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[EN] During DNA replication replicative polymerases move in discrete mechanical steps along the DNA template. To address how the chemical cycle is coupled to mechanical motion of the enzyme, here we use optical tweezers to study the translocation mechanism of individual bacteriophage Phi29 DNA polymerases during processive DNA replication. We determine the main kinetic parameters of the nucleotide incorporation cycle and their dependence on external load and nucleotide (dNTP) concentration. The data is inconsistent with power stroke models for translocation, instead supports a loose-coupling mechanism between chemical catalysis and mechanical translocation during DNA replication. According to this mechanism the DNA polymerase works by alternating between a dNTP/PPi-free state, which diffuses thermally between pre- and post-translocated states, and a dNTP/PPi-bound state where dNTP binding stabilizes the post-translocated state. We show how this thermal ratchet mechanism is used by the polymerase to generate work against large opposing loads (~50 pN). ; We thank Stephan Grill laboratory (MPI-CBG, Dresden) for help with data collection and E. Galburt, M. Manosas and M. De Vega for critical reading of the manuscript. Spanish Ministry of Economy and Competitiveness [BFU2011-29038 to J.L.C., BFU2013-44202 to J.M.V., BFU2011-23645 to M.S., FIS2010-17440, GR35/10-A920GR35/10-A-911 to F.J.C., MAT2013-49455-EXP to J.R.A.-G. and BFU2012-31825 to B.I.]; Regional Government of Madrid [S2009/MAT 1507 to J.L.C. and CDS2007-0015 to M.S.]; European Molecular Biology Organization [ASTF 276-2012 to J.M.L.]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness [BFU2012-31825 to B.I.]. ; Morin, J.; Cao, F.; Lázaro, J.; Arias-Gonzalez, JR.; Valpuesta, J.; Carrascosa, J.; Salas, M. (2015). Mechano-chemical kinetics of DNA replication: identification of the translocation step of a replicative DNA polymerase. Nucleic Acids Research. 43(7):3643-3652. https://doi.org/10.1093/nar/gkv204 ; S ; 3643 ; 3652 ; 43 ...

Experiments on animal hearts (rat, rabbit, guinea pig, etc.) have demonstrated that mechano-calcium feedback (MCF) and mechano-electric feedback (MEF) are very important for myocardial self-regulation because they adjust the cardiomyocyte contractile function to various mechanical loads and to mechanical interactions between heterogeneous myocardial segments in the ventricle walls. In in vitro experiments on these animals, MCF and MEF manifested themselves in several basic classical phenomena (e.g., load dependence, length dependence of isometric twitches, etc.), and in the respective responses of calcium transients and action potentials. However, it is extremely difficult to study simultaneously the electrical, calcium, and mechanical activities of the human heart muscle in vitro. Mathematical modeling is a useful tool for exploring these phenomena. We have developed a novel model to describe electromechanical coupling and mechano-electric feedbacks in the human cardiomyocyte. It combines the 'ten Tusscher-Panfilov' electrophysiological model of the human cardiomyocyte with our module of myocardium mechanical activity taken from the 'Ekaterinburg-Oxford' model and adjusted to human data. Using it, we simulated isometric and afterloaded twitches and effects of MCF and MEF on excitation-contraction coupling. MCF and MEF were found to affect significantly the duration of the calcium transient and action potential in the human cardiomyocyte model in response to both smaller afterloads as compared to bigger ones and various mechanical interventions applied during isometric and afterloaded twitches. © 2020 The Author(s). ; Russian Foundation for Basic Research, RFBR: 18‑01‑00059 ; The work was carried out within the framework of the IIP UrB RAS themes (Nos. AAAA‑A18‑118020590031‑8, AAAA‑A18‑118020590134‑6) and was supported by RFBR (18‑01‑00059) and by Act 211 Government of the Russian Federation, contract No. 02.A03.21.0006.

[EN] Genomes contain rare guanine-rich sequences capable of assembling into four-stranded helical structures, termed G-quadruplexes, with potential roles in gene regulation and chromosome stability. Their mechanical unfolding has only been reported to date by all-atom simulations, which cannot dissect the major physical interactions responsible for their cohesion. Here, we propose a mesoscopic model to describe both the mechanical and thermal stability of DNA G-quadruplexes, where each nucleotide of the structure, as well as each central cation located at the inner channel, is mapped onto a single bead. In this framework we are able to simulate loading rates similar to the experimental ones, which are not reachable in simulations with atomistic resolution. In this regard, we present single-molecule force-induced unfolding experiments by a high-resolution optical tweezers on a DNA telomeric sequence capable of adopting a G-quadruplex conformation. Fitting the parameters of the model to the experiments we find a correct prediction of the rupture-force kinetics and a good agreement with previous near equilibrium measurements. Since G-quadruplex unfolding dynamics is halfway in complexity between secondary nucleic acids and tertiary protein structures, our model entails a nanoscale paradigm for non-equilibrium processes in the cell. ; Work supported by the Spanish Ministry of Economy and Competitiveness (MINECO), grant No. FIS2014-55867, co-financed by FEDER funds. We also thank the support of the Aragon Government and Fondo Social Europeo to FENOL group. Work in J.R.A.-G. laboratory was supported by a grant from MINECO, No. MAT2015-71806-R). ; Bergues-Pupo, A.; Gutiérrez, I.; Arias-Gonzalez, JR.; Falo, F.; Fiasconaro, A. (2017). Mesoscopic model for DNA G-quadruplex unfolding. Scientific Reports. 7:1-13. https://doi.org/10.1038/s41598-017-10849-2 ; S ; 1 ; 13 ; 7 ; Arias-Gonzalez, J. R. Single-molecule portrait of DNA and RNA double helices. Integr. Biol. 6, 904 (2014). ; Burge, S., Parkinson, G. N., Hazel, P., ...

