Dataset - Harmon et al 2015

Excel Results file for Harmon et al 2015

Ultrasensitive Polarized Up-Conversion of Tm³⁺–Yb³⁺ Doped β‑NaYF₄ Single Nanorod

Up-conversion luminescence in rare earth ions (REs) doped nanoparticles has attracted considerable research attention for the promising applications in solid-state lasers, three-dimensional displays, solar cells, biological imaging, and so forth. However, there have been no reports on REs doped nanoparticles to investigate their polarized energy transfer up-conversion, especially for single particle. Herein, the polarized energy transfer up-conversion from REs doped fluoride nanorods is demonstrated in a single particle spectroscopy mode for the first time. Unique luminescent phenomena, for example<i>,</i> sharp energy level split and singlet-to-triplet transitions at room temperature, multiple discrete luminescence intensity periodic variation with polarization direction, are observed upon excitation with 980 nm linearly polarized laser. Furthermore, nanorods with the controllable aspect ratio and symmetry are fabricated for analysis of the mechanism of polarization anisotropy. The comparative experiments suggest that intraions transition properties and crystal local symmetry dominate the polarization anisotropy, which is also confirmed by density functional theory calculations. Taking advantage of the REs based up-conversion, potential application in polarized microscopic multi-information transportation is suggested for the polarization anisotropy from REs doped fluoride single nanorod or nanorod array

Efficient Dual-Modal NIR-to-NIR Emission of Rare Earth Ions Co-doped Nanocrystals for Biological Fluorescence Imaging

A novel approach has been developed for the realization of efficient near-infrared to near-infrared (NIR-to-NIR) upconversion and down-shifting emission in nanophosphors. The efficient dual-modal NIR-to-NIR emission is realized in a β-NaGdF₄/Nd³⁺@NaGdF₄/Tm³⁺–Yb³⁺ core–shell nanocrystal by careful control of the identity and concentration of the doped rare earth (RE) ion species and by manipulation of the spatial distributions of these RE ions. The photoluminescence results reveal that the emission efficiency increases at least 2-fold when comparing the materials synthesized in this study with those synthesized through traditional approaches. Hence, these core–shell structured nanocrystals with novel excitation and emission behaviors enable us to obtain tissue fluorescence imaging by detecting the upconverted and down-shifted photoluminescence from Tm³⁺ and Nd³⁺ ions, respectively. The reported approach thus provides a new route for the realization of high-yield emission from RE ion doped nanocrystals, which could prove to be useful for the design of optical materials containing other optically active centers

Establishment of a mouse model for the complete mosquito-mediated transmission cycle of Zika virus

<div><p>Zika virus (ZIKV) is primarily transmitted by <i>Aedes</i> mosquitoes in the subgenus <i>Stegomyia</i> but can also be transmitted sexually and vertically in humans. STAT1 is an important downstream factor that mediates type I and II interferon signaling. In the current study, we showed that mice with STAT1 knockout (<i>Stat1</i>^-/-) were highly susceptible to ZIKV infection. As low as 5 plaque-forming units of ZIKV could cause viremia and death in <i>Stat1</i>^-/- mice. ZIKV replication was initially detected in the spleen but subsequently spread to the brain with concomitant reduction of the virus in the spleen in the infected mice. Furthermore, ZIKV could be transmitted from mosquitoes to <i>Stat1</i>^<i>-/-</i> mice back to mosquitoes and then to naïve <i>Stat1</i>^<i>-/-</i> mice. The 50% mosquito infectious dose of viremic <i>Stat1</i>^<i>-/-</i> mouse blood was close to 810 focus-forming units (ffu)/ml. Our further studies indicated that the activation of macrophages and conventional dendritic cells were likely critical for the resolution of ZIKV infection. The newly developed mouse and mosquito transmission models for ZIKV infection will be useful for the evaluation of antiviral drugs targeting the virus, vector, and host.</p></div

Proinflammatory cytokines were not involved in ZIKV-dependent mortality.

<p><b>(A)</b><i>Stat1</i>^<i>-/-</i>, <i>Stat1</i>^<i>-/-</i>× <i>Il6</i>^<i>-/-</i> and <i>Stat1</i>^<i>-/-</i>× <i>Tnfa</i>^<i>-/-</i> (n = 3) were challenged with ZIKV (1×10³ pfu/mouse, ip) and monitored daily. <b>(B)</b> <i>Stat1</i>^-/-, <i>Stat1</i>^-/-× <i>Il6</i>^-/-, and <i>Stat1</i>^-/-× <i>Tnfa</i>^-/- mice were challenged with Dengue virus by intravenous injection (D2Y98P strain, 1×10³ pfu/mouse) and mouse survival rates were determined daily.</p

Threshold of ZIKV infection in mosquitoes.

<p><b>(A)</b> Experimental design. <b>(B)</b> Six <i>Stat1</i>^-/- mice were infected with 5, 50 or 500 pfu of ZIKV intraperitoneally. Mouse body weights and survival rates were monitored daily. Virus titers in serum from day 2, 3 and 4 post-infection were determined (n = 2). <b>(C)</b> Starved mosquitoes were allowed to take blood meals from the ZIKV-infected mice (#1 to #6) in <b>B</b> on day 2 post-infection. Mosquitoes obtained blood meal from the same mouse were housed and grouped together. Virus titer and infection rate in each mosquito group were measured on day 7 post-blood meal (n = 7–14). <b>(D)</b> Based on the mouse serum data and their corresponding infection rate in mosquitoes, the mosquito infectious dose of 50% (MID50) was estimated.</p

ZIKV infection caused the expansion of PDCA⁺ dendritic cells but not the activation of F4/80⁺Ly6G^- macrophages in <i>Stat1</i>^-/- mice.

