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Protein-protein interactions are at the heart of all cellular processes, with the ribosome emerging as a platform, orchestrating the nascent-chain interplay dynamics. Here, to study the characteristics governing co-translational protein folding and complex assembly, we combine selective ribosome profiling, imaging, and N-terminomics with all-atoms molecular dynamics. Focusing on conserved N-terminal acetyltransferases (NATs), we uncover diverging co-translational assembly pathways, where highly homologous subunits serve opposite functions. We find that only a few residues serve as "hotspots," initiating co-translational assembly interactions upon exposure at the ribosome exit tunnel. These hotspots are characterized by high binding energy, anchoring the entire interface assembly. Alpha-helices harboring hotspots are highly thermolabile, folding and unfolding during simulations, depending on their partner subunit to avoid misfolding. In vivo hotspot mutations disrupted co-translational complexation, leading to aggregation. Accordingly, conservation analysis reveals that missense NATs variants, causing neurodevelopmental and neurodegenerative diseases, disrupt putative hotspot clusters. Expanding our study to include phosphofructokinase, anthranilate synthase, and nucleoporin subcomplex, we employ AlphaFold-Multimer to model the complexes' complete structures. Computing MD-derived interface energy profiles, we find similar trends. Here, we propose a model based on the distribution of interface energy as a strong predictor of co-translational assembly.

NEXT-100 is currently being constructed at the Laboratorio Subterráneo de Canfranc in the Spanish Pyrenees and will search for neutrinoless double beta decay using a high-pressure gaseous time projection chamber (TPC) with 100 kg of xenon. Charge amplification is carried out via electroluminescence (EL) which is the process of accelerating electrons in a high electric field region causing secondary scintillation of the medium proportional to the initial charge. The NEXT-100 EL and cathode regions are made from tensioned hexagonal meshes of 1 m diameter. This paper describes the design, characterization, and installation of these parts for NEXT-100. Simulations of the electric field are performed to model the drift and amplification of ionization electrons produced in the detector under various EL region alignments and rotations. Measurements of the electrostatic breakdown voltage in air characterize performance under high voltage conditions and identify breakdown points. The electrostatic deflection of the mesh is quantified and fit to a first-principles mechanical model. Measurements were performed with both a standalone test EL region and with the NEXT-100 EL region before its installation in the detector. Finally, we describe the parts as installed in NEXT-100, following their deployment in Summer 2023.

Changes in chromosome numbers, including polyploidy and dysploidy events, play a key role in eukaryote evolution as they could expediate reproductive isolation and have the potential to foster phenotypic diversification. Deciphering the pattern of chromosome-number change within a phylogeny currently relies on probabilistic evolutionary models. All currently available models assume time homogeneity, such that the transition rates are identical throughout the phylogeny. Here, we develop heterogeneous models of chromosome-number evolution that allow multiple transition regimes to operate in distinct parts of the phylogeny. The partition of the phylogeny to distinct transition regimes may be specified by the researcher or, alternatively, identified using a sequential testing approach. Once the number and locations of shifts in the transition pattern are determined, a second search phase identifies regimes with similar transition dynamics, which could indicate on convergent evolution. Using simulations, we study the performance of the developed model to detect shifts in patterns of chromosome-number evolution and demonstrate its applicability by analyzing the evolution of chromosome numbers within the Cyperaceae plant family. The developed model extends the capabilities of probabilistic models of chromosome-number evolution and should be particularly helpful for the analyses of large phylogenies that include multiple distinct subclades.

In this short review, we provide an update of recent developments in Kramers' theory of reaction rates. After a brief introduction stressing the importance of this theory initially developed for chemical reactions, we briefly present the main theoretical formalism starting from the generalized Langevin equation and continue by showing the main points of the modern Pollak, Grabert and Hänggi theory. Kramers' theory is then sketched for quantum and classical surface diffusion. As an illustration the surface diffusion of Na atoms on a Cu(110) surface is discussed showing escape rates, jump distributions and diffusion coefficients as a function of reduced friction. Finally, some very recent applications of turnover theory to different fields such as nanoparticle levitation, microcavity polariton dynamics and simulation of reaction in liquids are presented. We end with several open problems and future challenges faced up by Kramers turnover theory.

Social media data are transforming sustainability science. However, challenges from restrictions in data accessibility and ethical concerns regarding potential data misuse have threatened this nascent field. Here, we review the literature on the use of social media data in environmental and sustainability research. We find that they can play a novel and irreplaceable role in achieving the UN Sustainable Development Goals by allowing a nuanced understanding of human-nature interactions at scale, observing the dynamics of social-ecological change, and investigating the co-construction of nature values. We reveal threats to data access and highlight scientific responsibility to address trade-offs between research transparency and privacy protection, while promoting inclusivity. This contributes to a wider societal debate of social media data for sustainability science and for the common good.

