1,721,003 research outputs found
NMR spectroscopy to study the fate of metallodrugs in cells
No full textMetal-based drugs can modulate various biological processes and exhibit a rich variety of properties that foster their use in biomedicine and chemical biology. On the way to intracellular targets, ligand exchange and redox reactions can take place, thus making metallodrug speciation in vivo a challenging task. Advances in NMR spectroscopy have made it possible to move from solution to live-cell studies and elucidate the transport of metallodrugs and interactions with macromolecular targets in a physiological setting. In turn, the electronic properties and supramolecular chemistry of metal complexes can be exploited to characterize drug delivery nanosystems by NMR. The recent evolution of in-cell NMR methodology is presented with special emphasis on metal-related processes. Applications to paradigmatic cases of platinum and gold drugs are highlighted
Interference between copper transport systems and platinum drugs
Full text linkCisplatin, or cis-diamminedichloridoplatinum(II) cis-[PtCl2(NH3)2], is a platinum-based anticancer drug largely used for the treatment of various types of cancers, including testicular, ovarian and colorectal carcinomas, sarcomas, and lymphomas. Together with other platinum-based drugs, cisplatin triggers malignant cell death by binding to nuclear DNA, which appears to be the ultimate target. In addition to passive diffusion across the cell membrane, other transport systems, including endocytosis and some active or facilitated transport mechanisms, are currently proposed to play a pivotal role in the uptake of platinum-based drugs. In this review, an updated view of the current literature regarding the intracellular transport and processing of cisplatin will be presented, with special emphasis on the plasma membrane copper permease CTR1, the Cu-transporting ATPases, ATP7A and ATP7B, located in the trans-Golgi network, and the soluble copper chaperone ATOX1. Their role in eliciting cisplatin efficacy and their exploitation as pharmacological targets will be addressed
The zinc proteome of SARS-CoV-2
No full textZinc is an essential element for human health. Among its many functions, zinc ( II ) modulates the immune response to infections and, at high concentrations or in the presence of ionophores, inhibits the replication of various RNA viruses. Structural biology studies on severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) revealed that zinc ( II ) is the most common metal ion that binds to viral proteins. However, the number of zinc ( II ) -binding sites identified by experimental methods is far from exhaustive, as metal ions may be lost during protein purification protocols. To better define the zinc ( II ) -binding proteome of coronavirus, we leveraged the wealth of deposited structural data and state-of-the-art bioinformatics methods. Through this in silico approach, 15 experimental zinc ( II ) sites were identified and a further 22 were predicted in Spike, open reading frame ( ORF ) 3a/d, ORF8, and several nonstructural proteins, highlighting an essential role of zinc ( II ) in viral replication. Furthermore, the structural relationships between viral and eukaryotic sites ( typically zinc fingers ) indicate that SARS-CoV-2 can compete with human proteins for zinc ( II ) binding. Given the double-edged effect of zinc ( II ) ions, both essential and toxic to coronavirus, only the complete elucidation of the structural and regulatory zinc ( II ) - binding sites can guide selective antiviral strategies based on zinc supplementation
Platinum
No full textThe name platinum is derived from the Spanish term platina, which is literally translated into little silver. It is one of the rarest elements on Earth’s crust (the average abundance is approximately 5 mg kg!1) and the least reactive (the noblest among metals). It occurs in some nickel and copper ores along with some native deposits. Native platinum was first used by pre- Columbian South American natives to produce artefacts. The first European reference to platinum appeared in 1557 in the writings of the Italian humanist Julius Caesar Scaliger as a description of an unknown noble metal found in Mexico, ‘‘which no fire nor any Spanish artifice has yet been able to liquefy’’, but it was not until Antonio de Ulloa published a report on a new metal of Colombian origin in 1748 that it became investigated by scientists
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
The stepwise dissociation of the Zn(II)-bound Atox1 homodimer and its energetic asymmetry
No full textThe copper chaperone Atox1, which is featured by a peculiar CxxC metal-binding motif, is a protein involved in copper trafficking to the Golgi organelle, allowing the delivery of copper ions to specific target proteins in the secretory pathway. Various experimental studies suggest that this cysteine-containing protein may also be implicated in Zn(II) ion binding, functioning as a regulatory factor. However, despite the relevance of this interaction, the mechanism of zinc ion dissociation from the Atox1 homodimer has not yet been elucidated. We herein devised a simulation workflow based on the combination of parallel bias metadynamics and free energy perturbation theory, to predict the dissociation of the zinc ion from the Atox1 homodimer. The freeenergy simulations successfully predicted the dissociation free energy differences of the process, disclosing a mechanism based on a stepwise dissociation pathway of the zinc ion from the Atox1 homodimer
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