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Hypothesis: The Psychedelic Ayahuasca Heals Traumatic Memories via a Sigma 1 Receptor-Mediated Epigenetic-Mnemonic Process
Get PDFCopyright © 2018 Inserra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Ayahuasca ingestion modulates brain activity, neurotransmission, gene expression and epigenetic regulation. N,N-Dimethyltryptamine (DMT, one of the alkaloids in Ayahuasca) activates sigma 1 receptor (SIGMAR1) and others. SIGMAR1 is a multi-faceted stress-responsive receptor which promotes cell survival, neuroprotection, neuroplasticity, and neuroimmunomodulation. Simultaneously, monoamine oxidase inhibitors (MAOIs) also present in Ayahuasca prevent the degradation of DMT. One peculiarity of SIGMAR1 activation and MAOI activity is the reversal of mnemonic deficits in pre-clinical models. Since traumatic memories in post-traumatic stress disorder (PTSD) are often characterised by “repression” and PTSD patients ingesting Ayahuasca report the retrieval of such memories, it cannot be excluded that DMT-mediated SIGMAR1 activation and the concomitant MAOIs effects during Ayahuasca ingestion might mediate such “anti-amnesic” process. Here I hypothesise that Ayahuasca, via hyperactivation of trauma and emotional memory-related centres, and via its concomitant SIGMAR1- and MAOIs- induced anti-amnesic effects, facilitates the retrieval of traumatic memories, in turn making them labile (destabilised). As Ayahuasca alkaloids enhance synaptic plasticity, increase neurogenesis and boost dopaminergic neurotransmission, and those processes are involved in memory reconsolidation and fear extinction, the fear response triggered by the memory can be reprogramed and/or extinguished. Subsequently, the memory is stored with this updated significance. To date, it is unclear if new memories replace, co-exist with or bypass old ones. Although the mechanisms involved in memory are still debated, they seem to require the involvement of cellular and molecular events, such as reorganisation of homo and heteroreceptor complexes at the synapse, synaptic plasticity, and epigenetic re-modulation of gene expression. Since SIGMAR1 mobilises synaptic receptor, boosts synaptic plasticity and modulates epigenetic processes, such effects might be involved in the reported healing of traumatic memories in PTSD patients. If this theory proves to be true, Ayahuasca could come to represent the only standing pharmacological treatment which targets traumatic memories in PTSD. Lastly, since SIGMAR1 activation triggers both epigenetic and immunomodulatory programmes, the mechanism here presented could help understanding and treating other conditions in which the cellular memory is dysregulated, such as cancer, diabetes, autoimmune and neurodegenerative pathologies and substance addiction
Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules
Get PDFCopyright © 2016 Yan-Chuang Han et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Although it is possible to generate neural stem cells (NSC) from somatic cells by reprogramming technologies with transcription factors, clinical utilization of patient-specific NSC for the treatment of human diseases remains elusive. The risk hurdles are associated with viral transduction vectors induced mutagenesis, tumor formation from undifferentiated stem cells, and transcription factors-induced genomic instability. Here we describe a viral vector-free and more efficient method to induce mouse fibroblasts into NSC using small molecules. The small molecule-induced neural stem (SMINS) cells closely resemble NSC in morphology, gene expression patterns, self-renewal, excitability, and multipotency. Furthermore, the SMINS cells are able to differentiate into astrocytes, functional neurons, and oligodendrocytes in vitro and in vivo. Thus, we have established a novel way to efficiently induce neural stem cells (iNSC) from fibroblasts using only small molecules without altering the genome. Such chemical induction removes the risks associated with current techniques such as the use of viral vectors or the induction of oncogenic factors. This technique may, therefore, enable NSC to be utilized in various applications within clinical medicine
Combined Effects of Muricid Extract and 5-Fluorouracil on Intestinal Toxicity in Rats
Get PDFCopyright © 2015 Roger Yazbeck et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Chemotherapy drugs, such as 5-fluorouracil (5FU), are the standard approach for cancer and are associated with several peripheral toxicities. We previously demonstrated that Muricidae marine molluscs exhibit chemopreventive properties. This study investigated the combined effect of muricid extract derived from Dicathais orbita, with 5FU, on intestinal toxicity in rats. Groups of rats were orally gavaged water, muricid extract, or sunflower oil, with or without 5FU (150 mg/kg). Metabolic data was collected daily and small intestinal brush border enzyme activity was measured by sucrose breath test (SBT). Blood was collected by cardiac puncture for whole blood analysis. Intestinal biopsies were taken for histopathology. Neutrophil activity was measured by myeloperoxidase activity. No additional toxicity effects were observed in rats receiving the combination of 5FU and muricid extract compared to 5FU alone, as indicated by SBT, histopathology, and myeloperoxidase activity. Intestinal integrity was protected from 5FU-induced damage in the sunflower oil vehicle group, compared to controls, as measured by SBT, villus height, and crypt depth. We concluded that combination of muricid extract and 5FU did not confer any additional intestinal toxicity, further supporting its potential as a chemopreventive food product. In this model system, sunflower oil partially protected against 5FU-induced intestinal toxicity
Pressure Flow Analysis in the Assessment of Preswallow Pharyngeal Bolus Presence in Dysphagia