The use of thin liquid films has expanded beyond lubrication and coatings, and into applications in actuators and adaptive optical elements. In contrast to their predecessors, whose dynamics can be typically captured by modelling infinite or periodic films, these applications are characterized by a finite amount of liquid in an impermeable domain. The global mass conservation constraint, together with common boundary conditions (e.g. pinning), create quantitatively and qualitatively different dynamics than those of infinite films. Mathematically, this manifests itself as a non-self-adjoint problem. This work presents a combined theoretical and experimental study for this problem. We provide a time-dependent closed-form analytical solution for the linearized non-self-adjoint system that arises from these boundary conditions. We highlight that, in contrast to self-adjoint problems, here, special care should be given to deriving the adjoint problem to reconstruct the solution based on the eigenfunctions properly. We compare these solutions with those obtained for permeable and periodic boundary conditions, representing common models for self-adjoint thin-film problems. We show that, while the initial dynamics is nearly identical, the boundary conditions eventually affect the film deformation as well as its response time. To experimentally illustrate the dynamics and to validate the theoretical model, we fabricated an experimental set-up that subjects a thin liquid film to a prescribed normal force distribution through dielectrophoresis, and used high-frame-rate digital holography to measure the film deformation in real time. The experiments agree well with the model and confirm that confined films exhibit a different behaviour which could not be predicted by existing models.

Quatsome nanovesicles, formed through the self-assembly of cholesterol (CHOL) and cetyltrimethylammonium bromide (CTAB) in water, have shown long-term stability in terms of size and morphology, while at the same time exhibiting high CHOL-CTAB intermolecular binding energies. We hypothesize that CHOL/CTAB quatsomes are indeed thermodynamically stable nanovesicles, and investigate the mechanism underlying their formation.

[EN] Nahal Efe is the largest and best preserved Middle PPNB site in the Negev (Israel), constituting a privileged data source for reconstructing the animal exploitation and subsistence strategies of the hunter-gatherer communities that inhabited the Negev 10,000 years ago. The preliminary results of the study of the faunal assemblage from excavation seasons 2015–2019 are presented in this paper. The zooarchaeological study indicates that during the Middle PPNB the community of hunter-gatherers at Nahal Efe exploited a wide spectrum of animal species, favoured by the great potential in terms of animal resources that the site’s surroundings offered, in a contact area between different eco-zones. Large and middle-sized ungulates, small carnivores, hares, and birds were captured, revealing the variability and adaptability of the hunting strategies of the community at Nahal Efe. Hunting, as a source of animal-based food, focused on the exploitation of ibex (C. nubiana) and gazelle (G. gazella) in similar proportions, which were most probably transported complete or almost complete to the site and intensively processed. Finally, another remarkable aspect of the faunal assemblage is the deposit of remains of at least three species of diurnal raptors inside a pit in one of the excavated residential buildings (Unit 10), evidencing the exploitation of birds of prey, most probably to acquire raw materials (e.g. feathers and talons). The presence of fox remains at the site also seems to be related to the procurement of raw materials, furs in this case, but its consumption is also suspected., [FR] Nahal Efe est le plus grand et le mieux préservé des sites du PPNB moyen du Néguev (Israël), constituant une source de données privilégiée pour reconstruire les stratégies d’exploitation animale et de subsistance des communautés de chasseurs-cueilleurs habitant le Néguev il y a 10 000 ans. Les résultats préliminaires de l’étude de l’assemblage faunique des saisons de fouilles 2015-2019 sont présentés dans cet article. L’étude zooarchéologique indique qu’au cours du PPNB moyen, la communauté de chasseurscueilleurs de Nahal Efe a exploité un large spectre d’espèces animales, favorisé par le grand potentiel en termes de ressources animales qu’offrait l’environnement du site, dans une zone de contact entre différentes écozones. Des ongulés de grande et moyenne taille, des petits carnivores, des lièvres et des oiseaux ont été capturés, révélant la variabilité et l’adaptabilité des stratégies de chasse de la communauté de Nahal Efe. La chasse, en tant que source d’aliments d’origine animale, s’est concentrée sur l’exploitation du bouquetin (C. nubiana) et de la gazelle (G. gazella) dans des proportions similaires, qui ont très probablement été transportés complets ou presque complets sur le site et transformés de manière intensive. Par ailleurs, un autre aspect remarquable de l’assemblage faunique est le dépôt de restes d’au moins trois espèces de rapaces diurnes à l’intérieur d’une fosse dans l’un des bâtiments résidentiels fouillés (unité 10), ce qui témoigne de l’exploitation des oiseaux de proie, très probablement pour acquérir des matières premières (par exemple des plumes et des serres). La présence de restes de renards sur le site semble également liée à l’acquisition de matières premières, en l’occurrence des fourrures, mais sa consommation est également suspectée.

