Explore the vast range of titles available.

Scholars have noted the variety of ideological and religious perspectives present in the Tea Party movement. This study addresses why both religious and non-religious individuals may be involved in the Tea Party despite its cultural connection to 'traditional' conservative Christianity. The article explores Tea Party participation and commitment, arguing that group membership is sustained by the party's ability to create interaction rituals reflective of Christian culture as an acknowledgement of American Christian values. The Tea Party frames its ideology as sacred, thereby establishing group commitment and cohesion. As a result, it is capable of attracting constituents from inside and outside of the Religious Right. By validating the experiences of others and creating a system of interdependency, the Tea Party has the potential to create group solidarity leading to collective action and exceptional political influence.

Scholars have noted the variety of ideological and religious perspectives present in the Tea Party movement. This study addresses why both religious and nonreligious individuals may be involved in the Tea Party despite its cultural connection to ‘traditional’ conservative Christianity. The article explores Tea Party participation and commitment, arguing that group membership is sustained by the party’s ability to create interaction rituals reflective of Christian culture as an acknowledgement of American Christian values. The Tea Party frames its ideology as sacred, thereby establishing group commitment and cohesion. As a result, it is capable of attracting constituents from inside and outside of the Religious Right. By validating the experiences of others and creating a system of interdependency, the Tea Party has the potential to create group solidarity leading to collective action and exceptional political influence.

The pathogenesis of chronic obstructive pulmonary disease (COPD) remains unclear, but involves loss of alveolar surface area (emphysema) and airway inflammation (bronchitis) as the consequence of cigarette smoke (CS) exposure. Previously, we demonstrated that autophagy proteins promote lung epithelial cell death, airway dysfunction, and emphysema in response to CS; however, the underlying mechanisms have yet to be elucidated. Here, using cultured pulmonary epithelial cells and murine models, we demonstrated that CS causes mitochondrial dysfunction that is associated with a reduction of mitochondrial membrane potential. CS induced mitophagy, the autophagy-dependent elimination of mitochondria, through stabilization of the mitophagy regulator PINK1. CS caused cell death, which was reduced by administration of necrosis or necroptosis inhibitors. Genetic deficiency of PINK1 and the mitochondrial division/mitophagy inhibitor Mdivi-1 protected against CS-induced cell death and mitochondrial dysfunction in vitro and reduced the phosphorylation of MLKL, a substrate for RIP3 in the necroptosis pathway. Moreover, Pink1(-/-) mice were protected against mitochondrial dysfunction, airspace enlargement, and mucociliary clearance (MCC) disruption during CS exposure. Mdivi-1 treatment also ameliorated CS-induced MCC disruption in CS-exposed mice. In human COPD, lung epithelial cells displayed increased expression of PINK1 and RIP3. These findings implicate mitophagy-dependent necroptosis in lung emphysematous changes in response to CS exposure, suggesting that this pathway is a therapeutic target for COPD.

Chronic obstructive pulmonary disease (COPD) involves aberrant airway inflammatory responses to cigarette smoke (CS) that are associated with epithelial cell dysfunction, cilia shortening, and mucociliary clearance disruption. Exposure to CS reduced cilia length and induced autophagy in vivo and in differentiated mouse tracheal epithelial cells (MTECs). Autophagy-impaired (Becn1+/- or Map1lc3B-/-) mice and MTECs resisted CS-induced cilia shortening. Furthermore, CS increased the autophagic turnover of ciliary proteins, indicating that autophagy may regulate cilia homeostasis. We identified cytosolic deacetylase HDAC6 as a critical regulator of autophagy-mediated cilia shortening during CS exposure. Mice bearing an X chromosome deletion of Hdac6 (Hdac6-/Y) and MTECs from these mice had reduced autophagy and were protected from CS-induced cilia shortening. Autophagy-impaired Becn1-/-, Map1lc3B-/-, and Hdac6-/Y mice or mice injected with an HDAC6 inhibitor were protected from CS-induced mucociliary clearance (MCC) disruption. MCC was preserved in mice given the chemical chaperone 4-phenylbutyric acid, but was disrupted in mice lacking the transcription factor NRF2, suggesting that oxidative stress and altered proteostasis contribute to the disruption of MCC. Analysis of human COPD specimens revealed epigenetic deregulation of HDAC6 by hypomethylation and increased protein expression in the airways. We conclude that an autophagy-dependent pathway regulates cilia length during CS exposure and has potential as a therapeutic target for COPD.

