A Non-canonical Role of YAP/TEAD Is Required for Activation of Estrogen-Regulated Enhancers in Breast Cancer.

YAP/TEAD are nuclear effectors of the Hippo pathway, regulating organ size and tumorigenesis largely through promoter-associated function. However, their function as enhancer regulators remains poorly understood. Through an in vivo proximity-dependent labeling (BioID) technique, we identified YAP1 and TEAD4 protein as co-regulators of ERα on enhancers. The binding of YAP1/TEAD4 to ERα-bound enhancers is augmented upon E2 stimulation and is required for the induction of E2/ERα target genes and E2-induced oncogenic cell growth. Furthermore, their enhancer binding is a prerequisite for enhancer activation marked by eRNA transcription and for the recruitment of the enhancer activation machinery component MED1. The binding of TEAD4 on active ERE-containing enhancers is independent of its DNA-binding behavior, and instead, occurs through protein-tethering trans-binding. Our data reveal a non-canonical function of YAP1 and TEAD4 as ERα cofactors in regulating cancer growth, highlighting the potential of YAP/TEAD as possible actionable drug targets for ERα+ breast cancer.

LAMTOR1 inhibition of TRPML1-dependent lysosomal calcium release regulates dendritic lysosome trafficking and hippocampal neuronal function.

Lysosomes function not only as degradatory compartments but also as dynamic intracellular calcium ion stores. The transient receptor potential mucolipin 1 (TRPML1) channel mediates lysosomal Ca2+ release, thereby participating in multiple cellular functions. The pentameric Ragulator complex, which plays a critical role in the activation of mTORC1, is also involved in lysosomal trafficking and is anchored to lysosomes through its LAMTOR1 subunit. Here, we report that the Ragulator restricts lysosomal trafficking in dendrites of hippocampal neurons via LAMTOR1-mediated tonic inhibition of TRPML1 activity, independently of mTORC1. LAMTOR1 directly interacts with TRPML1 through its N-terminal domain. Eliminating this inhibition in hippocampal neurons by LAMTOR1 deletion or by disrupting LAMTOR1-TRPML1 binding increases TRPML1-mediated Ca2+ release and facilitates dendritic lysosomal trafficking powered by dynein. LAMTOR1 deletion in the hippocampal CA1 region of adult mice results in alterations in synaptic plasticity, and in impaired object-recognition memory and contextual fear conditioning, due to TRPML1 activation. Mechanistically, changes in synaptic plasticity are associated with increased GluA1 dephosphorylation by calcineurin and lysosomal degradation. Thus, LAMTOR1-mediated inhibition of TRPML1 is critical for regulating dendritic lysosomal motility, synaptic plasticity, and learning.

Restricted responses of AcMYB68 and AcERF74/75 enhanced waterlogging tolerance in kiwifruit.

Most of kiwifruit cultivars (e.g. Actinidia chinensis cv. Donghong, "DH") were sensitive to waterlogging, thus, waterlogging resistant rootstocks (e.g. Actinidia valvata Dunn, "Dunn") were widely used for kiwifruit industry. Those different species provided ideal materials to understand the waterlogging responses in kiwifruit. Compared to the weaken growth and root activities in "DH", "Dunn" maintained the relative high root activities under the prolonged waterlogging. Based on comparative analysis, transcript levels of pyruvate decarboxylase (PDCs) and alcohol dehydrogenase (ADHs) showed significantly difference between these two species. Both PDCs and ADHs had been significantly increased by waterlogging in "DH", while they were only limitedly triggered by 2 days stress and subsided during the prolonged waterlogging in "Dunn". Thus, 19 differentially expressed transcript factors (DETFs) had been isolated using weighted gene co-expression network analysis combined with transcriptomics and transcript levels of PDCs and ADHs in waterlogged "DH". Among these DETFs, dual luciferase and electrophoretic mobility shift assays indicated AcMYB68 could bind to and trigger the activity of AcPDC2 promoter. The stable over-expression of AcMYB68 significantly up-regulated the transcript levels of PDCs but inhibited the plant growth, especially the roots. Moreover, the enzyme activities of PDC in 35S::AcMYB68 were significantly enhanced during the waterlogging response than that in wild type plants. Most interestingly, comparative analysis indicated that the expression patterns of AcMYB68 and the previously characterized AcERF74/75 (the direct regulator on ADHs) either showed no responses (AcMYB68 and AcERF74) or very limited response (AcERF75) in "Dunn". Taken together, the restricted responses of AcMYB68 and AcERF74/75 in "Dunn" endow its waterlogging tolerance.