Ultrafast light-induced spatiotemporal dynamics in metals in the form of electron and/or phonon heating is a fundamental physical process that has tremendous practical relevance. In particular, understanding the resulting lateral heat transport is of key importance for various (opto)electronic applications and thermal management but has attracted little attention. Here, by using scanning ultrafast thermo-modulation microscopy to track the spatiotemporal electron diffusion in thin gold films, we show that a few picoseconds after the optical pump there is unexpected heat flow from phonons to electrons, accompanied by negative effective thermal diffusion, characterized by shrinking of the spatial region with increased temperature. Peculiarly, this occurs on the intermediate time scale, between the few picosecond long thermalization stage and the many picosecond stage dominated by thermoacoustic vibrations. We accurately reproduced these experimental results by calculating the spatiotemporal photothermal response based on the two-temperature model and an improvement of the standard permittivity model for gold. Our findings facilitate the design of nanoscale thermal management strategies in photonic, optoelectronic, and high-frequency electronic devices.

Novel species of fungi described in this study include those from various countries as follows: Australia, Aschersonia mackerrasiae on whitefly, Cladosporium corticola on bark of Melaleuca quinquenervia, Penicillium nudgee from soil under Melaleuca quinquenervia, Pseudocercospora blackwoodiae on leaf spot of Persoonia falcata, and Pseudocercospora dalyelliae on leaf spot of Senna alata. Bolivia, Aspicilia lutzoniana on fully submersed siliceous schist in high-mountain streams, and Niesslia parviseta on the lower part and apothecial discs of Erioderma barbellatum onatwig. Brazil, Cyathus bonsai on decaying wood, Geastrum albofibrosum from moist soil with leaf litter, Laetiporus pratigiensis on a trunk of a living unknown hardwood tree species, and Scytalidium synnematicum on dead twigs of unidentified plant. Bulgaria, Amanita abscondita on sandy soil in a plantation of Quercus suber. Canada, Penicillium acericola on dead bark of Acer saccharum, and Penicillium corticola on dead bark of Acer saccharum. China, Colletotrichum qingyuanense on fruit lesion of Capsicum annuum. Denmark, Helminthosphaeria leptospora on corticioid Neohypochnicium cremicolor. Ecuador (Galapagos), Phaeosphaeria scalesiae on Scalesia sp. Finland, Inocybe jacobssonii on calcareouss oils in dry forests and park habitats. France, Cortinarius rufomyrrheus on sandy soil under Pinus pinaster, and Periconia neominutissima on leaves of Poaceae. India, Coprinopsis fragilis on decaying bark of logs, Filoboletus keralensis on unidentified woody substrate, Penicillium sankaranii from soil, Physisporinus tamilnaduensis on the trunk of Azadirachta indica, and Poronia nagaraholensis on elephant dung. Iran, Neosetophoma fic on infected leaves of Ficus elastica. Israel, Cnidariophoma eilatica (incl. Cnidariophoma gen. nov.) from Stylophora pistillata. Italy, Lyophyllum obscurum on acidic soil. Namibia, Aureobasidium faidherbiae on dead leaf of Faidherbia albida, and Aureobasidium welwitschiae on dead leaves of W

In this Reply, we show that criticisms of perturbation theory for grazing-incidence fast-atom diffraction (GIFAD) are ill-founded. We show explicitly that our formulation (W. Allison, S. Miret-Artés and E. Pollak, Phys. Chem. Chem. Phys., 2022, 24, 15851) provides a similar precision in describing the observed phenomena as ab initio potentials. Since that is the main criterion to distinguish between methods, it seems reasonable to conclude that the perturbation approach using a Morse-type potential reproduces the essential aspects of the dynamics correctly. In addition we expand on the historical context and summarize the physical insights provided by our methods.

