IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection

In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cutaneous defense against Zika virus infection. Transcriptional and phenotypic profiling of epidermal keratinocytes treated with IL-27 demonstrated activation of antiviral proteins OAS1, OAS2, OASL, and MX1 in the skin of both mice and humans. IL-27–mediated antiviral protein induction was found to occur in a STAT1- and IRF3-dependent but STAT2-independent manner. Moreover, using IL27ra mice, we demonstrate a significant role for IL-27 in inhibiting Zika virus morbidity and mortality following cutaneous, but not intravenous, inoculation. Together, our results demonstrate a critical and previously unrecognized role for IL-27 in cutaneous innate antiviral immunity against Zika virus

Climate adaptation for rural water and sanitation systems in the Solomon Islands: A community scale systems model for decision support

Delivering water and sanitation services are challenging in data poor rural settings in developing countries. In this paper we develop a Bayesian Belief Network model that supports decision making to increase the availability of safe drinking water in five flood-prone rural communities in the Solomon Islands. We collected quantitative household survey data and qualitative cultural and environmental knowledge through community focus group discussions. We combined these data to develop our model, which simulates the state of eight water sources and ten sanitation types and how they are affected by season and extreme events. We identify how climate and current practices can threaten the availability of drinking water for remote communities. Modelling of climate and intervention scenarios indicate that water security could be best enhanced through increased rainwater harvesting (assuming proper installation and maintenance). These findings highlight how a systems model can identify links between and improve understanding of water and sanitation, community behaviour, and the impacts of extreme events. The resultant BBN provides a tool for decision support to enhance opportunities for climate resilient water and sanitation service provision

Autophagy in major human diseases

Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders