Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

Health-seeking beliefs of cardiovascular patients: A qualitative study

Objectives: The study aims were to (a) describe the experiences of Chinese Australians with heart disease following discharge from hospital for an acute cardiac event; (b) identify patterns and cultural differences of Chinese Australians following discharge from hospital; and (c) illustrate the illness/health seeking behaviors and health beliefs of Chinese Australians. Design: Qualitative study. Methods: Interview data were obtained from the following sources: (a) focus groups of Chinese community participants without heart disease; (b) interviews with patients recently discharged from hospital following an admission for an acute cardiac event; and (c) interviews with Chinese-born health professionals working in Australia. Qualitative thematic analysis was undertaken. Results: Study themes generated from the data were: (1) linking traditional values and beliefs with Western medicine; (2) reverence for health professionals and family; and (3) juxtaposing traditional beliefs and self-management. Conclusions: Considering the influence of cultural values in developing health care plans and clinical decision making is important. © 2011 Elsevier Ltd

The intracellular trafficking mechanism of Lipofectamine-based transfection reagents and its implication for gene delivery

Lipofectamine reagents are widely accepted as "gold-standard" for the safe delivery of exogenous DNA or RNA into cells. Despite this, a satisfactory mechanism-based explanation of their superior efficacy has remained mostly elusive thus far. Here we apply a straightforward combination of live cell imaging, single-particle tracking microscopy, and quantitative transfection-efficiency assays on live cells to unveil the intracellular trafficking mechanism of Lipofectamine/DNA complexes. We find that Lipofectamine, contrary to alternative formulations, is able to efficiently avoid active intracellular transport along microtubules, and the subsequent entrapment and degradation of the payload within acidic/digestive lysosomal compartments. This result is achieved by random Brownian motion of Lipofectamine-containing vesicles within the cytoplasm. We demonstrate here that Brownian diffusion is an efficient route for Lipofectamine/DNA complexes to avoid metabolic degradation, thus leading to optimal transfection. By contrast, active transport along microtubules results in DNA degradation and subsequent poor transfection. Intracellular trafficking, endosomal escape and lysosomal degradation appear therefore as highly interdependent phenomena, in such a way that they should be viewed as a single barrier on the route for efficient transfection. As a matter of fact, they should be evaluated in their entirety for the development of optimized non-viral gene delivery vectors

The Instanton Density at Finite Temperatures

For {\it low} T new strict results for the instanton density n(T) are reported. Using the PCAC methods, we express n(T) in terms of {\it vacuum} average values of certain operators, times their {\it calculated} T-dependence. At high T, we discuss the {\it applicability} limits of the perturbative results. We further speculate about possible behaviour of n(T) at $T\sim T_c$

Dual Superconductor Scenario of Confinement: A Systematic Study of Gribov Copy Effects

We perform a study of the effects from maximal abelian gauge Gribov copies in the context of the dual superconductor scenario of confinement, on the basis of a novel approach for estimation of systematic uncertainties from incomplete gauge fixing. We present numerical results, in SU(2) lattice gauge theory, using the overrelaxed simulated annealing gauge fixing algorithm. We find abelian and non-abelian string tensions to differ significantly, their ratio being 0.92(4) at BETA = 2.5115. An approximate factorization of the abelian potential into monopole and photon contributions has been confirmed, the former giving rise to the abelian string tension.Comment: 35 pages uucompressed LaTeX with 10 encapsuled postscript figure

Observing Long Colour Flux Tubes in SU(2) Lattice Gauge Theory

We present results of a high statistics study of the chromo field distribution between static quarks in SU(2) gauge theory on lattices of volumes 16^4, 32^4, and 48^3*64, with physical extent ranging from 1.3 fm up to 2.7 fm at beta=2.5, beta=2.635, and beta=2.74. We establish string formation over physical distances as large as 2 fm. The results are tested against Michael's sum rules. A detailed investigation of the transverse action and energy flux tube profiles is provided. As a by-product, we obtain the static lattice potential in unpreceded accuracy.Comment: 66 pages, 29 figures, uuencoded latex file with epsfigures (450 K), supplementary full colour figures are available via ftp, CERN-TH.7413/94 (extended version

The health of women and girls determines the health and well-being of our modern world: A White Paper From the International Council on Women's Health Issues

The International Council on Women's Health Issues (ICOWHI) is an international nonprofit association dedicated to the goal of promoting health, health care, and well-being of women and girls throughout the world through participation, empowerment, advocacy, education, and research. We are a multidisciplinary network of women's health providers, planners, and advocates from all over the globe. We constitute an international professional and lay network of those committed to improving women and girl's health and quality of life. This document provides a description of our organization mission, vision, and commitment to improving the health and well-being of women and girls globally

Using shared needles for subcutaneous inoculation can transmit bluetongue virus mechanically between ruminant hosts

Bluetongue virus (BTV) is an economically important arbovirus of ruminants that is transmitted by Culicoides spp. biting midges. BTV infection of ruminants results in a high viraemia, suggesting that repeated sharing of needles between animals could result in its iatrogenic transmission. Studies defining the risk of iatrogenic transmission of blood-borne pathogens by less invasive routes, such as subcutaneous or intradermal inoculations are rare, even though the sharing of needles is common practice for these inoculation routes in the veterinary sector. Here we demonstrate that BTV can be transmitted by needle sharing during subcutaneous inoculation, despite the absence of visible blood contamination of the needles. The incubation period, measured from sharing of needles, to detection of BTV in the recipient sheep or cattle, was substantially longer than has previously been reported after experimental infection of ruminants by either direct inoculation of virus, or through blood feeding by infected Culicoides. Although such mechanical transmission is most likely rare under field condition, these results are likely to influence future advice given in relation to sharing needles during veterinary vaccination campaigns and will also be of interest for the public health sector considering the risk of pathogen transmission during subcutaneous inoculations with re-used needles