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Controlled transport of water molecules through membranes and capillaries is important in areas as diverse as water purification and healthcare technologies.sup.1-7. Previous attempts to control water permeation through membranes (mainly polymeric ones) have concentrated on modulating the structure of the membrane and the physicochemical properties of its surface by varying the pH, temperature or ionic strength.sup.3,8. Electrical control over water transport is an attractive alternative; however, theory and simulations.sup.9-14 have often yielded conflicting results, from freezing of water molecules to melting of ice.sup.14-16 under an applied electric field. Here we report electrically controlled water permeation through micrometre-thick graphene oxide membranes.sup.17-21. Such membranes have previously been shown to exhibit ultrafast permeation of water.sup.17,22 and molecular sieving properties.sup.18,21, with the potential for industrial-scale production. To achieve electrical control over water permeation, we create conductive filaments in the graphene oxide membranes via controllable electrical breakdown. The electric field that concentrates around these current-carrying filaments ionizes water molecules inside graphene capillaries within the graphene oxide membranes, which impedes water transport. We thus demonstrate precise control of water permeation, from ultrafast permeation to complete blocking. Our work opens up an avenue for developing smart membrane technologies for artificial biological systems, tissue engineering and filtration. The rapid water transport through graphene oxide membranes can be switched off by introducing localized electric fields within the membranes that ionize surrounding water molecules and thus block transport., Author(s): K.-G. Zhou [sup.1] [sup.2] , K. S. Vasu [sup.1] [sup.2] , C. T. Cherian [sup.1] [sup.2] , M. Neek-Amal [sup.3] [sup.4] , J. C. Zhang [sup.5] , H. Ghorbanfekr-Kalashami [...]

When viewed as an elementary particle, the electron has spin and charge. When binding to the atomic nucleus, it also acquires an angular momentum quantum number corresponding to the quantized atomic orbital it occupies. Even if electrons in solids form bands and delocalize from the nuclei, in Mott insulators they retain their three fundamental quantum numbers: spin, charge and orbital. The hallmark of one-dimensional physics is a breaking up of the elementary electron into its separate degrees of freedom. The separation of the electron into independent quasi-particles that carry either spin (spinons) or charge (holons) was first observed fifteen years ago. Here we report observation of the separation of the orbital degree of freedom (orbiton) using resonant inelastic X-ray scattering on the one-dimensional Mott insulator Sr2CuO3. We resolve an orbiton separating itself from spinons and propagating through the lattice as a distinct quasi-particle with a substantial dispersion in energy over momentum, of about 0.2 electronvolts, over nearly one Brillouin zone. [ABSTRACT FROM AUTHOR]

When viewed as an elementary particle, the electron has spin and charge. When binding to the atomic nucleus, it also acquires an angular momentum quantum number corresponding to the quantized atomic orbital it occupies. Even if electrons in solids form bands and delocalize from the nuclei, in Mott insulators they retain their three fundamental quantum numbers: spin, charge and orbital. The hallmark of one-dimensional physics is a breaking up of the elementary electron into its separate degrees of freedom. The separation of the electron into independent quasi-particles that carry either spin (spinons) or charge (holons) was first observed fifteen years ago. Here we report observation of the separation of the orbital degree of freedom (orbiton) using resonant inelastic X-ray scattering on the one-dimensional Mott insulator Sr2CuO3. We resolve an orbiton separating itself from spinons and propagating through the lattice as a distinct quasi-particle with a substantial dispersion in energy over momentum, of about 0.2 electronvolts, over nearly one Brillouin zone. [ABSTRACT FROM AUTHOR]

