Antibodies are a principal determinant of immunity for most RNA viruses and have 54 promise to reduce infection or disease during major epidemics. The novel 55 coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections 56 and hundreds of thousands of deaths to date 1,2 . In response, we used a rapid 57 antibody discovery platform to isolate hundreds of human monoclonal antibodies 58 (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five 59 major classes based on their reactivity to subdomains of S protein as well as their 60 cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic 61 SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding 62 domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and 63 demonstrates the speed and robustness of new antibody discovery methodologies. 64 65 Human mAbs to the viral surface spike (S) glycoprotein mediate immunity to other 66 betacoronaviruses including SARS-CoV 3-7 and Middle East respiratory syndrome 67 (MERS) 8-17 . Because of this, we and others have hypothesized that human mAbs may 68 have promise for use in prophylaxis, post-exposure prophylaxis, or treatment of SARS-69 CoV-2 infection 18 . MAbs can neutralize betacoronaviruses by several mechanisms 70 including blocking of attachment of the S protein RBD to a receptor on host cells (which 71 for SARS-CoV and SARS-CoV-2 1 is angiotensin-converting enzyme 2 [ACE2]) 12 . We 72 hypothesized that the SARS-CoV-2 S protein would induce diverse human neutralizing 73 antibodies following natural infection. While antibody discovery usually takes months 74 to years, there is an urgent need to both characterize the human immune response to 75 SARS-CoV-2 infection and to develop potential medical countermeasures. Using Zika 76 virus as a simulated pandemic pathogen and leveraging recent technological advances 77in synthetic genomics and single-cell sequencing, we recently isolated hundreds of 78 was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

Dental enamel, a hierarchical material composed primarily of hydroxylapatite nanowires, is susceptible to degradation by plaque biofilm-derived acids. The solubility of enamel strongly depends on the presence of Mg(2+), F(-), and CO3(2-). However, determining the distribution of these minor ions is challenging. We show—using atom probe tomography, x-ray absorption spectroscopy, and correlative techniques—that in unpigmented rodent enamel, Mg(2+) is predominantly present at grain boundaries as an intergranular phase of Mg-substituted amorphous calcium phosphate (Mg-ACP). In the pigmented enamel, a mixture of ferrihydrite and amorphous iron-calcium phosphate replaces the more soluble Mg-ACP, rendering it both harder and more resistant to acid attack. These results demonstrate the presence of enduring amorphous phases with a dramatic influence on the physical and chemical properties of the mature mineralized tissue.

A Gd(III)-nanodiamond conjugate [Gd(III)-ND] was prepared and characterized, enabling detection of nanodiamonds by MR imaging. The Gd(III)-ND particles significantly reduced the T1 of water protons with a per-Gd(III) relaxivity of 58.82 ± 1.18 mM−1s−1 at 1.5 Tesla (60 MHz). This represents a tenfold increase compared to the monomer Gd(III) complex (r1 = 5.42 ± 0.20 mM−1s−1) and is among the highest per-Gd(III) relaxivities reported.

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Conjugate agent: A GdIII enriched DNA‐AuNP conjugate for intracellular magnetic resonance and fluorescence imaging is reported. The agent exhibits high relaxivity per particle and high cell uptake properties that provide a means to image and map small cell populations.

Gadolinium(III) nanoconjugate contrast agents (CAs) have distinct advantages over their small-molecule counterparts in magnetic resonance imaging. In addition to increased Gd(III) payload, a significant improvement in proton relaxation efficiency, or relaxivity (r1), is often observed. In this work, we describe the synthesis and characterization of a nanoconjugate CA created by covalent attachment of Gd(III) to thiolated DNA (Gd(III)–DNA), followed by surface conjugation onto gold nanostars (DNA–Gd@stars). These conjugates exhibit remarkable r1 with values up to 98 mM−1 s−1. Additionally, DNA–Gd@stars show efficient Gd(III) delivery and biocompatibility in vitro and generate significant contrast enhancement when imaged at 7 T. Using nuclear magnetic relaxation dispersion analysis, we attribute the high performance of the DNA–Gd@stars to an increased contribution of second-sphere relaxivity compared to that of spherical CA equivalents (DNA–Gd@spheres). Importantly, the surface of the gold nanostar contains Gd(III)–DNA in regions of positive, negative, and neutral curvature. We hypothesize that the proton relaxation enhancement observed results from the presence of a unique hydrophilic environment produced by Gd(III)–DNA in these regions, which allows second-sphere water molecules to remain adjacent to Gd(III) ions for up to 10 times longer than diffusion. These results establish that particle shape and second-sphere relaxivity are important considerations in the design of Gd(III) nanoconjugate CAs.

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One way to image the molecular pathology in Alzheimer’s disease (AD) is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early stage biomarkers that instigate memory loss comprise of Aβ oligomers (AβOs). Here we report a sensitive molecular magnetic resonance imaging (MRI) contrast probe that is specific for AβOs. We attach oligomer-specific antibodies onto magnetic nanostructures and show the complex is stable and it binds to AβOs on cells and brain tissues to give a MRI signal. When intranasally administered to an AD mouse model, the probe readily reached hippocampal AβOs. In isolated samples of human brain tissue, we observed an MRI signal that distinguished AD from controls. Such nanostructures that target neurotoxic AβOs are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage AD diagnosis and disease management.