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10.1073/pnas.1218599110 | 104,253,229 | Immunoresponsive gene 1 ( Irg1 ) is highly expressed in mammalian macrophages during inflammation, but its biological function has not yet been elucidated. Here, we identify Irg1 as the gene coding for an enzyme producing itaconic acid (also known as methylenesuccinic acid) through the decarboxylation of cis -aconitate... | 10.1038/s42255-022-00694-7 | This paper reports the discovery of IRG1 as the enzyme that catalyses the conversion of cis -aconitate to itaconic acid in mammals. |
10.1126/science.1172051 | 83,552,167 | Bright Shiny Beetles The beautiful iridescent colors found on the wings of butterflies and on the bodies of beetles have attracted the attention of brilliant minds over the past centuries, starting with Newton, who understood that these colors must involve “thin film structures.” In 1911 Michelson described the metalli... | 10.1038/s44222-022-00014-4 | This article reports the ability of the scarab beetle to reflect structural colour from its external surfaces in the form of left-handed CPL. |
10.1126/science.aba0980 | 20,854,123 | Surfactant-assisted seeded growth of metal nanoparticles (NPs) can be engineered to produce anisotropic gold nanocrystals with high chiroptical activity through the templating effect of chiral micelles formed in the presence of dissymmetric cosurfactants. Mixed micelles adsorb on gold nanorods, forming quasihelical pat... | 10.1038/s44222-022-00014-4 | This article reports the use of mixed chiral micelles as a template for the synthesis of chiral gold nanorods that exhibit plasmon modes with high dissymmetry factors. |
10.1073/pnas.1324214111 | 103,753,166 | Significance A modular 3D brain-like cortical tissue is constructed with silk protein-based scaffold and ECM composite and primary cortical neurons. This tissue responds in vitro with biochemical and electrophysiological outcomes, mimicking observations of brain homeostasis and mechanical injury responses. | 10.1038/s44222-023-00027-7 | This paper presents the first functional, multi-compartmental, scaffold-based cortical CNS model comprising primary cortical neurons from rodents embedded in a porous silk fibroin scaffold and collagen hydrogel |
10.1126/science.aax2537 | 20,784,223 | The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 ( NOVA1 ) plays a key role in neural development and function. NOVA1 also includes a protein-coding difference between the modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance of an amino a... | 10.1038/s44222-023-00027-7 | This article reports the creation of brain organoids with archaic gene variants found in non-human hominins (Neanderthals and Denisovans), enabling unprecedented comparative analyses of traits separating humans and extinct relatives in 3D CNS tissues |
10.3389/fnano.2021.643507 | 84,038,820 | The therapy of neural nerve injuries that involve the disruption of axonal pathways or axonal tracts has taken a new dimension with the development of tissue engineering techniques. When peripheral nerve injury (PNI), spinal cord injury (SCI), traumatic brain injury (TBI), or neurodegenerative disease occur, the intric... | 10.1038/s44222-023-00027-7 | This review provides a comprehensive and up-to-date discussion of biomaterials and synthetic materials for neural tissue engineering |
10.1126/scitranslmed.3003453 | 41,528,593 | Mucus-penetrating particles improve drug delivery to the mucosal surface of the mouse vagina and deliver acyclovir for enhanced protection against vaginal herpes infection in mice. | 10.1038/s44222-023-00040-w | This article reports the design of mucus-penetrating nanoparticles for uniform drug delivery to the vaginal epithelium, and more effective protection against herpes simplex virus 2 challenge in mice than the soluble drug. |
10.1126/sciadv.abm1032 | 136,143,616 | Proinflammatory cytokines have been approved by the Food and Drug Administration for the treatment of metastatic melanoma and renal carcinoma. However, effective cytokine therapy requires high-dose infusions that can result in antidrug antibodies and/or systemic side effects that limit long-term benefits. To overcome t... | 10.1038/s44222-023-00040-w | This article reports the development of an interleukin-2 cytokine factory with alginate microcapsules for reducing ovarian cancer tumour burden following intraperitoneal administration. |
10.1126/scitranslmed.abc6245 | 125,125,857 | Inflammation contributes to nearly 4 million global premature births annually. Here, we used a mouse model of intrauterine inflammation to test clinically used formulations, as well as engineered nanoformulations, for the prevention of preterm birth (PTB). We observed that neither systemic 17a-hydroxyprogesterone capro... | 10.1038/s44222-023-00040-w | This article reports the use of mucoinert nanosuspensions of histone deacetylase inhibitors for preventing preterm birth and promoting birth of live pups with neurotypical development in a murine model of intrauterine inflammation. |
10.1126/sciadv.1600349 | 59,298,734 | The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus. As enhancement of placental growth and function can alleviate maternal symptoms and improve fetal growth in animal models, we have developed a method for targeted delivery of pa... | 10.1038/s44222-023-00040-w | This article reports the design of tumour-homing peptide-targeted liposomes for in vivo accumulation in the placenta and demonstrates that delivery of insulin-like growth factor 2 can improve fetal weight distribution in a murine model of fetal growth restriction. |
10.1126/sciadv.aba1028 | 59,255,542 | Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)–mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small... | 10.1038/s44222-023-00040-w | This article reports the identification of ionizable lipid nanoparticle formulations for mRNA delivery to the fetal liver, lungs and intestines following vitelline vein administration in murine fetuses. |
10.1038/s41467-018-04894-2 | 125,125,995 | Abstract Genetic diseases can be diagnosed early during pregnancy, but many monogenic disorders continue to cause considerable neonatal and pediatric morbidity and mortality. Early intervention through intrauterine gene editing, however, could correct the genetic defect, potentially allowing for normal organ developmen... | 10.1038/s44222-023-00040-w | This article reports safe and effective in utero gene editing in murine β-thalassemia fetuses following vitelline vein administration of polymeric nanoparticles encapsulating peptide nucleic acids and donor DNAs. |
