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Interferon (IFN)-γ is a central regulator of cell-mediated immunity in human health and disease, but reduced expression of the target receptors impairs signaling activity and leads to immunotherapy resistance. Although intracellular expression of IFN-γ restores the signaling and downstream functions, we lack the tools to activate the IFNG gene instead of cell surface receptors. This paper introduces the design and characterization of an artificial transcription factor (ATF) protein that recognizes the IFNG gene with six zinc finger domains, which are dovetailed to a VP64 signaling domain that promotes gene transcription and translation. Biological studies with human Jurkat T cells reveal that the ATF amplifies IFNG gene transcription and translation, and also stimulates gene transcription for multiple class I and II HLA alleles and interferon-stimulated genes (ISGs). Biophysical characterization showed the recombinant ATF protein recognizes the human IFNG gene with nanomolar affinity (KD = 5.27 ± 0.3 nM), adopts a protein secondary structure associated with the ββα-fold of zinc finger domains, and is resistant to thermal denaturation. These studies demonstrate that transcriptional targeting of cytokine genes, rather than surface receptors, activates cytokine expression and shows significant potential for directing immune function.

Chagas disease is a vector-borne parasitic disease of major public health importance. Current prevention efforts are based on triatomine vector control to reduce transmission to humans. Success of vector control interventions depends on their acceptability and value to affected communities. We aimed to identify opportunities for and barriers to improved vector control strategies in the Yucatan peninsula, Mexico.We employed a sequence of qualitative and quantitative research methods to investigate knowledge, attitudes and practices surrounding Chagas disease, triatomines and vector control in three rural communities. Our combined data show that community members are well aware of triatomines and are knowledgeable about their habits. However, most have a limited understanding of the transmission dynamics and clinical manifestations of Chagas disease. While triatomine control is not a priority for community members, they frequently use domestic insecticide products including insecticide spray, mosquito coils and plug-in repellents. Families spend about $32 US per year on these products. Alternative methods such as yard cleaning and window screens are perceived as desirable and potentially more effective. Screens are nonetheless described as unaffordable, in spite of a cost comparable to the average annual spending on insecticide products.Further education campaigns and possibly financing schemes may lead families to redirect their current vector control spending from insecticide products to window screens. Also, synergism with mosquito control efforts should be further explored to motivate community involvement and ensure sustainability of Chagas disease vector control.

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The risk of residential overheating and mortality is increasing due to the effects of global warming and the urban heat island effect and needs to be addressed through climate change adaptation. ‘Adaptation pathways’ have become widely recognised as an adaptation planning approach, but they have not been utilised for long-term planning for city-scale urban heat risk management. This paper applies adaptation pathway methodology to urban heat risk management. We use spatially coherent downscaled probabilistic climate change projections that account for changes in urban-land cover and the urban heat island to appraise adaptation pathways and inform long-term adaptation planning. We demonstrate that adaptation strategies focusing solely on urban greening or building level adaptation based on current best practice are unlikely to cope with the increasing levels of risk. Air-conditioning may play a growing role in managing heat-risk; however, increasing air-conditioning will exacerbate the urban heat island and further increase the risks of overheating.