Defect engineering of metal-oxide interface for proximity of photooxidation and photoreduction.

Close proximity between different catalytic sites is crucial for accelerating or even enabling many important catalytic reactions. Photooxidation and photoreduction in photocatalysis are generally separated from each other, which arises from the hole-electron separation on photocatalyst surface. Here, we show with widely studied photocatalyst Pt/[Formula: see text] as a model, that concentrating abundant oxygen vacancies only at the metal-oxide interface can locate hole-driven oxidation sites in proximity to electron-driven reduction sites for triggering unusual reactions. Solar hydrogen production from aqueous-phase alcohols, whose hydrogen yield per photon is theoretically limited below 0.5 through conventional reactions, achieves an ultrahigh hydrogen yield per photon of 1.28 through the unusual reactions. We demonstrated that such defect engineering enables hole-driven CO oxidation at the Pt-[Formula: see text] interface to occur, which opens up room-temperature alcohol decomposition on Pt nanoparticles to [Formula: see text] and adsorbed CO, accompanying with electron-driven proton reduction on Pt to [Formula: see text].

LaOCl-Coupled Polymeric Carbon Nitride for Overall Water Splitting through a One-Photon Excitation Pathway.

It is a challenge to explore photocatalytic materials for sunlight-driven water splitting owing to the limited choice of a single semiconductor with suitable band energy levels but with a minimized band gap for light harvesting. Here, we report a one-photon excitation pathway by coupling polymeric carbon nitride (PCN) semiconductor with LaOCl to achieve overall water splitting. This artificial photosynthesis composite catalyzes the decomposition of H2 O into H2 and O2 , with evolution rates of 22.3 and 10.7 µmol h-1 , respectively. The high photocatalytic performance of PCN/LaOCl can be ascribed to the simultaneously accomplished reduction and oxidation of water on LaOCl and PCN domains, respectively, as well as the fast charge separation and migration induced by the interfacial electric field related to LaOCl modification. This study provides new insights on the development of composite photocatalysts for pure water splitting based on polymer-based materials via charge modulation.

Genome-wide dynamics of alternative polyadenylation in rice.

Alternative polyadenylation (APA), in which a transcript uses one of the poly(A) sites to define its 3'-end, is a common regulatory mechanism in eukaryotic gene expression. However, the potential of APA in determining crop agronomic traits remains elusive. This study systematically tallied poly(A) sites of 14 different rice tissues and developmental stages using the poly(A) tag sequencing (PAT-seq) approach. The results indicate significant involvement of APA in developmental and quantitative trait loci (QTL) gene expression. About 48% of all expressed genes use APA to generate transcriptomic and proteomic diversity. Some genes switch APA sites, allowing differentially expressed genes to use alternate 3' UTRs. Interestingly, APA in mature pollen is distinct where differential expression levels of a set of poly(A) factors and different distributions of APA sites are found, indicating a unique mRNA 3'-end formation regulation during gametophyte development. Equally interesting, statistical analyses showed that QTL tends to use APA for regulation of gene expression of many agronomic traits, suggesting a potential important role of APA in rice production. These results provide thus far the most comprehensive and high-resolution resource for advanced analysis of APA in crops and shed light on how APA is associated with trait formation in eukaryotes.

Insight into the mechanism for the methanol synthesis via the hydrogenation of CO2 over a Co-modified Cu(100) surface: A DFT study.