10.1093/acrefore/9780190236557.013.847 | 152,189,044 | Perceptual learning is the training-induced improvement in the accuracy or speed of relevant perceptual decisions about what is seen, heard, or felt. It occurs in all sensory modalities and in most tasks. The magnitude and generalizability of this learning may, however, depend on the stimulus modality, the level of sen... | 10.1038/s44159-022-00107-2 | This book provides a systematic treatment of the major phenomena, physiological basis, computational models and applications of perceptual learning in the context of brain plasticity and balancing system stability and adaptability |
10.1073/pnas.88.11.4966 | 103,782,850 | In terms of functional anatomy, where does learning occur when, for a basic visual discrimination task, performance improves with practice (perceptual learning)? We report remarkable long-term learning in a simple texture discrimination task where learning is specific for retinal input. This learning is (i) local (in a... | 10.1038/s44159-022-00107-2 | This paper reports long-term location-specific learning in a texture discrimination task and proposes training-induced representation enhancement in the primary visual cortex |
10.1002/9781119170174.epcn217 | 32,930,322 | Abstract Perceptual learning refers to a long‐term change in the ability to extract perceptual information from the environment that arises via experience or practice. In this chapter, we first explore many examples of perceptual learning in relatively simple as well as in more complex tasks. Furthermore, we do so acro... | 10.1038/s44159-022-00107-2 | This chapter explores perceptual learning in relatively simple and more complex tasks across sensory modalities (including vision, audition, touch, taste and smell) |
10.1146/annurev-psych-010814-015214 | 83,245,367 | Visual perceptual learning (VPL) is long-term performance increase resulting from visual perceptual experience. Task-relevant VPL of a feature results from training of a task on the feature relevant to the task. Task-irrelevant VPL arises as a result of exposure to the feature irrelevant to the trained task. At least t... | 10.1038/s44159-022-00107-2 | This paper proposes feature-based plasticity that enhances the representation of the learned features and task-based plasticity that improves the processing of the trained task to explain task-relevant and task-irrelevant perceptual learning |
10.7551/mitpress/5295.001.0001 | 60,079,287 | An overview of the field of perceptual learning—the study of the permanent changes in cortical structure caused by external stimuli. Perceptual learning is the specific and relatively permanent modification of perception and behavior following sensory experience. It encompasses parts of the learning process that are in... | 10.1038/s44159-022-00107-2 | This edited volume presents advances made in the field of perceptual learning from 1992 to 2002 |
10.3389/fnins.2021.734970 | 134,044,230 | Pathologies affecting central vision, and macular degeneration (MD) in particular, represent a growing health concern worldwide, and the leading cause of blindness in the Western World. To cope with the loss of central vision, MD patients often develop compensatory strategies, such as the adoption of a Preferred Retina... | 10.1038/s44159-022-00107-2 | This paper reviews non-invasive rehabilitative interventions for central vision loss and suggests an integrated approach that combines vision, oculomotor and cognitive training |
10.1073/pnas.1312552110 | 82,924,141 | Improvements in performance on visual tasks due to practice are often specific to a retinal position or stimulus feature. Many researchers suggest that specific perceptual learning alters selective retinotopic representations in early visual analysis. However, transfer is almost always practically advantageous, and it ... | 10.1038/s44159-022-00107-2 | This paper introduces a novel network architecture with both location-specific and location-independent representations to model partial feature and partial location specificity in perceptual learning |
10.1126/science.aar3617 | 62,535,159 | Magnetic insulators are a key resource for next-generation spintronic and topological devices. The family of layered metal halides promises varied magnetic states, including ultrathin insulating multiferroics, spin liquids, and ferromagnets, but device-oriented characterization methods are needed to unlock their potent... | 10.1038/s42254-019-0110-y | The first demonstration of spin filtering and giant tunnel magnetoresistance using 2D CrI 3 as a tunnel barrier |
10.1038/s41467-018-04953-8 | 29,316,146 | Abstract Magnetic layered van der Waals crystals are an emerging class of materials giving access to new physical phenomena, as illustrated by the recent observation of 2D ferromagnetism in Cr 2 Ge 2 Te 6 and CrI 3 . Of particular interest in semiconductors is the interplay between magnetism and transport, which has re... | 10.1038/s42254-019-0110-y | The first demonstration of spin filtering and giant tunnel magnetoresistance using 2D CrI 3 as a tunnel barrier |
10.1126/science.aar4851 | 62,212,922 | Magnetic multilayer devices that exploit magnetoresistance are the backbone of magnetic sensing and data storage technologies. Here, we report multiple-spin-filter magnetic tunnel junctions (sf-MTJs) based on van der Waals (vdW) heterostructures in which atomically thin chromium triiodide (CrI 3 ) acts as a spin-filter... | 10.1038/s42254-019-0110-y | The first demonstration of spin filtering and giant tunnel magnetoresistance using 2D CrI 3 as a tunnel barrier |
10.1038/ncomms9260 | 104,359,440 | Abstract Topological insulators do not allow conduction in the bulk, yet they support edge modes that travel along the boundary only in one direction, determined by the carried electron spin, with inherent robustness to defects and disorder. Topological insulators have inspired analogues in photonics and optics, in whi... | 10.1038/s42254-019-0030-x | Together with Yang et al. (2015) and Ni et al. (2015), this paper proposes using circulation of a fluid to break time-reversal symmetry to realize the quantum Hall effect in sound |
10.1073/pnas.1507413112 | 107,155,393 | Topological mechanical metamaterials are artificial structures whose unusual properties are protected very much like their electronic and optical counterparts. Here, we present an experimental and theoretical study of an active metamaterial—composed of coupled gyroscopes on a lattice—that breaks time-reversal symmetry.... | 10.1038/s42254-019-0030-x | This work uses electric motors to break time-reversal symmetry to realize a mechanical Chern insulator |
10.1126/science.aab0239 | 20,701,439 | A topological insulator, as originally proposed for electrons governed by quantum mechanics, is characterized by a dichotomy between the interior and the edge of a finite system: The bulk has an energy gap, and the edges sustain excitations traversing this gap. However, it has remained an open question whether the same... | 10.1038/s42254-019-0030-x | This is the first realization of the analogy of the QSH effect in a mechanical system |
