TREM2-dependent effects on microglia in Alzheimer\u27s Disease

Alzheimer’s disease (AD) is a late-onset dementia characterized by the deposition of amyloid plaques and formation of neurofibrillary tangles (NFTs) which lead to neuronal loss and cognitive deficits. Abnormal protein aggregates in the AD brain are also associated with reactive microglia and astrocytes. Whether this glial response is beneficial or detrimental in AD pathology is under debate. Microglia are the resident innate immune cells in the central nervous system (CNS) that survey the surrounding environment. Genome-wide association studies (GWAS) have identified the R47H variant of triggering receptor expressed on myeloid cell 2 (TREM2) as a risk factor for late-onset AD (LOAD) with an odds ratio of 4.5. TREM2 is an immunoreceptor primarily present on microglia in the CNS that binds to polyanionic molecules. The transmembrane domain of TREM2 signals through DAP12, an adaptor protein that contains an immunoreceptor tyrosine-based activation motif (ITAM), which mediates TREM2 signaling and promotes microglial activation and survival. In mouse models of AD, Trem2 haplodeficiency and deficiency lead to reduced microglial clustering around amyloid β (Aβ) plaques, suggesting TREM2 is required for plaque-associated microglial responses. Recently, TREM2 has been shown to enhance microglial metabolism through the mammalian target of rapamycin (mTOR) pathway. Although aberrant metabolism has long been associated with AD, not much was known regarding how metabolism in microglia might affect disease progression. In this review, we discuss the role of TREM2 and metabolism in AD pathology, highlighting how TREM2-mediated microglial metabolism modulates AD pathogenesis

Embodied spirituality

The main findings on embodied spirituality within the Toronto Blessing are presented in this article. The aim of this study is to interpret ecstatic religious experiences from a psychological point of view. The theoretical framework is interdisciplinary, using theories from ego-psychology, social psychology, sociology, cultural anthropology, and ritual theory. Regarding the latter notion, Thomas Csordas has developed cultural phenomenology, which is a culturally constructed way of understanding a situation through using bodily senses in a sort of sensory engagement that is linked with inter-subjectivity. This way of thinking assumes that the body can impart knowledge and help us understand apparently non-rational phenomena. Ecstatic phenomena can be interpreted as bodily knowledge, a habitus, stored or saved in the body to be later activated in a cultural and ritual context

Dropped object impact analysis on subsea pipelines

This thesis studies the response of a subsea pipeline's structure when a dropped object hits it. The pipeline and seabed were modelled using solid elements, while the container model was imported from Aker Solutions and is composed of shell elements. LS-DYNA, a finite element software, was used to conduct the analysis. The key parameters studied in this research were impact force, internal energy, and pipeline deformation. Thirteen different cases have been analysed in addition to three cases used in a mesh convergence test. The impact scenarios have been described in Table 8, Chapter 4.11 and the three mesh convergence cases have been described in Table 9, Chapter 4.11. The thesis includes a literature study of relevant standards and previous research that has been conducted. DNVGL-RP-C204 and DNVGL-RP-F107 are the applicable standards for dropped objects in this thesis. DNVGL-RP-C204 provides essential information on calculating impact velocity, dissipation of strain energy, and force-deformation curve for tubular members. At the same time, DNVGL-RP-F107 presents information on drop probability in crane lifting operations, the hit probability onto a subsea pipeline, and various protection methods available in the industry. A mesh convergence study was carried out to determine the optimal mesh size for the models. This involved comparing three models with the same properties, apart from the mesh size, and observing at which mesh size the outcome converged. The objective was to identify the largest feasible mesh size that would have little to no impact on the precision of the results. A comprehensive parametric study of the subsea pipeline was conducted to analyse its response to the different cases. This involved testing for various scenarios on the pipeline under different conditions, such as altering the soil parameters, protection method, yield strength, and the impact angle of the container. The container's velocity was kept constant at 10 m/s in all the impact scenarios. The impact angle was identified as a crucial factor in the extent of damage inflicted on the pipeline. The use of concrete coating reduced the deformation and the internal energy in the pipeline. With a flexible seabed, the internal energy was reduced for the scenario with coating. However, that was not the case for the unprotected pipeline. The possible reason is explained in this thesis. By increasing the pipeline’s yield strength, the internal energy and deformation of the pipeline were significantly reduced

Enforced Heteronormative Socio-Cultural Structures in Garage Olimpo and “Cambio de armas”

In Argentina, before and during the Proceso (1976-1983), fear and terror were used as weapons to control the populace and wage war against supposed subversives. The 1999 film Garage Olimpo, by Marco Bechis, and Luisa Valenzuela’s short story, “Cambio de armas” (written in 1977, published in 1982), attempt to make sense of this epoch through visual and textual means. I argue that male antagonists force female protagonists to enact strict gender roles that uphold a heteronormative socio-cultural structure. In both texts, heterosexual cultural norms are defined and enforced by males within the authoritarian hierarchy. In particular, power is maintained and gender roles are enforced by captors who feign “normalcy;” by spies who monitor the women’s actions; and by a system that perpetuates the illusion of control by those in power

A Model Disciplinary Policy and Procedures for Meridian Elementary School in the Kent school district, Kent, Washington

The purpose of this project was to develop and implement a model disciplinary policy and procedures for Meridian Elementary School in the Kent school district, Kent, Washington. To accomplish this purpose, a review ofrelated literature was conducted. Additionally, related info1mation and materials from selected sources was obtained and analyzed

IL-15 sustains IL-7R-independent ILC2 and ILC3 development

The signals that maintain tissue-resident innate lymphoid cells (ILC) in different microenvironments are incompletely understood. Here we show that IL-7 receptor (IL-7R) is not strictly required for the development of any ILC subset, as residual cells persist in the small intestinal lamina propria (siLP) of adult and neonatal Il7ra(−/−) mice. Il7ra(−/−) ILC2 primarily express an ST2(−) phenotype, but are not inflammatory ILC2. CCR6(+) ILC3, which express higher Bcl-2 than other ILC3, are the most abundant subset in Il7ra(−/−) siLP. All ILC subsets are functionally competent in vitro, and are sufficient to provide enhanced protection to infection with C. rodentium. IL-15 equally sustains wild-type and Il7ra(−/−) ILC survival in vitro and compensates for IL-7R deficiency, as residual ILCs are depleted in mice lacking both molecules. Collectively, these data demonstrate that siLP ILCs are not completely IL-7R dependent, but can persist partially through IL-15 signalling

Grid, vev, farge

Skriftlig del av masterprosjekt. Avdeling Kunst og håndverk, 202