A comprehensive density functional theory calculation was employed to investigate the reaction mechanism of methanol synthesis on a Co-modified Cu(100) surface via CO2 hydrogenation. The Cu(100) surface with embedded small Co clusters prepared experimentally was employed as a model system to explore the effects of Co dopant on the catalytic performance of Cu(100) surface towards CH3OH synthesis. The activation energy barriers and the reaction energies of 16 elementary surface reactions were determined. Our calculated results show that the most favorable reaction pathway for the hydrogenation of CO2 to CH3OH follows the sequence of CO2 → HCOO* →H2COO* →H2COOH* →H2CO* →H3CO* →H3COH*, and the OH* group hydrogenation to H2 O* is the rate-limiting step with an activation barrier of 112.3 kJ/mol. It is noted that, since the strength of Co-O bond is stronger than that of Cu-O bond, the introducing of Co dopant on the Cu surface can facilitate the formation of key intermediates for the CH3OH synthesis. Especially, the stability of the unstable dioxomethylene intermediate (H2COO*) found on the pure Cu(100) surface can be obviously enhanced on the Co-doped Cu(100) surface. As a result, with respect to the undoped surface, the productivity and selectivity towards CH3OH production on the Cu(100) surface will be improved after dispersing small Co clusters on the surface.

Contribution of reactive oxygen species (ROS) to genotoxicity of nitrobenzene on V. faba.

Nitrobenzene is an important organic intermediate widely used in industry that can be hazardous to the environment. In our previous study, nitrobenzene showed genotoxic effect on soybean and tobacco plants at concentrations in the culture medium higher than 10 mg/L. The genotoxicity of nitrobenzene has been hypothesized to be multifactorial and reflective of the generation of free radicals; however, the mechanism has not been fully elucidated. The aim of this study was to investigate the relationship between the induction of genotoxicity and the production of free radicals in young seedlings of V. faba exposed to nitrobenzene, nitrobenzene + Vitamin C, and the controls (distilled water or Vitamin C). Micronucleus and chromosome aberration assays performed on root and leaf tissue of V. faba seedlings exposed to nitrobenzene (25 mg/L) demonstrated genotoxic effects which were partly reduced by Vitamin C at 25 mg/L. Increases in lipid peroxidase, O2•-, H2O2, superoxide dismutase and catalase activities were also observed in these tissues along with an attenuation of their induction by Vitamin C. Concomitant occurrence of genotoxicity and the generation of free radicals that are attenuated in the presence of Vitamin C, a scavenger of cellular free radicals, indicate that reactive oxygen species may contributes to genotoxicity of nitrobenzene in V. faba. These results are valuable for further understanding the genotoxicity mechanism of nitrobenzene.

Boosting the photocatalytic activity and stability of Cu2O for CO2 conversion by LaTiO2N.

Cu2O is one of the most promising photocatalysts for visible light driven CO2 conversion, but its practical application in artificial photosynthesis is challenged to severe photocorrosion. Herein, a Cu2O/LaTiO2N composite is successfully synthesized by loading Cu2O on LaTiO2N through an ascorbic acid reduction method, which significantly improves the stability and activity of Cu2O for visible light driven photocatalytic CO2 conversion, and shows higher photocatalytic performance than most Cu2O-based photocatalysts reported. The superior photocatalytic performance is attributed to the formation of type-II heterojunction between Cu2O and LaTiO2N, which facilitates the separation and transfer of photogenerated electrons and holes. This work provides an effective strategy for the construction of stable and efficient Cu2O-based photocatalysts.

Contextual fear memory impairment in Angelman syndrome model mice is associated with altered transcriptional responses.

Angelman syndrome (AS) is a rare neurogenetic disorder caused by UBE3A deficiency and characterized by severe developmental delay, cognitive impairment, and motor dysfunction. In the present study, we performed RNA-seq on hippocampal samples from both wildtype (WT) and AS male mice, with or without contextual fear memory recall. There were 281 recall-associated differentially expressed genes (DEGs) in WT mice and 268 DEGs in AS mice, with 129 shared by the two genotypes. Gene ontology analysis showed that extracellular matrix and stimulation-induced response genes were prominently enriched in recall-associated DEGs in WT mice, while nuclear acid metabolism and tissue development genes were highly enriched in those from AS mice. Further analyses showed that the 129 shared DEGs belonged to nuclear acid metabolism and tissue development genes. Unique recall DEGs in WT mice were enriched in biological processes critical for synaptic plasticity and learning and memory, including the extracellular matrix network clustered around fibronectin 1 and collagens. In contrast, AS-specific DEGs were not enriched in any known pathways. These results suggest that memory recall in AS mice, while altering the transcriptome, fails to recruit memory-associated transcriptional programs, which could be responsible for the memory impairment in AS mice.

