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Investigating hypnosis and trances
\"Examines the science and lore behind hypnosis and trances\"--Amazon.com.
Book
Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond
Discovery and characterization of the cytokine receptor-cytokine-decoy receptor triad formed by receptor activator of nuclear factor kappa-B ligand (RANKL)-receptor activator of NF-κB (RANK)-osteoprotegerin (OPG) have led not only to immense advances in understanding the biology of bone homeostasis, but have also crystalized appreciation of the critical regulatory relationship that exists between bone and immunity, resulting in the emergence of the burgeoning field of osteoimmunology. RANKL-RANK-OPG are members of the tumor necrosis factor (TNF) and TNF receptor superfamilies, and share signaling characteristics common to many members of each. Developmentally regulated and cell-type specific expression patterns of each of these factors have revealed key regulatory functions for RANKL-RANK-OPG in bone homeostasis, organogenesis, immune tolerance, and cancer. Successful efforts at designing and developing therapeutic agents targeting RANKL-RANK-OPG have been undertaken for osteoporosis, and additional efforts are underway for other conditions. In this review, we will summarize the basic biology of the RANKL-RANK-OPG system, relate its cell-type specific functions to system-wide mechanisms of development and homeostasis, and highlight emerging areas of interest for this cytokine group.
Journal Article
Drug therapy for osteoporosis in older adults
The goal of osteoporosis management is to prevent fractures. Several pharmacological agents are available to lower fracture risk, either by reducing bone resorption or by stimulating bone formation. Bisphosphonates are the most widely used anti-resorptives, reducing bone turnover markers to low premenopausal concentrations and reducing fracture rates (vertebral by 50–70%, non-vertebral by 20–30%, and hip by ~40%). Bisphosphonates bind avidly to bone mineral and have an offset of effect measured in months to years. Long term, continuous use of oral bisphosphonates is usually interspersed with drug holidays of 1–2 years, to minimise the risk of atypical femoral fractures. Denosumab is a monoclonal antibody against RANKL that potently inhibits osteoclast development and activity. Denosumab is administered by subcutaneous injection every 6 months. Anti-fracture effects of denosumab are similar to those of the bisphosphonates, but there is a pronounced loss of anti-resorptive effect from 7 months after the last injection, which can result in clusters of rebound vertebral fractures. Two classes of anabolic drugs are now available to stimulate bone formation. Teriparatide and abaloparatide both target the parathyroid hormone-1 receptor, and are given by daily subcutaneous injection for up to 2 years. Romosozumab is an anti-sclerostin monoclonal antibody that stimulates bone formation and inhibits resorption. Romosozumab is given as monthly subcutaneous injections for 1 year. Head-to-head studies suggest that anabolic agents have greater anti-fracture efficacy and produce larger increases in bone density than anti-resorptive drugs. The effects of anabolic agents are transient, so transition to anti-resorptive drugs is required. The optimal strategy for cycling anabolics, anti-resorptives, and off-treatment periods remains to be determined.
Journal Article
Mechanisms of joint destruction in rheumatoid arthritis — immune cell–fibroblast–bone interactions
Rheumatoid arthritis (RA) is characterized by inflammation and destruction of bone and cartilage in affected joints. Autoimmune responses lead to increased osteoclastic bone resorption and impaired osteoblastic bone formation, the imbalance of which underlies bone loss in RA, which includes bone erosion, periarticular bone loss and systemic osteoporosis. The crucial role of osteoclasts in bone erosion has been demonstrated in basic studies as well as by the clinical efficacy of antibodies targeting RANKL, an important mediator of osteoclastogenesis. Synovial fibroblasts contribute to joint damage by stimulating both pro-inflammatory and tissue-destructive pathways. New technologies, such as single-cell RNA sequencing, have revealed the heterogeneity of synovial fibroblasts and of immune cells including T cells and macrophages. To understand the mechanisms of bone damage in RA, it is important to clarify how the immune system promotes the tissue-destructive properties of synovial fibroblasts and influences bone cells. The interaction between immune cells and fibroblasts underlies the imbalance between regulatory T cells and T helper 17 cells, which in turn exacerbates not only inflammation but also bone destruction, mainly by promoting RANKL expression on synovial fibroblasts. An improved understanding of the immune mechanisms underlying joint damage and the interplay between the immune system, synovial fibroblasts and bone will contribute to the identification of novel therapeutic targets in RA.In this Review, the authors provide an overview of the mechanisms contributing to joint damage in rheumatoid arthritis, particularly the interactions among immune cells, fibroblasts and bone, and discuss how this knowledge could inform the development of novel therapies.
Journal Article
Trance and Transfiguration in Rock Art and literature, Unisa Press/Routledge 2025
Academic courses on psychedelic drugs and religion are very popular among Ivy League universities, notably, Brown University, Berkeley, Duke, and Harvard University. Current research articles and books abound on the topic (see for example Johnson (2022), Richards (2016), Cherniak et al (2022)). The prevalence of the field speaks to its acceptance by mainstream academia. Medical research is also recognising the benefits of psychedelic drugs in the treatment of depression and addiction (Kuypers 2020).
