Researching peers and disaster vulnerable communities: an insider perspective

Conducting research among peers and communities that a researcher also serves may be both daunting and rewarding. Researching peers may make the researcher feel uncomfortable raising certain questions that are sensitive or that could be construed to be testing their competencies. This paper is inclined more towards showing that it is advantageous to be an insider, whose position can facilitate collection of information that could not have been accessed, or revealed to an outsider. The paper reports on fieldwork conducted in a low-income country in Sub-Sahara Africa as part of a doctoral study with communities affected by disasters and those that work with such communities. The paper demonstrates the complexities of conducting such research and provides some insights that may be useful to insiders, outsiders or “in-betweeners” embarking on fieldwork in low-income countries and among vulnerable population struggling with manifold stresses and shocks

EDITORIAL

Ligand-mediated drug delivery systems have enormous potential for improving the efficacy of cancer treatment. In particular, Arg-Gly-Asp peptides are promising ligand molecules for targeting α_vβ₃/α_vβ₅ integrins, which are overexpressed in angiogenic sites and tumors, such as intractable human glioblastoma (U87MG). We here achieved highly efficient drug delivery to U87MG tumors by using a platinum anticancer drug-incorporating polymeric micelle (PM) with cyclic Arg-Gly-Asp (cRGD) ligand molecules. Intravital confocal laser scanning microscopy revealed that the cRGD-linked polymeric micelles (cRGD/m) accumulated rapidly and had high permeability from vessels into the tumor parenchyma compared with the PM having nontargeted ligand, “cyclic-Arg-Ala-Asp” (cRAD). As both cRGD/m- and cRAD-linked polymeric micelles have similar characteristics, including their size, surface charge, and the amount of incorporated drugs, it is likely that the selective and accelerated accumulation of cRGD/m into tumors occurred <i>via</i> an active internalization pathway, possibly transcytosis, thereby producing significant antitumor effects in an orthotopic mouse model of U87MG human glioblastoma

Graphene/Polyurethane Nanocomposites for Improved Gas Barrier and Electrical Conductivity

Recently developed strategies for isolating single-layer carbon sheets from graphite have enabled production of electrically conductive, mechanically robust polymer nanocomposites with enhanced gas barrier performance at extremely low loading. In this article, we present processing, morphology, and properties of thermoplastic polyurethane (TPU) reinforced with exfoliated graphite. For the first time, we compare carbon sheets exfoliated from graphite oxide (GO) via two different processes: chemical modification (isocyanate treated GO, iGO) and thermal exfoliation (thermally reduced GO, TRG), and three different methods of dispersion: solvent blending, in situ polymerization, and melt compounding. Incorporation of as low as 0.5 wt % of TRG produced electrically conductive TPU. Up to a 10-fold increase in tensile stiffness and 90% decrease in nitrogen permeation of TPU were observed with only 3 wt % iGO, implying a high aspect ratio of exfoliated platelets. Real- and reciprocal-space morphological characterization indicated that solvent-based blending techniques more effectively distribute thin exfoliated sheets in the polymer matrix than melt processing. This observation is in good qualitative agreement with the dispersion level inferred from solid property enhancements. Although also processed in solvents, property increase via in situ polymerization was not as pronounced because of reduced hydrogen bonding in the TPU produced

Immunohistological findings of AAA after treatment by rapamycin nanoparticles.

(A–E) Micrographs of the rat AAA at 7 days after elastase infusion; the sections were immunostained for CD68 (brown). Abundant infiltrations of CD68-positive cells are observed in the AAA after injections of PBS (A), free/RAP-0.1 (B) and free/RAP-1 (C), whereas scarce after injections of RAP/nano-0.1 (D) and RAP/nano-1 (E). To quantify the density of CD68-positive cells in AAA wall, CD68-positive cell density of each section was calculated (F). Black dots represent the specific values in each group. Long and short bars represent mean and standard deviation, respectively. *p p < 0.05 (Dunnett’s test).</p

Microscopic distribution of Alexa647-labeled rapamycin nanoparticles in the rat AAA.

<p>(A) Confocal laser scanning micrograph of the rat AAA 7-days post induction and 24 hours after injection of the Alexa647-labeled rapamycin nanoparticles. Note the abundant accumulation of Alexa647-labeled rapamycin nanoparticles (red dots) distributed in the media and adventitia with progressive destruction of the wall structure. Nuclei are stained by Hoechst33342 (blue dots), and elastic laminae of the media are visualized by intrinsic fluorescence (green). L indicates the lumen, scale bar = 500 μm. (B) Micrograph of the cross sections stained for CD68 (green). Co-localization with Alexa647-labelled rapamycin nanoparticles (red dots) appears as a yellow color. The majority of nanoparticle dots were co-localized with CD68-positive cells (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157813#pone.0157813.s001" target="_blank">S1A Fig</a>). Scale bar = 10 μm. (C) Micrograph of the cross sections stained for αSMA (green). There is little co-localization with Alexa647-labeled rapamycin nanoparticles (red dots, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157813#pone.0157813.s001" target="_blank">S1B Fig</a>). Scale bar = 10 μm.</p

Accumulation of Alexa647-labeled rapamycin nanoparticles in the AAA rat model.