A widely-known paradigm in optomechanical systems involves coupling the square of the position of a mechanical oscillator to an electromagnetic field. We discuss how, in the so-called resolved sideband regime, this system allows to simulate dynamics similar to ordinary optomechanics, where the position of the oscillator is coupled to the field, but with the roles of the oscillator and the field interchanged. We show that realisation of this system is within reach, and that it opens the door to an otherwise inaccessible parameter regime. ; This work was partially supported by COST Actions MP1403, MP1405, CA15117, and CA15220. We acknowledge funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 732894 (FETPRO HOT). D.E.B. acknowledges the hospitality of the University of Malta and the University of Vienna. ; non peer-reviewed

Environmental chemistry is a new, fast developing science aimed at deciphering fundamental mechanisms ruling the behaviour of pollutants in ecosystems. Applying this knowledge to current environmental issues leads to the remediation of environmental media, and to new, low energy, low emission, sustainable processes. This book describes the state-of-the-art advances regarding the pollution of water, soils, atmosphere, food and living organisms by toxic metals, fossil fuels, pesticides and other organic pollutants. Furthermore, the eco-toxicology section presents novel bio-assays to assess the toxicity of various pollutants such as dioxins and endocrine disrupters within complex media. The green chemistry section highlights novel chemical reactions based upon environmentally friendly conditions. The analytical chemistry section describes very sensitive methods which trace the fate of pollutants in complex ecosystems. TOC:From the contents: Analytical Chemistry.- Toxic Metals.- Organic Pollutants.- Polycyclic Aromatic Compounds.- Pesticides.- Green Chemistry.- Ecotoxicology

Many controversial issues revolve around complex scientific arguments which can be better understood with at least a minimal knowledge and understanding of the chemical reactions and processes going on in the world around us.This textbook offers an accessible introduction to chemical principles and concepts, and applies them to relevant environmental situations and issues. Written for students who have not taken A' level chemistry, this book bridges the gap between GSCE chemistry and first year undergraduate level.

The study of biophysical properties of single cells is becoming increasingly relevant in cell biology and pathology. The measurement and tracking of magnitudes such as cell stiffness, morphology, and mass or refractive index have brought otherwise inaccessible knowledge about cell physiology, as well as innovative methods for high-throughput labelfree cell classification. In this work, we present hollow resonator devices based on suspended glass microcapillaries for the simultaneous measurement of single-cell buoyant mass and reflectivity with a throughput of 300 cells/minute. In the experimental methodology presented here, both magnitudes are extracted from the devices' response to a single probe, a focused laser beam that enables simultaneous readout of changes in resonance frequency and reflected optical power of the devices as cells flow within them. Through its application to MCF-7 human breast adenocarcinoma cells and MCF-10A nontumorigenic cells, we demonstrate that this mechano-optical technique can successfully discriminate pathological from healthy cells of the same tissue type. ; This work was supported by the European Union's Horizon 2020 research and innovation program under European Research Council Grant 681275-LIQUIDMASS-ERC-CoG2015 and by the Spanish Science, Innovation and Universities Ministry through project CELLTANGLE reference RTI2018- 099369-B-I00, project MOMPs reference TEC2017-89765-R and Ramon y Cajal grant RYC-2017-21640 to P.M.K.; by the ́ Comunidad de Madrid (iLUNG B2017/BMD-3884) with support from EU (FEDER, FSE). E.G.-S. received funding from Fundacion General CSIC (Programa ComFuturo), as ́ well as Marie-Sklodowska Curie Actions (H2020-MSCA-IF2015) under NOMBIS project (703354).The service from the Micro and Nanofabrication Laboratory (MiNa) and X-SEM Laboratory, is funded by MCIU (CSIC13-4E-1794) and EU (FEDER, FSE). We have received support for part of the publication fee by CSIC open access publication support initiative through URICI. ; Peer reviewed