Latent Class Analysis of University Lecturers' Switch to Online Teaching during the First COVID-19 Lockdown: The Role of Educational Technology, Self-Efficacy, and Institutional Support

The switch to emergency remote teaching (ERT) due to the first COVID-19 lockdown demanded a lot from university lecturers yet did not pose the same challenge to all of them. This study sought to explain differences among lecturers ( n = 796) from universities in France, Germany, Switzerland, and the UK in their use of educational technology for teaching, institutional support, and personal factors. Guided by the Social Cognitive Theory (SCT), lecturers' behavior (educational technology use), environment (institutional support), and personal factors (ERT self-efficacy, continuance intentions, and demographics) were examined. Latent class analysis was employed to identify different types of lecturers in view of educational technology use, while multinomial regression and Wald chi-square test were used to distinguish classes. The largest latent class were Presenters (45.6%), who focused on content delivery, followed by Strivers (22.1%), who strived for social interaction, Routineers (19.6%), who were ready for online teaching, and Evaders (12.7%), who evaded using technology for educational purposes. Both personal factors and perceived institutional support explained class membership significantly. Accordingly, Evaders were older, less experienced, and rarely perceived institutional support as useful. Routineers , the Evaders' counterparts, felt most self-efficient in ERT and held the highest continuance intentions for educational technology use. This research suggests that universities engage lecturers in evidence-based professional development that seeks shared visions of digital transformation, networks and communities, and design-based research

Excitotoxic neuronal cell death during an oligodendrocyte-directed CD8+ T cell attack in the CNS gray matter

Background: Neural-antigen reactive cytotoxic CD8+ T cells contribute to neuronal dysfunction and degeneration in a variety of inflammatory CNS disorders. Facing excess numbers of target cells, CNS-invading CD8+ T cells cause neuronal cell death either via confined release of cytotoxic effector molecules towards neurons, or via spillover of cytotoxic effector molecules from 'leaky’ immunological synapses and non-confined release by CD8+ T cells themselves during serial and simultaneous killing of oligodendrocytes or astrocytes. Methods: Wild-type and T cell receptor transgenic CD8+ T cells were stimulated in vitro, their activation status was assessed by flow cytometry, and supernatant glutamate levels were determined using an enzymatic assay. Expression regulation of molecules involved in vesicular glutamate release was examined by quantitative real-time PCR, and mechanisms of non-vesicular glutamate release were studied by pharmacological blocking experiments. The impact of CD8+ T cell-mediated glutamate liberation on neuronal viability was studied in acute brain slice preparations. Results: Following T cell receptor stimulation, CD8+ T cells acquire the molecular repertoire for vesicular glutamate release: (i) they upregulate expression of glutaminase required to generate glutamate via deamination of glutamine and (ii) they upregulate expression of vesicular proton-ATPase and vesicular glutamate transporters required for filling of vesicles with glutamate. Subsequently, CD8+ T cells release glutamate in a strictly stimulus-dependent manner. Upon repetitive T cell receptor stimulation, CD25high CD8+ T effector cells exhibit higher estimated single cell glutamate release rates than CD25low CD8+ T memory cells. Moreover, glutamate liberation by oligodendrocyte-reactive CD25high CD8+ T effector cells is capable of eliciting collateral excitotoxic cell death of neurons (despite glutamate re-uptake by glia cells and neurons) in intact CNS gray matter. Conclusion: Glutamate release may represent a crucial effector pathway of neural-antigen reactive CD8+ T cells, contributing to excitotoxicity in CNS inflammation.<br

CD4+ CD25+ FoxP3+ regulatory T cells suppress cytotoxicity of CD8+ effector T cells: implications for their capacity to limit inflammatory central nervous system damage at the parenchymal level

<p>Abstract</p> <p>Background</p> <p>CD4⁺CD25⁺forkhead box P3 (FoxP3)⁺regulatory T cells (T reg cells) are known to suppress adaptive immune responses, key control tolerance and autoimmunity.</p> <p>Methods</p> <p>We challenged the role of CD4⁺T reg cells in suppressing established CD8⁺T effector cell responses by using the OT-I/II system <it>in vitro </it>and an OT-I-mediated, oligodendrocyte directed <it>ex vivo </it>model (ODC-OVA model).</p> <p>Results</p> <p>CD4⁺T reg cells dampened cytotoxicity of an ongoing CD8⁺T effector cell attack <it>in vitro </it>and within intact central nervous system tissue <it>ex vivo</it>. However, their suppressive effect was limited by the strength of the antigen signal delivered to the CD8⁺T effector cells and the ratio of regulatory to effector T cells. CD8⁺T effector cell suppression required T cell receptor-mediated activation together with costimulation of CD4⁺T reg cells, but following activation, suppression did not require restimulation and was antigen non-specific.</p> <p>Conclusions</p> <p>Our results suggest that CD4⁺T reg cells are capable of suppressing CD8⁺T effector cell responses at the parenchymal site, that is, limiting parenchymal damage in autoimmune central nervous system inflammation.</p

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

The switch to online teaching during the first COVID-19 lockdown: A comparative study at four European universities

In 2020, for the first time in history, COVID-19 measures necessitated emergency online teaching to ensure continuity of education. Although institutional support was offered to lecturers, the situation posed an extraordinary challenge for university teaching. Using a comparative approach, this study surveys lecturers from different countries and their use of educational technology for emergency online teaching. Its focus lies on the relationships between use of educational technology, online teaching self-efficacy and attitudes towards educational technology. Overall and according to reports, the use of educational technology increased significantly compared to pre-pandemic conditions. The universities studied had different levels of digitalization, which influenced lecturers’ use of educational technology. Furthermore, lecturers differed in terms of self-efficacy, attitude, and perception. Regarding factors affecting educational technology use, results showed that especially pre-pandemic experiences with educational technology, as well as self-efficacy and perceptual variables influenced the use of educational technology during the pandemic. Based on these results, it is advisable for universities to embrace this ad hoc switch to online teaching as an opportunity for purposeful digitalization of university teaching

The switch to online teaching during the first COVID-19 lockdown: A comparative study at four European universities

In 2020, for the first time in history, COVID-19 measures necessitated emergency online teaching to ensure continuity of education. Although institutional support was offered to lecturers, the situation posed an extraordinary challenge for university teaching. Using a comparative approach, this study surveys lecturers from different countries and their use of educational technology for emergency online teaching. Its focus lies on the relationships between use of educational technology, online teaching self-efficacy and attitudes towards educational technology. Overall and according to reports, the use of educational technology increased significantly compared to pre-pandemic conditions. The universities studied had different levels of digitalization, which influenced lecturers' use of educational technology. Furthermore, lecturers differed in terms of self-efficacy, attitude, and perception. Regarding factors affecting educational technology use, results showed that especially pre-pandemic experiences with educational technology, as well as self-efficacy and perceptual variables influenced the use of educational technology during the pandemic. Based on these results, it is advisable for universities to embrace this ad hoc switch to online teaching as an opportunity for purposeful digitalization of university teaching

Murine K2P_{2P}5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P_{2P}3.1-and KV_{V}1.3-Dependent Mechanisms

Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K$_{2P}$5.1(TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K$_{2P}$5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K$_{2P}$5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K$_{2P}$5.1 knockout (K$_{2P}$5.1$^{-/-}$ mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K$_{2P}$5.1$^{-/-}$ mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K$_{2P}$3.1 and K$_{V}$1.3 seems to counterbalance the deletion of K$_{2P}$5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K$_{2P}$5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K$_{2P}$5.1-targeting drugs