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1.
Environ Sci Ecotechnol ; 22: 100474, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39247805

RESUMO

Improving electrification feasibility is essential for reducing emissions from non-electric energy sources, thereby enhancing air quality and public health. Concurrently, climate mitigation actions, such as carbon pricing policies, have significant potential to alleviate increasing carbon dioxide (CO2) and other co-emitted air pollutants. However, the interactions between climate policy and the improvement of electrification feasibility at the provincial level remain unclear, collectively impacting the net-zero transition of energy-intensive sectors. Here we combine a technologically rich economic-energy-environment model with air quality modeling across China to examine the health, climate, and economic implications of large-scale upgrades in electrification feasibility and climate policies from 2017 to 2030. The results indicate that advancing electrification feasibility, coupled with adopting carbon pricing policies, is likely to facilitate a transition towards electricity-dominant energy systems. Improved electrification feasibility is projected to yield a 7-25% increase in nationwide climate benefits and a 5-14% increase in health benefits by 2030. These incremental benefits, coupled with reduced economic costs, result in a 22-68% increase in net benefits. However, regionally, improvements in electrification feasibility will lead to heightened power demand and unintended emissions from electric energy production in certain provinces (e.g., Nei Mongol) due to the coal-dominated power system. Additionally, in major coal-producing provinces like Shanxi and Shaanxi, enhanced electrification feasibility exacerbates the negative economic impacts of climate policies. This study provides quantitative insights into how improving electrification feasibility reshapes energy evolution and the benefit-cost profile of climate policy at the provincial level. The findings underscore the necessity of a well-designed compensation scheme between affected and unaffected provinces and coordinated emission mitigation across the power and other end-use sectors.

2.
Nat Mater ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39191981

RESUMO

Twist engineering has emerged as a powerful approach for modulating electronic properties in van der Waals heterostructures. While theoretical works have predicted the modulation of spin texture in graphene-based heterostructures by twist angle, experimental studies are lacking. Here, by performing spin precession experiments, we demonstrate tunability of the spin texture and associated spin-charge interconversion with twist angle in WSe2/graphene heterostructures. For specific twist angles, we detect a spin component radial with the electron's momentum, in addition to the standard orthogonal component. Our results show that the helicity of the spin texture can be reversed by twist angle, highlighting the critical role of the twist angle in the spin-orbit properties of WSe2/graphene heterostructures and paving the way for the development of spin-twistronic devices.

3.
Chem Res Toxicol ; 37(8): 1445-1452, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39041427

RESUMO

Tandem lesions, which are defined by two or more contiguously damaged nucleotides, are a hallmark of ionizing radiation. Recently, tandem lesions containing 5-formyl-2'-deoxyuridine (5-fdU) flanked by a 5'-8-OxodGuo or Fapy•dG were discovered, and they are more mutagenic in human cells than the isolated lesions. In the current study, we examined replication of these tandem lesions in Escherichia coli. Bypass efficiency of both tandem lesions was reduced by 30-40% compared to the isolated lesions. Mutation frequencies (MFs) of isolated 8-OxodGuo and Fapy•dG were low, and no mutants were isolated from replication of a 5-fdU construct. The types of mutations from 8-OxodGuo were targeted G → T transversion, whereas Fapy•dG predominantly gave G → T and G deletion. 5'-8-OxodGuo-5-fdU also gave exclusively G → T mutation, which was 3-fold and 11-fold greater, without and with SOS induction, respectively, compared to that of an isolated 8-OxodGuo. In mutY/mutM cells, the MF of 8-OxodGuo and 5'-8-OxodGuo-5-fdU increased 13-fold and 7-fold, respectively. The MF of 5'-8-OxodGuo-5-fdU increased 2-fold and 3-fold in Pol II- and Pol IV-deficient cells, respectively, suggesting that these polymerases carry out largely error-free bypass. The MF of 5'- Fapy•dG-5-fdU was similar without (13 ± 1%) and with (16 ± 2%) SOS induction. Unlike the complex mutation spectrum reported earlier in human cells for 5'- Fapy•dG-5-fdU, with G → T as the major type of errors, in E. coli, the mutations were predominantly from deletion of 5-fdU. We postulate that removal of adenine-incorporated opposite 8-OxodGuo by Fpg and MutY repair proteins is partially impaired in the tandem 5'-8-OxodGuo-5-fdU, resulting in an increase in the G → T mutations, whereas a slippage mechanism may be operating in the 5'- Fapy•dG-5-fdU mutagenesis. This study showed that not only are these tandem lesions more mutagenic than the isolated lesions but they may also exhibit different types of mutations in different organisms.