Unravelling the origin and evolution of precancerous lesions is crucial for effectively preventing malignant transformation, yet our current knowledge remains limited 1-3 . Here we used a base editor-enabled DNA barcoding system 4 to comprehensively map single-cell phylogenies in mouse models of intestinal tumorigenesis induced by inflammation or loss of the Apc gene. Through quantitative analysis of high-resolution phylogenies including 260,922 single cells from normal, inflamed and neoplastic intestinal tissues, we identified tens of independent cell lineages undergoing parallel clonal expansions within each lesion. We also found polyclonal origins of human sporadic colorectal polyps through bulk whole-exome sequencing and single-gland whole-genome sequencing. Genomic and clinical data support a model of polyclonal-to-monoclonal transition, with monoclonal lesions representing a more advanced stage. Single-cell RNA sequencing revealed extensive intercellular interactions in early polyclonal lesions, but there was significant loss of interactions during monoclonal transition. Therefore, our data suggest that colorectal precancer is often founded by many different lineages and highlight their cooperative interactions in the earliest stages of cancer formation. These findings provide insights into opportunities for earlier intervention in colorectal cancer., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The fabrication of scalable all-perovskite tandem solar cells is considered an attractive route to commercialize perovskite photovoltaic modules 1 . However, the certified efficiency of 1-cm 2 -scale all-perovskite tandem solar cells lags behind their small-area (approximately 0.05-cm 2 ) counterparts 2,3 . This performance deficit originates from inhomogeneity in wide-bandgap (WBG) perovskite solar cells (PSCs) at a large scale. The inhomogeneity is known to be introduced at the bottom interface and within the perovskite bulk itself 4,5 . Here we uncover another crucial source for the inhomogeneity-the top interface formed during the deposition of the electron transport layer (ETL; C 60 ). Meanwhile, the poor ETL interface is also a notable limitation of device performance. We address this issue by introducing a mixture of 4-fluorophenethylamine (F-PEA) and 4-trifluoromethyl-phenylammonium (CF3-PA) to create a tailored 2D perovskite layer (TTDL), in which F-PEA forms a 2D perovskite at the surface, reducing contact losses and inhomogeneity, and CF3-PA enhances charge extraction and transport. As a result, we demonstrate a high open-circuit voltage (V oc ) of 1.35 V and an efficiency of 20.5% in 1.77-eV WBG PSCs at a square-centimetre scale. By stacking with a narrow-bandgap (NBG) perovskite subcell, we report 1.05-cm 2 all-perovskite tandem cells delivering 28.5% (certified 28.2%) efficiency, the highest reported so far. Our work showcases the importance of treating the top perovskite/ETL contact for upscaling PSCs., Competing Interests: Competing interests: H.T. is the founder, chief scientific officer and chairman of Renshine Solar Co. Ltd., a company that is commercializing perovskite photovoltaics. S.D.S. is a co-founder of Swift Solar. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Reliable control of the conductivity and its polarity in semiconductors is at the heart of modern electronics 1-7 , and has led to key inventions including diodes, transistors, solar cells, photodetectors, light-emitting diodes and semiconductor lasers. For archetypal semiconductors such as Si and GaN, positive (p)- and negative (n)-type conductivities are achieved through the doping of electron-accepting and electron-donating elements into the crystal lattices, respectively 1-6 . For halide perovskites, which are an emerging class of semiconductors, mechanisms for reliably controlling charge conduction behaviours while maintaining high optoelectronic qualities are yet to be discovered. Here we report that the p- and n-type characteristics in a wide-bandgap perovskite semiconductor can be adjusted by incorporating a phosphonic acid molecular dopant with strong electron-withdrawing abilities. The resultant carrier concentrations were more than 10 13  cm -3 for the p- and n-type samples, with Hall coefficients ranging from -0.5 m 3  C -1 (n-type) to 0.6 m 3  C -1 (p-type). A shift of the Fermi level across the bandgap was observed. Importantly, the transition from n- to p-type conductivity was achieved while retaining high photoluminescence quantum yields of 70-85%. The controllable doping in the emissive perovskite semiconductor enabled the demonstration of ultrahigh brightness (more than 1.1 × 10 6  cd m -2 ) and exceptional external quantum efficiency (28.4%) in perovskite light-emitting diodes with a simple architecture., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In eukaryotes, DNA compacts into chromatin through nucleosomes 1,2 . Replication of the eukaryotic genome must be coupled to the transmission of the epigenome encoded in the chromatin 3,4 . Here we report cryo-electron microscopy structures of yeast (Saccharomyces cerevisiae) replisomes associated with the FACT (facilitates chromatin transactions) complex (comprising Spt16 and Pob3) and an evicted histone hexamer. In these structures, FACT is positioned at the front end of the replisome by engaging with the parental DNA duplex to capture the histones through the middle domain and the acidic carboxyl-terminal domain of Spt16. The H2A-H2B dimer chaperoned by the carboxyl-terminal domain of Spt16 is stably tethered to the H3-H4 tetramer, while the vacant H2A-H2B site is occupied by the histone-binding domain of Mcm2. The Mcm2 histone-binding domain wraps around the DNA-binding surface of one H3-H4 dimer and extends across the tetramerization interface of the H3-H4 tetramer to the binding site of Spt16 middle domain before becoming disordered. This arrangement leaves the remaining DNA-binding surface of the other H3-H4 dimer exposed to additional interactions for further processing. The Mcm2 histone-binding domain and its downstream linker region are nested on top of Tof1, relocating the parental histones to the replisome front for transfer to the newly synthesized lagging-strand DNA. Our findings offer crucial structural insights into the mechanism of replication-coupled histone recycling for maintaining epigenetic inheritance., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The metabotropic glutamate receptors (mGlus) have key roles in modulating cell excitability and synaptic transmission in response to glutamate (the main excitatory neurotransmitter in the central nervous system) 1 . It has previously been suggested that only one receptor subunit within an mGlu homodimer is responsible for coupling to G protein during receptor activation 2 . However, the molecular mechanism that underlies the asymmetric signalling of mGlus remains unknown. Here we report two cryo-electron microscopy structures of human mGlu2 and mGlu4 bound to heterotrimeric G i protein. The structures reveal a G-protein-binding site formed by three intracellular loops and helices III and IV that is distinct from the corresponding binding site in all of the other G-protein-coupled receptor (GPCR) structures. Furthermore, we observed an asymmetric dimer interface of the transmembrane domain of the receptor in the two mGlu-G i structures. We confirmed that the asymmetric dimerization is crucial for receptor activation, which was supported by functional data; this dimerization may provide a molecular basis for the asymmetric signal transduction of mGlus. These findings offer insights into receptor signalling of class C GPCRs.

