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Biology subjects

Freeman, E. A.

Publications and source records attributed to Freeman, E. A..

2 recordsLinked to original sources

Utilizing citizen science to model the distribution of Aedes aegypti in West Africa

In a rapidly urbanizing region such as West Africa, Aedes mosquitoes pose an emerging threat of infectious disease that is compounded by limited vector surveillance. Citizen science has been proposed as a way to fill surveillance gaps by training local residents to collect and share information on disease vectors. Increasing citizen science efforts can begin to bridge the gaps in our current knowledge of Aedes distribution while engaging locals with mosquito control and public health efforts. Understanding the distribution of disease vectors in West Africa can inform researchers and public health officials on where to conduct disease surveillance and focus public health interventions. We aimed to compare citizen science data to published literature observations of Aedes mosquitoes and to quantify how incorporating citizen science changes our understanding of Aedes mosquito distribution in West Africa. We utilized citizen science data collected through NASAs GLOBE Observer mobile phone application and data from a previously published literature review on Aedes mosquito distribution to examine the contribution of citizen science to understanding the distribution of Ae. aegypti in West Africa using Maximum Entropy modeling. Combining citizen science and literature-derived observations improved the fit of the model compared to models created by each data source alone, but did not alleviate location bias within the models, likely due to lack of widespread observations. Understanding Ae. aegypti distribution will require greater investment in Aedes mosquito surveillance in the region, and citizen science should be utilized as a tool in this mission to increase the reach of surveillance.

ecology↗

Synergistic Recruitment of UbcH7~Ub and Phosphorylated Ubl Domain Triggers Parkin Activation

The mechanism of activation and ubiquitin conjugation by the E3 ligase parkin is pivotal to understand the molecular pathology of early-onset Parkinsons disease. Parkin is normally autoinhibited but is activated by the kinase PINK1 that phosphorylates parkins N-terminal ubiquitin-like (pUbl) domain and ubiquitin. How these alter the structure of parkin to allow recruitment of an E2~Ub conjugate to enhance ubiquitination is an unresolved question. We present the structure of an incoming E2~Ub conjugate with the phospho-ubiquitin bound C-terminus of parkin (R0RBR). We show the UbcH7~Ub conjugate is recruited by R0RBR parkin in the open state whereby conjugated ubiquitin binds to the RING1/IBR interface. Further, NMR experiments indicate there is re-modelling near the RING0/RING2 interface remote from the E2-binding site. This, and parkin phosphorylation lead to rapid reactivity of the RING2(Rcat) catalytic cysteine in parkin, needed for ubiquitin transfer. Parkin phosphorylation also leads to relocation and weak interaction of the pUbl domain with the RING0 domain that is enhanced upon E2~Ub recruitment indicating these events act synergistically to drive parkin activity.

biochemistry↗