Platinum-Nucleos(t)ide Compounds as Possible Antimetabolites for Antitumor/Antiviral Therapy: Properties and Perspectives

Nucleoside analogues (NAs) are a family of compounds which include a variety of purine and pyrimidine derivatives, widely used as anticancer and antiviral agents. For their ability to compete with physiological nucleosides, NAs act as antimetabolites exerting their activity by interfering with the synthesis of nucleic acids. Much progress in the comprehension of their molecular mechanisms has been made, including providing new strategies for potentiating anticancer/antiviral activity. Among these strategies, new platinum-NAs showing a good potential to improve the therapeutic indices of NAs have been synthesized and studied. This short review aims to describe the properties and future perspectives of platinum-NAs, proposing these complexes as a new class of antimetabolites

Adaptive resilience of and through urban ecosystem services : a transdisciplinary approach to sustainability in Barcelona

Unidad de excelencia María de Maeztu CEX2019-000940-MEcosystem services (ES) from urban green and blue infrastructure (GBI) provide cities and their citizens with benefits necessary to cope with present and future sustainability challenges. Long-term comprehensive urban greening strategies, policies, and plans are thus central to the development of sustainable, liveable, and resilient cities. However, urban greening strategies are increasingly tailored to provide short-term benefits, overlooking the dynamic character of cities, which face both changes in the capacity of GBI to provide benefits (e.g., in the face of climate change) as well dynamic needs and preferences for benefits over time as a result of changing demographic compositions. Starting with a literature review on GBI-relevant policies for the city of Barcelona, we: (1) investigated the presence of resilience thinking in the city's GBI-relevant policies through the application of the urban ecosystem services resilience assessment matrix; (2) investigated resilience thinking in the city's policies through the co-development of scenario narratives of possible futures and their implications for ES; and (3) applied the narratives through a participatory approach to enhance stakeholder thinking on adaptive policies based on possible shifts in ES provision and needs. Application of the matrix identified two main gaps to current GBI-relevant policies related to two main aspects of resilience: recognition and assessment of possible future disturbances and changes, and low understanding of social and structural diversity. Through the co-development of four future scenario narratives (aging and shrinking population, enhanced tourism, gender inequalities, and global warming), stakeholders identified the most susceptible ES in the city of Barcelona. Workshop participants indicated mental well-being, regulation of microclimate, social cohesion, air purification, physical recreation, runoff control, and soil permeability as ES with the widest capacity-demand mismatch. The results elicited discussion around GBI and ES resilience, addressing the need for intersectoral policy integration (including housing, education, and mobility) and for fostering a wider understanding of the role of institutions in providing for a resilient urban future. Through the use of scenario narratives, and highlighting the potential of co-creation, the proposed approach enhances critical thought around ES resilience among key players in the city. The study thereby supports the development of a comprehensive resilience strategy for Barcelona and indicates pathways for how other cities can change their current urban trajectory towards sustained ES flows

A NMR-Based Metabolomic Approach to Investigate the Antitumor Effects of the Novel [Pt(η1-C2H4OMe)(DMSO)(phen)]+ (phen = 1,10-Phenanthroline) Compound on Neuroblastoma Cancer Cells

none7NMR-based metabolomics is a very effective tool to assess the tumor response to drugs by providing insights for their mode of action. Recently, a novel Pt(II) complex, [Pt(ƞ1-C2H4OMe)(DMSO)(phen)]+ (phen 1,10-phenanthroline), Pt-EtOMeSOphen, was synthesized and studied for its antitumor activity against eight human cancer cell lines. Pt-EtOMeSOphen showed higher cytotoxic effects than cisplatin in most of the cancer cell lines and in particular against the neuroblastoma cell line (SH-SY5Y). In this study, the mechanism of action of Pt-EtOMeSOphen on SH-SY5Y cells was investigated using 1H NMR-based metabolomics and compared with cisplatin. ­e observed time response of SH-SY5Y cells under treatment revealed a faster action of PtEtOMeSOphen compared with cisplatin, with a response already observed after six hours of exposure, suggesting a cytosolic target. NMR-based metabolomics demonstrated a peculiar alteration of the glutathione metabolism pathway and the diacylglycerol expression.De Castro, Federica; Stefano, Erika; De Luca, Erik; Muscella, Antonella; Marsigliante, Santo; Benedetti, Michele; Fanizzi, Francesco PaoloDe Castro, Federica; Stefano, Erika; De Luca, Erik; Muscella, Antonella; Marsigliante, Santo; Benedetti, Michele; Fanizzi, Francesco Paol

