Molluscum contagiosum infection with features of primary cutaneous anaplastic large cell lymphoma

CD30+ T cell pseudolymphomas (CD30+ PSL) are a group of benign inflammatory cutaneous disorders that can develop in settings of viral infections or drug reactions. Owing to their histological similarities to malignant lymphomas, these benign infiltrates are occasionally misdiagnosed as malignant, causing significant concerns for patients and physicians. Herein, we report a patient with CD30+ PSL associated with molluscum contagiosum whose initial biopsy revealed atypical large CD30-expressing cells, leading to a misdiagnosis of primary cutaneous anaplastic large cell lymphoma and referral to our cutaneous lymphoma clinic. We report this case to demonstrate that reactive CD30+ infiltrate associated with molluscum contagiosum can be mistaken for T-cell lymphomas and patients should be reassured in these cases

Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening

Computational techniques such as structure-based virtual screening require carefully prepared 3D models of potential small-molecule ligands. Though powerful, existing commercial programs for virtual-library preparation have restrictive and/or expensive licenses. Freely available alternatives, though often effective, do not fully account for all possible ionization, tautomeric, and ring-conformational variants. We here present Gypsum-DL, a free, robust open-source program that addresses these challenges. As input, Gypsum-DL accepts virtual compound libraries in SMILES or flat SDF formats. For each molecule in the virtual library, it enumerates appropriate ionization, tautomeric, chiral, cis/trans isomeric, and ring-conformational forms. As output, Gypsum-DL produces an SDF file containing each molecular form, with 3D coordinates assigned. To demonstrate its utility, we processed 1558 molecules taken from the NCI Diversity Set VI and 56,608 molecules taken from a Distributed Drug Discovery (D3) combinatorial virtual library. We also used 4463 high-quality protein-ligand complexes from the PDBBind database to show that Gypsum-DL processing can improve virtual-screening pose prediction. Gypsum-DL is available free of charge under the terms of the Apache License, Version 2.0

On the identification of twinning in body-centred cubic nanoparticles

Many metals and alloys, including Fe and W, adopt body-centred cubic (BCC) crystal structures and nanoparticles of these metals are gaining significant scientific and industrial relevance. Twinning has a marked effect on catalytic activity, yet there is little evidence for or against the presence of twinning in BCC nanoparticles. Here, we explore the potential shapes of twinned BCC nanoparticles, and predict their electron microscopy and diffraction signatures. BCC single crystal and twinned shapes often appear similar and diffraction patterns along common, low-index zone axes are often indistinguishable, casting doubt on many claims of single crystallinity. We conclude by outlining how nanoparticles can be characterized to conclusively prove the presence or absence of twinning

Native Conformation and Canonical Disulfide Bond Formation Are Interlinked Properties of HIV-1 Env Glycoproteins

We investigated whether there is any association between a native-like conformation and the presence of only the canonical (i.e., native) disulfide bonds in the gp120 subunits of a soluble recombinant human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein. We used a mass spectrometry (MS)-based method to map the disulfide bonds present in nonnative uncleaved gp140 proteins and native-like SOSIP.664 trimers based on the BG505 env gene. Our results show that uncleaved gp140 proteins were not homogeneous, in that substantial subpopulations (20 to 80%) contained aberrant disulfide bonds. In contrast, the gp120 subunits of the native-like SOSIP.664 trimer almost exclusively retained the canonical disulfide bond pattern. We also observed that the purification method could influence the proportion of an Env protein population that contained aberrant disulfide bonds. We infer that gp140 proteins may always contain a variable but substantial proportion of aberrant disulfide bonds but that the impact of this problem can be minimized via design and/or purification strategies that yield native-like trimers. The same factors may also be relevant to the production and purification of monomeric gp120 proteins that are free of aberrant disulfide bonds

Decoration of plasmonic Mg nanoparticles by partial galvanic replacement.

Plasmonic structures have attracted much interest in science and engineering disciplines, exploring a myriad of potential applications owing to their strong light-matter interactions. Recently, the plasmonic concentration of energy in subwavelength volumes has been used to initiate chemical reactions, for instance by combining plasmonic materials with catalytic metals. In this work, we demonstrate that plasmonic nanoparticles of earth-abundant Mg can undergo galvanic replacement in a nonaqueous solvent to produce decorated structures. This method yields bimetallic architectures where partially oxidized 200-300 nm Mg nanoplates and nanorods support many smaller Au, Ag, Pd, or Fe nanoparticles, with potential for a stepwise process introducing multiple decoration compositions on a single Mg particle. We investigated this mechanism by electron-beam imaging and local composition mapping with energy-dispersive X-ray spectroscopy as well as, at the ensemble level, by inductively coupled plasma mass spectrometry. High-resolution scanning transmission electron microscopy further supported the bimetallic nature of the particles and provided details of the interface geometry, which includes a Mg oxide separation layer between Mg and the other metal. Depending on the composition of the metallic decorations, strong plasmonic optical signals characteristic of plasmon resonances were observed in the bulk with ultraviolet-visible spectrometry and at the single particle level with darkfield scattering. These novel bimetallic and multimetallic designs open up an exciting array of applications where one or multiple plasmonic structures could interact in the near-field of earth-abundant Mg and couple with catalytic nanoparticles for applications in sensing and plasmon-assisted catalysis.Support for this project was provided by the EU Framework Programme for Research and Innovation Horizon 2020 (Starting Grant SPECs 804523). J.A. wishes to acknowledge financial support from Natural Sciences and Engineering Research Council of Canada and “Fonds de Recherche Québec – Nature et Technologies” postdoctoral fellowships (BP and B3X programs). C.B. is thankful for funding from the Engineering and Physical Sciences Research Council (Standard Research Studentship (DTP) EP/R513180/1), and E.R.H. for support from the EPSRC NanoDTC Cambridge (EP/L015978/1). S.M.C. acknowledges support from the Henslow Research Fellowship at Girton College, Cambridge. We acknowledge access and support in the use of the electron Physical Sciences Imaging Centre (MG21980) at the Diamond Light Source, U.K

