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Dynamic histone modification patterns coordinating DNA processes
No full textSignificant effort has been spent attempting to unravel the causal relationship between histone post-translational modifications and fundamental DNA processes, including transcription, replication, and repair. However, less attention has been paid to understanding the reciprocal influence-that is, how DNA processes, in turn, shape the distribution and patterns of histone modifications and how these changes convey information, both temporally and spatially, from one process to another. Here, we review how histone modifications underpin the widespread bidirectional crosstalk between different DNA processes, which allow seemingly distinct phenomena to operate as a unified whole.Publication of this work was funded by the EMERGIA 2021 program (EMC21_00222) from the Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía to G.M.-Z. The G.M.-Z. laboratory was also supported by grant PID2021-127432N A-I00, funded by MCIN/AEI/10.13039/501100011033 and by FEDER, UE, and by grant CNS2022-135600, funded by MICIU/AEI/10.13039/501100011033 and by European Union NextGenerationEU/PRTR. A.J.B. was supported by grants from Cancer Research UK (RG96894 and C6946/A24843) and the Wellcome Trust (WT203144). All figures were created in Biorender.com. The authors apologize to colleagues whose important studies they were unable to cite owing to space constraints.Peer reviewe
Mouse ZGRF1 helicase facilitates DNA repair and maintains efficient fertility
No full textThe recently characterised human ZGRF1 helicase promotes genomic stability by facilitating DNA interstrand crosslink repair. In its absence, human cells exhibit greater sensitivity towards anti-cancer drugs such as mitomycin C and camptothecin. Moreover, the downregulation of ZGRF1 expression is associated with increased survival in cancer patients. These attributes point to ZGRF1 as a potential anti-cancer drug target. Here, we investigated the role of ZGRF1 in tumorigenesis using the mouse model. We generated a ZGRF1 mutant mouse and find that it is viable and displays normal development. However, at a cellular level, mouse embryonic fibroblasts exhibit sensitivity to ICLs and show elevated levels of the DNA damage marker γH2AX. In the absence of ZGRF1, the rates of tumorigenesis and tumour-free survival in Eμ-Myc and Trp53 knockout mice remained largely unaffected. These findings suggest a potential role for ZGRF1 in the proliferation of specific cancer types, highlighting avenues for further research in other cancer models. Additionally, beyond its known function in DNA repair, our study also reveals that ZGRF1 promotes meiotic recombination and that its loss results in reduced fertility in mice manifested as a 30 % reduction in meiotic crossovers and a 15 % reduction in litter size.This study was supported by the Novo Nordisk Foundation (NNF19OC0055203 and NNF22OC0074308) to ML and JRG, respectively, and the Danish National Research Foundation (DNRF115) to ML, AL-C and IDH. We thank Ketan J. Patel for providing us with the cryopreserved Adh5 KO sperm straws and Paula E. Cohen for providing us with the rabbit anti-MLH3 antibody. We would also like to thank Patricia González from the Histopathology Core Unit at CNIO, and the caretakers from the Mouse Genetic Unit for the technical assistance. Lastly, we thank Eva R. Hoffmann for advice on meiotic spreads.Peer reviewe
Disclosing the Intra-Catalyst Non-Covalent Interactions in Tetrahydropyran-Based Dipeptidic Catalysts
No full textHerein, we describe how minor structural modifications to our bifunctional organocatalysts based on sugar amino acids (SAAs) can alter the network of non-covalent interactions (NCIs) within the catalyst, leading to significant changes in their catalytic activity. This is attributed to the intra-catalyst NCIs, which induce conformational changes that are reflected in the transition state of the rate-determining step of the Michael addition of aldehydes to trans-β-nitrostyrenes. Through kinetic experiments, conformational analysis, and DFT calculations, we found that the presence of a methoxy group at the C4 position of the tetrahydropyran ring reduces the catalytic activity by a factor of five compared to the catalyst without the methoxy group. Additionally, we have identified the different intra-catalyst NCIs, both attractive and repulsive, that drive the conformational changes, ultimately modifying the energy levels of the transition states of the rate- and enantioselectivity-determining step of the reaction.Grants (PID2021-128047NB-I00, PID2022-139318NB-I00 and RED2022-134287-T) were funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”, and the Canary Islands Government (ProID2020010004, ACIISI/FEDER, UE). J. B.-G. thanks the Spanish MEC for an FPU fellowship.Peer reviewe
Dodecanuclear [NiII8Ln4] clusters: rings of corner-sharing {NiII2Ln2} cubanes (Ln = Dy, Gd, Y}
No full text[Description of methods used for collection/generation of data] Magnetisation data were collected on MPMS-XL and MPMS3 SQUID magnetometers equipped with 5 and 7 T magnets, respectively. Diamagnetic corrections were applied using Pascal's constants.