Influence of socio-cultural factors and gender on waste behaviour of travellers: Insights from 11 touristic destinations in Europe

In the course of a global increase of tourism, the need to deal with waste generation, management and prevention caused by tourism activities requires increased attention. In this regard, tourists’ behaviour is a crucial factor for improving the efficacy and efficiency of the waste strategies in place. Tourists’ behaviour has been extensively studied in terms of environmental awareness, while less attention has been given to behaviour and attitudes of tourists in terms of waste generation and prevention. Especially, the socio-cultural and gender component have been hardly addressed in available research. There is some evidence about differences in environmental attitudes and behaviour between tourists from different countries of origin, just as there is evidence of different attitudes towards the environment between men and women, but these two sets of evidences are not integrated, and certainly not with regard to waste behaviour. The present study was developed as part of the H2020 project “URBANWASTE” that aims at understanding the influence of tourism on waste management and production and at developing eco-innovative and gender sensitive strategies for waste prevention and management in 11 European pilot cases. Particularly, this study aimed at analysing and understanding the role and effect of socio-cultural factors (e.g. place of residence, age, education) and gender on ‘waste behaviour’ of tourists; the study includes the tourists’ behaviour at home in comparison to their behaviour on holidays and accounts, hence, also for ‘behavioural gaps’ between home- vs. holiday-behaviour

Wireframe DNA Origami for the Cellular Delivery of Platinum(II)-Based Drugs

The DNA origami method has revolutionized the field of DNA nanotechnology since its introduction. These nanostructures, with their customizable shape and size, addressability, nontoxicity, and capacity to carry bioactive molecules, are promising vehicles for therapeutic delivery. Different approaches have been developed for manipulating and folding DNA origami, resulting in compact lattice-based and wireframe designs. Platinum-based complexes, such as cisplatin and phenanthriplatin, have gained attention for their potential in cancer and antiviral treatments. Phenanthriplatin, in particular, has shown significant antitumor properties by binding to DNA at a single site and inhibiting transcription. The present work aims to study wireframe DNA origami nanostructures as possible carriers for platinum compounds in cancer therapy, employing both cisplatin and phenanthriplatin as model compounds. This research explores the assembly, platinum loading capacity, stability, and modulation of cytotoxicity in cancer cell lines. The findings indicate that nanomolar quantities of the ball-like origami nanostructure, obtained in the presence of phenanthriplatin and therefore loaded with that specific drug, reduced cell viability in MCF-7 (cisplatin-resistant breast adenocarcinoma cell line) to 33%, while being ineffective on the other tested cancer cell lines. The overall results provide valuable insights into using wireframe DNA origami as a highly stable possible carrier of Pt species for very long time-release purposes

Probing Lattice Dynamics and Electronic Resonances in Hexagonal Ge and SixGe1-x Alloys in Nanowires by Raman Spectroscopy

Recent advances in nanowire synthesis have enabled the realization of crystal phases that in bulk are attainable only under extreme conditions, i . e ., high temperature and/or high pressure. For group IV semiconductors this means access to hexagonal-phase Si x Ge 1- x nanostructures (with a 2H type of symmetry), which are predicted to have a direct band gap for x up to 0.5-0.6 and would allow the realization of easily processable optoelectronic devices. Exploiting the quasi-perfect lattice matching between GaAs and Ge, we synthesized hexagonal-phase GaAs-Ge and GaAs-Si x Ge 1- x core-shell nanowires with x up to 0.59. By combining position-, polarization-, and excitation wavelength-dependent μ-Raman spectroscopy studies with first-principles calculations, we explore the full lattice dynamics of these materials. In particular, by obtaining frequency-composition calibration curves for the phonon modes, investigating the dependence of the phononic modes on the position along the nanowire, and exploiting resonant Raman conditions to unveil the coupling between lattice vibrations and electronic transitions, we lay the grounds for a deep understanding of the phononic properties of 2H-Si x Ge 1- x nanostructured alloys and of their relationship with crystal quality, chemical composition, and electronic band structure

Towards a new classification of galaxies: principal component analysis of CALIFA circular velocity curves

