Two structurally-unrelated small molecule chemotypes, represented by compounds PAV-617 and PAV-951, with antiviral activity in cell culture against monkeypox virus (MPXV) and human immunodeficiency virus (HIV) respectively, were studied for anti-cancer efficacy. Each exhibited apparent pan-cancer cytotoxicity, reasonable pharmacokinetics, and non-toxicity in mice at active concentrations. Anti-tumor properties of each compound were validated in mouse xenografts against A549 human lung cancer. The targets of these compounds are unconventional: each binds to a different transient, energy-dependent multi-protein complex containing the protein KAP-1(TRIM28), an allosteric modulator known to broadly regulate mechanisms underlying viral and nonviral disease states including cancer. Treatment with these compounds alters the target multi-protein complexes in a manner consistent with allosteric modulation as their mechanism of action. These compounds appear to remove a block, crucial for cancer survival and progression, on the homeostatic linkage of uncontrolled cellular proliferation to apoptosis. These compounds may provide starting points for development of next-generation non-toxic, cancer therapeutics.
In recent years early learning and child care (ELCC) has become a significant priority area for many provincial governments, including New Brunswick (NB). The NB consortium perceives ELCC as instrumental to achieving broader economic prosperity and social well-being. In hopes of problematizing rather than normalizing the contemporary spotlight on ELCC, I interrogate how school readiness has become the selectively targeted problem for which pre-school developmental testing is proposed as the solution. The specific means purported to address school readiness in NB is the Early Years Evaluation – Direct Assessment (EYE-DA). While EYE-DA testing is ongoing and powerful, I conclude that the recent pan-Canadian uptake of curriculum frameworks and pedagogical documentation may incite counter possibilities and provocations for those of us working with young children.
The child-future join is pervasive in childhood studies and popular culture. Instead of disavowing the relation, I consider what might be generated if we “stay with the trouble” of its cocomposition in the making of worlds. To do so, I turn to a zombie child named Melanie from The Girl with All the Gifts to grapple with how the end of the world might not be a cause for mourning, how fiery landscapes can allow for species regeneration, and how viruses might incite counternarratives of community amid contagion.
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