Heat capacity measurements were carried out on a PPMS equipped with a 9 T magnet and a 3He cryostat, using a thin pressed pellet (ca. 1 mg) of a polycrystalline sample of 2, thermalized by ca. 0.2 mg of Apiezon N grease, whose contribution was subtracted using a phenomenological expression.[Methods for processing the data] An indirect estimation of DS and DT was performed in accordance with standard thermodynamic formulations.The solvothermal reaction of NiCl2.6H2O with 1,3,5-tri(2-hydroxyethyl)-1,3,5-triazacyclohexane, LH3, and Ln(OAc)3.4H2O in the presence of salicylaldehyde in MeOH leads to the formation of the dodecanuclear isostructural species [NiII8Ln4(L’)8(OAc)4(OH)8(H2O)4].xH2O (Ln= Dy, x=6 (1); Gd, x= 24 (2); Y, x= 10 (3); L’ = the dianion of the Schiff-base resulting from the reaction of salicylaldehyde and ethanolamine). The metallic core of the clusters describes a ring a of corner-sharing {Ni2Ln2} cubanes assembled on a central, planar rectangular {Ln4} unit. Magnetization studies conducted on complexes 1 - 3 demonstrate the presence of dominant ferromagnetic exchange at low temperatures, which is largely attributed to the Ni⋯Ni interactions. The significant magnetocaloric effect observed in the Gd analogue has been assessed through heat-capacity and magnetization measurements.This work has received support from EU (MSCA-DN MolCal, 101119865), MICIU/AEI/10.13039/501100011033/ and ERDF/EU (PID2021-124734OB-C21, CEX2023-001286-S), Gobierno de Aragón (E11-23R, E12-23R). CJM and TGT would like to thank the National Recovery and Resilience Plan Greece 2.0 (Award Number TAEDR-0535821), funded by the European Union − NextGenerationEU.With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2023-001286-S).Peer reviewe
Nanomechanical spectrometry of Escherichia coli by multifrequency tracking
Get PDFTrabajo presentado en el 17th International Workshop on Nanomechanical Sensing, celebrado de forma híbrida (presencial-online) desde Calgary, Alberta (Canadá), del 15 al 18 de junio de 202
Low-bandgap oligothiophene-naphthalimide oligomeric semiconductors for thermoelectric applications
Get PDFState-of-the-art p-type organic conjugated polymers are mostly thiophene-based semiconductors. Still, novel chemical design and a fresh perspective on different polymer backbones could pave the way for new high-performing materials and a deep understanding of donor-acceptor conjugated assemblies. Herein we designed and synthesized two novel electroactive oligomeric materials based on a donor terthiophene unit endowed with a strong electron-withdrawing naphthalimide unit. This molecular assembly has been polymerized using a palladium cross-coupling reaction with two different linkers, 1,1,1,2,2,2-hexabutyldistannane and (4,8-bis((2-ethylhexyl)oxy)benzo[1,2-b:4,5-b’]dithiophene-2,6diyl)bis(trimethylstannane), to obtain the target polymers NIP3T-poly and NIP3T-BDT-poly, respectively. Both polymers exhibited an extended absorption up to 1000 nm and higher hole field-effect mobilities of up to 1.8 x 10-3 cm2V-1s-1, in comparison to the molecular assembly NIP3T, and precisely tuned energy levels that make them compatible with common p-type dopants like 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ). After optimizing the doping level, we obtained a thermoelectric figure of merit up to zT = 0.02 for NIP3T-BDT-poly, comparable with benchmark F4TCNQ-vapor doped polythiophenes.This work was financially supported by the European Commission through the Marie Skłodowska-Curie project HORATES (GA-955837), MICINN (PID2022-138908NB-C33, PID2022-141393OB-I00 and TED2021-129886BC43), through the “Severo Ochoa” Programme for Centers of Excellence in R&D (CEX2023-001263-S) and the UCM (INV.GR.00.1819.10759). MJAN gratefully acknowledges Universidad Rey Juan Carlos for his postdoctoral contract. S. RG. is thankful to Marie Skłodowska Curie Cofund, Beatriu de Pinós Fellowship (AGAUR-2019 BP 00200) and Marie Sklodowska-Curie Actions (H2020-MSCA-IF-2020) for Grant Agreement No. 101025608, IDEAL. We thank Anders Mårtensson for help with SEC measurements and Dr. Agustín Mihi (ICMAB-CSIC) for providing access to the Bruker IR spectrophotometry equipment, and Prof. Joaquim Puigdollers (UPC) for fruitful discussionsWith funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2023-001263-S).Peer reviewe