We present a galaxy classification system for 238 (E1-Sdm) CALIFA (Calar Alto Legacy Integral Field Area) galaxies based on the shapes and amplitudes of their circular velocity curves (CVCs). We infer the CVCs from the de-projected surface brightness of the galaxies, after scaling by a constant mass-to-light ratio based on stellar dynamics - solving axisymmetric Jeans equations via fitting the second velocity moment $V_{\mathrm{rms}}=\sqrt{V^2+\sigma^2}$ of the stellar kinematics. We use principal component analysis (PCA) applied to the CVC shapes to find characteristic features and use a $k$-means classifier to separate circular curves into classes. This objective classification method identifies four different classes, which we name slow-rising (SR), flat (FL), round-peaked (RP) and sharp-peaked (SP) circular curves. SR are typical for low-mass, late-type (Sb-Sdm), young, faint, metal-poor and disc-dominated galaxies. SP are typical for high-mass, early-type (E1-E7), old, bright, metal-rich and bulge-dominated galaxies. FL and RP appear presented by galaxies with intermediate mass, age, luminosity, metallicity, bulge-to-disk ratio and morphologies (E4-S0a, Sa-Sbc). The discrepancy mass factor, $f_d=1-M_{*}/M_{dyn}$, have the largest value for SR and SP classes ($\sim$ 74 per cent and $\sim$ 71 per cent, respectively) in contrast to the FL and RP classes (with $\sim$ 59 per cent and $\sim$ 61 per cent, respectively). Circular curve classification presents an alternative to typical morphological classification and appears more tightly linked to galaxy evolution.Comment: Accepted for publication in MNRAS (Minor changes), 123 pages, 19 figures, 87 Tables (containing the basic properties of the 238 E1-Sdm galaxies; the five main Principal Component Eigenvectors; the five main Principal Components - PC_i; the Multi-Gaussian Expansion models - MGEs; the circular velocity curve models and their uncertainties

Automated Motion Analysis of Bony Joint Structures from Dynamic Computer Tomography Images: A Multi-Atlas Approach

Dynamic computer tomography (CT) is an emerging modality to analyze in-vivo joint kinematics at the bone level, but it requires manual bone segmentation and, in some instances, landmark identification. The objective of this study is to present an automated workflow for the assessment of three-dimensional in vivo joint kinematics from dynamic musculoskeletal CT images. The proposed method relies on a multi-atlas, multi-label segmentation and landmark propagation framework to extract bony structures and detect anatomical landmarks on the CT dataset. The segmented structures serve as regions of interest for the subsequent motion estimation across the dynamic sequence. The landmarks are propagated across the dynamic sequence for the construction of bone embedded reference frames from which kinematic parameters are estimated. We applied our workflow on dynamic CT images obtained from 15 healthy subjects on two different joints: thumb base (n = 5) and knee (n = 10). The proposed method resulted in segmentation accuracies of 0.90 ± 0.01 for the thumb dataset and 0.94 ± 0.02 for the knee as measured by the Dice score coefficient. In terms of motion estimation, mean differences in cardan angles between the automated algorithm and manual segmentation, and landmark identification performed by an expert were below 1◦. Intraclass correlation (ICC) between cardan angles from the algorithm and results from expert manual landmarks ranged from 0.72 to 0.99 for all joints across all axes. The proposed automated method resulted in reproducible and reliable measurements, enabling the assessment of joint kinematics using 4DCT in clinical routine

The Gene Wiki in 2011: community intelligence applied to human gene annotation

The Gene Wiki is an open-access and openly editable collection of Wikipedia articles about human genes. Initiated in 2008, it has grown to include articles about more than 10 000 genes that, collectively, contain more than 1.4 million words of gene-centric text with extensive citations back to the primary scientific literature. This growing body of useful, gene-centric content is the result of the work of thousands of individuals throughout the scientific community. Here, we describe recent improvements to the automated system that keeps the structured data presented on Gene Wiki articles in sync with the data from trusted primary databases. We also describe the expanding contents, editors and users of the Gene Wiki. Finally, we introduce a new automated system, called WikiTrust, which can effectively compute the quality of Wikipedia articles, including Gene Wiki articles, at the word level. All articles in the Gene Wiki can be freely accessed and edited at Wikipedia, and additional links and information can be found at the project's Wikipedia portal page: http://en.wikipedia.org/wiki/Portal:Gene_Wiki

Programmable models of growth and mutation of cancer-cell populations

In this paper we propose a systematic approach to construct mathematical models describing populations of cancer-cells at different stages of disease development. The methodology we propose is based on stochastic Concurrent Constraint Programming, a flexible stochastic modelling language. The methodology is tested on (and partially motivated by) the study of prostate cancer. In particular, we prove how our method is suitable to systematically reconstruct different mathematical models of prostate cancer growth - together with interactions with different kinds of hormone therapy - at different levels of refinement.Comment: In Proceedings CompMod 2011, arXiv:1109.104