Responsibility, complexity science and education: Dilemmas and uncertain responses

While complexity science is gaining interest among educational theorists, its constructs do not speak to educational responsibility or related core issues in education of power and ethics. Yet certain themes of complexity, as taken up in educational theory, can help unsettle the more controlling and problematic discourses of educational responsibility such as the potential to limit learning and subjectivity or to prescribe social justice. The purpose of this article is to critically examine complexity science against notions of responsibility in terms of implications for education. First, themes of complexity science prominent in contemporary educational writing are explained. Then dilemmas of responsibility in complexity are explored, such as what forms and meanings responsibility can have in a ‘complexified’ perspective of education, how care for others is mobilised, and how desire can be understood. Analyses of ethical action grounded in complexity science are then examined, as well as theories of the ethical subject and participatory responsibility that are congruent with certain tenets of a complexity ontology. Finally, the possibility of an educational vision of responsibility animated by complexity theories is considered, drawing from related writings of Bai, Biesta, Derrida, Levinas and Varela

In silico design of novel probes for the atypical opioid receptor MRGPRX2

The primate-exclusive MRGPRX2 G protein-coupled receptor (GPCR) has been suggested to modulate pain and itch. Despite putative peptide and small molecule MRGPRX2 agonists, selective nanomolar potency probes have not yet been reported. To identify a MRGPRX2 probe, we first screened 5,695 small molecules and found many opioid compounds activated MRGPRX2, including (−)- and (+)-morphine, hydrocodone, sinomenine, dextromethorphan and the prodynorphin-derived peptides, dynorphin A, dynorphin B, and α- and β-neoendorphin. We used these to select for mutagenesis-validated homology models and docked almost 4 million small molecules. From this docking, we predicted ZINC-3573, which represents a potent MRGPRX2-selective agonist, showing little activity against 315 other GPCRs and 97 representative kinases, and an essentially inactive enantiomer. ZINC-3573 activates endogenous MRGPRX2 in a human mast cell line inducing degranulation and calcium release. MRGPRX2 is a unique atypical opioid-like receptor important for modulating mast cell degranulation, which can now be specifically modulated with ZINC-3573

GM1 ganglioside reduces behavioral dysfunction following cortical focal ischemia

The functional consequences of corticalfocalischemia and the effect of monosialoganglioside (GM1) treatment on learning/performance of a spatial reversal task were investigated. Corticalfocalischemia was induced by a permanent occlusion of the left common carotid artery and the ipsilateral middle cerebral artery, with a 1-h clamping of the contralateral carotid artery. Twenty-six rats were randomly assigned to three groups: sham controls, a saline-treated ischemic group, and a GM1ganglioside-treated ischemic group (10 mg/kg/day: IM). Fifteen days after surgery rats were trained on a spatial reversal task in a two-lever operant chamber where food reward was contingent on lever pressing. Training continued from day 15 to day 21 after surgery. Corticalfocalischemia resulted in learning/performance deficits that were reduced byGM1ganglioside treatment. The cognitive deficits were characterized by a significantly higher number of nonperseverative erros and number of responses to criterion. There was a significant difference between left and right lever performance in the saline-treated ischemic group, which was absent in shams and GM1-treated ischemic rats. On all mearures GM1-treated rats were not different from sham controls

GM1 Ganglioside Treatment of Spontaneously Hypertensive Stroke Prone Rats

Many reports indicate that GM1 ganglioside is effective in reducing CNS ischemic injury in animal models. These models employ invasive surgery to induce ischemic damage in otherwise healthy animals. The purpose of this study was to determine if the beneficial effects of GM1 could be generalized to Spontaneously Hypertensive Rats-Stroke Prone (SHRSP). The SHRSP strain develops a pathology similar to those observed in patients with stroke. The SHRSP have risk factors that include hypertension, fibrinoid necrosis, and sensitivity to diet. Female SHRSP were randomly assigned to GM1- or saline-treatment conditions. Rats were fed a stroke-inducing diet. Daily body weights, weekly blood pressure, time of stroke onset, and age at death were recorded. Spontaneous activity and performance on a tail-hang test were assessed thrice weekly. The results indicate that GM1 treatment did not delay the time of stroke onset or death. GM1 did reduce hyperactivity in the initial stages of the ischemic pathology, but did not prevent the marked decline in behavioral activity observed at later time points. There were no differences in weight loss, performance on the tail-hang test, or number of CNS injury-related symptoms observed. These findings suggest that GM1 was not as effective in decreasing mortality, weight loss, or behavioral deficits in SHRSP as previously reported using other animal models of ischemia. Distinguishing between those animal models in which GM1 is more and less effective may be useful in determining under which clinical situations GM1 is likely to be most suitable