We present photometric and spectroscopic observations of SN 2020bio, a double-peaked Type IIb supernova (SN) discovered within a day of explosion, primarily obtained by Las Cumbres Observatory and Swift. SN 2020bio displays a rapid and long-lasting initial decline throughout the first week of its light curve, similarly to other well-studied Type IIb SNe. This early-time emission is thought to originate from the cooling of the extended outer hydrogen-rich (H-rich) envelope of the progenitor star that is shock heated by the SN explosion. We compare SN 2020bio to a sample of other double-peaked Type IIb SNe in order to investigate its progenitor properties. Analytical model fits to the early-time emission give progenitor radius (≈100–1500 R⊙) and H-rich envelope mass (≈0.01–0.5 M⊙) estimates that are consistent with other Type IIb SNe. However, SN 2020bio displays several peculiarities, including (1) weak H spectral features indicating a greater amount of mass loss than other Type IIb progenitors; (2) an underluminous secondary light-curve peak that implies a small amount of synthesized 56Ni (MNi ≈0.02 M⊙); and (3) low-luminosity nebular [O i] and interaction-powered nebular features. These observations are more consistent with a lower-mass progenitor (MZAMS ≈ 12 M⊙) that was stripped of most of its H-rich envelope before exploding. This study adds to the growing diversity in the observed properties of Type IIb SNe and their progenitors.

Reliably scoring and ranking candidate models of protein complexes and assigning their oligomeric state from the structure of the crystal lattice represent outstanding challenges. A community-wide effort was launched to tackle these challenges. The latest resources on protein complexes and interfaces were exploited to derive a benchmark dataset consisting of 1677 homodimer protein crystal structures, including a balanced mix of physiological and non-physiological complexes. The non-physiological complexes in the benchmark were selected to bury a similar or larger interface area than their physiological counterparts, making it more difficult for scoring functions to differentiate between them. Next, 252 functions for scoring protein-protein interfaces previously developed by 13 groups were collected and evaluated for their ability to discriminate between physiological and non-physiological complexes. A simple consensus score generated using the best performing score of each of the 13 groups, and a cross-validated Random Forest (RF) classifier were created. Both approaches showed excellent performance, with an area under the Receiver Operating Characteristic (ROC) curve of 0.93 and 0.94, respectively, outperforming individual scores developed by different groups. Additionally, AlphaFold2 engines recalled the physiological dimers with significantly higher accuracy than the non-physiological set, lending support to the reliability of our benchmark dataset annotations. Optimizing the combined power of interface scoring functions and evaluating it on challenging benchmark datasets appears to be a promising strategy.

We present a UV spectroscopic study of ionized outflows in 21 active galactic nuclei (AGN), observed with the Hubble Space Telescope (HST). The targets of the Supermassive Black Hole Winds in X-rays (SUBWAYS) sample were selected with the aim to probe the parameter space of the underexplored AGN between the local Seyfert galaxies and the luminous quasars at high redshifts. Our targets, spanning redshifts of 0.1–0.4 and bolometric luminosities (Lbol) of 1045–1046 erg s−1, have been observed with a large multi-wavelength campaign using XMM-Newton, NuSTAR, and HST. Here, we model the UV spectra and look for different types of AGN outflows that may produce either narrow or broad UV absorption features. We examine the relations between the observed UV outflows and other properties of the AGN. We find that 60% of our targets show a presence of outflowing H I absorption, while 40% exhibit ionized outflows seen as absorption by either C IV, N V, or O VI. This is comparable to the occurrence of ionized outflows seen in the local Seyfert galaxies. All UV absorption lines in the sample are relatively narrow, with outflow velocities reaching up to −3300 km s−1. We did not detect any UV counterparts to the X-ray ultra-fast outflows (UFOs), most likely due to their being too highly ionized to produce significant UV absorption. However, all SUBWAYS targets with an X-ray UFO that have HST data demonstrate the presence of UV outflows at lower velocities. We find significant correlations between the column density (N) of the UV ions and Lbol of the AGN, with NH I decreasing with Lbol, while NO VI is increasing with Lbol. This is likely to be a photoionization effect, where toward higher AGN luminosities, the wind becomes more ionized, resulting in less absorption by neutral or low-ionization ions and more absorption by high-ionization ions. In addition, we find that N of the UV ions decreases as their outflow velocity increases. This may be explained by a mechanical power that is eva

The Laser Interferometer Space Antenna (LISA) has two scientific objectives of cosmological focus: to probe the expansion rate of the universe, and to understand stochastic gravitational-wave backgrounds and their implications for early universe and particle physics, from the MeV to the Planck scale. However, the range of potential cosmological applications of gravitational-wave observations extends well beyond these two objectives. This publication presents a summary of the state of the art in LISA cosmology, theory and methods, and identifies new opportunities to use gravitational-wave observations by LISA to probe the universe.