Journal Article
Osteoclast differentiation by RANKL and OPG signaling pathways
IntroductionIn bone tissue, bone resorption by osteoclasts and bone formation by osteoblasts are repeated continuously. Osteoclasts are multinucleated cells that derive from monocyte-/macrophage-lineage cells and resorb bone. In contrast, osteoblasts mediate osteoclastogenesis by expressing receptor activator of nuclear factor-kappa B ligand (RANKL), which is expressed as a membrane-associated cytokine. Osteoprotegerin (OPG) is a soluble RANKL decoy receptor that is predominantly produced by osteoblasts and which prevents osteoclast formation and osteoclastic bone resorption by inhibiting the RANKL–RANKL receptor interaction.Materials and MethodsIn this review, we would like to summarize our experimental results on signal transduction that regulates the expression of RANKL and OPG.ResultsUsing OPG gene-deficient mice, we have demonstrated that OPG and sclerostin produced by osteocytes play an important role in the maintenance of cortical and alveolar bone. In addition, it was shown that osteoclast-derived leukemia inhibitory factor (LIF) reduces the expression of sclerostin in osteocytes and promotes bone formation. WP9QY (W9) is a peptide that was designed to be structurally similar to one of the cysteine-rich TNF-receptortype-I domains. Addition of the W9 peptide to bone marrow culture simultaneously inhibited osteoclast differentiation and stimulated osteoblastic cell proliferation. An anti-sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) antibody inhibited multinucleated osteoclast formation induced by RANKL and macrophage colony-stimulating factor (M-CSF). Pit-forming activity of osteoclasts was also inhibited by the anti-Siglec-15 antibody. In addition, anti-Siglec-15 antibody treatment stimulated the appearance of osteoblasts in cultures of mouse bone marrow cells in the presence of RANKL and M-CSF.ConclusionsBone mass loss depends on the RANK–RANKL–OPG system, which is a major regulatory system of osteoclast differentiation induction, activation, and survival.
Journal Article
Recent advances in osteoclast biology
The bone is an essential organ for locomotion and protection of the body, as well as hematopoiesis and mineral homeostasis. In order to exert these functions throughout life, bone tissue undergoes a repeating cycle of osteoclastic bone resorption and osteoblastic bone formation. The osteoclast is a large, multinucleated cell that is differentiated from monocyte/macrophage lineage cells by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). RANKL transduces its signal through the signaling receptor, RANK. RANKL/RANK signaling activates NFATc1, the master regulator of osteoclastogenesis, to induce osteoclastogenic gene expression. Many types of cells express RANKL to support osteoclastogenesis depending on the biological context and the dysregulation of RANKL signaling leads to bone diseases such as osteoporosis and osteopetrosis. This review outlines the findings on osteoclast and RANKL/RANK signaling that have accumulated to date.
Journal Article
Osteoblast-Osteoclast Communication and Bone Homeostasis
Bone remodeling is tightly regulated by a cross-talk between bone-forming osteoblasts and bone-resorbing osteoclasts. Osteoblasts and osteoclasts communicate with each other to regulate cellular behavior, survival and differentiation through direct cell-to-cell contact or through secretory proteins. A direct interaction between osteoblasts and osteoclasts allows bidirectional transduction of activation signals through EFNB2-EPHB4, FASL-FAS or SEMA3A-NRP1, regulating differentiation and survival of osteoblasts or osteoclasts. Alternatively, osteoblasts produce a range of different secretory molecules, including M-CSF, RANKL/OPG, WNT5A, and WNT16, that promote or suppress osteoclast differentiation and development. Osteoclasts also influence osteoblast formation and differentiation through secretion of soluble factors, including S1P, SEMA4D, CTHRC1 and C3. Here we review the current knowledge regarding membrane bound- and soluble factors governing cross-talk between osteoblasts and osteoclasts.
Journal Article
The Local Scenes and Global Culture of Psytrance
This lively textual symposium offers a collection of formative research on the culture of global psytrance (psychedelic trance). As the first book to address the diverse transnationalism of this contemporary electronic dance music phenomenon, the collection hosts interdisciplinary research addressing psytrance as a product of intersecting local and global trajectories. Contributing to theories of globalization, postmodernism, counterculture, youth subcultures, neotribes, the carnivalesque, music scenes and technologies, dance ritual and spirituality, chapters introduce psytrance in Goa, the UK, Israel, Japan, the US, Italy, Czech Republic, Portugal and Australia. As a global occurrence indebted to 1960s psychedelia, sharing music production technologies and DJ techniques with electronic dance music scenes, and harnessing the communication capabilities of the Internet, psytrance and its cultural implications are thoroughly discussed in this first scholarly volume of its kind.
Graham St John is a Research Associate at the University of Queensland’s Centre for Critical and Cultural Studies, and was recently a Postdoctoral Research Fellow in Interactive Media and Production at the University of Regina, Saskatchewan
List of Plates and Figures Psytrance: An Introduction, Graham St John Section I: Goa Trance 1: Goa is a State of Mind: On the Ephemerality of Psychedelic Social Emplacements, Luther Elliott 2: The Decline of Electronic Dance Scenes: The Case of Psytrance in Goa Anthony, D’Andrea 3: The Ghost of Goa Trance: A Retrospective, Arun Saldanha Section II: Global Psytrance 4: Infinite Noise Spirals: The Musical Cosmopolitanism of Psytrance, Hillegonda Rietveld 5: Psychedelic Trance Music Making in the UK: Rhizomatic Craftsmanship and the Global Market Place, Charles de Ledesma 6: Re-evaluating Musical Genre in UK Psytrance, Robin Lindop 7: (En)Countering the Beat: Paradox in Israeli Psytrance, Joshua I. Schmidt Section III: Liminal Culture 8: DemenCZe: Psychedelic Madhouse in the Czech Republic, Botond Vitos 9: Dionysus Returns: Contemporary Tuscan Trancers and Euripides’ The Bacchae, Chiara Baldini 10: Weaving the Underground Web: Neotribalism and Psytrance on Tribe.net, Jenny Ryan 11: Narratives in Noise: Reflexivity, Migration and Liminality in the Australian Psytrance Scene, Alex Lambert 12: Liminal Culture and Global Movement: The Transitional World of Psytrance, Graham St John Notes on Contributors Index
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