The use of solar energy to produce molecular hydrogen and oxygen (H2 and O2) from overall water splitting is a promising means of renewable energy storage. In the past 40 years, various inorganic and organic systems have been developed as photocatalysts for water splitting driven by visible light. These photocatalysts, however, still suffer from low quantum efficiency and/or poor stability. We report the design and fabrication of a metal-free carbon nanodot-carbon nitride (C3N4) nanocomposite and demonstrate its impressive performance for photocatalytic solar water splitting. We measured quantum efficiencies of 16% for wavelength λ = 420 ± 20 nanometers, 6.29% for λ = 580 ± 15 nanometers, and 4.42% for λ = 600 ± 10 nanometers, and determined an overall solar energy conversion efficiency of 2.0%. The catalyst comprises low-cost, Earth-abundant, environmentally friendly materials and shows excellent stability.

A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and openshell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Møller-Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr 2 dimer, exploring zeolitecatalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube.Keywords quantum chemistry, software, electronic structure theory, density functional theory, electron correlation, computational modelling, Q-Chem Disciplines Chemistry CommentsThis article is from Molecular Physics: An International Journal at the Interface Between Chemistry and Physics 113 (2015): 184, doi:10.1080/00268976.2014. RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. Authors 185A summary of the technical advances that are incorporated in the fourth major release of the Q-CHEM quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Møller-Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly corre...

Understanding the origin of high activity of Fe-N-C electrocatalysts in oxygen reduction reaction (ORR) is critical but still challenging for developing efficient sustainable nonprecious metal catalysts in fuel cells and metal-air batteries. Herein, we developed a new highly active Fe-N-C ORR catalyst containing Fe-N(x) coordination sites and Fe/Fe3C nanocrystals (Fe@C-FeNC), and revealed the origin of its activity by intensively investigating the composition and the structure of the catalyst and their correlations with the electrochemical performance. The detailed analyses unambiguously confirmed the coexistence of Fe/Fe3C nanocrystals and Fe-N(x) in the best catalyst. A series of designed experiments disclosed that (1) N-doped carbon substrate, Fe/Fe3C nanocrystals or Fe-N(x) themselves did not deliver the high activity; (2) the catalysts with both Fe/Fe3C nanocrystals and Fe-N(x) exhibited the high activity; (3) the higher content of Fe-N(x) gave the higher activity; (4) the removal of Fe/Fe3C nanocrystals severely degraded the activity; (5) the blocking of Fe-N(x) downgraded the activity and the recovery of the blocked Fe-N(x) recovered the activity. These facts supported that the high ORR activity of the Fe@C-FeNC electrocatalysts should be ascribed to that Fe/Fe3C nanocrystals boost the activity of Fe-N(x). The coexistence of high content of Fe-N(x) and sufficient metallic iron nanoparticles is essential for the high ORR activity. DFT calculation corroborated this conclusion by indicating that the interaction between metallic iron and Fe-N4 coordination structure favored the adsorption of oxygen molecule. These new findings open an avenue for the rational design and bottom-up synthesis of low-cost highly active ORR electrocatalysts.