Conventional epitaxy plays a crucial role in current state-of-the art semiconductor technology, as it provides a path for accurate control at the atomic scale of thin films and nanostructures, to be used as the building blocks in nanoelectronics, optoelectronics, sensors, etc. Four decades ago, the terms “van der Waals” (vdW) and “quasi-vdW (Q-vdW) epitaxy” were coined to explain the oriented growth of vdW layers on 2D and 3D substrates, respectively. The major difference with conventional epitaxy is the weaker interaction between the epi-layer and the epi-substrates. Indeed, research on Q-vdW epitaxial growth of transition metal dichalcogenides (TMDCs) has been intense, with oriented growth of atomically thin semiconductors on sapphire being one of the most studied systems. Nonetheless, there are some striking and not yet understood differences in the literature regarding the orientation registry between the epi-layers and epi-substrate and the interface chemistry. Here we study the growth of WS2 via a sequential exposure of the metal and the chalcogen precursors in a metal–organic chemical vapor deposition (MOCVD) system, introducing a metal-seeding step prior to the growth. The ability to control the delivery of the precursor made it possible to study the formation of a continuous and apparently ordered WO3 mono- or few-layer at the surface of a c-plane sapphire. Such an interfacial layer is shown to strongly influence the subsequent quasi-vdW epitaxial growth of the atomically thin semiconductor layers on sapphire. Hence, here we elucidate an epitaxial growth mechanism and demonstrate the robustness of the metal-seeding approach for the oriented formation of other TMDC layers. This work may enable the rational design of vdW and quasi-vdW epitaxial growth on different material systems.

Plant domestication represents a major turning point in human history, resulting in the shift from a hunting/gathering/fishing-based economy to food production. Combining the analysis of ground stone tools and dental calculus, the PATH project aims to investigate dynamics of plant consumption, and the knowledge and toolkits involved in their processing.

Histones shape chromatin structure and the epigenetic landscape. H1, the most diverse histone in the human genome, has 11 variants. Due to the high structural similarity between the H1s, their unique functions in transferring information from the chromatin to mRNA-processing machineries have remained elusive. Here, we generated human cell lines lacking up to five H1 subtypes, allowing us to characterize the genomic binding profiles of six H1 variants. Most H1s bind to specific sites, and binding depends on multiple factors, including GC content. The highly expressed H1.2 has a high affinity for exons, whereas H1.3 binds intronic sequences. H1s are major splicing regulators, especially of exon skipping and intron retention events, through their effects on the elongation of RNA polymerase II (RNAPII). Thus, H1 variants determine splicing fate by modulating RNAPII elongation.

A centrally important question for researchers of media and communication is whether any type of individual-level behavior (e.g., digital media use) or normative attitude (e.g., norms of good citizenship) contributes to equalizing patterns of political participation, which often favor higher-status groups. Drawing on a two-wave repeated panel telephone survey that uses a nationally representative sampling frame, the study’s research design facilitates a robust analysis of how citizenship norms and digital media use affect political participation, with a focus on comparing higher- and lower-status groups. Specifically, the study analyzes a survey conducted in 2018 (Wave 1) and 2019 (Wave 2) among Israeli citizens, with a representative sampling of the generally higher-status Jewish majority and the lower-status Arab minority. The findings indicate that citizenship norms and digital media use in Wave 1 have a time-ordered positive effect on nonelectoral participation in Wave 2 for both Jewish and Arab citizens of Israel. However, the findings also show that for voting, the only statistically significant determinant is citizens’ Jewish or Arab identity. At a time when many democracies are facing severe challenges due to democratic erosion and social disintegration, this study contributes a normatively encouraging finding that key factors identified in the literature on citizenship norms and digital media use do not contribute to participatory inequalities between the Jewish majority and Arab minority in Israel. The findings also show, however, that it is essential to look beyond digital media use patterns to mobilize lower-status groups to become politically engaged in electoral-oriented politics.

DNA replication is a complex process tightly regulated to ensure faithful genome duplication, and its perturbation leads to DNA damage and genomic instability. Replication stress is commonly associated with slow and stalled replication forks. Recently, accelerated replication has emerged as a non-canonical form of replication stress. However, the molecular basis underlying fork acceleration is largely unknown. Here, we show that mutated HRAS activation leads to increased topoisomerase 1 (TOP1) expression, causing aberrant replication fork acceleration and DNA damage by decreasing RNA-DNA hybrids or R-loops. In these cells, restoration of TOP1 expression or mild replication inhibition rescues the perturbed replication and reduces DNA damage. Furthermore, TOP1 or RNaseH1 overexpression induces accelerated replication and DNA damage, highlighting the importance of TOP1 equilibrium in regulating R-loop homeostasis to ensure faithful DNA replication and genome integrity. Altogether, our results dissect a mechanism of oncogene-induced DNA damage by aberrant replication fork acceleration.

