1,720,966 research outputs found
Effect of molecular crowding on the biological identity of liposomes: an overlooked factor at the bio-nano interface
No full textOnce embedded in a physiological environment, the surface of nanoparticles (NPs) gets covered with a biomolecular corona (BC) that alters their synthetic characteristics and subsequently gives them a peculiar biological identity. Despite recent studies having clarified the role of NP composition, surface chemistry and biological source (e.g., human/animal serum or plasma) in the formation of the BC, little is known about the possible impact of molecular crowding. To fill this gap, we used a cationic liposomal formulation as a model system and studied its biological identity upon incubation with human plasma, at a fixed liposome-to-plasma volume ratio and different concentrations. We carried out dynamic light scattering measurements to quantify the size and zeta potential of the investigated systems and gel electrophoresis to evaluate the composition of the corresponding coronas. Our findings suggest that NP stability may be compromised by molecular crowding, but the corona composition is stable over a wide range of concentrations, which extend over more than two orders of magnitude. As the biological identity of NPs eventually determines their final fate in vivo, we predict that this study could contribute to the development of a safe and effective nanosystem for the targeted delivery of therapeutic agents
Reproducibility of biomolecular corona experiments: a primer for reliable results
No full textThe biomolecular corona is a key component controlling the identity of nanomaterials
in physiological environments. Studies aimed at identifying factors
shaping the biomolecular corona have proliferated in the last decade but have
been performed by research groups with different backgrounds. Efforts made
within the scientific community to guarantee the reproducibility of experimental
data have identified protocol standardization as an indispensable step
for advancing knowledge in this arena. To contribute to fulfill this gap, here
the relevance of interoperator variability in biomolecular corona studies and
the benefits arising from automated systems usage are explored. Moreover,
the role of molecular crowding during nanoparticle-biofluid incubation
and the effect of washing the pellet during corona isolation are thoroughly
investigated. It is believed that the findings will help researchers enhance the
accuracy of experimental design and reporting
Efficient pancreatic cancer detection through personalized protein corona of gold nanoparticles
No full textCharacterization of the personalized protein corona (PC) that forms around nanomaterials upon exposure to human plasma is emerging as powerful technology for early cancer detection. However, low material stability and interbatch variability have limited its clinical application so far. Here, we present a nanoparticle-enabled blood (NEB) test that uses 120 nm gold nanoparticles (NPs) as the accumulator of blood plasma proteins. In the test, the personalized PC of gold NPs is characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. As a paradigmatic case study, pancreatic ductal adenocarcinoma (PDAC) was chosen due to the lack of effective detection strategies that lead to poor survival rate after diagnosis (<1 year) and extremely low 5-years survival rate (15-20%). Densitometric analysis of 75 protein patterns (28 from healthy subjects and 47 from PDAC patients) allowed us to distinguish nononcological and PDAC patients with good sensitivity (78.6%) and specificity (85.3%). The gold NEB test is completely aligned to affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverable to end users criteria stated by the World Health Organization for cancer screening and detection. Thus, it could be very useful in clinical practice at the first level of investigation to decide whether to carry out more invasive analyses or not
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
A mechanistic explanation of the inhibitory role of the protein corona on liposomal gene expression
No full textThe past three decades have witnessed fast advances in the use of cationic liposome-DNA complexes (lipoplexes) for gene delivery applications. However, no lipoplex formulation has reached into the clinical practice so far. The primary drawback limiting clinical use of lipoplexes is the lack of mechanistic understanding of their low transfection efficiency (TE) in vivo. In physiological environments, lipoplexes are coated by a protein corona (PC) that mediates the interactions with the cell machinery. Here we show that the formation of PC can change the interactions of multicomponent (MC) lipoplexes with our cell model (i.e., HeLa). At the highest lipoplex concentration, the formation of PC can reduce the TE of MC lipoplexes from 60% to <5%. Combining dynamic light scattering and synchrotron small-angle X-ray scattering (SAXS), we clarify that the formation of PC modifies physical-chemical properties of MC lipoplexes so as to affect their TE. Moreover, we examined single transfection barriers by a combination of fluorescence-activated cell sorting, single-cell real-time fluorescence confocal microscopy, and synchrotron SAXS. We demonstrate that PC formation has the ability to modify the relative contribution of caveolae-mediated endocytosis and macropinocytosis in lipoplexes uptake, in favor of the latter, increasing accumulation of PC-decorated lipoplexes into degradative lysosomal compartments. Finally, we report evidences that PC reduces the structural stability of lipoplexes against solubilization by cellular lipids, likely favoring premature DNA release and cytosolic digestion by DNAase. These combined effects revealed here offer a comprehensive mechanistic explanation on the reason behind reduction in gene expression of MC lipoplexes
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
The biomolecular corona of gold nanoparticles in a controlled microfluidic environment
No full textNanoparticles (NPs) exposed to biological media are coated by proteins and other biomolecules forming a biomolecular corona (BC) on the particle surface. Recent studies have shown that shear stress as that created by laminar fluid flow generates more complex coronas with systematic changes in composition with respect to counterparts formed under static incubation. However, in most studies reported so far, dynamic environments have been produced by peristaltic pumps and comparing experimental results appears challenging. On the other side, generating shear stress by microfluidic devices could help to remove user variability and ensure better reproducibility of experimental data. This study was therefore aimed at exploring formation of NP-BC in a microfluidic environment. To this end, 100 nm gold nanoparticles and human plasma (HP) were used as models for nano-formulation and biological medium. We injected gold nanoparticles and HP in each of the islets of a remote-controlled microfluidic cartridge. Static incubation was used as a reference. BC-decorated NPs were thoroughly characterized by dynamic light scattering (DLS), micro-electrophoresis (ME), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) and nano-liquid chromatography tandem mass spectrometry (nano-LC MS/MS). By varying the incubation time from 30 s to 2.5 min we demonstrate that BC is already determined by the earliest exposure time point and does not appreciably evolve in time. DLS and ME results demonstrate that the BC formed in a microfluidic chip is thicker and more negatively charged than its counterpart formed under static incubation. SDS-PAGE and nano-LC MS/MS revealed that the incubation procedure had a major effect on BC composition. As an example, immunoglobulins are the most abundant plasma proteins of the BC generated in a microfluidic environment (relative protein abundance ∼30%), while tissue leakage proteins (relative protein abundance ∼26%) are the most enriched proteins when the BC is formed upon static incubation. Potential implications in emerging biomedical research arenas are discussed
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