Assuntos
8-Hidroxi-2'-Desoxiguanosina , Escherichia coli , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Desoxiuridina/análogos & derivados , Desoxiuridina/química , Desoxiuridina/farmacologia , Mutagênicos/toxicidade , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Mutação , Mutagênese , Dano ao DNA
4.
J Org Chem ; 89(16): 11304-11322, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39052894

RESUMO

The manuscript reports on 7-deazapurine and pyrimidine nucleoside and oligonucleotide cycloadducts formed by the inverse electron demand Diels-Alder (iEDDA) reaction with 3,6-di(pyrid-2-yl)-1,2,4,5-tetrazine. Cycloadducts were constructed from ethynylated and vinylated nucleobases. Oligonucleotides were synthesized containing iEDDA modifications, and the impact on duplex stability was investigated. iEDDA reactions were performed on nucleoside triple bond side chains. Oxidation was not required in these cases as dihydropyridazine intermediates are not formed. In contrast, oxidation is necessary for reactions performed on alkenyl compounds. This was verified on 5-vinyl-2'-deoxyuridine. A diastereomeric mixture of 1,2-dihydropyridazine cycloadduct intermediates was isolated, characterized, and later oxidized. 12-mer oligonucleotides containing 1,2-pyridazine inverse Diels-Alder cycloadducts and their precursors were hybridized to short DNA duplexes. For that, a series of phosphoramidites was prepared. DNA duplexes with 7-functionalized 7-deazaadenines and 5-functionalized pyrimidines display high duplex stability when spacer units are present between nucleobases and pyridazine cycloadducts. A direct connectivity of the pyridazine moiety to nucleobases as reported for metabolic labeling of vinyl nucleosides reduced duplex stability strongly. Oligonucleotides bearing linkers with and without pyridazine cycloadducts attached to the 7-deazaadenine nucleobase significantly reduced mismatch formation with dC and dG.


Assuntos
Pareamento de Bases , Reação de Cicloadição , Oligonucleotídeos , Piridazinas , Piridazinas/química , Oligonucleotídeos/química , Purinas/química , Estrutura Molecular , Nucleosídeos de Pirimidina/química , DNA/química , Pareamento Incorreto de Bases
5.
Nucleic Acids Res ; 52(9): 5392-5405, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38634780

RESUMO

N6-(2-deoxy-α,ß-d-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido-pyrimidine (Fapy•dG) is formed from a common intermediate and in comparable amounts to the well-studied mutagenic DNA lesion 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). Fapy•dG preferentially gives rise to G → T transversions and G → A transitions. However, the molecular basis by which Fapy•dG is processed by DNA polymerases during this mutagenic process remains poorly understood. To address this we investigated how DNA polymerase ß (Pol ß), a model mammalian polymerase, bypasses a templating Fapy•dG, inserts Fapy•dGTP, and extends from Fapy•dG at the primer terminus. When Fapy•dG is present in the template, Pol ß incorporates TMP less efficiently than either dCMP or dAMP. Kinetic analysis revealed that Fapy•dGTP is a poor substrate but is incorporated ∼3-times more efficiently opposite dA than dC. Extension from Fapy•dG at the 3'-terminus of a nascent primer is inefficient due to the primer terminus being poorly positioned for catalysis. Together these data indicate that mutagenic bypass of Fapy•dG is likely to be the source of the mutagenic effects of the lesion and not Fapy•dGTP. These experiments increase our understanding of the promutagenic effects of Fapy•dG.