Cells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown. Here, we identify the poly-(ADP-ribose) polymerases PARP1 and PARP2 as constitutive interactors of XPC. Their interaction results in the XPC-stimulated synthesis of poly-(ADP-ribose) (PAR) by PARP1 at UV lesions, which in turn enables the recruitment and activation of the PAR-regulated chromatin remodeler ALC1. PARP2, on the other hand, modulates the retention of ALC1 at DNA damage sites. Notably, ALC1 mediates chromatin expansion at UV-induced DNA lesions, leading to the timely clearing of CPD lesions. Thus, we reveal how chromatin containing difficult-to-repair DNA lesions is primed for repair, providing insight into mechanisms of chromatin plasticity during GGR.

Empirical observations of how labs conduct research indicate that the adoption rate of open practices for transparent, reproducible, and collaborative science remains in its infancy. This is at odds with the overwhelming evidence for the necessity of these practices and their benefits for individual researchers, scientific progress, and society in general. To date, information required for implementing open science practices throughout the different steps of a research project is scattered among many different sources. Even experienced researchers in the topic find it hard to navigate the ecosystem of tools and to make sustainable choices. Here, we provide an integrated overview of community-developed resources that can support collaborative, open, reproducible, replicable, robust and generalizable neuroimaging throughout the entire research cycle from inception to publication and across different neuroimaging modalities. We review tools and practices supporting study inception and planning, data acquisition, research data management, data processing and analysis, and research dissemination. An online version of this resource can be found at https://oreoni.github.io. We believe it will prove helpful for researchers and institutions to make a successful and sustainable move towards open and reproducible science and to eventually take an active role in its future development.

DNA replication is a complex process tightly regulated to ensure faithful genome duplication, and its perturbation leads to DNA damage and genomic instability. Replication stress is commonly associated with slow and stalled replication forks. Recently, accelerated replication has emerged as a non-canonical form of replication stress. However, the molecular basis underlying fork acceleration is largely unknown. Here, we show that mutated HRAS activation leads to increased topoisomerase 1 (TOP1) expression, causing aberrant replication fork acceleration and DNA damage by decreasing RNA-DNA hybrids or R-loops. In these cells, restoration of TOP1 expression or mild replication inhibition rescues the perturbed replication and reduces DNA damage. Furthermore, TOP1 or RNaseH1 overexpression induces accelerated replication and DNA damage, highlighting the importance of TOP1 equilibrium in regulating R-loop homeostasis to ensure faithful DNA replication and genome integrity. Altogether, our results dissect a mechanism of oncogene-induced DNA damage by aberrant replication fork acceleration.

Cells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown. Here, we identify the poly-(ADP-ribose) polymerases PARP1 and PARP2 as constitutive interactors of XPC. Their interaction results in the XPC-stimulated synthesis of poly-(ADP-ribose) (PAR) by PARP1 at UV lesions, which in turn enables the recruitment and activation of the PAR-regulated chromatin remodeler ALC1. PARP2, on the other hand, modulates the retention of ALC1 at DNA damage sites. Notably, ALC1 mediates chromatin expansion at UV-induced DNA lesions, leading to the timely clearing of CPD lesions. Thus, we reveal how chromatin containing difficult-to-repair DNA lesions is primed for repair, providing insight into mechanisms of chromatin plasticity during GGR.

LIS1 (PAFAH1B1) plays a major role in the developing cerebral cortex, and haploinsufficient mutations cause human lissencephaly type 1. We have studied morphological and functional properties of the cerebral cortex of mutant mice harboring a deletion in the first exon of the mouse Lis1 (Pafah1b1) gene, which encodes for the LisH domain. The Lis1/sLis1 animals had an overall unaltered cortical structure but showed an abnormal distribution of cortical GABAergic interneurons (those expressing calbindin, calretinin, or parvalbumin), which mainly accumulated in the deep neocortical layers. Interestingly, the study of the oscillatory activity revealed an apparent inability of the cortical circuits to produce correct activity patterns. Moreover, the fast spiking (FS) inhibitory GABAergic interneurons exhibited several abnormalities regarding the size of the action potentials, the threshold for spike firing, the time course of the action potential after-hyperpolarization (AHP), the firing frequency, and the frequency and peak amplitude of spontaneous excitatory postsynaptic currents (sEPSC’s). These morphological and functional alterations in the cortical inhibitory system characterize the Lis1/sLis1 mouse as a model of mild lissencephaly, showing a phenotype less drastic than the typical phenotype attributed to classical lissencephaly. Therefore, the results described in the present manuscript corroborate the idea that mutations in some regions of the Lis1 gene can produce phenotypes more similar to those typically described in schizophrenic and autistic patients and animal models.