Uninterrupted embryonic growth leading to viviparous propagule formation in woody mangrove.

Vivipary is a rare sexual reproduction phenomenon where embryos germinate directly on the maternal plants. However, it is a common genetic event of woody mangroves in the Rhizophoraceae family. The ecological benefits of vivipary in mangroves include the nurturing of seedlings in harsh coastal and saline environments, but the genetic and molecular mechanisms of vivipary remain unclear. Here we investigate the viviparous embryo development and germination processes in mangrove Kandelia obovata by a transcriptomic approach. Many key biological pathways and functional genes were enriched in different tissues and stages, contributing to vivipary. Reduced production of abscisic acid set a non-dormant condition for the embryo to germinate directly. Genes involved in the metabolism of and response to other phytohormones (gibberellic acid, brassinosteroids, cytokinin, and auxin) are expressed precociously in the axis of non-vivipary stages, thus promoting the embryo to grow through the seed coat. Network analysis of these genes identified the central regulatory roles of LEC1 and FUS3, which maintain embryo identity in Arabidopsis. Moreover, photosynthesis related pathways were significantly up-regulated in viviparous embryos, and substance transporter genes were highly expressed in the seed coat, suggesting a partial self-provision and maternal nursing. We conclude that the viviparous phenomenon is a combinatorial result of precocious loss of dormancy and enhanced germination potential during viviparous seed development. These results shed light on the relationship between seed development and germination, where the continual growth of the embryo replaces a biphasic phenomenon until a mature propagule is established.

Adaptive roots of mangrove Avicennia marina: Structure and gene expressions analyses of pneumatophores.

The Avicennia marina is a mangrove species widely distributed throughout the tropical and subtropical intertidal wetlands. To adapt to adverse tidal waves and hypoxia environments, A. marina has evolved a sophisticated root system to better secure itself on the muddy soil with downward-grown anchor roots and upward-grown aerial roots, called pneumatophores. However, the process behind the development of a negative-gravitropic pneumatophore is not understood. Paraffin sections reveal anatomical differences among the shoots, anchor roots, and gas exchanging pneumatophores, clearly reflecting their functional diversions. The pneumatophore, in particular, contains abundant aerenchyma tissues and a thin cap structure at the tip. Transcriptomic analyses of both anchor roots and pneumatophores were performed to elucidate gene expression dynamics during the formation of pneumatophores. The results show that the plant hormone auxin regulates multiple different root initiations. The auxin related gene IAA19 plays a key role in pneumatophore development while the interaction of ethylene and abscisic acid is important for aerenchyma formation. Moreover, the molecular mechanisms behind pneumatophore anti-gravitropic growth may be regulated by the reduced strength of the statolith formation signaling pathway. These results shed light on the mechanistic understanding of pneumatophore formation in mangrove plants.

Changes in neurodegeneration-related miRNAs in brains from CAPN1-/- mice.

Calpain-1 knock-out (KO) mice exhibit enhanced susceptibility to neurodegeneration due to the lack of the neuroprotective function of calpain-1. Dicer has been shown to play a fundamental role in the biogenesis of most miRNAs. Here, we identified 45 differentially expressed miRNAs (DE miRNAs) in the brain of calpain-1 KO mice, as compared to wild-type mice. In particular, among all the DE miRNAs, 7 neurodegeneration-related miRNAs were found to be down-regulated in calpain-1 KO mice. We also found that Dicer is cleaved by calpain-1 in mouse brain, which generates an active fragment of Dicer with RNAse III activity and increases miRNA formation. Levels of active Dicer were reduced in brain homogenates from calpain-1 KO mice and incubation with calpain-1 and calcium restored Dicer activity and miRNA expression. Our results indicate that calpain-1 deletion results in decreased levels of active Dicer and changes in neurodegenerative-related miRNAs. These findings could account for some of the pathological changes found in brain of various mammals, including humans, with calpain-1 mutations or down-regulation.