<p>Splenocytes isolated from wild type (n = 1), <i>Stat1</i>^-/- mice (n = 3) and <i>Ifnar</i>^-/- mice (n = 3) without or with ZIKV infection (60 h post-infection, 4x10⁴ pfu/mouse) were subject to FACS analysis using side scattered light (SSC) for granulocyte <b>(A)</b> and specific markers for dendritic cells <b>(C,E,G)</b> and macrophage cells <b>(I,K)</b>. 7-Aminoactinomycin D (7-AAD) and CD45 were used to exclude dead and non-hematopoietic cells, respectively. For quantitation analysis, the percentage of specific subpopulations to the gated population was calculated for each splenocyte preparation. Quantifications of the subpopulations of immune cells were shown in <b>(B,D,F,H,J,L)</b>. *, p ≤ 0.05; **, p ≤ 0.01 <b><i>Stat1</i></b>^<b>-/-</b> <b>mice were less competent to activate splenic cDCs and macrophages than <i>Ifnar</i></b>^<b>-/-</b> <b>mice after ZIKV infection</b>.</p

Establishing a complete mosquito-mediated ZIKV transmission cycle.

<p><b>(A)</b> Experimental design for establishing a complete ZIKV transmission cycle. <b>(B)</b> <i>A</i>. <i>aegypti</i> mosquitoes were injected in the thorax with ZIKV (400 pfu/mosquito) and viral titers were determined by plaque assay by homogenization whole mosquitoes 7 days later (n = 15). <b>(C)</b> To confirm the infectivity, viral titers were determined by focus-forming assay by homoginizing mosquito salivary gland 4 or 7 days later (n = 8 or 2). The ZIKV-infection rate (I.R.) was calculated. <b>(D)</b> <i>Stat1</i>^-/- mice (n = 3) were bitten by 1–3 or 6–12 ZIKV-carrying mosquitoes (day 4 or 7 post-thoracic injection). Weights and survival were monitored daily. Virus titers in serum collected from mosquito-bitten mice day 2 post-mosquito exposure were determined by focus-forming assay. <b>(E)</b> Mosquitoes were starved overnight and allowed to take blood meals from the ZIKV-infected mice (<b>Group b</b> and <b>d</b> mice in <b>D</b>; day 2 post-ZIKV infection). The <b>Group e</b> and <b>f</b> mosquitoes took blood from <b>Group b</b> and <b>d</b> mice, respectively. Virus titers in mosquito midguts collected right after the blood meal (Day 0), 4 and 7 days later were measured by focus forming assay (n = 5–20). Infection rate was calculated. <b>(F)</b> Legs and wings collected from the <b>Group e</b> and <b>f</b> mosquitoes were also subject to virus detection (n = 10–12). <b>(G)</b> <i>Stat1</i>^-/- mice (<b>Group g</b> or <b>h</b>; n = 4) were bitten by the ZIKV-infected mosquitoes from <b>Group e</b> or <b>f</b>, respectively (day 7 post-infection in <b>E,</b> 6–9 mosquitoes/mouse). Weights and survival rates were monitored daily.</p

Infection of <i>Stat1</i>^-/- mice with ZIKV.

<p><b>(A)</b> 12–16 week-old <i>Stat1</i>^-/- mice (n = 4–7) were infected intraperitoneally (i.p.) with various doses of ZIKV (4×10³, 4×10⁴, or 4×10⁶ pfu/mouse). Weights and survival rates were monitored daily. Nine week-old <i>Ifnar</i>^-/- mice were infected i.p. with 4×10⁴ pfu/mouse in parallel. <b>(B)</b> Serum samples were collected from ZIKV infected <i>Stat1</i>^-/- mice (4×10⁴ pfu/mouse) and virus titers were measured by plaque assay. <b>(C)</b> Photograph of liver and spleen collected from ZIKV infected (1×10³ pfu/mouse) (D7^#) and uninfected <i>Stat1</i>^-/- mice (Mock) on D7 post-infection. <b>(D)</b> ZIKV and cyclophilin A (CPH, a house keeping gene) RNA expression in various tissues was measured by quantitative RT-PCR (n = 3–4) to obtain quantification cycle (Cq) values. Relative ZIKV gene expression level was calculated as ZIKV(_Cq)/CPH(_Cq). D3 and D5 samples were collected from mice infected with 4×10⁴ pfu/mouse and D7^# samples were from mice infected with 1×10³ pfu/mouse. <b>(E)</b> ZIKV viral protein expression in spleens harvested at D3 and D5 post-infection (4×10⁴ pfu/mouse) and D7 post-infection (1×10³ pfu/mouse) were examined by immunoblotting with specific antibodies for NS1 and capsid. <b>(F)</b> NS1 protein expression in spleens and brains 7 days post-infection (1×10³ pfu/mouse) was also evaluated. <b>(G)</b> Determination of serum NS1 concentrations by ELISA. Culture medium collected from Vero cells infected with DENV or ZIKV were used as a positive control for NS1. *, p ≤ 0.05; **, p ≤ 0.01.</p

ZIKV replication and assessment of apoptosis in various organs in infected <i>Stat1</i>^-/- mice.

<p><b>(A)</b> Liver, spleen, and brain tissues harvested from ZIKV-infected and uninfected <i>Stat1</i>^-/- mice were subjected to immunohistochemistry with an anti-NS1 antibody. <b>(B)</b> Cell death in infected tissues was determined using the TUNEL method. Tissues were collected 3 and 7 days post-infection with 4×10⁴ pfu/mouse. TUNEL⁺ signals were examined by fluorescence microscopy and images from 5–10 randomly selected 200X magnification fields were analyzed by ImageJ software (NIH).</p