To sink, swim, twin, or nucleate: A critical appraisal of crystal aggregation processes

Crystal aggregates in igneous rocks have been variously ascribed to growth processes (e.g., twinning, heterogeneous nucleation, epitaxial growth, dendritic growth), or dynamical processes (e.g., synneusis, accumulation during settling). We tested these hypotheses by quantifying the relative orientation of adjacent crystals using electron backscatter diffraction. Both olivine aggregates from Kīlauea volcano (Hawaiʻi, USA) and chromite aggregates from the Bushveld Complex (South Africa) show diverse attachment geometries inconsistent with growth processes. Near-random attachments in chromite aggregates are consistent with accumulation by settling of individual crystals. Attachment geometries and prominent geochemical differences across grain boundaries in olivine aggregates are indicative of synneusis

Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits

Background: The trimeric envelope glycoproteins (Env) on the surface of HIV-1 virions are the targets for neutralizing antibodies (NAbs). No candidate HIV-1 immunogen has yet induced potent, broadly active NAbs (bNAbs). Part of the explanation may be that previously tested Env proteins inadequately mimic the functional, native Env complex. Trimerization and the proteolytic processing of Env precursors into gp120 and gp41 profoundly alter antigenicity, but soluble cleaved trimers are too unstable to serve as immunogens. By introducing stabilizing mutations (SOSIP), we constructed soluble, cleaved Env trimers derived from the HIV-1 subtype A isolate BG505 that resemble native Env spikes on virions both structurally and antigenically. Results: We used surface plasmon resonance (SPR) to quantify antibody binding to different forms of BG505 Env: the proteolytically cleaved SOSIP.664 trimers, cleaved gp120-gp41ECTO protomers, and gp120 monomers. Non-NAbs to the CD4-binding site bound only marginally to the trimers but equally well to gp120-gp41ECTO protomers and gp120 monomers, whereas the bNAb VRC01, directed to the CD4bs, bound to all three forms. In contrast, bNAbs to V1V2 glycan-dependent epitopes bound preferentially (PG9 and PG16) or exclusively (PGT145) to trimers. We also explored the antigenic consequences of three different features of SOSIP.664 gp140 trimers: the engineered inter-subunit disulfide bond, the trimer-stabilizing I559P change in gp41ECTO, and proteolytic cleavage at the gp120-gp41ECTO junction. Each of these three features incrementally promoted native-like trimer antigenicity. We compared Fab and IgG versions of bNAbs and validated a bivalent model of IgG binding. The NAbs showed widely divergent binding kinetics and degrees of binding to native-like BG505 SOSIP.664. High off-rate constants and low stoichiometric estimates of NAb binding were associated with large amounts of residual infectivity after NAb neutralization of the corresponding BG505.T332N pseudovirus. Conclusions: The antigenicity and structural integrity of cleaved BG505 SOSIP.664 trimers render these proteins good mimics of functional Env spikes on virions. In contrast, uncleaved gp140s antigenically resemble individual gp120-gp41ECTO protomers and gp120 monomers, but not native trimers. Although NAb binding to functional trimers may thus be both necessary and sufficient for neutralization, the kinetics and stoichiometry of the interaction influence the neutralizing efficacy of individual NAbs

Optoplasmonic effects in highly curved surfaces for catalysis, photothermal heating, and SERS

Surface curvature can be used to focus light and alter optical processes. Here, we show that curved surfaces (spheres, cylinders, and cones) with a radius of around 5 μm lead to maximal optoplasmonic properties including surface-enhanced Raman scattering (SERS), photocatalysis, and photothermal processes. Glass microspheres, microfibers, pulled fibers, and control flat substrates were functionalized with well-dispersed and dense arrays of 45 nm Au NP using polystyrene-block-poly-4-vinylpyridine (PS-b-P4VP) and chemically modified with 4-mercaptobenzoic acid (4-MBA, SERS reporter), 4-nitrobenzenethiol (4-NBT, reactive to plasmonic catalysis), or 4-fluorophenyl isocyanide (FPIC, photothermal reporter). The various curved substrates enhanced the plasmonic properties by focusing the light in a photonic nanojet and providing a directional antenna to increase the collection efficacy of SERS photons. The optoplasmonic effects led to an increase of up to 1 order of magnitude of the SERS response, up to 5 times the photocatalytic conversion of 4-NBT to 4,4′-dimercaptoazobenzene when the diameter of the curved surfaces was about 5 μm and a small increase in photothermal effects. Taken together, the results provide evidence that curvature enhances plasmonic properties and that its effect is maximal for spherical objects around a few micrometers in diameter, in agreement with a theoretical framework based on geometrical optics. These enhanced plasmonic effects and the stationary-phase-like plasmonic substrates pave the way to the next generation of sensors, plasmonic photocatalysts, and photothermal devices