Assuntos
DNA Polimerase beta , Replicação do DNA , Formamidas , Furanos , Pirimidinas , Humanos , Cristalografia por Raios X , DNA/química , DNA/metabolismo , DNA Polimerase beta/metabolismo , DNA Polimerase beta/química , Cinética , Modelos Moleculares , Pirimidinas/química , Pirimidinas/metabolismo , Furanos/química , Furanos/metabolismo , Formamidas/metabolismo , Mutagênese
6.
bioRxiv ; 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38293220

RESUMO

N6-(2-deoxy-α,ß-D-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido-pyrimidine (Fapy•dG) is formed from a common intermediate and in comparable amounts to the well-studied mutagenic DNA lesion 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo). Fapy•dG preferentially gives rise to G → T transversions and G → A transitions. However, the molecular basis by which Fapy•dG is processed by DNA polymerases during this mutagenic process remains poorly understood. To address this we investigated how DNA polymerase ß (Pol ß), a model mammalian polymerase, bypasses a templating Fapy•dG, inserts Fapy•dGTP, and extends from Fapy•dG at the primer terminus. When Fapy•dG is present in the template, Pol ß incorporates TMP less efficiently than either dCMP or dAMP. Kinetic analysis revealed that Fapy•dGTP is a poor substrate but is incorporated ∼3-times more efficiently opposite dA than dC. Extension from Fapy•dG at the 3'-terminus of a nascent primer is inefficient due to the primer terminus being poorly positioned for catalysis. Together these data indicate that mutagenic bypass of Fapy•dG is likely to be the source of the mutagenic effects of the lesion and not Fapy•dGTP. These experiments increase our understanding of the promutagenic effects of Fapy•dG.

7.
Adv Mater ; 36(18): e2310768, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38237911

RESUMO

A charge density wave (CDW) represents an exotic state in which electrons are arranged in a long-range ordered pattern in low-dimensional materials. Although the understanding of the fundamental character of CDW is enriched after extensive studies, its practical application remains limited. Here, an unprecedented demonstration of a tunable charge-spin interconversion (CSI) in graphene/1T-TaS2 van der Waals heterostructures is shown by manipulating the distinct CDW phases in 1T-TaS2. Whereas CSI from spins polarized in all three directions is observed in the heterostructure when the CDW phase does not show commensurability, the output of one of the components disappears, and the other two are enhanced when the CDW phase becomes commensurate. The experimental observation is supported by first-principles calculations, which evidence that chiral CDW multidomains in the heterostructure are at the origin of the switching of CSI. The results uncover a new approach for on-demand CSI in low-dimensional systems, paving the way for advanced spin-orbitronic devices.

8.
Nat Commun ; 14(1): 8350, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102120

RESUMO

The transition to low-carbon electricity is crucial for meeting global climate goals. However, given the uneven spatial distribution and temporal variability of renewable resources, balancing the supply and demand of electricity will be challenging when relying on close to 100% shares of renewable energy. Here, we use an electricity planning model with hourly supply-demand projections and high-resolution renewable resource maps, to examine whether transcontinental power pools reliably meet the growing global demand for renewable electricity and reduce the system cost. If all suitable sites for renewable energy are available for development, transcontinental trade in electricity reduces the annual system cost of electricity in 2050 by 5-52% across six transcontinental power pools compared to no electricity trade. Under land constraints, if only the global top 10% of suitable renewable energy sites are available, then without international trade, renewables are unable to meet 12% of global demand in 2050. Introducing transcontinental power pools with the same land constraints, however, enables renewables to meet 100% of future electricity demand, while also reducing costs by up to 23% across power pools. Our results highlight the benefits of expanding regional transmission networks in highly decarbonized but land-constrained future electricity systems.

9.
Nat Commun ; 14(1): 7253, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37945570

RESUMO

Two-dimensional magnets and superconductors are emerging as tunable building-blocks for quantum computing and superconducting spintronic devices, and have been used to fabricate all two-dimensional versions of traditional devices, such as Josephson junctions. However, novel devices enabled by unique features of two-dimensional materials have not yet been demonstrated. Here, we present NbSe2/CrSBr van der Waals superconducting spin valves that exhibit infinite magnetoresistance and nonreciprocal charge transport. These responses arise from a unique metamagnetic transition in CrSBr, which controls the presence of localized stray fields suitably oriented to suppress the NbSe2 superconductivity in nanoscale regions and to break time reversal symmetry. Moreover, by integrating different CrSBr crystals in a lateral heterostructure, we demonstrate a superconductive spin valve characterized by multiple stable resistance states. Our results show how the unique physical properties of layered materials enable the realization of high-performance quantum devices based on novel working principles.