10.1038/ncomms11744 | 41,749,265 | Abstract The unique conduction properties of condensed matter systems with topological order have recently inspired a quest for the similar effects in classical wave phenomena. Acoustic topological insulators, in particular, hold the promise to revolutionize our ability to control sound, allowing for large isolation in... | 10.1038/s42254-019-0030-x | This is a theoretical and numerical study of a Floquet topological insulator for sound |
10.1101/2021.04.26.441262 | 83,163,284 | Abstract The human brain vasculature is of vast medical importance: its dysfunction causes disability and death, and the specialized structure it forms—the blood-brain barrier—impedes treatment of nearly all brain disorders. Yet, no molecular atlas of the human brain vasculature exists. Here, we develop Vessel Isolatio... | 10.1038/s44161-021-00014-4 | This study identified a human atlas of brain vasculature with cell-specific gene expression datasets in BBB endothelial cells, mural cell pericytes and other vascular-associated cell types |
10.1126/scitranslmed.aaw8954 | 41,283,230 | A growing body of evidence shows that epileptic activity is frequent but often undiagnosed in patients with Alzheimer’s disease (AD) and has major therapeutic implications. Here, we analyzed electroencephalogram (EEG) data from patients with AD and found an EEG signature of transient slowing of the cortical network tha... | 10.1038/s44161-021-00014-4 | This study identified paroxysmal slow-wave events as an electroencephalogram manifestation of nonconvulsive seizures in patients with AD and suggested that BBB pathology is an underlying mechanism and a promising therapeutic target |
10.1126/science.aaa9297 | 83,509,089 | Weyl physics emerges in the laboratory Weyl fermions—massless particles with half-integer spin—were once mistakenly thought to describe neutrinos. Although not yet observed among elementary particles, Weyl fermions may exist as collective excitations in so-called Weyl semimetals. These materials have an unusual band st... | 10.1038/s42254-019-0088-5 | A pioneering ARPES study reporting the experimental discovery of Weyl fermions in condensed matter systems |
10.1126/science.1239834 | 41,702,484 | Topological Replicas When a periodic perturbation couples strongly to electrons in a solid, replicas of the original electronic levels are predicted to develop at certain energies—the so-called Floquet-Bloch states. Such conditions can be achieved by shining light on a solid, but the effect is challenging to observe. W... | 10.1038/s42254-019-0088-5 | A time-resolved ARPES study reporting the observation of Floquet–Bloch states on the surface of Bi 2 Se 3 |
10.1126/science.1245085 | 62,621,248 | A 3D Graphene? Discoveries of materials with exciting electronic properties have propelled condensed matter physics over the past decade. Two of the best-known examples, graphene and topological insulators, have something in common: a linear energy-momentum relationship—the Dirac dispersion—in their two-dimensional (2D... | 10.1038/s42254-019-0088-5 | Experimental study reporting the discovery of 3D massless Dirac fermions in a topological Dirac semimetal |
10.1126/science.aan4596 | 62,023,731 | A topological superconductor A promising path toward topological quantum computing involves exotic quasiparticles called the Majorana bound states (MBSs). MBSs have been observed in heterostructures that require careful nanofabrication, but the complexity of such systems makes further progress tricky. Zhang et al. iden... | 10.1038/s42254-019-0088-5 | Study in which high-resolution laser-ARPES measurements provide direct evidence for the existence of topological superconductivity on the (001) surface of an iron-based superconductor |
10.1111/boc.201600024 | 83,171,707 | Electron microscopy (EM) has been a key imaging method to investigate biological ultrastructure for over six decades. In recent years, novel volume EM techniques have significantly advanced nanometre‐scale imaging of cells and tissues in three dimensions. Previously, this had depended on the slow and error‐prone manual... | 10.1038/s43586-022-00131-9 | This comprehensive review of the main SEM-based vEM techniques is a must read for those who are starting in the field, as the authors clearly address the potential and limitations of FIB-SEM, SBF-SEM and array tomography, from sample preparation to image analysis |
10.1038/ncomms8923 | 41,719,019 | Abstract Large-scale connectomics requires dense staining of neuronal tissue blocks for electron microscopy (EM). Here we report a large-volume dense en-bloc EM staining protocol that overcomes the staining gradients, which so far substantially limited the reconstructable volumes in three-dimensional (3D) EM. Our proto... | 10.1038/s43586-022-00131-9 | This important update in sample preparations for vEM imaging addresses the uneven staining gradients of samples up to 1 mm in diameter |
10.1242/jcs.181842 | 41,450,471 | Intravital microscopy provides dynamic understanding of multiple cell biological processes, but its limited resolution has so far precluded structural analysis. Because it is difficult to capture rare and transient events, only few attempts were made to observe specific developmental and pathological processes in anima... | 10.1038/s43586-022-00131-9 | This work demonstrates the power of multimodal correlative microscopy for identifying, targeting and acquiring a specific ROI within a large sample volume |
10.1101/2021.05.29.446289 | 103,666,104 | Abstract We acquired a rapidly preserved human surgical sample from the temporal lobe of the cerebral cortex. We stained a 1 mm 3 volume with heavy metals, embedded it in resin, cut more than 5000 slices at ∼30 nm and imaged these sections using a high-speed multibeam scanning electron microscope. We used computational... | 10.1038/s43586-022-00131-9 | This work is a tour de force on vEM and automated segmentation of a cubic millimetre of human cerebral cortex with excellent ultrastructural preservation that allows analysis of human cortical circuits at the synaptic level, including identification of main neuron types, glia and blood vessels |
10.1111/j.1600-0854.2008.00859.x | 29,180,699 | The zebrafish is a powerful vertebrate system for cell and developmental studies. In this study, we have optimized methods for fast freezing and processing of zebrafish embryos for electron microscopy (EM). We show that in the absence of primary chemical fixation, excellent ultrastructure, preservation of green fluores... | 10.1038/s43586-022-00131-9 | This work is one of the first demonstrations of preservation of fluorescent protein emission after embedding in resin for electron microscopy, raising the possibility of high-accuracy post-embedding vCLEM |
