1,720,964 research outputs found
Redesigning human ferritin nanocages for therapeutic applications: from cancer treatment to hypercholesterolemia management
Full text linkProtein-based nanoparticles are increasingly significant in nanomedicine due to their biocompatibility, specificity, and modifiability, offering innovative solutions to therapeutic challenges. Among these, human ferritin stands out for its versatility. Its hollow structure, along with the ability to modify both internal and external surfaces chemically or genetically, makes it an ideal candidate for a variety of applications, including targeted drug delivery, molecular imaging, immunotherapy, and vaccine development. Given these unique properties, this Ph.D. research explores the potential of human H ferritin (HFn) by modifying its surfaces for two distinct biomedical applications. The first objective focuses on enhancing ferritin’s ability to encapsulate hydrophobic drugs, addressing a major limitation in drug delivery systems. By incorporating four or six tryptophan residues per subunit, oriented towards the nanoparticle’s internal cavity, we increased its hydrophobicity, with the aim to improve its capacity to encapsulate hydrophobic chemotherapeutic agents. Detailed characterization revealed that only the variant with four tryptophan residues per subunit retained the ability to disassemble and reassemble correctly. To demonstrate the potential of this modification, we tested the loading capacity of this mutant with ellipticine, a natural hydrophobic indole alkaloid with anticancer properties. Our findings showed that this mutant was far more efficient at loading ellipticine compared to wild-type ferritin. We further evaluated the versatility of this nanoparticle by also encapsulating doxorubicin, a commonly used anticancer drug. Both ellipticine- and doxorubicin-loaded nanoparticles were tested on a promyelocytic leukemia cell line, where efficient drug uptake by the cells and the expected cytotoxic effects were observed. The second objective targets hypercholesterolemia, a major risk factor for cardiovascular disease, by focusing on Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), a protein that regulates cholesterol levels. PCSK9 decreases the number of LDL receptors on liver cells by promoting their degradation, impairing the clearance of LDL cholesterol from the bloodstream. To counteract this, HFn was genetically modified to display 24 copies of a 13-amino acid peptide (Pep2-8) on its surface, previously identified as the smallest PCSK9 inhibitor. Biochemical analysis confirmed precise control over nanoparticle size and morphology, as well as strong PCSK9-binding affinity in the high picomolar range. Functional studies in HepG2 liver cells showed enhanced LDL receptor recycling and LDL uptake, confirming the effectiveness of this multivalent nanoparticle in promoting cholesterol clearance. Together, these findings highlight the multifunctional nature of human H ferritin, making it as a promising platform that can be tailored for diverse therapeutic interventions, from targeted cancer treatment to the modulation of critical physiological pathways in various diseases. The ability to engineer ferritin nanoparticles to display different peptides or proteins further expands its versatility, opening avenues for the development of multifunctional therapeutics with the potential to target multiple pathways simultaneously
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
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
Immobilization of Lathyrus cicera Amine Oxidase on Magnetic Microparticles for Biocatalytic Applications
Full text linkAmine oxidases are enzymes belonging to the class of oxidoreductases that are widespread, from bacteria to humans. The amine oxidase from Lathyrus cicera has recently appeared in the landscape of biocatalysis, showing good potential in the green synthesis of aldehydes. This enzyme catalyzes the oxidative deamination of a wide range of primary amines into the corresponding aldehydes but its use as a biocatalyst is challenging due to the possible inactivation that might occur at high product concentrations. Here, we show that the enzyme’s performance can be greatly improved by immobilization on solid supports. The best results are achieved using amino-functionalized magnetic microparticles: the immobilized enzyme retains its activity, greatly improves its thermostability (4 h at 75 °C), and can be recycled up to 8 times with a set of aromatic ethylamines. After the last reaction cycle, the overall conversion is about 90% for all tested substrates, with an aldehyde production ranging between 100 and 270 mg depending on the substrate used. As a proof concept, one of the aldehydes thus produced was successfully used for the biomimetic synthesis of a non-natural benzylisoquinoline alkaloid
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
Engineered Ferritin with Eu3+ as a Bright Nanovector: A Photoluminescence Study
No full textFerritin nanoparticles play many important roles in theranostic and bioengineering applications and have been successfully used as nanovectors for the targeted delivery of drugs due to their ability to specifically bind the transferrin receptor (TfR1, or CD71). They can be either genetically or chemically modified for encapsulating therapeutics or probes in their inner cavity. Here, we analyzed a new engineered ferritin nanoparticle, made of the H chain mouse ferritin (HFt) fused with a specific lanthanide binding tag (LBT). The HFt-LBT has one high affinity lanthanide binding site per each of the 24 subunits and a tryptophane residue within the tag that acts as an antenna able to transfer the energy to the lanthanide ions via a LRET process. In this study, among lanthanides, we selected europium for its red emission that allows to reduce overlap with tissue auto-fluorescence. Steady state emission measurements and time-resolved emission spectroscopy have been employed to investigate the interaction between the HFt-LBT and the Eu3+ ions. This allowed us to identify the Eu3+ energy states involved in the process and to pave the way for the future use of HFt-LBT Eu3+ complex in theranostics
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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