The exchange of off-resonant photons between quantum optical emitters in cavity QED or quantum nanophotonic setups induces interactions between them which can be harnessed for quantum information and simulation purposes. So far, these interactions have been mostly characterized for two-level emitters, which restrict their application to engineering quantum gates among qubits or simulating spin-1/2 quantum many-body models. Here, we show how to harness multilevel emitters with several optical transitions to engineer a wide class of photon-mediated interactions between effective spin-1 systems. We characterize their performance through analytical and numerical techniques and provide specific implementations based on the atomic level structure of Alkali atoms. Our results expand the quantum simulation toolbox available in such cavity QED and quantum nanophotonic setups and open up different ways of engineering entangling gates among qutrits.

Monocular polyplopia (ghost or multiple images) is a serious visual impediment for some people who report seeing two (diplopia), three (triplopia) or even more images. Polyplopia is expected to appear if the point spread function (PSF) has multiple intensity cores (a dense concentration of a large portion of the radiant flux contained in the PSF) relatively separated from each other, each of which contributes to a distinct image. We present a theory that assigns these multiple PSF cores to specific features of aberrated wavefronts, thereby accounting optically for the perceptual phenomenon of monocular polyplopia. The theory provides two major conclusions. First, the most likely event giving rise to multiple PSF cores is the presence of hyperbolic, or less probably elliptical, umbilic caustics (using the terminology of catastrophe optics). Second, those umbilic caustics formed on the retinal surface are associated with certain points of the wave aberration function, called cusps of Gauss, where the gradient of a curvature function vanishes. However, not all cusps of Gauss generate those umbilic caustics. We also provide necessary conditions for those cusps of Gauss to be fertile. To show the potential of this theoretical framework for understanding the nature and origin of polyplopia, we provide specific examples of ocular wave aberration functions that induce diplopia and triplopia. The polyplopia effects in these examples are illustrated by depicting the multi-core PSFs and the convolved retinal images for clinical letter charts, both through computer simulations and through experimental recording using an adaptive optics set-up. The number and location of cores in the PSF is thus a potentially useful metric for the existence and severity of polyplopia in spatial vision. These examples also help explain why physiological pupil constriction might reduce the incidence of ghosting and multiple images of daily objects that affect vision with dilated pupils. This mecha

In conventional Bardeen-Cooper-Schrieffer superconductors, Cooper pairs of electrons of opposite spin (i.e., singlet structure) form the ground state. Equal-spin triplet pairs (ESTPs), as in superfluid 3He, are of great interest for superconducting spintronics and topological superconductivity, yet remain elusive. Recently, odd-parity ESTPs were predicted to arise in (few-)monolayer superconducting NbSe2, from the noncollinearity between the out-of-plane Ising spin-orbit field (due to the lack of inversion symmetry in monolayer NbSe2) and an applied in-plane magnetic field. These ESTPs couple to the singlet order parameter at finite field. Using van der Waals tunnel junctions, we perform spectroscopy of superconducting NbSe2 flakes, of 2–25 monolayer thickness, measuring the quasiparticle density of states (DOS) as a function of applied in-plane magnetic field up to 33 T. In flakes ≲15 monolayers thick the DOS has a single superconducting gap. In these thin samples, the magnetic field acts primarily on the spin (vs orbital) degree of freedom of the electrons, and superconductivity is further protected by the Ising field. The superconducting energy gap, extracted from our tunneling spectra, decreases as a function of the applied magnetic field. However, in bilayer NbSe2, close to the critical field (up to 30 T, much larger than the Pauli limit), superconductivity appears to be more robust than expected from Ising protection alone. Our data can be explained by the above-mentioned ESTPs.