10.1083/jcb.202010039 | 100,504,608 | Microtubules play a major role in intracellular trafficking of vesicles in endocrine cells. Detailed knowledge of microtubule organization and their relation to other cell constituents is crucial for understanding cell function. However, their role in insulin transport and secretion is under debate. Here, we use FIB-SE... | 10.1038/s43586-022-00131-9 | This compelling work illustrates the power of FIB-SEM imaging at a 4 nm isovoxel resolution — the fine detail of the most intimate parts of a mammalian endocrine cell is depicted and state-of-the-art morphometric analysis enables the description of inter-organelle interactions |
10.1101/2020.08.21.260984 | 101,179,925 | Abstract Nervous systems coordinate effectors across the body during movements. We know little about the cellular-level structure of synaptic circuits for such body-wide control. Here we describe the whole-body synaptic connectome and cell-type complement of a three-segmented larva of the marine annelid Platynereis dum... | 10.1038/s43586-022-00131-9 | This work is a fascinating example of the power of vEM to obtain the complete whole-body synaptic connectome of the larva of a marine annelid, including the specific pathways from sensory neurons to different effector systems. This approach addresses how synaptic circuits control the entire body of the animal |
10.1073/pnas.1221359110 | 38,211,741 | Hominins with morphology similar to present-day humans appear in the fossil record across Eurasia between 40,000 and 50,000 y ago. The genetic relationships between these early modern humans and present-day human populations have not been established. We have extracted DNA from a 40,000-y-old anatomically modern human ... | 10.1038/s43586-020-00011-0 | This study presents the first application of in-solution target enrichment at the genome scale and describes sequence for a full chromosome of an approximately 40,000-year-old anatomically modern human from China |
10.1073/pnas.1314445110 | 104,387,887 | Significance Outside of permafrost, no contiguous DNA sequences have been generated from material older than ∼120,000 y. By improving our ability to sequence very short DNA fragments, we have recovered the mitochondrial genome sequence of a >300,000-y-old cave bear from Sima de los Huesos, a Spanish cave site that i... | 10.1038/s43586-020-00011-0 | This study reports a new DNA extraction method from ancient osseous remains that is tailored to the ultrashort and extensively damaged nature of aDNA molecules. This methodology allowed the retrieval of full mitochondrial genome sequences from 300,000-year-old cave bear specimens preserved in Atapuerca, Spain |
10.1038/ncomms6257 | 83,551,917 | Abstract The Great Hungarian Plain was a crossroads of cultural transformations that have shaped European prehistory. Here we analyse a 5,000-year transect of human genomes, sampled from petrous bones giving consistently excellent endogenous DNA yields, from 13 Hungarian Neolithic, Copper, Bronze and Iron Age burials i... | 10.1038/s43586-020-00011-0 | This study reports the first matched empirical evidence establishing better DNA preservation rates in petrosal bones, which paved the way for future studies at the population scale, and also presents complete genomes of Mesolithic hunter–gatherers and Neolithic farmers in the Caucasus, supporting direct early contact b... |
10.1126/science.281.5375.402 | 122,860,503 | DNA from excrements can be amplified by means of the polymerase chain reaction. However, this has not been possible with ancient feces. Cross-links between reducing sugars and amino groups were shown to exist in a Pleistocene coprolite from Gypsum Cave, Nevada. A chemical agent, N -phenacylthiazolium bromide, that clea... | 10.1038/s43586-020-00011-0 | This article reports the first application of next-generation DNA sequencing to ancient specimens and describes the metagenomic nature of paleontological remains together with megabase-scale data from the woolly mammoth genome |
10.1126/science.1084114 | 62,577,607 | Genetic analyses of permafrost and temperate sediments reveal that plant and animal DNA may be preserved for long periods, even in the absence of obvious macrofossils. In Siberia, five permafrost cores ranging from 400,000 to 10,000 years old contained at least 19 different plant taxa, including the oldest authenticate... | 10.1038/s43586-020-00011-0 | This article reports the first analysis of environmental DNA prior to the advent of next-generation DNA sequencing and establishes the long-term DNA persistence of paleocommunities within sediments |
10.1073/pnas.0704665104 | 123,031,244 | High-throughput direct sequencing techniques have recently opened the possibility to sequence genomes from Pleistocene organisms. Here we analyze DNA sequences determined from a Neandertal, a mammoth, and a cave bear. We show that purines are overrepresented at positions adjacent to the breaks in the ancient DNA, sugge... | 10.1038/s43586-020-00011-0 | This article presents the first statistical model of post-mortem DNA degradation and its impact on nucleotide misincorporation patterns, which provides the basis of important criteria for data authentication |
10.1098/rstb.2013.0624 | 80,321,051 | The challenge of sequencing ancient DNA has led to the development of specialized laboratory protocols that have focused on reducing contamination and maximizing the number of molecules that are extracted from ancient remains. Despite the fact that success in ancient DNA studies is typically obtained by screening many ... | 10.1038/s43586-020-00011-0 | This study reports the first method for DNA library preparation that is compatible with full automation and also describes various approaches aimed at authenticating data while minimizing the impact of post-mortem DNA misincorporation on downstream analyses |
10.1534/genetics.112.145037 | 20,852,835 | Abstract Population mixture is an important process in biology. We present a suite of methods for learning about population mixtures, implemented in a software package called ADMIXTOOLS, that support formal tests for whether mixture occurred and make it possible to infer proportions and dates of mixture. We also descri... | 10.1038/s43586-020-00011-0 | This article describes the statistical methodology forming the core of most subsequent aDNA studies and aims at investigating population structure and admixture patterns |
10.1073/pnas.1602248113 | 61,461,836 | Protein structure determination by proton-detected magic-angle spinning (MAS) NMR has focused on highly deuterated samples, in which only a small number of protons are introduced and observation of signals from side chains is extremely limited. Here, we show in two fully protonated proteins that, at 100-kHz MAS and abo... | 10.1038/s43586-020-00002-1 | This paper describes the first de novo structure obtained from 1 H-detected solid-state NMR experiments |