Understanding human organ formation is a scientific challenge with far-reaching medical implications 1 , 2 . Three-dimensional stem-cell cultures have provided insights into human cell differentiation 3 , 4 . However, current approaches use scaffold-free stem-cell aggregates, which develop non-reproducible tissue shapes and variable cell-fate patterns. This limits their capacity to recapitulate organ formation. Here we present a chip-based culture system that enables self-organization of micropatterned stem cells into precise three-dimensional cell-fate patterns and organ shapes. We use this system to recreate neural tube folding from human stem cells in a dish. Upon neural induction 5 , 6 , neural ectoderm folds into a millimetre-long neural tube covered with non-neural ectoderm. Folding occurs at 90% fidelity, and anatomically resembles the developing human neural tube. We find that neural and non-neural ectoderm are necessary and sufficient for folding morphogenesis. We identify two mechanisms drive folding: (1) apical contraction of neural ectoderm, and (2) basal adhesion mediated via extracellular matrix synthesis by non-neural ectoderm. Targeting these two mechanisms using drugs leads to morphological defects similar to neural tube defects. Finally, we show that neural tissue width determines neural tube shape, suggesting that morphology along the anterior–posterior axis depends on neural ectoderm geometry in addition to molecular gradients 7 . Our approach provides a new route to the study of human organ morphogenesis in health and disease. Stem cells cultured in a micropattern-constrained platform  form a quantitative and robust model of human neural tube morphogenesis.

A hallmark of cancer is the avoidance of immune destruction. This process has been primarily investigated in locally advanced or metastatic cancer 1 – 3 ; however, much less is known about how pre-malignant or early invasive tumours evade immune detection. Here, to understand this process in early colorectal cancers (CRCs), we investigated how naive colon cancer organoids that were engineered in vitro to harbour Apc -null, Kras G12D and Trp53 -null (AKP) mutations adapted to the in vivo native colonic environment. Comprehensive transcriptomic and chromatin analyses revealed that the endoderm-specifying transcription factor SOX17 became strongly upregulated in vivo. Notably, whereas SOX17 loss did not affect AKP organoid propagation in vitro, its loss markedly reduced the ability of AKP tumours to persist in vivo. The small fraction of SOX17-null tumours that grew displayed notable interferon-γ (IFNγ)-producing effector-like CD8 + T cell infiltrates in contrast to the immune-suppressive microenvironment in wild-type counterparts. Mechanistically, in both endogenous Apc -null pre-malignant adenomas and transplanted organoid-derived AKP CRCs, SOX17 suppresses the ability of tumour cells to sense and respond to IFNγ, preventing anti-tumour T cell responses. Finally, SOX17 engages a fetal intestinal programme that drives differentiation away from LGR5 + tumour cells to produce immune-evasive LGR5 − tumour cells with lower expression of major histocompatibility complex class I (MHC-I). We propose that SOX17 is a transcription factor that is engaged during the early steps of colon cancer to orchestrate an immune-evasive programme that permits CRC initiation and progression. Transcriptomic and chromatin accessibility analyses of naive and transplanted colon cancer organoids in a mouse model reveal a key role for the transcription factor SOX17 in establishing a permissive immune environment for tumour cells.

Background Achievement emotions play an important role in learning, significantly affecting well-being, learning satisfaction, and academic achievement, yet their application to healthcare education remains sparse. To address this gap, this study adapted the Achievement Emotions Questionnaire– Short Version (AEQ-S) in healthcare education. The objective is to assess the applicability, demonstrate its application, and guide future research in achievement emotions within this field. Methods This study involved 296 pre-service students enrolled in interprofessional education (IPE) from various disciplines, including Chinese Medicine, Engineering, Law, Medicine, Nursing, Pharmacy, Speech and Hearing Sciences, and Social Work, who completed the adapted AEQ-S in IPE context (AEQ-SIPE) before and after the IPE. Confirmatory factor analysis (CFA) and multiple linear regression were employed to examine the acceptability of AEQ-S. Results The 32-item AEQ-SIPE capturing eight emotions (hope, pride, enjoyment, anxiety, anger, shame, boredom, and hopelessness) yielded good model fit: CFI = 0.937, NFI = 0.904, IFI = 0.937, TLI = 0.928, RMSEA = 0.076) and high internal reliability (α = 0.90 to 0.96). Regression analyses indicated that the eight emotions accounted for a significant amount of variance in explaining well-being and achievement outcomes. Pride positively predicted satisfaction in life, positive affect, and learning satisfaction, while shame negatively predicted satisfaction in life but positively predicted positive and negative affect. Conclusion This study highlights the critical importance of achievement emotions in healthcare education and confirms the AEQ-SIPE as a valid tool for exploring these emotions in IPE. It sets the stage for future research to further investigate and understand the role of achievement emotions in this context.