A remarkable number of SARS-CoV-2 variants and other as yet unmonitored lineages harbor amino-acid substitutions with the potential to modulate the interface between the spike receptor-binding domain (RBD) and its receptor ACE2. The naturally occurring Q498Y substitution, which is present in currently circulating SARS-CoV-2 variants, has drawn the attention of several investigations. While computational predictions and in vitro binding studies suggest that Q498Y increases the binding affinity of the spike protein for ACE2, experimental in vivo models of infection have shown that a triple mutant carrying the Q498Y replacement is fatal in mice. To accurately characterize the binding kinetics of the RBD Q498Y–ACE2 interaction, biolayer interferometry analyses were performed. A significant enhancement of the RBD–ACE2 binding affinity relative to a reference SARS-CoV-2 variant of concern carrying three simultaneous replacements was observed. In addition, the RBD Q498Y mutant bound to ACE2 was crystallized. Compared with the structure of its wild-type counterpart, the RBD Q498Y–ACE2 complex reveals the conservation of major hydrogen-bond interactions and a more populated, nonpolar set of contacts mediated by the bulky side chain of Tyr498 that collectively lead to this increase in binding affinity. In summary, these studies contribute to a deeper understanding of the impact of a relevant mutation present in currently circulating SARS-CoV-2 variants which might lead to stronger host–pathogen interactions.

Nanotubes of transition metal dichalcogenides such as WS2 and MoS2 offer unique quasi-1D properties and numerous potential applications. Replacing sulfur by selenium would yield ternary WS2(1–x)Se2x (0 ≤ x ≤ 1; WSSe) nanotubes, which are expected to reveal strong modulation in their absorption edge as a function of selenium content, xSe. Solid WO2.72 oxide nanowhiskers were employed as a sacrificial template to gain a high yield of the nanotubes with a rather uniform size distribution. Though sulfur and selenium belong to the same period, their chemical reactivity with oxide nanowhiskers differed appreciably. Here, the closed ampoule technique was utilized to achieve the completion of the solid–vapor reaction in short time scales instead of the conventional flow reactor method. The structure and chemical composition of the nanotubes were analyzed in detail. X-ray and electron diffractions indicated a systematic modulation of the WSSe lattice upon increasing the selenium content. Detailed chemical mapping showed that the sulfur and selenium atoms are distributed in random positions on the anion lattice site of the nanotubes. The optical excitonic features and absorption edges of the WSSe nanotubes do not vary linearly with the composition xSe, which was further confirmed by density functional theory calculations. The WSSe nanotubes were shown to exhibit strong light–matter interactions forming exciton–polariton quasiparticles, which was corroborated by finite-difference time-domain simulations. Transient absorption analysis permitted following the excited state dynamics and elucidating the mechanism of the strong coupling. Thus, nanotubes of the ternary WSSe alloys offer strong band gap tunability, which would be useful for multispectral vision devices and other optoelectronic applications.

Responses of terrestrial ecosystems to climate change have been explored in many regions worldwide. While continued drying and warming may alter process rates and deteriorate the state and performance of ecosystems, it could also lead to more fundamental changes in the mechanisms governing ecosystem functioning. Here we argue that climate change will induce unprecedented shifts in these mechanisms in historically wetter climatic zones, towards mechanisms currently prevalent in dry regions, which we refer to as ‘dryland mechanisms’. We discuss 12 dryland mechanisms affecting multiple processes of ecosystem functioning, including vegetation development, water flow, energy budget, carbon and nutrient cycling, plant production and organic matter decomposition. We then examine mostly rare examples of the operation of these mechanisms in non-dryland regions where they have been considered irrelevant at present. Current and future climate trends could force microclimatic conditions across thresholds and lead to the emergence of dryland mechanisms and their increasing control over ecosystem functioning in many biomes on Earth.

Type Ia supernovae are thermonuclear explosions of white dwarf stars. They play a central role in the chemical evolution of the Universe and are an important measure of cosmological distances. However, outstanding questions remain about their origins. Despite extensive efforts to obtain natal information from their earliest signals, observations have thus far failed to identify how the majority of them explode. Here, we present infant-phase detections of SN 2018aoz from a very low brightness of −10.5 AB absolute magnitude, revealing a hitherto unseen plateau in the B band that results in a rapid redward colour evolution between 1.0 and 12.4 hours after the estimated epoch of first light. The missing B-band flux is best explained by line-blanket absorption from Fe-peak elements in the outer 1% of the ejected mass. The observed B − V colour evolution of the supernova also matches the prediction from an over-density of Fe-peak elements in the same outer 1% of the ejected mass, whereas bluer colours are expected from a purely monotonic distribution of Fe-peak elements. The presence of excess nucleosynthetic material in the extreme outer layers of the ejecta points to enhanced surface nuclear burning or extended subsonic mixing processes in some normal type Ia SN explosions.