10.1126/science.aaa6111 | 104,000,114 | A hierarchy of protein motions Functioning proteins are not static but explore complex conformational energy landscapes. Lewandowski et al. used multinuclear solid-state nuclear magnetic resonance experiments to measure protein motion over a broad range of temperatures and time scales. Above 160 K there was a strong co... | 10.1038/s43586-020-00002-1 | This study provides a quantitative analysis of the coupling of protein and solvent dynamics using relaxation NMR spectroscopy |
10.1038/s41467-018-08252-0 | 41,467,082 | Abstract Lignin is a complex aromatic biopolymer that strengthens and waterproofs plant secondary cell walls, enabling mechanical stability in trees and long-distance water transport in xylem. Lignin removal is a key step in paper production and biomass conversion to biofuels, motivating efforts to re-engineer lignin b... | 10.1038/s43586-020-00002-1 | This solid-state NMR study provides the first comprehensive molecular-level structural insights into lignin–polysaccharide interactions in plant secondary cell walls |
10.1073/pnas.1009219107 | 103,821,657 | Nanocrystals of apatitic calcium phosphate impart the organic-inorganic nanocomposite in bone with favorable mechanical properties. So far, the factors preventing crystal growth beyond the favorable thickness of ca . 3 nm have not been identified. Here we show that the apatite surfaces are studded with strongly bound c... | 10.1038/s43586-020-00002-1 | This study employs 13 C chemical shifts and 13 C– 31 P distance NMR spectroscopy experiments to show that the calcium phosphate surfaces in bone are studded with citrate molecules, which stabilize the apatite nanocrystals in bone |
10.1126/science.aac7730 | 41,477,270 | Solving the problems with Li-air batteries Li-air batteries come as close as possible to the theoretical limits for energy density in a battery. By weight, this is roughly 10 times higher than conventional lithium-ion batteries and would be sufficient to power cars with a range comparable to those with gasoline engines... | 10.1038/s43586-020-00002-1 | This paper describes how to overcome key challenges in engineering of lithium–air batteries and the use of 7 Li and 1 H NMR spectroscopy to determine the discharge products and elucidate the origin of protons in the formed LiOH |
10.1126/science.1238339 | 20,415,091 | We determined the heterogeneous mesoscale spatial apportionment of functional groups in a series of multivariate metal-organic frameworks (MTV-MOF-5) containing BDC (1,4-benzenedicarboxylate) linkers with different functional groups—B (BDC-NH 2 ), E (BDC-NO 2 ), F [(BDC-(CH 3 ) 2 ], H [BDC-(OC 3 H 5 ) 2 ], and I [BDC-(... | 10.1038/s43586-020-00002-1 | This paper shows how solid-state NMR combined with molecular simulations can map the spatial distributions of linkers in multivariate metal–organic framework materials as random, well-mixed or clustered |
10.1002/ange.201803397 | 103,915,751 | Abstract Increasing greenhouse gas emissions have resulted in greater motivation to find novel carbon dioxide (CO 2 ) reduction technologies, where the reduction of CO 2 to valuable chemical commodities is desirable. Molybdenum‐dependent formate dehydrogenase (Mo‐FDH) from Escherichia coli is a metalloenzyme that is ab... | 10.1038/s41929-019-0408-2 | The CO 2 fixation performed by the cobaltocene functionalized poly allylamine redox polymer immobilized formate dehydrogenase achieved almost 100 Faradaic efficiency |
10.1002/anie.201612500 | 40,767,532 | Abstract Nitrogenases are the only enzymes known to reduce molecular nitrogen (N 2 ) to ammonia (NH 3 ). By using methyl viologen ( N , N ′‐dimethyl‐4,4′‐bipyridinium) to shuttle electrons to nitrogenase, N 2 reduction to NH 3 can be mediated at an electrode surface. The coupling of this nitrogenase cathode with a bioa... | 10.1038/s41929-019-0408-2 | Bioelectrochemical N 2 fixation based on nitrogenase powered by hydrogen fuel cells was developed in this study |
10.1073/pnas.1706371114 | 61,603,413 | We demonstrate the synthesis of NH 3 from N 2 and H 2 O at ambient conditions in a single reactor by coupling hydrogen generation from catalytic water splitting to a H 2 -oxidizing bacterium Xanthobacter autotrophicus , which performs N 2 and CO 2 reduction to solid biomass. Living cells of X. autotrophicus may be dire... | 10.1038/s41929-019-0408-2 | The inorganic–biological hybrid bioelectrocatalytic system fixes atmospheric N 2 into NH 3 or soluble biomass with high fluxes and energy efficiency |
10.1073/pnas.94.25.13554 | 38,730,187 | The large potential of redox enzymes to carry out formation of high value organic compounds motivates the search for innovative strategies to regenerate the cofactors needed by their biocatalytic cycles. Here, we describe a bioreactor where the reducing power to the cycle is supplied directly to purified cytochrome CYP... | 10.1038/s41929-019-0408-2 | A bioreactor where the reducing equivalent to the cycle is supplied to P450cam through putidaredoxin with an antimony doped tin oxide working electrode |
10.1002/cssc.201900413 | 32,972,795 | Abstract Chiral alcohols constitute important building blocks that can be produced enantioselectively by using nicotinamide adenine dinucleotide (phosphate) [NAD(P)H]‐dependent oxidoreductases. For NAD(P)H regeneration, electricity delivers the cheapest reduction equivalents. Enzymatic electrosynthesis suffers from cof... | 10.1038/s41929-019-0408-2 | Demonstrated microbial electrosynthesis using resting E. coli as a biocatalytic chassis for a production platform towards fine chemicals through electric power |
10.1002/anie.201509653 | 26,867,967 | Abstract Biorefineries aim to convert biomass into a spectrum of products ranging from biofuels to specialty chemicals. To achieve economically sustainable conversion, it is crucial to streamline the catalytic and downstream processing steps. In this work, a route that combines bio‐ and electrocatalysis to convert gluc... | 10.1038/s41929-019-0408-2 | This study reported a route that combines bio- and electrocatalysis to convert glucose into bio-based unsaturated nylon-6,6 |
10.1126/sciadv.aat9669 | 123,397,520 | Molecular catalyst system enables recycling of polymeric consumer products. | 10.1038/s41929-021-00648-4 | This article reports the hydrogenolysis of poly(lactic acid), PET and polycarbonate using a molecular Ru catalyst, achieving high conversion and selectivity to small molecule diol products with high tolerance towards polymer additives, as demonstrated by effective depolymerization of a variety of consumer-grade plastic... |