The EMPIRE Survey: Systematic Variations in the Dense Gas Fraction and Star Formation Efficiency from Full-disk Mapping of M51
Get PDFWe present the first results from the EMPIRE survey, an IRAM large program that is mapping tracers of high-density molecular gas across the disks of nine nearby star-forming galaxies. Here, we present new maps of the 3 mm transitions of HCN, HCO, and HNC across the whole disk of our pilot target, M51. As expected, dense gas correlates with tracers of recent star formation, filling the "luminosity gap" between Galactic cores and whole galaxies. In detail, we show that both the fraction of gas that is dense, traced by HCN/CO, and the rate at which dense gas forms stars, traced by IR/HCN, depend on environment in the galaxy. The sense of the dependence is that high-surface-density, high molecular gas fraction regions of the galaxy show high dense gas fractions and low dense gas star formation efficiencies. This agrees with recent results for individual pointings by Usero et al. but using unbiased whole-galaxy maps. It also agrees qualitatively with the behavior observed contrasting our own Solar Neighborhood with the central regions of the Milky Way. The sense of the trends can be explained if the dense gas fraction tracks interstellar pressure but star formation occurs only in regions of high density contrast. © 2016. The American Astronomical Society. All rights reserved.We thank Gaëlle Dumas for assisting with data reduction and Fabian Walter for helpful discussions and feedback on the draft. F.B., M.J., and D.C. acknowledge support from DFG grant BI 1546/1-1. A.H. acknowledges support from the Centre National d'Etudes Spatiales (CNES). A.U. acknowledges support from Spanish MINECO grants AYA2012-32295 and FIS2012-32096. J.P. thanks the CNRS/INSU programme PCMI for support. N.T. acknowledges funding from DFG grant SCHI 536/8-2 as part of the priority program SPP 1573 "Physics of the Interstellar Medium."Peer reviewe
Retrieving past quantum features with deep hybrid classical-quantum reservoir computing
No full textMachine learning techniques have achieved impressive results in recent years and the possibility of harnessing the power of quantum physics opens new promising avenues to speed up classical learning methods. Rather than viewing classical and quantum approaches as exclusive alternatives, their integration into hybrid designs has gathered increasing interest, as seen in variational quantum algorithms, quantum circuit learning, and kernel methods. Here we introduce deep hybrid classical-quantum reservoir computing for temporal processing of quantum states where information about, for instance, the entanglement or the purity of past input states can be extracted via a single-step measurement. We find that the hybrid setup cascading two reservoirs not only inherits the strengths of both of its constituents but is even more than just the sum of its parts, outperforming comparable non-hybrid alternatives. The quantum layer is within reach of state-of-the-art multimode quantum optical platforms while the classical layer can be implemented in silico.We acknowledge the Spanish State Research Agency, through the María de Maeztu project CEX2021-001164-M funded by the MCIU/AEI/10.13039/501100011033 and by ERDF, EU and through the COQUSY project PID2022-140506NB-C21 and -C22 funded by MCIU/AEI/10.13039/501100011033 and by ERDF, EU, MINECO through the QUANTUM SPAIN project, and EU through the RTRP—NextGenerationEU within the framework of the Digital Spain 2025 Agenda. JN gratefully acknowledges financial support from the Academy of Finland under Project No. 348854. GLG is funded by the Spanish Ministerio de Educación y Formación Profesional/Ministerio de Universidades and co-funded by the University of the Balearic Islands through the Beatriz Galindo program (BG20/00085).With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001164-M).Peer reviewe