10.
DNA Repair (Amst) ; 129: 103527, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37467631

RESUMO

Modified nucleotides often hinder and/or decrease the fidelity of DNA polymerases. Tandem lesions, which are comprised of DNA modifications at two contiguous nucleotide positions, can be even more detrimental to genome stability. Recently, tandem lesions containing 5-formyl-2'-deoxyuridine (5fdU) flanked at the 5'-position by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo) or N-(2-deoxy-α,ß-D-erythropentofuranosyl)-N-(2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy•dG) were discovered. We examined the replication of 5'- 8-OxodGuo-5fdU and 5'-Fapy•dG-5fdU tandem lesions in HEK 293T cells and several polymerase deficient variants by transfecting single-stranded vectors containing them. The local sequence of the tandem lesions encompasses the 273 codon of the p53 gene, a mutational hot-spot. The bypass efficiency and mutation spectra of the tandem lesions were compared to those of the isolated lesions. Replication of weakly mutagenic 5-fdU is little changed when part of the 5'- 8-OxodGuo-5fdU tandem lesion. G → T transversions attributable to 8-OxodGuo increase > 10-fold when the tandem lesion is bypassed. 5'-Fapy•dG-5fdU has a synergistic effect on the error-prone bypass of both lesions. The mutation frequency (MF) of 5'-Fapy•dG-5fdU increases 3-fold compared to isolated Fapy•dG. In addition, a 5'-adjacent Fapy•dG significantly increases the MF of 5fdU. The major mutation, G → T transversions, decrease by almost a third in hPol κ- cells, which is the opposite effect when isolated Fapy•dG in the same sequence context is replicated in HEK 293T cells in the same sequence. Steady-state kinetics indicate that hPol κ contributes to greater G → T transversions by decreasing the specificity constant for dCTP compared to an isolated Fapy•dG. The greater conformational freedom of Fapy•dG compared to 8-OxodGuo and its unusual ability to epimerize at the anomeric center is believed to be the source of the complex effects of 5'-Fapy•dG-5fdU on replication.


Assuntos
DNA Polimerase Dirigida por DNA , Mutagênicos , Humanos , 8-Hidroxi-2'-Desoxiguanosina , Mutagênese , Nucleotídeos , Desoxiguanosina , Dano ao DNA
11.
Nano Lett ; 23(10): 4406-4414, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37140909

RESUMO

Graphene is a light material for long-distance spin transport due to its low spin-orbit coupling, which at the same time is the main drawback for exhibiting a sizable spin Hall effect. Decoration by light atoms has been predicted to enhance the spin Hall angle in graphene while retaining a long spin diffusion length. Here, we combine a light metal oxide (oxidized Cu) with graphene to induce the spin Hall effect. Its efficiency, given by the product of the spin Hall angle and the spin diffusion length, can be tuned with the Fermi level position, exhibiting a maximum (1.8 ± 0.6 nm at 100 K) around the charge neutrality point. This all-light-element heterostructure shows a larger efficiency than conventional spin Hall materials. The gate-tunable spin Hall effect is observed up to room temperature. Our experimental demonstration provides an efficient spin-to-charge conversion system free from heavy metals and compatible with large-scale fabrication.