Role of Calpain-1 in Neurogenesis.

While calpains have been implicated in neurogenesis for a long time, there is still little information regarding the specific contributions of various isoforms in this process. We took advantage of the availability of mutant mice with complete deletion of calpain-1 to analyze its contribution to neurogenesis. We first used the incorporation of BrdU in newly-generated cells in the subgranular zone of the dentate gyrus to determine the role of calpain-1 deletion in neuronal proliferation. Our results showed that the lack of calpain-1 decreased the rate of cell proliferation in adult hippocampus. As previously shown, it also decreased the long-term survival of newly-generated neurons. We also used data from previously reported RNA and miRNA sequencing analyses to identify differentially expressed genes in brain of calpain-1 knock-out mice related to cell division, cell migration, cell proliferation and cell survival. A number of differentially expressed genes were identified, which could play a significant role in the changes in neurogenesis in calpain-1 knock out mice. The results provide new information regarding the role of calpain-1 in neurogenesis and have implications for better understanding the pathologies associated with calpain-1 mutations in humans.

Chemically stable fluorescent anti-counterfeiting labels achieved by UV-induced photolysis of nanocellulose.

Carbon-based fluorescent security labels are effective methods to prevent counterfeiting. However, the properties of poor optical stability, complex and energy-consuming synthesis processes and weak bonding with substrates of carbon-based fluorescent materials limit their application prospects. Here, a novel in situ fluorescent patterning strategy is developed to achieve covert, chemically stable and solvent-tolerant cellulose-based security labels by UV exposure. The unsaturated double bonds as the origin of the fluorescence were generated during the photodegradation process under UV exposure. The fluorescent emission of cellulose-based materials reveals excellent stability under acidic, alkaline, reducing, oxidizing and non-polar solvent environments. These advantages give the cellulose nanofiber based security label fantastic potential applications.

OBV (obscure vein), a C2H2 zinc finger transcription factor, positively regulates chloroplast development and bundle sheath extension formation in tomato (Solanum lycopersicum) leaf veins.

Leaf veins play an important role in plant growth and development, and the bundle sheath (BS) is believed to greatly improve the photosynthetic efficiency of C4 plants. The OBV mutation in tomato (Solanum lycopersicum) results in dark veins and has been used widely in processing tomato varieties. However, physiological performance has difficulty explaining fitness in production. In this study, we confirmed that this mutation was caused by both the increased chlorophyll content and the absence of bundle sheath extension (BSE) in the veins. Using genome-wide association analysis and map-based cloning, we revealed that OBV encoded a C2H2L domain class transcription factor. It was localized in the nucleus and presented cell type-specific gene expression in the leaf veins. Furthermore, we verified the gene function by generating CRISPR/Cas9 knockout and overexpression mutants of the tomato gene. RNA sequencing analysis revealed that OBV was involved in regulating chloroplast development and photosynthesis, which greatly supported the change in chlorophyll content by mutation. Taken together, these findings demonstrated that OBV affected the growth and development of tomato by regulating chloroplast development in leaf veins. This study also provides a solid foundation to further decipher the mechanism of BSEs and to understand the evolution of photosynthesis in land plants.

Plasmonic nanopapers: flexible, stable and sensitive multiplex PUF tags for unclonable anti-counterfeiting applications.

Highly flexible and stable plasmonic nanopaper comprised of silver nanocubes and cellulose nanofibres was fabricated through a self-assembly-assisted vacuum filtration method. It shows significant enhancement of the fluorescence emission with an enhancement factor of 3.6 and Raman scattering with an enhancement factor of ∼104, excellent mechanical properties with tensile strength of 62.9 MPa and Young's modulus of 690.9 ± 40 MPa, and a random distribution of Raman intensity across the whole nanopaper. The plasmonic nanopapers were encoded with multiplexed optical signals including surface plasmon resonance, fluorescence and SERS for anti-counterfeiting applications, thus increasing security levels. The surface plasmon resonance and fluorescence information is used as the first layer of security and can be easily verified by the naked eye, while the unclonable SERS mapping is used as the second layer of security and can be readily authenticated by Raman spectroscopy using a computer vision technique.

