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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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39 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Challenges and Solutions for Leave-One-Out Biosensor Design in the Context of a Rugged Fitness Landscape

The leave-one-out (LOO) green fluorescent protein (GFP) approach to biosensor design combines computational protein design with split protein reconstitution. LOO-GFPs reversibly fold and gain fluorescence upon encountering the target peptide, which can be redefined by computational design of the LOO site. Such an approach can be used to create reusable biosensors for the early detection of emerging biological threats. Enlightening biophysical inferences for nine LOO-GFP biosensor libraries are presented, with target sequences from dengue, influenza, or HIV, replacing beta strands 7, 8, or 11. An initially low hit rate was traced to components of the energy function, manifesting in the over-rewarding of over-tight side chain packing. Also, screening by colony picking required a low library complexity, but designing a biosensor against a peptide of at least 12 residues requires a high-complexity library. This double-bind was solved using a “piecemeal” iterative design strategy. Also, designed LOO-GFPs fluoresced in the unbound state due to unwanted dimerization, but this was solved by fusing a fully functional prototype LOO-GFP to a fiber-forming protein, Drosophila ultrabithorax, creating a biosensor fiber. One influenza hemagglutinin biosensor is characterized here in detail, showing a shifted excitation/emission spectrum, a micromolar affinity for the target peptide, and an unexpected photo-switching ability.

Chemistry↗
DOE OSTI2020

High Rate of Non-Human Feeding by Aedes aegypti Reduces Zika Virus Transmission in South Texas

Mosquito-borne viruses are emerging or re-emerging globally, afflicting millions of people around the world. Aedes aegypti, the yellow fever mosquito, is the principal vector of dengue, Zika, and chikungunya viruses, and has well-established populations across tropical and subtropical urban areas of the Americas, including the southern United States. While intense arboviral epidemics have occurred in Mexico and further south in the Americas, local transmission in the United States has been minimal. Here, we study Ae. aegypti and Culex quinquefasciatus host feeding patterns and vertebrate host communities in residential environments of South Texas to identify host-utilization relative to availability. Only 31% of Ae. aegypti blood meals were derived from humans, while 50% were from dogs and 19% from other wild and domestic animals. In Cx. quinquefasciatus, 67% of blood meals were derived from chicken, 22% came from dogs, 9% from various wild avian species, and 2% from other mammals including one human, one cat, and one pig. We developed a model for the reproductive number, R0, for Zika virus (ZIKV) in South Texas relative to northern Mexico using human disease data from Tamaulipas, Mexico. We show that ZIKV R0 in South Texas communities could be greater than one if the risk of human exposure to Ae. aegypti bites in these communities is at least 60% that of Northern Mexico communities. The high utilization of non-human vertebrates and low risk of human exposure in South Texas diminishes the outbreak potential for human-amplified urban arboviruses transmitted by Ae. aegypti.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Antithetic effect of interferon-α on cell-free and cell-to-cell HIV-1 infection

In HIV-1-infected individuals, transmitted/founder (TF) virus contributes to establish new infection and expands during the acute phase of infection, while chronic control (CC) virus emerges during the chronic phase of infection. TF viruses are more resistant to interferon-alpha (IFN-α)-mediated antiviral effects than CC virus, however, its virological relevance in infected individuals remains unclear. Here we perform an experimental-mathematical investigation and reveal that IFN-α strongly inhibits cell-to-cell infection by CC virus but only weakly affects that by TF virus. Surprisingly, IFN-α enhances cell-free infection of HIV-1, particularly that of CC virus, in a virus-cell density-dependent manner. We further demonstrate that LY6E, an IFN-stimulated gene, can contribute to the density-dependent enhancement of cell-free HIV-1 infection. Altogether, our findings suggest that the major difference between TF and CC viruses can be explained by their resistance to IFN-α-mediated inhibition of cell-to-cell infection and their sensitivity to IFN-α-mediated enhancement of cell-free infection.

59 BASIC BIOLOGICAL SCIENCES↗