12.
Chem Res Toxicol ; 36(5): 782-789, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37093780

RESUMO

7,8-Dihydro-8-oxo-2'-deoxyguanosine (8-OxodGuo) is a ubiquitous DNA damage formed by oxidation of 2'-deoxyguanosine. In this study, plasmid DNA containing 8-OxodGuo located in three mutational hot spots of human cancers, codons 248, 249, and 273 of the Tp53 tumor suppressor gene, was replicated in HEK 293T cells. 8-OxodGuo was only a weak block of replication, and the bypass was largely error-free. The mutations (1-5%) were primarily G → T transversions, and the mutation frequency was generally lower than that of the chemically related Fapy·dG. A unique 8-OxodGuo mutation spectrum was observed at each site, as reflected by replication in translesion synthesis (TLS) polymerase- or hPol λ-deficient cells. In codon 248 (CG*G) and 249 (AG*G), where G* denotes 8-OxodGuo, hPol η and hPol ζ carried out largely error-free bypass of the lesion, whereas hPol κ and hPol ι were involved mostly in error-prone TLS, resulting in G → T mutations. 8-OxodGuo bypass in codon 273 (CG*T) was unlike the other two sites, as hPol κ participated in the mostly error-free bypass of the lesion. Yet, in all three sites, including codon 273, simultaneous deficiency of hpol κ and hPol ι resulted in reduction of G → T transversions. This indicates a convincing role of these two TLS polymerases in error-prone bypass of 8-OxodGuo. Although the dominant mutation was G → T in each site, in codon 249, and to a lesser extent in codon 248, significant semi-targeted single-base deletions also occurred, which suggests that 8-OxodGuo can initiate slippage of a base near the lesion site. This study underscores the importance of sequence context in 8-OxodGuo mutagenesis in human cells. It also provides a more comprehensive comparison between 8-OxodGuo and the sister lesion, Fapy·dG. The greater mutagenicity of the latter in the same sequence contexts indicates that Fapy·dG is a biologically significant lesion and biomarker on par with 8-OxodGuo.


Assuntos
Genes p53 , Mutagênicos , Humanos , 8-Hidroxi-2'-Desoxiguanosina , Mutação , Mutagênese , Replicação do DNA , Dano ao DNA , Desoxiguanosina
13.
Environ Sci Technol ; 57(7): 2898-2906, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36758223

RESUMO

China's power system is highly regulated and uses an "equal-share" dispatch approach. However, market mechanisms are being introduced to reduce generation costs and improve system reliability. Here, we quantify the climate and human health impacts brought about by this transition, modeling China's power system operations under economic dispatch. We find that significant reductions in mortality related to air pollution (11%) and CO2 emissions (3%) from the power sector can be attained by economic dispatch, relative to the equal-share approach, through more efficient coal-powered generation. Additional health and climate benefits can be achieved by incorporating emission externalities in electricity generation costs. However, the benefits of the transition to economic dispatch will be unevenly distributed across China and may lead to increased health damage in some regions. Our results show the potential of dispatch decision-making in electricity generation to mitigate the negative impacts of power plant emissions with existing facilities in China.


Assuntos
Poluição do Ar , Humanos , Reprodutibilidade dos Testes , Poluição do Ar/análise , Clima , Carvão Mineral , Centrais Elétricas , China , Dióxido de Carbono/análise
14.
Nat Commun ; 13(1): 6790, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357377

RESUMO

Optical detection techniques are among the most powerful methods used to characterize spintronic phenomena. The spin orientation can affect the light polarization, which, by the reciprocal mechanism, can modify the spin density. Numerous recent experiments, report local changes in the spin density induced by a circularly polarized focused laser beam. These effects are typically probed electrically, by detecting the variations of the photoresistance or photocurrent associated to the reversal of the light helicity. Here we show that in general, when the light helicity is modified, the beam profile is slightly altered, and the barycenter of the laser spot is displaced. Consequently, the temperature gradients produced by the laser heating will be modulated, producing thermo-electric signals that alternate in phase with the light polarization. These unintended signals, having no connection with the electron spin, appear under the same experimental conditions and can be easily misinterpreted. We show how this contribution can be experimentally assessed and removed from the measured data. We find that even when the beam profile is optimized, this effect is large, and completely overshadows the spin related signals in all the materials and experimental conditions that we have tested.