10.1126/science.abc5441 | 20,411,348 | The current scale of plastics production and the accompanying waste disposal problems represent a largely untapped opportunity for chemical upcycling. Tandem catalytic conversion by platinum supported on γ-alumina converts various polyethylene grades in high yields (up to 80 weight percent) to low-molecular-weight liqu... | 10.1038/s41929-021-00648-4 | This report outlines an exciting, solvent-free strategy to convert polyethylene to alkylaromatics using a tandem hydrogenolysis/aromatization approach by coupling the exothermic hydrogenolysis and endothermic aromatization to achieve a thermodynamically favourable process |
10.1557/mrs.2020.194 | 75,827,813 | Abstract | 10.1038/s41928-022-00862-3 | A perspective article that describes neuronal properties and biocomputational primitives that are not usually captured by emerging neuromorphic devices. |
10.1126/science.aad3087 | 107,285,337 | Faster elimination inside a cavity Metals are adept at shuffling molecular bonds. They pry apart two atoms and then pair each one with a different partner. Sometimes the atoms get stuck on the metal, though, and the newly partnered products aren't released. Kaphan et al. designed a strategy for accelerating this elimin... | 10.1038/s41929-020-00528-3 | The Raymond tetrahedral host catalyses reductive elimination of ethane from a gold (III) complex with up to 10 7 -times rate acceleration, demonstrating the ability of hosts to increase the rate of elementary organometallic steps without changing inner sphere ligands. |
10.1016/j.trci.2015.06.003 | 4,855,307 | Abstract Background The lipoprotein‐associated phospholipase A 2 inhibitor (Lp‐PLA 2 ), rilapladib (SB659032), is being evaluated as a potential treatment to slow the progression of Alzheimer's disease (AD). Methods One hundred twenty‐four subjects with possible mild AD and with neuroimaging evidence of cerebrovascular... | 10.1038/s43587-022-00213-z | This article presents the results of a clinical trial examining the use of rilapladib, an LP-PLA 2 inhibitor, in patients with AD |
10.26434/chemrxiv.14233244.v1 | 35,587,184 | <p>Electrochemical reactors often employ high surface area electrocatalysts to accelerate volumetric reaction rates and increase productivity. While electrocatalysts can alleviate kinetic overpotentials, diffusional resistances at the pore-scale often prevent full catalyst utilization. The effect of intraparticle... | 10.1038/s43586-022-00164-0 | This work demonstrates the coupling of diffusion reaction-governing equations with macroscopic catalytic rates to quantify the extent of internal mass transfer limitations |
10.1002/adma.201806296 | 20,606,469 | Abstract Electrochemical energy storage by making H 2 an energy carrier from water splitting relies on four elementary reactions, i.e., the hydrogen evolution reaction (HER), hydrogen oxidation reaction (HOR), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR). Herein, the central objective is to reco... | 10.1038/s43586-022-00164-0 | This work expands our coverage on the collection and analysis of reaction rates, kinetics and normalization of catalyst activity |
10.1038/srep13801 | 104,442,947 | Abstract Microkinetic analyses of aqueous electrochemistry involving gaseous H 2 or O 2 , i.e., hydrogen evolution reaction (HER), hydrogen oxidation reaction (HOR), oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), are revisited. The Tafel slopes used to evaluate the rate determining steps generally... | 10.1038/s43586-022-00164-0 | This work utilizes microkinetic modelling to demonstrate how different rate-limiting steps and surface coverages impact Tafel slopes and reaction orders |
10.26434/chemrxiv-2022-vk5z9 | 127,111,464 | The thermodynamic activity of a reacting species, rather than the concentration of that species, generally determines the rate of a kinetically-limited reaction. In this work we demonstrate the need for the explicit accounting of reacting species’ thermodynamic activities in solution, especially when conducting electro... | 10.1038/s43586-022-00164-0 | This work demonstrates how accounting for the thermodynamic activities of species can impact reaction order measurements, potentially leading to faulty mechanistic interpretations |
10.1002/wcms.1499 | 4,616,756 | Abstract Electrified interfaces play a prime role in energy technologies, from batteries and capacitors to heterogeneous electrocatalysis. The atomistic understanding and modeling of these interfaces is challenging due to the structural complexity and the presence of the electrochemical potential. Including the potenti... | 10.1038/s43586-022-00164-0 | This outstanding review paper offers a detailed discussion on the different methodologies developed to model the electrochemical interface, including the computational hydrogen electrode, constant potential and constant electric field approaches (as summarized in the paper in Fig. 3) |
10.3390/pr8121634 | 103,696,192 | Although alkaline water electrolysis (AWE) is the most widespread technology for hydrogen production by electrolysis, its electrochemical and fluid dynamic optimization has rarely been addressed simultaneously using Computational Fluid Dynamics (CFD) simulation. In this regard, a two-dimensional (2D) CFD model of an AW... | 10.1038/s43586-022-00164-0 | This work introduces important engineering parameters that need to be taken into account when designing electrochemical cells |
10.1038/s41591-021-01536-x | 134,133,494 | Abstract Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, rando... | 10.1038/s44161-022-00032-w | The PRESERVED-HF randomized clinical trial showed that the SGLT2-inhibitor dapagliflozin unequivocally improved health status and exercise capacity in patients with HFpEF who fit a cardiometabolic, congested phenotype that is typically associated with high levels of systemic inflammation |
10.1038/s41586-020-2797-4 | 62,598,710 | Abstract Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a... | 10.1038/s44161-022-00032-w | This study provided a picture of human heart at single-cell resolution which will be useful for the study of intercellular cross-talk |
10.1073/pnas.1621047114 | 80,989,672 | Significance Aging is a risk factor for heart diseases, and it is also known to impact on several immunological processes. Nevertheless, most studies addressing the cardio-immune cross-talk have focused on juvenile rather than senescent animal models. In the present study, we addressed this gap and found that immunolog... | 10.1038/s44161-022-00032-w | Study exploring the dynamics of T cells in cardiac aging, establishing causality between T cell behavior and myocardial aging |
10.1161/circulationaha.113.007101 | 107,309,777 | Background— The mechanisms by which the heart adapts to chronic pressure overload, producing compensated hypertrophy and eventually heart failure (HF), are still not well defined. We aimed to investigate the involvement of T cells in the progression to HF using a transverse aortic constriction (TAC) model. Methods and ... | 10.1038/s44161-022-00032-w | Seminal study pointing to the role of T cells in cardiac hypertrophy and heart failure development. |