The organization of genomic DNA into nucleosomes profoundly affects all DNA-related processes in eukaryotes. The histone chaperone known as 'facilitates chromatin transcription' (FACT 1 ) (consisting of subunits SPT16 and SSRP1) promotes both disassembly and reassembly of nucleosomes during gene transcription, DNA replication and DNA repair 2 . However, the mechanism by which FACT causes these opposing outcomes is unknown. Here we report two cryo-electron-microscopic structures of human FACT in complex with partially assembled subnucleosomes, with supporting biochemical and hydrogen-deuterium exchange data. We find that FACT is engaged in extensive interactions with nucleosomal DNA and all histone variants. The large DNA-binding surface on FACT appears to be protected by the carboxy-terminal domains of both of its subunits, and this inhibition is released by interaction with H2A-H2B, allowing FACT-H2A-H2B to dock onto a complex containing DNA and histones H3 and H4 (ref. 3 ). SPT16 binds nucleosomal DNA and tethers H2A-H2B through its carboxy-terminal domain by acting as a placeholder for DNA. SSRP1 also contributes to DNA binding, and can assume two conformations, depending on whether a second H2A-H2B dimer is present. Our data suggest a compelling mechanism for how FACT maintains chromatin integrity during polymerase passage, by facilitating removal of the H2A-H2B dimer, stabilizing intermediate subnucleosomal states and promoting nucleosome reassembly. Our findings reconcile discrepancies regarding the many roles of FACT and underscore the dynamic interactions between histone chaperones and nucleosomes.

DNA and histone modifications have notable effects on gene expression 1 . Being the most prevalent internal modification in mRNA, the N 6 -methyladenosine (m 6 A) mRNA modification is as an important post-transcriptional mechanism of gene regulation 2-4 and has crucial roles in various normal and pathological processes 5-12 . However, it is unclear how m 6 A is specifically and dynamically deposited in the transcriptome. Here we report that histone H3 trimethylation at Lys36 (H3K36me3), a marker for transcription elongation, guides m 6 A deposition globally. We show that m 6 A modifications are enriched in the vicinity of H3K36me3 peaks, and are reduced globally when cellular H3K36me3 is depleted. Mechanistically, H3K36me3 is recognized and bound directly by METTL14, a crucial component of the m 6 A methyltransferase complex (MTC), which in turn facilitates the binding of the m 6 A MTC to adjacent RNA polymerase II, thereby delivering the m 6 A MTC to actively transcribed nascent RNAs to deposit m 6 A co-transcriptionally. In mouse embryonic stem cells, phenocopying METTL14 knockdown, H3K36me3 depletion also markedly reduces m 6 A abundance transcriptome-wide and in pluripotency transcripts, resulting in increased cell stemness. Collectively, our studies reveal the important roles of H3K36me3 and METTL14 in determining specific and dynamic deposition of m 6 A in mRNA, and uncover another layer of gene expression regulation that involves crosstalk between histone modification and RNA methylation.

Strigolactones (SLs), a newly discovered class of carotenoid-derived phytohormones, are essential for developmental processes that shape plant architecture and interactions with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Despite the rapid progress in elucidating the SL biosynthetic pathway, the perception and signalling mechanisms of SL remain poorly understood. Here we show that DWARF 53 (D53) acts as a repressor of SL signalling and that SLs induce its degradation. We find that the rice (Oryza sativa) d53 mutant, which produces an exaggerated number of tillers compared to wild-type plants, is caused by a gain-of-function mutation and is insensitive to exogenous SL treatment. The D53 gene product shares predicted features with the class I Clp ATPase proteins and can form a complex with the α/β hydrolase protein DWARF 14 (D14) and the F-box protein DWARF 3 (D3), two previously identified signalling components potentially responsible for SL perception. We demonstrate that, in a D14- and D3-dependent manner, SLs induce D53 degradation by the proteasome and abrogate its activity in promoting axillary bud outgrowth. Our combined genetic and biochemical data reveal that D53 acts as a repressor of the SL signalling pathway, whose hormone-induced degradation represents a key molecular link between SL perception and responses.

