbn1 mgR/mgR (mgR), and Fbn1 C1039G/+10,11. Neptune et al. demonstrated that dysregulation of TGF-β activation contributed to the development of pulmonary emphysema in Fbn1 mgΔ/mgΔ and mgR mice 10. The Fbn1 mgΔ/mgΔ mouse model represents a severe case of MFS; these mice produce approximately 10% of normal fibrillin-1. Because they are severely affected, Fbn1 mg/mgΔ mice die of cardiovascular complications around
Background. The leading cause of mortality in patients with Marfan syndrome (MFS) is thoracic aortic aneurysm and dissection. Notch signaling is essential for vessel morphogenesis and function. However, the role of Notch signaling in aortic pathology and aortic smooth muscle cell (SMC) differentiation in Marfan syndrome (MFS) is not completely understood. Methods. RNA-sequencing on ascending aortic tissue from a mouse model of MFS, Fbn1mgR/mgR, and wild-type controls was performed. Notch 3 expression and activation in aortic tissue were confirmed with real-time RT-PCR, immunohistochemistry, and Western blot. Fbn1mgR/mgR and wild-type mice were treated with a γ-secretase inhibitor, DAPT, to block Notch activation. Aortic aneurysms and rupture were evaluated with connective tissue staining, ultrasound, and life table analysis. Results. The murine RNA-sequencing data were validated with mouse and human MFS aortic tissue, demonstrating elevated Notch3 activation in MFS. Data further revealed that upregulation and activation of Notch3 were concomitant with increased expression of SMC contractile markers. Inhibiting Notch3 activation with DAPT attenuated aortic enlargement and improved survival of Fbn1mgR/mgR mice. DAPT treatment reduced elastin fiber fragmentation in the aorta and reversed the differentiation of SMCs. Conclusions. Our data demonstrated that matrix abnormalities in the aorta of MFS are associated with increased Notch3 activation. Enhanced Notch3 activation in MFS contributed to aortic aneurysm formation in MFS. This might be mediated by inducing a contractile phenotypic change of SMC. Our results suggest that inhibiting Notch3 activation may provide a strategy to prevent and treat aortic aneurysms in MFS.
As more and more Pentecostal theologians are pursuing formal training in academic theology and philosophy, they are becoming increasingly sensitive to the importance of being conscious of one's theological method in systematic theology. This article is a suggestion that Pentecostal theologians would benefit from adopting as one guideline for their theological method a form of lex orandi, lex credendi called 'the rule of spirituality and the rule of doctrine', which involves a reciprocal relationship between Pentecostal spirituality and doctrine. The goal ofthe relationship is doctrinal theology that is informed by legitimate aspects of Pentecostal spirituality and that is able to correct illegitimate aspects of it. After the method is established, three aspects of Pentecostal spirituality are chosen to inform a Pentecostal doctrine ofthe Lord's Supper. Finally, aspects of this doctrine ofthe Supper are employed to critique other aspects of Pentecostal spirituality.
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