Search

Elwyn Richardson’s experimental approach to teaching and learning and Oruaiti was officially sanctioned, but the history of education in Aotearoa/New Zealand shows that teachers have been typically conformist. In this article, I suggest that positivist paradigms from the industrial age continue to shape classroom teaching, partly because of norms of individualism, and partly because neoliberal understandings have become central in the functioning of our schools and society. Teaching is an activity that promotes the ethics of a community or society by promulgating some ideas and marginalising others. In Aotearoa/New Zealand, many of our students struggle with the collective orientation of their community traditions and the societal emphasis on individualism. Modernist beliefs in social progress through technology still permeate education policy. Promoting communitarian understandings requires more open-ended approaches to teaching such as Richardson demonstrated. With digital technologies gaining progressively greater influence in schools, the opportunities for social connectedness have been enhanced alongside an increasing emphasis on individual devices. This article briefly explores interconnections between experimentation, context and community. [ABSTRACT FROM PUBLISHER]

Background: Cancer is a devastating type of disease. New and innovative ways to tackle cancers that have so far proved refractive to conventional therapies is urgently needed. It is becoming increasingly clear that, in addition to conventional therapeutics targeting by small molecules, that tumor cell metabolism presents new opportunities to target selectively specific cancer cell populations. Metabolic defects in cancer cells can be manifested in many ways that might not be readily apparent, such as altering epigenetic gene regulation for example. The complex rewiring of metabolic pathways gives tumor cells a special advantage over differentiated cells, since they deplete body stores as fuel for their growth and proliferation. Tumor metabolism looks simpler when we consider that some enzymatic switches are in a neoglucogenic direction thereby depleting body stores. However, these pathways may be inadequately switched on by catabolic hormones (glucagon, epinephrine and cortisol) in a specific situation where anabolism is activated by, for example insulin released from beta pancreatic cells or IGF, inducing mitosis and synthesis that are powered by glucose catabolism. Such a hybrid metabolic situation would be reached if a pancreatic beta cell mechanism, mediated by GABA, failed to silence neighboring alpha cells and delta cells. The inhibitory transmitter GABA hyperpolarizes alpha and delta cells via their GABA A receptors, and blocks the release of glucagon and somatostatin. Alternatively, an anomaly of alpha cell channels, would lead to a similar situation. Whatever is the alteration, anabolism fails to silence catabolism and enzymatic switches controlled by kinases and phosphatases adopt an inadequate direction, leading to a hybrid metabolic rewiring found in cancer. It is daring to formulate such a hypothesis as this. However, it is quite possible that the starting point in cancer is an alteration of the endocrine pancreas, suppressing the mechanism by which beta cells silence the neighboring alpha and delta cells, with GABA and Zn2+ [ABSTRACT FROM AUTHOR]

Objective C1 inhibitor (C1-INH) is an endogenous inhibitor of complement and kinin systems. We have explored the efficacy and the therapeutic window of the recently available human recombinant (rh) C1-INH on ischemic brain injury and investigated its mechanism of action in comparison with that of plasma-derived (pd) C1-INH. Methods rhC1-INH was administered intravenously to C57Bl/6 mice undergoing transient or permanent ischemia, and its protective effects were evaluated by measuring infarct volume and neurodegeneration. The binding profiles of rhC1-INH and pdC1-INH were assessed in vitro using surface plasmon resonance. Their localization in the ischemic brain tissue was determined by immunohistochemistry and confocal analysis. The functional consequences of rhC1-INH and pdC1-INH administration on complement activation were analyzed by enzyme-linked immunosorbent assay on plasma samples. Results rhC1-INH markedly reduced cerebral damage when administered up to 18 hours after transient ischemia and up to 6 hours after permanent ischemia, thus showing a surprisingly wide therapeutic window. In vitro rhC1-INH bound mannose-binding lectin (MBL), a key protein in the lectin complement pathway, with high affinity, whereas pdC1-INH, which has a different glycosylation pattern, did not. In the ischemic brain, rhC1-INH was confined to cerebral vessels, where it colocalized with MBL, whereas pdC1-INH diffused into the brain parenchyma. In addition, rhC1-INH was more active than pdC1-INH in inhibiting MBL-induced complement activation. Interpretation rhC1-INH showed a surprisingly wider time window of efficacy compared with the corresponding plasmatic protein. We propose that the superiority of rhC1-INH is due to its selective binding to MBL, which emerged as a novel target for stroke treatment. Ann Neurol 2009;66:332-342 [ABSTRACT FROM AUTHOR]