Long-Term Anaerobic Structured Fixed-Bed Reactor Operation for Domestic Sewage Treatment: Performance and Metal Dynamics
No full text16 Páginas.-- 3 Figuras.-- 4 TablasTo achieve optimal performance, anaerobic digestion (AD) requires well-balanced operation conditions, steady physical¿chemical conditions, and adequate nutrient concentrations. The use of anaerobic structured-bed reactor (ASTBR) presents these conditions. However, several additional investigations are required to elucidate robustness to treat domestic sewage (DS). This pioneering study investigated the performance of an ASTBR in treating DS across four decreasing hydraulic retention times (HRTs) (12, 8, 6, and 5 h). The study aimed to assess organic matter removal, the influence on physical¿chemical parameters, and the monitoring of trace metals (TMs) during long-term operation (614 days). Overall, the results underscore the viability of employing ASTBR for DS treatment, achieving an average chemical oxygen demand (COD) removal efficiency of 70%. The system demonstrated consistent long-term operation over 614 days, maintaining stability even with decreasing hydraulic retention times (HRTs). The average effluent concentration of volatile fatty acids (VFAs) was 20.4 ± 3.3 mg L¿1, with a pH value averaging 7.2 ± 0.1. TM concentrations at an HRT of 12 h exhibited higher levels in the effluent compared to the influent, gradually decreasing over the course of operation and ultimately stabilizing at levels similar to those observed in the influent. The concentrations of metals, including Ba, Cr, Fe, Mn, Ni, Pb, Se, and Zn, monitored in the effluent samples adhered to the allowable discharge thresholds as stipulated by Brazilian regulations.This research was funded by Coordination for the Improvement of Higher Education Personnel (CAPES)—finance code 001; National Council for Scientific and Technological Development (CNPq) processes 406751/2013-7, 150475/2016-0 and 308663/2021-7; and São Paulo Research Foundation (FAPESP) processes 2015/06246-7, 2018/00213-8, and 2018/18367-1
Innovative salt replacement for green Spanish-style olives using potassium, calcium, and magnesium chlorides during packaging
No full text16 Páginas.--4 Figuras.-- 3 TablasThis work aimed to enhance green Spanish-style Manzanilla table olives by replacing salt with K, Ca, and Mg chlorides in innovative packaging, utilising Response Surface Methodology (RSM). Both the added replacers and naturally occurring minerals were considered. RSM allowed the development of predictive models for K, Ca, Mg, and Mn (initially present) in olive flesh and their contributions to Reference Daily Intakes (RDI) based on the added salts. The sodium content in the new products decreased from 1.4 g/100 g flesh to 0.68 g/100 g flesh, while K, Ca, and Mg concentrations could increase up to 0.50, 0.45 and 0.15 g/100 g flesh, respectively. Added salt contributions to RDI could reach 25, 60, and 44 % for K, Ca, and Mg. Minimal differences between analytical data-derived minerals and predicted values were minimal, suggesting reliable model performance for nutrition labelling. Results assist the industry in creating nutritionally enhanced table olive products.This work was partly funded by the Ministry of Economy and Competitiveness from the Spanish government through projects AGL2009-07436/ALI and AGL2010-15494/ALI, partially financed by European Regional Development Funds (ERDF) and Junta de Andalucía through financial assistance to group AGR-125.
J.M. Moreno-Baquero thanks CSIC for their JAE fellowship.Peer reviewe