<p>(A) Representative images of macroscopic distribution of Alexa647 in the aorto-iliac specimens as imaged using the IVIS® imaging system. Abundant signals of Alexa647 were specifically distributed in the AAA at 4, 8, 16, and 24 hours after injection of Alexa647-labeled rapamycin nanoparticles (red-staining, at 1, 4, 8, and 24 hours, <i>n</i> = 4; at 16 hours, <i>n</i> = 3). (B) The plasma clearance of rapamycin nanoparticles in the rat model. The residual ratio of rapamycin nanoparticles in the plasma was high at 1 hour after injection. (C) Fluorescence intensities of the lysates of AAA and the thoracic aorta are shown as adjusted absorbance values. The values of AAA were significantly higher than those of the thoracic aorta at 8, 16, and 24 hours after injection. Data represent the means ± s.d. N.C. indicates negative control. *<i>p</i> < 0.05, †<i>p</i> < 0.01 (unpaired Student’s <i>t</i>-test).</p

Histopathological findings of AAAs after treatment with rapamycin nanoparticles.

<p>Low power field images (A-E, scale bar = 500 μm) and high power field images (F-O, scale bar = 100 μm) of the rat AAA at 7 days after elastase infusion. The sections were stained by hematoxylin-eosin (A-J) or via the Elastica van Gieson method (K-O). During the process of AAA development, the rats received intravenous injections of PBS (A,F,K), free/RAP-0.1 (B,G,L), free/RAP-1 (C,H,M), RAP/nano-1 (D,I,N), or RAP/nano-1 (E,J,O). The size of the AAA after injections of RAP/nano-0.1 (D) and RAP/nano-1 (E) are smaller than those after the other injections (A–C). Considerable numbers of inflammatory cells are observed in the AAA after injections of PBS (F), free/RAP-0.1 (G), and free/RAP-1 (H), with concomitant destruction of the medial elastic laminae (K–M). L indicates the lumen.</p

New approach to evaluating the effects of a drug on protein complexes with quantitative proteomics, using the SILAC method and bioinformatic approach

Protein–protein interactions (PPIs) lead the formation of protein complexes that perform biochemical reactions that maintain the living state of the living cell. Although therapeutic drugs should influence the formation of protein complexes in addition to PPI network, the methodology analyzing such influences remain to be developed. Here, we demonstrate that a new approach combining HPLC (high performance liquid chromatography) for separating protein complexes, and the SILAC (stable isotope labeling using amino acids in cell culture) method for relative protein quantification, enable us to identify the protein complexes influenced by a drug. We applied this approach to the analysis of thalidomide action on HepG2 cells, assessed the identified proteins by clustering data analyses, and assigned 135 novel protein complexes affected by the drug. We propose that this approach is applicable to elucidating the mechanisms of actions of other therapeutic drugs on the PPI network, and the formation of protein complexes. We developed a new approach detecting protein complexes affected with a drug by analysis of protein-protein interaction using a combination of IEC and SILAC LC-MS/MS.</p

Sequentially Self-Assembled Nanoreactor Comprising Tannic Acid and Phenylboronic Acid-Conjugated Polymers Inducing Tumor-Selective Enzymatic Activity

The construction of enzyme delivery systems, which can control enzymatic activity at a target site, is important for efficient enzyme–prodrug therapy/diagnosis. Herein we report a facile technique to construct a systemically applicable β-galactosidase (β-Gal)-loaded ternary complex comprising tannic acid (TA) and phenylboronic acid-conjugated polymers through sequential self-assembly in aqueous solution. At physiological conditions, the ternary complex exhibited a hydrodynamic diameter of ∼40 nm and protected the loaded β-Gal from unfavorable degradation by proteinase. Upon cellular internalization, the ternary complex recovered β-Gal activity by releasing the loaded β-Gal. The intravenously injected ternary complex thereby delivered β-Gal to the target tumor in a subcutaneous tumor model and exerted enhanced and selective enzymatic activity at the tumor site. Sequential self-assembly with TA and phenylboronic acid-conjugated polymers may offer a novel approach for enzyme–prodrug theragnosis

Therapeutic efficacy of rapamycin nanoparticles in the AAA rat model.

<p>The diameter of the abdominal aorta in the rat AAA model was measured before, immediately after, and 7 days after elastase infusion. The diameter ratio is expressed for each rat as the ratio of the diameter after elastase infusion to the diameter before elastase infusion. During the process of AAA formation, the rats received intravenous injections of following suspension or solvent (<i>n</i> = 6/group); i) phosphate buffered saline (PBS), ii) 0.1 mg/kg free rapamycin (free/RAP-0.1), iii) 1 mg/kg free rapamycin (free/RAP-1), iv) 0.1 mg/kg rapamycin nanoparticles (RAP/nano-0.1), or v) 1 mg/kg rapamycin nanoparticles (RAP/nano-1). RAP/nano-0.1 and RAP/nano-1 enhanced the inhibitory effect on AAA enlargement compared with free/RAP-0.1 and free/RAP-1, respectively. Data represent the means ± s.d. N.S. indicates no significant difference, *<i>p</i> < 0.05 (Dunnett’s test), †<i>p</i> < 0.01 (unpaired Student’s <i>t</i>-test).</p