10.1038/ncomms14680 | 103,957,431 | Abstract Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF de... | 10.1038/s44161-022-00032-w | Study demonstrating therapeutic feasibility of targeting T cells in heart failure models. |
10.1084/jem.20070657 | 103,780,449 | Hypertension promotes atherosclerosis and is a major source of morbidity and mortality. We show that mice lacking T and B cells (RAG-1−/− mice) have blunted hypertension and do not develop abnormalities of vascular function during angiotensin II infusion or desoxycorticosterone acetate (DOCA)–salt. Adoptive transfer of... | 10.1038/s44161-022-00032-w | This study pinpoints immune cells as mediators of hypertensive effects on vasculature. |
10.1084/jem.20171274 | 104,418,140 | Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging and heart failure with preserved ejection fraction, remain unclear. Here we show that cardiac macrophages expand in ... | 10.1038/s44161-022-00032-w | Data reported in this study implicate cardiac macrophages as therapeutic targets for cardiac fibrosis leading to diastolic dysfunction. |
10.3390/cells10113164 | 133,917,663 | The gut microbiota is responsible for recovering energy from food, providing hosts with vitamins, and providing a barrier function against exogenous pathogens. In addition, it is involved in maintaining the integrity of the intestinal epithelial barrier, crucial for the functional maturation of the gut immune system. T... | 10.1038/s42255-022-00696-5 | A review article discussing the high-fat Western diet and the contribution of the gut microbiota to chronic inflammation. |
10.7554/elife.61548 | 41,493,270 | Population stratification continues to bias the results of genome-wide association studies (GWAS). When these results are used to construct polygenic scores, even subtle biases can cumulatively lead to large errors. To study the effect of residual stratification, we simulated GWAS under realistic models of demographic ... | 10.1038/s43586-021-00056-9 | This paper investigates the effects of residual population structure on GWAS in simulated populations with different demographic histories and shows that commonly used methods such as principal components of common variants cannot correct for recent population stratification |
10.1126/science.aan6877 | 125,270,661 | Genetic variants provide a nurturing environment Genetic variants in parents may affect the fitness of their offspring, even if the child does not carry the allele. This indirect effect is referred to as “genetic nurture.” Kong et al. used data from genome-wide association studies of educational attainment to construct... | 10.1038/s43586-021-00056-9 | This paper shows for the first time that part of the signal in the GWAS for some traits is from ‘indirect genetic effects’ that act through parents rather than directly on the index individual, and shows how these can be disentangled with family data |
10.1371/journal.pmed.1003498 | 83,460,240 | Background Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD. Methods and findings Using data from UK Biobank on 306,654 individuals... | 10.1038/s43586-021-00056-9 | This paper recalibrated risk prediction models in the UK Biobank to what would be expected in an unbiased UK population to account for the bias caused by UK Biobank participants being healthier and wealthier, which is seldom considered in other studies in this field. |
10.7554/elife.39725 | 20,354,583 | Several recent papers have reported strong signals of selection on European polygenic height scores. These analyses used height effect estimates from the GIANT consortium and replication studies. Here, we describe a new analysis based on the the UK Biobank (UKB), a large, independent dataset. We find that the signals o... | 10.1038/s43586-021-00056-9 | This paper shows that the polygenic selection signal of height in European-ancestry individuals is strongly attenuated when using GWAS summary statistics generated from the UK Biobank rather than the largest GWAS meta-analysis (GIANT consortium) |
10.1126/science.aap9282 | 20,804,269 | The highest power conversion efficiencies (PCEs) reported for perovskite solar cells (PSCs) with inverted planar structures are still inferior to those of PSCs with regular structures, mainly because of lower open-circuit voltages ( V oc ). Here we report a strategy to reduce nonradiative recombination for the inverted... | 10.1038/s43246-022-00291-x | (This study verified the high open-circuit voltage of over 1.2 V in the inverted perovskite solar cells) |
10.1126/science.abm8566 | 128,115,227 | Further enhancing the performance and stability of inverted perovskite solar cells (PSCs) is crucial for their commercialization. We report that the functionalization of multication and halide perovskite interfaces with an organometallic compound, ferrocenyl-bis-thiophene-2-carboxylate (FcTc 2 ), simultaneously enhance... | 10.1038/s43246-022-00291-x | (This study achieved the champion performance in the inverted perovskite solar cells) |
10.1038/s41560-019-0529-5 | 104,336,390 | Abstract Improving the long-term stability of perovskite solar cells is critical to the deployment of this technology. Despite the great emphasis laid on stability-related investigations, publications lack consistency in experimental procedures and parameters reported. It is therefore challenging to reproduce and compa... | 10.1038/s43246-022-00291-x | (This paper summarized a series of protocols for stability testing of perovskite solar cells) |
10.1038/s41467-021-24150-4 | 131,169,611 | Abstract Chemical descriptors encode the physicochemical and structural properties of small molecules, and they are at the core of chemoinformatics. The broad release of bioactivity data has prompted enriched representations of compounds, reaching beyond chemical structures and capturing their known biological properti... | 10.1038/s42256-022-00463-x | The generation of bioactivity signatures or fingerprints is reported using a collection of DNNs derived from broadly released bioactivity data that are relevant to capturing known biological properties, showing a substantial improvement in performance across a series of biophysics and physiology activity prediction ben... |
10.1093/bioinformatics/btaa880 | 85,526,674 | Abstract Motivation Drug–target interaction (DTI) prediction is a foundational task for in-silico drug discovery, which is costly and time-consuming due to the need of experimental search over large drug compound space. Recent years have witnessed promising progress for deep learning in DTI predictions. However, the fo... | 10.1038/s42256-022-00463-x | A molecular interaction transformer (MolTrans) was developed that uses knowledge-inspired sub-structural pattern mining to better extract substructure semantic relations from massive unlabelled biomedical data to improve prediction of ligand–target interactions |