15.
Nano Lett ; 22(19): 7992-7999, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36162104

RESUMO

One of the major obstacles to realizing spintronic devices such as MESO logic devices is the small signal magnitude used for magnetization readout, making it important to find materials with high spin-to-charge conversion efficiency. Although intermixing at the junction of two materials is a widely occurring phenomenon, its influence on material characterization and the estimation of spin-to-charge conversion efficiencies are easily neglected or underestimated. Here, we demonstrate all-electrical spin-to-charge conversion in BixSe1-x nanodevices and show how the conversion efficiency can be overestimated by tens of times depending on the adjacent metal used as a contact. We attribute this to the intermixing-induced compositional change and the properties of a polycrystal that lead to drastic changes in resistivity and spin Hall angle. Strategies to improve the spin-to-charge conversion signal in similar structures for functional devices are discussed.

16.
Comput Methods Programs Biomed ; 225: 107059, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35964422

RESUMO

BACKGROUND AND OBJECTIVE: At present, there is a lack of efficient modeling methods for bionic artificial bone scaffolds, and the tissue fluid/nutrient mass transport characteristics of bone scaffolds has not been evaluated sufficiently. This study aims to explore an effective and efficient modeling method for biomimetic porous bone scaffolds for biological three-dimensional printing based on the imitation of the histomorphological characteristics of human vertebral cancellous bone. The fluid mass transport and mechanical characteristics of the porous scaffolds were evaluated and compared with those of a human cancellous bone,and the relationship between the geometric parameters (e.g., the size, number, shape of pores and porosity) and the performence of biomimetic porous bone scaffolds are revealed. METHODS: The bionic modeling design method proposed in this study considers the biological characteristics of vertebral cancellous tissue and performs imitation and design of vertebrae-like two-dimensional slices images.It then reconstructs the slices layer-by-layer to form porous scaffolds with a three-dimensional reconstruction method, similar to computed tomography image reconstruction. By controlling the design parameters, this method can easily realize the formation of plate-like (femoral cancellous bone-like) or rod-like (vertebral cancellous bone-like) porous scaffolds. The flow characterization of porous structures was performed using the computational fluid simulation method. RESULTS: The flow characterization results showed that the permeability of the porous scaffolds and human bone was 10-8∼10-9m2,and when the porosity of the porous scaffolds was higher than 70%, the permeability was higher than that of human vertebrae with a porosity of 82%. The maximum shear stress of the designed porous scaffolds and human vertebra were less than 0.8Mpa, which was conducive to cell adhesion, cell migration, and cell differentiation. The results of 3D printing and mechanical testing showed good printability and reflected the relationship between the mechanical properties and design parameters. CONCLUSIONS: The design method proposed in this study has many controllable parameters, which can be adjusted to generate diversified functional porous structures to meet specific needs, increase the potential of bone scaffold design, and leave room for meeting the new requirements for bone scaffold characteristics in the future.


Assuntos
Engenharia Tecidual , Alicerces Teciduais , Biônica , Osso e Ossos , Humanos , Porosidade , Impressão Tridimensional , Engenharia Tecidual/métodos , Alicerces Teciduais/química
17.
J Am Chem Soc ; 144(18): 8054-8065, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35499923

RESUMO

N6-(2-Deoxy-α,ß-d-erythro-pentofuranosyl)-2,6-diamino-4-hydroxy-5-formamido pyrimidine (Fapy•dG) is a prevalent form of genomic DNA damage. Fapy•dG is formed in greater amounts under anoxic conditions than the well-studied, chemically related 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodGuo). Fapy•dG is more mutagenic in mammalian cells than 8-oxodGuo. A distinctive property of Fapy•dG is facile epimerization, but prior works with Fapy•dG analogues have precluded determining its effect on chemistry. We present crystallographic characterization of natural Fapy•dG in duplex DNA and as the template base for DNA polymerase ß (Pol ß). Fapy•dG adopts the ß-anomer when base paired with cytosine but exists as a mixture of α- and ß-anomers when promutagenically base paired with adenine. Rotation about the bond between the glycosidic nitrogen atom and the pyrimidine ring is also affected by the opposing nucleotide. Sodium cyanoborohydride soaking experiments trap the ring-opened Fapy•dG, demonstrating that ring opening and epimerization occur in the crystalline state. Ring opening and epimerization are facilitated by propitious water molecules that are observed in the structures. Determination of Fapy•dG mutagenicity in wild type and Pol ß knockdown HEK 293T cells indicates that Pol ß contributes to G → T transversions but also suppresses G → A transitions. Complementary kinetic studies have determined that Fapy•dG promotes mutagenesis by decreasing the catalytic efficiency of dCMP insertion opposite Fapy•dG, thus reducing polymerase fidelity. Kinetic studies have determined that dCMP incorporation opposite the ß-anomer is ∼90 times faster than the α-anomer. This research identifies the importance of anomer dynamics, a feature unique to formamidopyrimidines, when considering the incorporation of nucleotides opposite Fapy•dG and potentially the repair of this structurally unusual lesion.