Bacteria and archaea acquire resistance to viruses and plasmids by integrating short fragments of foreign DNA into clustered regularly interspaced short palindromic repeats (CRISPRs). These repetitive loci maintain a genetic record of all prior encounters with foreign transgressors. CRISPRs are transcribed and the long primary transcript is processed into a library of short CRISPR-derived RNAs (crRNAs) that contain a unique sequence complementary to a foreign nucleic-acid challenger. In Escherichia coli, crRNAs are incorporated into a multisubunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defence), which is required for protection against bacteriophages. Here we use cryo-electron microscopy to determine the subnanometre structures of Cascade before and after binding to a target sequence. These structures reveal a sea-horse-shaped architecture in which the crRNA is displayed along a helical arrangement of protein subunits that protect the crRNA from degradation while maintaining its availability for base pairing. Cascade engages invading nucleic acids through high-affinity base-pairing interactions near the 5' end of the crRNA. Base pairing extends along the crRNA, resulting in a series of short helical segments that trigger a concerted conformational change. This conformational rearrangement may serve as a signal that recruits a trans-acting nuclease (Cas3) for destruction of invading nucleic-acid sequences., (© 2011 Macmillan Publishers Limited. All rights reserved)

Establishing precise synaptic connections is crucial to the development of functional neural circuits. The direction-selective circuit in the retina relies upon highly selective wiring of inhibitory inputs from starburst amacrine cells (SACs) onto four subtypes of ON-OFF direction-selective ganglion cells (DSGCs), each preferring motion in one of four cardinal directions. It has been reported in rabbit that the SACs on the 'null' sides of DSGCs form functional GABA (γ-aminobutyric acid)-mediated synapses, whereas those on the preferred sides do not. However, it is not known how the asymmetric wiring between SACs and DSGCs is established during development. Here we report that in transgenic mice with cell-type-specific labelling, the synaptic connections from SACs to DSGCs were of equal strength during the first postnatal week, regardless of whether the SAC was located on the preferred or null side of the DSGC. However, by the end of the second postnatal week, the strength of the synapses made from SACs on the null side of a DSGC significantly increased whereas those made from SACs located on the preferred side remained constant. Blocking retinal activity by intraocular injections of muscimol or gabazine during this period did not alter the development of direction selectivity. Hence, the asymmetric inhibition between the SACs and DSGCs is achieved by a developmental program that specifically strengthens the GABA-mediated inputs from SACs located on the null side, in a manner not dependent on neural activity.

Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics.

Ribozymes enhance chemical reaction rates using many of the same catalytic strategies as protein enzymes. In the hepatitis delta virus (HDV) ribozyme, site-specific self-cleavage of the viral RNA phosphodiester backbone requires both divalent cations and a cytidine nucleotide. General acid-base catalysis, substrate destabilization and global and local conformational changes have all been proposed to contribute to the ribozyme catalytic mechanism. Here we report ten crystal structures of the HDV ribozyme in its pre-cleaved state, showing that cytidine is positioned to activate the 2'-OH nucleophile in the precursor structure. This observation supports its proposed role as a general base in the reaction mechanism. Comparison of crystal structures of the ribozyme in the pre- and post-cleavage states reveals a significant conformational change in the RNA after cleavage and that a catalytically critical divalent metal ion from the active site is ejected. The HDV ribozyme has remarkable chemical similarity to protein ribonucleases and to zymogens for which conformational dynamics are integral to biological activity. This finding implies that RNA structural rearrangements control the reactivity of ribozymes and ribonucleoprotein enzymes.

The self-cleaving ribozyme of the hepatitis delta virus (HDV) is the only catalytic RNA known to be required for the viability of a human pathogen. We obtained crystals of a 72-nucleotide, self-cleaved form of the genomic HDV ribozyme that diffract X-rays to 2.3 A resolution by engineering the RNA to bind a small, basic protein without affecting ribozyme activity. The co-crystal structure shows that the compact catalytic core comprises five helical segments connected as an intricate nested double pseudoknot. The 5'-hydroxyl leaving group resulting from the self-scission reaction is buried deep within an active-site cleft produced by juxtaposition of the helices and five strand-crossovers, and is surrounded by biochemically important backbone and base functional groups in a manner reminiscent of protein enzymes.