10.1093/bib/bbab159 | 80,578,197 | Abstract Graph machine learning (GML) is receiving growing interest within the pharmaceutical and biotechnology industries for its ability to model biomolecular structures, the functional relationships between them, and integrate multi-omic datasets — amongst other data types. Herein, we present a multidisciplinary aca... | 10.1038/s42256-022-00463-x | This is an informed review of the applications of GNNs and their variants in various components of drug discovery. |
10.1039/d1sc05579h | 132,904,227 | Deep learning-accelerated docking coupled with computational hit selection strategies enable the identification of inhibitors for the SARS-CoV-2 main protease from a chemical library of 40 billion small molecules. | 10.1038/s42256-022-00463-x | About 40 billion molecules were computational screened against SARS-CoV-2 main protease, returning a large number of experimentally confirmed inhibitors using a fully automated end-to-end drug discovery protocol that integrates machine learning and human expertise. |
10.1126/science.1254234 | 60,078,211 | The Haber-Bosch process to produce ammonia for fertilizer currently relies on carbon-intensive steam reforming of methane as a hydrogen source. We present an electrochemical pathway in which ammonia is produced by electrolysis of air and steam in a molten hydroxide suspension of nano-Fe 2 O 3 . At 200°C in an electroly... | 10.1038/s41929-018-0092-7 | Nanoscale iron oxide, combined with steam and air in a molten hydroxide electrolyte, enable Faradaic efficiencies of up to 35% for electrochemical nitrogen reduction to ammonia |
10.1002/adma.201606550 | 41,659,962 | As the NN bond in N 2 is one of the strongest bonds in chemistry, the fixation of N 2 to ammonia is a kinetically complex and energetically challenging reaction and, up to now, its synthesis is still heavily relying on energy and capital intensive Haber–Bosch process (150–350 atm, 350–550 °C), wherein the input of H 2... | 10.1038/s41929-018-0092-7 | One of the highest Faradaic efficiencies reported to date for ambient temperature and pressure electrochemical nitrogen reduction suggests that this reported catalyst structure and composition may be promising for greater N 2 selectivity |
10.1093/eurpub/ckz185.161 | 81,991,270 | Abstract Background The Nordic countries - Norway, Sweden, Finland, Iceland, Denmark - combine liberal and open-market economies with public welfare and universal health services. As separate countries with differences in culture and lifestyle, important health differences may exist between them. The aim of this study ... | 10.1038/s41893-022-00978-6 | A comprehensive global study of many risk factors and causes of deaths, including ambient air pollution. |
10.1073/pnas.1803222115 | 104,407,808 | Exposure to ambient fine particulate matter (PM 2.5 ) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM 2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondha... | 10.1038/s41893-022-00978-6 | This paper reports the mortality estimates due to ambient PM 2.5 exposure and a relative risk function based on more recent epidemiological evidence. |
10.1073/pnas.121164898 | 19,276,475 | Homologous DNA recombination is a fundamental, regenerative process within living organisms. However, in most organisms, homologous recombination is a rare event, requiring a complex set of reactions and extensive homology. We demonstrate in this paper that Beta protein of phage λ generates recombinants in chromosomal ... | 10.1038/s43586-020-00006-x | This article was the first to thoroughly examine the possibility of recombineering with ssDNA as a template |
10.1073/pnas.1520040113 | 62,264,555 | Currently available tools for multiplex bacterial genome engineering are optimized for a few laboratory model strains, demand extensive prior modification of the host strain, and lead to the accumulation of numerous off-target modifications. Building on prior development of multiplex automated genome engineering (MAGE)... | 10.1038/s43586-020-00006-x | This work first describes the transient suppression of MMR by expression of a dominant negative MutL. |
10.1126/science.1241459 | 104,322,458 | Changing the Code Easily and efficiently expanding the genetic code could provide tools to genome engineers with broad applications in medicine, energy, agriculture, and environmental safety. Lajoie et al. (p. 357 ) replaced all known UAG stop codons with synonymous UAA stop codons in Escherichia coli MG1655, as well a... | 10.1038/s43586-020-00006-x | This landmark article is the first to report a fully recoded organism, in this case an E. coli strain with 321 TAG stop codon reassignments, produced with MAGE |
10.1073/pnas.2434959100 | 83,207,962 | Homologous recombination can be used to generate recombinants on episomes or directly on the Escherichia coli chromosome with PCR products or synthetic single-stranded DNA (ssDNA) oligonucleotides (oligos). Such recombination is possible because bacteriophage λ-encoded functions, called Red, efficiently recombine linea... | 10.1038/s43586-020-00006-x | This is the first article to describe evasion of mismatch repair as an effective strategy to improve the ARF |
10.1073/pnas.2001588117 | 100,351,763 | Exploiting bacteriophage-derived homologous recombination processes has enabled precise, multiplex editing of microbial genomes and the construction of billions of customized genetic variants in a single day. The techniques that enable this, multiplex automated genome engineering (MAGE) and directed evolution with rand... | 10.1038/s43586-020-00006-x | This work describes SEER, a method for adapting MAGE to new bacterial species, and the improvement of ARF to ultra-high frequency in E. coli and C. freundii. |
10.1128/mbio.01467-18 | 103,901,658 | We sought to develop a system that could increase the usefulness of oligonucleotide-mediated recombineering of bacterial chromosomes by expanding the types of modifications generated by an oligonucleotide (i.e., insertions and deletions) and by making recombinant formation a selectable event. This paper describes such ... | 10.1038/s43586-020-00006-x | This inventive article describes the pairing of recombineering with site-specific recombinases to ease genomic deletions and fusions in mycobacteria |
10.1073/pnas.1801646115 | 41,542,547 | Antibiotic development is frequently plagued by the rapid emergence of drug resistance. However, assessing the risk of resistance development in the preclinical stage is difficult. Standard laboratory evolution approaches explore only a small fraction of the sequence space and fail to identify exceedingly rare resistan... | 10.1038/s43586-020-00006-x | This article describes DIvERGE, an important technique for diversification of targeted genomic loci |
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