Assuntos
Desoxicitidina Monofosfato , Mutagênicos , 8-Hidroxi-2'-Desoxiguanosina , Animais , DNA/química , Adutos de DNA , Dano ao DNA , Replicação do DNA , Desoxicitidina Monofosfato/metabolismo , Desoxiguanosina , Cinética , Mamíferos/genética , Mamíferos/metabolismo , Mutagênese , Mutagênicos/química , Estresse Oxidativo , Pirimidinas/química
18.
Nat Commun ; 13(1): 1192, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35256602

RESUMO

Friction plays an essential role in most physical processes that we experience in our everyday life. Examples range from our ability to walk or swim, to setting boundaries of speed and fuel efficiency of moving vehicles. In magnetic systems, the displacement of chiral domain walls (DW) and skyrmions (SK) by Spin Orbit Torques (SOT), is also prone to friction. Chiral damping (αc), the dissipative counterpart of the Dzyaloshinskii Moriya Interaction (DMI), plays a central role in these dynamics. Despite experimental observation, and numerous theoretical studies confirming its existence, the influence of chiral damping on DW and SK dynamics has remained elusive due to the difficulty of discriminating from DMI. Here we unveil the effect that αc has on the flow motion of DWs and SKs driven by current and magnetic field. We use a static in-plane field to lift the chiral degeneracy. As the in-plane field is increased, the chiral asymmetry changes sign. When considered separately, neither DMI nor αc can explain the sign reversal of the asymmetry, which we prove to be the result of their competing effects. Finally, numerical modelling unveils the non-linear nature of chiral dissipation and its critical role for the stabilization of moving SKs.

19.
Nat Mater ; 21(5): 526-532, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35256792

RESUMO

Chiral materials are an ideal playground for exploring the relation between symmetry, relativistic effects and electronic transport. For instance, chiral organic molecules have been intensively studied to electrically generate spin-polarized currents in the last decade, but their poor electronic conductivity limits their potential for applications. Conversely, chiral inorganic materials such as tellurium have excellent electrical conductivity, but their potential for enabling the electrical control of spin polarization in devices remains unclear. Here, we demonstrate the all-electrical generation, manipulation and detection of spin polarization in chiral single-crystalline tellurium nanowires. By recording a large (up to 7%) and chirality-dependent unidirectional magnetoresistance, we show that the orientation of the electrically generated spin polarization is determined by the nanowire handedness and uniquely follows the current direction, while its magnitude can be manipulated by an electrostatic gate. Our results pave the way for the development of magnet-free chirality-based spintronic devices.


Assuntos
Nanofios , Eletricidade , Eletricidade Estática , Estereoisomerismo , Telúrio
20.
Nat Commun ; 12(1): 5663, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611147

RESUMO

The costs and benefits of climate change mitigation are known to be distributed unevenly across time and space, while their intergenerational distribution across nations has not been evaluated. Here, we analyze the lifetime costs and benefits of climate change mitigation by age cohorts across countries under the Paris Agreement. Our results show that the age cohorts born prior to 1960 generally experience a net reduction in lifetime gross domestic product per capita. Age cohorts born after 1990 will gain net benefits from climate change mitigation in most lower income countries. However, no age cohorts enjoy net benefits regardless of the birth year in many higher income countries. Furthermore, the cost-benefit disparity among old and young age cohorts is expected to widen over time. Particularly, lower income countries are expected to have much larger cost-benefit disparity between the young and the old. Our findings highlight the challenges in building consensus for equitable climate policy among nations and generations.

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