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Xu, Hua

Publications and source records attributed to Xu, Hua.

Viral afterlife: SARS-CoV-2 as a reservoir of immunomimetic peptides that reassemble into proinflammatory supramolecular complexes

It is unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to the strong but ineffective inflammatory response that characterizes severe Coronavirus disease 2019 (COVID-19), with amplified immune activation in diverse cell types, including cells without angiotensin-converting enzyme 2 receptors necessary for infection. Proteolytic degradation of SARS-CoV-2 virions is a milestone in host viral clearance, but the impact of remnant viral peptide fragments from high viral loads is not known. Here, we examine the inflammatory capacity of fragmented viral components from the perspective of supramolecular self-organization in the infected host environment. Interestingly, a machine learning analysis to SARS-CoV-2 proteome reveals sequence motifs that mimic host antimicrobial peptides (xenoAMPs), especially highly cationic human cathelicidin LL-37 capable of augmenting inflammation. Such xenoAMPs are strongly enriched in SARS-CoV-2 relative to low-pathogenicity coronaviruses. Moreover, xenoAMPs from SARS-CoV-2 but not low-pathogenicity homologs assemble double-stranded RNA (dsRNA) into nanocrystalline complexes with lattice constants commensurate with the steric size of Toll-like receptor (TLR)-3 and therefore capable of multivalent binding. Such complexes amplify cytokine secretion in diverse uninfected cell types in culture (epithelial cells, endothelial cells, keratinocytes, monocytes, and macrophages), similar to cathelicidin’s role in rheumatoid arthritis and lupus. The induced transcriptome matches well with the global gene expression pattern in COVID-19, despite using <0.3% of the viral proteome. Delivery of these complexes to uninfected mice boosts plasma interleukin-6 and CXCL1 levels as observed in COVID-19 patients.

60 APPLIED LIFE SCIENCES↗

A guide to the BRAIN Initiative Cell Census Network data ecosystem

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman primate (NHP) brains. Here, we provide a guide to the cellular and spatial approaches employed by the BICCN, and to accessing and using these data and extensive resources, including the BRAIN Cell Data Center (BCDC), which serves to manage and integrate data across the ecosystem. We illustrate the power of the BICCN data ecosystem through vignettes highlighting several BICCN analysis and visualization tools. Finally, we present emerging standards that have been developed or adopted toward Findable, Accessible, Interoperable, and Reusable (FAIR) neuroscience. The combined BICCN ecosystem provides a comprehensive resource for the exploration and analysis of cell types in the brain.

59 BASIC BIOLOGICAL SCIENCES↗

EPS (Electric Particulate Suspension) Microgravity Technology Provides NASA with New Tools

The Electric Particulate Suspension is a fire safety ignition test system being developed at Iowa State University with NASA support for evaluating combustion properties of powders, powder-gas mixtures, and pure gases in microgravity and gravitational atmospheres (quenching distance, ignition energy, flammability limits). A separate application is the use of EPS technology to control heat transfer in vacuum and space environment enclosures. In combustion testing, ignitable powders (aluminum, magnesium) are introduced in the EPS test cell and ignited by spark, while the addition of inert particles act as quenching media. As a combustion research tool, the EPS method has potential as a benchmark design for quenching powder flames that would provide NASA with a new fire safety standard for powder ignition testing. The EPS method also supports combustion modeling by providing accurate measurement of flame-quenching distance as an important parameter in laminar flame theory since it is closely related to characteristic flame thickness and flame structure. In heat transfer applications, inert powder suspensions (copper, steel) driven by electric fields regulate heat flow between adjacent surfaces enclosures both in vacuum (or gas) and microgravity. This simple E-field control can be particularly useful in space environments where physical separation is a requirement between heat exchange surfaces.

Colver, Gerald M.↗

Quenching Combustible Dust Mixtures Using Electric Particulate Suspensions (EPS): A New Testing Method For Microgravity

The Electric Particulate Suspension (EPS) is a combustion ignition system being developed at Iowa State University for evaluating quenching effects of powders in microgravity (quenching distance, ignition energy, flammability limits). Because of the high cloud uniformity possible and its simplicity, the EPS method has potential for "benchmark" design of quenching flames that would provide NASA and the scientific community with a new fire standard. Microgravity is expected to increase suspension uniformity even further and extend combustion testing to higher concentrations (rich fuel limit) than is possible at normal gravity. Two new combustion parameters are being investigated with this new method: (1) the particle velocity distribution and (2) particle-oxidant slip velocity. Both walls and (inert) particles can be tested as quenching media. The EPS method supports combustion modeling by providing accurate measurement of flame-quenching distance as a parameter in laminar flame theory as it closely relates to characteristic flame thickness and flame structure. Because of its design simplicity, EPS is suitable for testing on the International Space Station (ISS). Laser scans showing stratification effects at 1-g have been studied for different materials, aluminum, glass, and copper. PTV/PIV and a leak hole sampling rig give particle velocity distribution with particle slip velocity evaluated using LDA. Sample quenching and ignition energy curves are given for aluminum powder. Testing is planned for the KC-135 and NASA s two second drop tower. Only 1-g ground-based data have been reported to date.

Colver, Gerald M.↗