Genetic imprinting, found in flowering plants and placental mammals, uses DNA methylation to yield gene expression that is dependent on the parent of origin 1 . DNA methyltransferase 3a (Dnmt3a) and its regulatory factor, DNA methyltransferase 3-like protein (Dnmt3L), are both required for the de novo DNA methylation of imprinted genes in mammalian germ cells. Dnmt3L interacts specifically with unmethylated lysine 4 of histone H3 through its amino-terminal PHD (plant homeodomain)-like domain 2 . Here we show, with the use of crystallography, that the carboxyterminal domain of human Dnmt3L interacts with the catalytic domain of Dnmt3a, demonstrating that Dnmt3L has dual functions of binding the unmethylated histone tail and activating DNA methyltransferase. The complexed C-terminal domains of Dnmt3a and Dnmt3L showed further dimerization through Dnmt3a-Dnmt3a interaction, forming a tetrameric complex with two active sites. Substitution of key non-catalytic residues at the Dnmt3a-Dnmt3L interface or the Dnmt3a-Dnmt3a interface eliminated enzymatic activity. Molecular modelling of a DNA-Dnmt3a dimer indicated that the two active sites are separated by about one DNA helical turn. The C-terminal domain of Dnmt3a oligomerizes on DNA to form a nucleoprotein filament. A periodicity in the activity of Dnmt3a on long DNA revealed a correlation of methylated CpG sites at distances of eight to ten base pairs, indicating that oligomerization leads Dnmt3a to methylate DNA in a periodic pattern. A similar periodicity is observed for the frequency of CpG sites in the differentially methylated regions of 12 maternally imprinted mouse genes. These results suggest a basis for the recognition and methylation of differentially methylated regions in imprinted genes, involving the detection of both nucleosome modification and CpG spacing.In both flowering plants and placental mammals, DNA methylation has a central role in imprinting, but in neither case is it clear how imprinted genes are targeted for methylation. Imprinted genes in mammals are often associated with differentially methylated regions (DMRs) 3 , which show DNA methylation patterns that depend on the parent of origin. How the imprinting machinery recognizes DMRs is unknown. The Dnmt3 family includes three members: two de novo CpG methyltransferases, namely Dnmt3a and Dnmt3b (ref. 4), and anCorrespondence and requests for materials should be addressed to A.J. [E-mail: a.jeltsch@jacobs-university.de] or X.C. [E-mail: xcheng@emory.edu]. * These authors contributed equally to this work.Author Information The X-ray structure of Dnmt3a-Dnmt3L C-terminal tetramer complex is deposited in the Protein Data Bank under ID code 2QRV. Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.Full Methods and any associated references are available in the online version of the paper at www.nature.com/nature.Supplementary Information is linked to the online version of the paper at www.nature.com/nature. We ...

PRMT1 is the predominant type I protein arginine methyltransferase in mammals and highly conserved among all eukaryotes. It is essential for early postimplantation development in mouse. Here we describe the crystal structure of rat PRMT1 in complex with the reaction product AdoHcy and a 19 residue substrate peptide containing three arginines. The results reveal a two-domain structure-an AdoMet binding domain and a barrel-like domain-with the active site pocket located between the two domains. Mutagenesis studies confirmed that two active site glutamates are essential for enzymatic activity, and that dimerization of PRMT1 is essential for AdoMet binding. Three peptide binding channels are identified: two are between the two domains, and the third is on the surface perpendicular to the strands forming the beta barrel.

BackgroundCircRNA has emerged as a new non-coding RNA that plays crucial roles in tumour initiation and development. ‘MiRNA sponge’ is the most reported role played by circRNAs in many tumours. The AKT/mTOR axis is a classic signalling pathway in cancers that sustains energy homeostasis through energy production activities, such as the Warburg effect, and blocks catabolic activities, such as autophagy. Additionally, the AKT/mTOR axis exerts a positive effect on EMT, which promotes tumour metastasis.MethodsWe detected higher circNRIP1 expression in gastric cancer by performing RNA-seq analysis. We verified the tumour promotor role of circNRIP1 in gastric cancer cells through a series of biological function assays. We then used a pull-down assay and dual-luciferase reporter assay to identify the downstream miR-149-5p of circNRIP1. Western blot analysis and immunofluorescence assays were performed to demonstrate that the circNRIP1-miR-149-5p-AKT1/mTOR axis is responsible for the altered metabolism in GC cells and promotes GC development. We then adopted a co-culture system to trace circNRIP1 transmission via exosomal communication and RIP experiments to determine that quaking regulates circNRIP1 expression. Finally, we confirmed the tumour suppressor role of microRNA-133a-3p in vivo in PDX mouse models.ResultsWe discovered that knockdown of circNRIP1 successfully blocked proliferation, migration, invasion and the expression level of AKT1 in GC cells. MiR-149-5p inhibition phenocopied the overexpression of circNRIP1 in GC cells, and overexpression of miR-149-5p blocked the malignant behaviours of circNRIP1. Moreover, it was proven that circNRIP1 can be transmitted by exosomal communication between GC cells, and exosomal circNRIP1 promoted tumour metastasis in vivo. We also demonstrated that quaking can promote circNRIP1 transcription. In the final step, the tumour promotor role of circNRIP1 was verified in PDX models.ConclusionsWe proved that circNRIP1 sponges miR-149-5p to affect the expression level of AKT1 and eventually acts as a tumour promotor in GC.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0935-5) contains supplementary material, which is available to authorized users.