Get PDFCopyright © 2015 Lara Ferris et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Objectives. Preswallow pharyngeal bolus presence is evident in patients with oropharyngeal dysphagia. Pressure flow analysis (PFA) using high resolution manometry with impedance (HRMI) with AIMplot software is a method for objective interpretation of pharyngeal and upper esophageal sphincter (UES) pressures and bolus flow patterns during swallowing. This study aimed to observe alterations in PFA metrics in the event of preswallow pharyngeal bolus presence as seen on videofluoroscopy (VFSS). Methods. Swallows from 40 broad dysphagia patients and 8 controls were recorded with a HRMI catheter during simultaneous VFSS. Evidence of bolus presence and level reached prior to pharyngeal swallow onset was recorded. AIMPlot software derived automated PFA functional metrics. Results. Patients with bolus movement to the pyriform sinuses had a higher SRI, indicating greater swallow dysfunction. Amongst individual metrics, TNadImp to PeakP was shorter and flow interval longer in patient groups compared to controls. A higher pharyngeal mean impedance and UES mean impedance differentiated the two patient groups. Conclusions. This pilot study identifies specific altered PFA metrics in patients demonstrating preswallow pharyngeal bolus presence to the pyriform sinuses. PFA metrics may be used to guide diagnosis and treatment of patients with oropharyngeal dysphagia and track changes in swallow function over time
Theoretical Modeling of Rock Breakage by Hydraulic and Mechanical Tool
Get PDFCopyright © 2014 Hongxiang Jiang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Rock breakage by coupled mechanical and hydraulic action has been developed over the past several decades, but theoretical study on rock fragmentation by mechanical tool with water pressure assistance was still lacking. The theoretical model of rock breakage by mechanical tool was developed based on the rock fracture mechanics and the solution of Boussinesq’s problem, and it could explain the process of rock fragmentation as well as predicating the peak reacting force. The theoretical model of rock breakage by coupled mechanical and hydraulic action was developed according to the superposition principle of intensity factors at the crack tip, and the reacting force of mechanical tool assisted by hydraulic action could be reduced obviously if the crack with a critical length could be produced by mechanical or hydraulic impact. The experimental results indicated that the peak reacting force could be reduced about 15% assisted by medium water pressure, and quick reduction of reacting force after peak value decreased the specific energy consumption of rock fragmentation by mechanical tool. The crack formation by mechanical or hydraulic impact was the prerequisite to improvement of the ability of combined breakage
Repeatability of a Short Food Frequency Questionnaire to Assess Calcium Intake in Older Australians
Get PDFCopyright © 2010 Michelle Miller et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Objective. To assess the repeatability of the validated Flinders Calcium Food Frequency Questionnaire for estimating dietary calcium intake in a sample of community dwelling older Australians. Methods. A test-retest repeatability study involving 100 subjects (65 years) living independently in metropolitan Adelaide, Australia. Estimates of daily calcium intake from the first and repeated administration were calculated from two versions (35-item and 15-item) of the . The intraclass correlation coefficient (ICC) was used to assess the repeatability. Results. Moderate and comparable ICC values (, ) were found across the two versions of the . Conclusion. Both versions demonstrated moderate repeatability, supporting the results of previous studies
Space, Transformation and Identity in E. M. Forster’s A Passage to India and Ahdaf Soueif’s The Map of Love
Get PDFThis paper examines the representation of urban spaces in E. M. Forster’s A Passage to India (1924) and Ahdaf Soueif’s The Map of Love (1999). In particular, it investigates how colonialism - as a cultural activity - produces traces of its hegemony and how these traces transform and fashion the colonial and post-colonial urban spaces in the two novels. Through examining how A Passage to India and The Map of Love present the utilization of space, this paper explores the ways colonialist superpowers have left traces of their presences which are marked in all of the spaces they subjugate and dominate. Interestingly, space and its concomitant socio-political divisions/hierarchies are viewed, by and large, through the responses/perspectives of the women characters in both novels represented by Forster’s Ms Quested and Mrs Moore and Soueif’s Lady Anna Winterbourne. The paper will also show how employing Edward Soja’s term of Thirdspace can illuminate the significance of the courtroom episode that each novel presents
Review of Irish Poets and Modern Greece: Heaney, Mahon, Cavafy, Seferis by Joanna Kruczkowska.
Get PDFReview of Irish Poets and Modern Greece: Heaney, Mahon, Cavafy, Seferis by Joanna Kruczkowska
Review of Return Narratives by Theodora D. Patrona
No full textReview of Return Narratives by Theodora D. Patron
Identity and Nation in Kazuo Ishiguro’s An Artist of the Floating World
Get PDFAn Artist of the Floating World (1986) looks back to Ishiguro’s first novel, A Pale View of Hills (1982) and anticipates his third, The Remains of the Day (1989) seeing that the painter Ono worries about a possible interference in his daughter marriage negotiations as a consequence of his support to the nationalist government, which compels him to undertake a self-evaluation of his career. By focusing on the Americanization of the Japanese culture and the generational gap created during the postwar period in Japan, the present article discusses universal conflicts that emerge from verticalized familial and social relationships through the lens of Ono who is having trouble to deal with his sense of guilt and internal conflict regarding his active participation as a nationalist propagandist artist of the empire during the war. His reminiscing reveals mechanisms of self-deception and repression to bury intolerable and unwelcome memories insofar as they are discussed against the backdrop of a unique fluid historical moment of intense upheaval and cultural change in Japan