Deletion of the Capn1 Gene Results in Alterations in Signaling Pathways Related to Alzheimer's Disease, Protein Quality Control and Synaptic Plasticity in Mouse Brain.

Calpains represent a family of calcium-dependent proteases participating in a multitude of functions under physiological or pathological conditions. Calpain-1 is one of the most studied members of the family, is ubiquitously distributed in organs and tissues, and has been shown to be involved in synaptic plasticity and neuroprotection in mammalian brain. Calpain-1 deletion results in a number of phenotypic alterations. While some of these alterations can be explained by the acute functions of calpain-1, the present study was directed at studying alterations in gene expression that could also account for these phenotypic modifications. RNA-seq analysis identified 354 differentially expressed genes (DEGs) in brain of calpain-1 knock-out mice, as compared to their wild-type strain. Most DEGs were classified in 10 KEGG pathways, with the highest representations in Protein Processing in Endoplasmic Reticulum, MAP kinase and Alzheimer's disease pathways. Most DEGs were down-regulated and validation of a number of these genes indicated a corresponding decreased expression of their encoded proteins. The results indicate that calpain-1 is involved in the regulation of a significant number of genes affecting multiple brain functions. They also indicate that mutations in calpain-1 are likely to be involved in a number of brain disorders.

Identification of putative key genes for coastal environments and cold adaptation in mangrove Kandelia obovata through transcriptome analysis.

Mangrove forests are an important contributor to the coastal marine environment. They have developed unique adaptations to the harsh coastal wetland, yet their geographic distribution is limited by environmental temperature. The adaptive strategies of mangrove at the molecular level, however, have not been addressed. In the present work, transcriptome analyses were performed on different cold damaged plants of a mangrove species, Kandelia obovata. From the samples collected in the field after a cold stress, we found that distinct expression profiles of many key genes are related to extreme temperature responses. These include transcription factors such as WRKY and bHLH, and other genes encoding proteins like SnRK2, PR-1, KCS, involving in the pathways of plant hormones, plant-pathogen interactions, and long chain fatty acid synthesis. We also examined the transcriptomes of eight tissues of K. obovata to identify candidate genes involved in adaptation and development. While stress-responsive genes were globally expressed, tissue-specific genes with diverse functions might be involved in tissue development and adaptability. For examples, genes encoding CYP724B1 and ABCB1 were specifically expressed in the fruit and root, respectively. Additionally, 26 genes were identified as positively selected genes in K. obovata, six of them were found to be involved in chilling stress response, seed germination and oxidation-reduction processes, suggesting their roles in stressful environment adaptation. Together, these results shed light into the K. obovata's natural responses to cold snaps at the molecular level, and reveal a global gene expression portrait across different tissues. It also provides a transcriptome resource for further molecular ecology studies and conservation planning of this and other mangrove plants in their native and adopted environments.

Photochemical route for synthesizing Co-P alloy decorated ZnIn2S4 with enhanced photocatalytic H2 production activity under visible light irradiation.

A series of amorphous Co-P alloy modified ZnIn2S4 composite samples were synthesized through a one-step photochemical method. The as-prepared samples were systematically characterized and the photocatalytic activity for H2 production under visible-light irradiation was investigated. It was found that the Co-P/ZnIn2S4 composite samples exhibited higher photocatalytic activity, which is 44 times higher than that of pure ZnIn2S4 and higher than that of the 1 wt% Pt/ZnIn2S4 sample. After modifying with amorphous Co-P alloy, the composite samples showed enhanced photocurrent, reduced photoelectric impedance, weakened fluorescence intensity and extended fluorescence lifetime, which accelerate the separation and transfer of photoinduced charge effectively, thus improving the catalytic activity of the composite sample. This work could provide a new strategy for the design and synthesis of low-cost, high-efficiency composite materials for photocatalytic hydrogen evolution and is promising for energy conversion and utilization.