Single-cell multi-omics analysis of the immune response in COVID-19

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255Funder: University College London, Birkbeck MRC Doctoral Training ProgrammeFunder: The Jikei University School of MedicineFunder: Action Medical Research (GN2779)Funder: NIHR Clinical Lectureship (CL-2017-01-004)Funder: NIHR (ACF-2018-01-004) and the BMA FoundationFunder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)Funder: Barbour FoundationFunder: ERC Consolidator and EU MRG-Grammar awardsFunder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)Funder: European Molecular Biology Laboratory (EMBL)Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

Germanium nanowires : synthesis, characterization, and utilization

textA supercritical fluid synthesis method was developed for the preparation of single crystal germanium (Ge) nanowires with diameters as small as 4 nanometer and several tens of micrometer in length. Alkanethiol protected gold nanocrystals were used to seed and direct nanowire growth. Nanowire processing and their implementation as building blocks in nanowire based devices requires rigorous control of nanowire surface chemistry, which differs from well-studied monolithic atomically-smooth single crystal substrate surface chemistry due to the nanowire’s high surface area to volume ratio and atomically rough surface. Ge nanowire surface oxidation was studied by Ge 3d x-ray photoelectron spectroscopy. A broad range of solution-phase routes to the Ge nanowire surface passivation were explored including sulfidation, hydride and chloride termination, and organic monolayer passivation. Nanowires with covalently bonded monolayer surface terminations formed via thermally-initiated hydrogermylation reactions with alkenes, alkynes or dienes exhibited excellent chemical stability compared to untreated or etched nanowire surfaces and enabled low contact resistance ohmic electrical contacts to be made to the nanowires. Device characteristics of single Ge nanowire devices fabricated with gold electrical contacts patterned by e-beam lithography were compared with devices prepared using focused e-beam or Ga-beam assisted Pt chemical vapor deposition. These device structures permitted direct investigation of the influence of nanowire surface chemistry, doping, and gate electrode architecture, on device operation. The impact of the surface chemistry on surface state dominated electron transport in single nanowire devices was investigated by room temperature field-effect measurements. The density and relaxation time distribution of electrically active surface states was found to be highly sensitive to the nanowire surface chemistry. Complimentary to the device measurements, fundamental electrical and optical properties were probed via electron energy loss spectroscopy on individual nanowires inside the transmission electron microscope. The volume plasmon energy increased with decreasing diameter for nanowires narrower than 24 nm. Below 24 nm, organic monolayer-coated nanowires also exhibited size-dependent Ge 3d core ionization spectra that shifted to higher energy with reduced diameter that are independent of probe position relative to the surface. In contrast, the Ge 3d edge for surface-oxidized nanowires exhibited a chemically-induced shift when positioned near the surface.Chemical Engineerin

Timing Matters: the Underappreciated Role of Temperature Ramp Rate for Shape Control and Reproducibility of Quantum Dot Synthesis

Understanding the coupled kinetic and thermodynamics factors governing colloidal nanocrystals nucleation and growth are critical factors in the predictable and reproducible synthesis of advanced nanomaterials. We show that the temporal temperature profile is decisive in tuning the particle shape from pseudo-spherical to monodisperse cubes. The shape of the nanocrystals was characterized by transmission electron microscopy and X-ray diffraction.We introduce a mechanism for the shape controlled synthesis in the context of temperature-dependent nucleation and growth and provide experimental evidence to support it.The authors would like to thank Richard Robinson for helpful discussions. This publication was based on work supported by Award No. KUS-C1-018-02, made by King Abdullah University of Science and Technology (KAUST). We also acknowledge the Cornell Center for Materials Science (NSF DMR-0520404)

Superlattice self-assembly: Watching nanocrystals in action

The assembly of colloidal nanocrystal building blocks into ordered superlattices presents many scientifically interesting and technologically important research challenges to create programmable matter from “crystals-of-crystals”. The formation of superlattices is a fascinating mesoscale phenomenon governed by the interplay of a range of thermodynamic and kinetic factors. We summarize the role of time-resolved X-ray scattering techniques combined with in situ sample environments to gain unique insights into the relevant processes

Formation of Epitaxially Connected Quantum Dot Solids: Nucleation and Coherent Phase Transition

The formation of epitaxially connected quantum dot solids involves a complex interplay of interfacial assembly, surface chemistry, and irreversible-directed attachment. We describe the basic mechanism in the context of a coherent phase transition with distinct nucleation and propagation steps. The proposed mechanism explains how defects in the preassembled structure influence nucleation and how basic geometric relationships govern the transformation from hexagonal assemblies of isolated dots to interconnected solids with square symmetry. We anticipate that new mechanistic insights will guide future advances in the formation of high-fidelity quantum dot solids with enhanced grain size, interconnectivity, and control over polymorph structures

Facile Synthesis of Colloidal CuO Nanocrystals for Light-Harvesting Applications

CuO is an earth-abundant, nontoxic, and low band-gap material; hence it is an attractive candidate for application in solar cells. In this paper, a synthesis of CuO nanocrystals by a facile alcohothermal route is reported. The nanocrystals are dispersible in a solvent mixture of methanol and chloroform, thus enabling the processing of CuO by solution. A bilayer solar cell comprising of CuO nanocrystals and phenyl-C61-butyric acid methyl ester (PCBM) achieved a power conversion efficiency of 0.04%, indicating the potential of this material for light-harvesting applications