Combinatorial readout of multiple covalent histone modifications is poorly understood. We provide insights into how an activating histone mark, in combination with linked repressive marks, is differentially 'read' by two related human demethylases, PHF8 and KIAA1718 (also known as JHDM1D). Both enzymes harbor a plant homeodomain (PHD) that binds Lys4-trimethylated histone 3 (H3K4me3) and a jumonji domain that demethylates either H3K9me2 or H3K27me2. The presence of H3K4me3 on the same peptide as H3K9me2 makes the doubly methylated peptide a markedly better substrate of PHF8, whereas the presence of H3K4me3 has the opposite effect, diminishing the H3K9me2 demethylase activity of KIAA1718 without adversely affecting its H3K27me2 activity. The difference in substrate specificity between the two is explained by PHF8 adopting a bent conformation, allowing each of its domains to engage its respective target, whereas KIAA1718 adopts an extended conformation, which prevents its access to H3K9me2 by its jumonji domain when its PHD engages H3K4me3.The control of gene expression in eukaryotes relies in part on the methylation status of histone proteins. Histone lysine modification is a dynamic process established by specific methyltransferases, including SET-domain proteins1 and a conventional methyltransferaselike protein Dot1 (ref. 2). These methylation marks can be 'erased' by protein lysine demethylases that include flavin-dependent monoamine oxidase LSD1 (ref.3) and α-ketoglutarate-Fe 2+ -dependent dioxygenases containing jumonji domains4 -6 . Protein modules, such as PHD finger protein (PHFs), detect the methylation status of histones by recognizing lysine in methylated 7-10 and unmethylated states11 , 12. The jumonji domain often associates with at least one additional recognizable protein domain within the same polypeptide 13 . For example, JMJD2A contains an N-terminal jumonji domain and CCorrespondence should be addressed to X.C. (xcheng@emory.edu). 4 These authors contributed equally to this work.Accession codes. Protein Data Bank: The coordinates and structure factors have been deposited with accession numbers 3KV4 (for PHF8 1-447 ), 3KV5 and 3KV6 (for KIAA1718 1-488 ) and 3KV9, 3KVA and 3KVB (for KIAA1718 92-488 ), respectively. Note: Supplementary information is available on the Nature Structural & Molecular Biology website. AUTHOR CONTRIBUTIONS J.R.H. performed crystallographic experiments; A.K.U. performed kinetic experiments; H.H.Q. and Y.S. provided initial expression constructs and the knowledge of specificities of individual PHD and jumonji domains; X.Z. generated hybrid enzymes; X.C. organized and designed the scope of the study and wrote the manuscript, and all others helped in analyzing data and revising the manuscript.Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions/. Structural studies revealed that the JMJD2A jumonji domain predominantly recognizes the backbone of the histone peptides (unusually for a sequence-specific enzyme), allowi...

DIM-5 is a SUV39-type histone H3 Lys9 methyltransferase that is essential for DNA methylation in N. crassa. We report the structure of a ternary complex including DIM-5, S-adenosyl-L-homocysteine, and a substrate H3 peptide. The histone tail inserts as a parallel strand between two DIM-5 strands, completing a hybrid sheet. Three post-SET cysteines coordinate a zinc atom together with Cys242 from the SET signature motif (NHXCXPN) near the active site. Consequently, a narrow channel is formed to accommodate the target Lys9 side chain. The sulfur atom of S-adenosyl-L-homocysteine, where the transferable methyl group is to be attached in S-adenosyl-L-methionine, lies at the opposite end of the channel, approximately 4 A away from the target Lys9 nitrogen. Structural comparison of the active sites of DIM-5, an H3 Lys9 trimethyltransferase, and SET7/9, an H3 Lys4 monomethyltransferase, allowed us to design substitutions in both enzymes that profoundly alter their product specificities without affecting their catalytic activities.