A 3D hierarchical TiO2/CaIn2S4/C3N4arrays photoanode with dual-heterojunction for enhanced photoelectrochemical performance.

A novel 3D hierarchical TiO2/CaIn2S4/C3N4arrays with dual heterojunctions photoanode is constructed by stepwise deposition of CaIn2S4nanosheets and ultrathin C3N4onto the well-aligned TiO2nanorods arrays. Integrating the merit of the superior ability of CaIn2S4and C3N4to harvest visible light, dual type-Ⅱ heterojunction band structure and one-dimensional ordered nanostructures, the TiO2/CaIn2S4/C3N4photoanode exhibits simultaneous significant improvements in visible-light harvesting, charge separation and electron transfer capability. At 1.23 V (versus reversible hydrogen electrode) under AM 1.5 G irradiation, the TiO2/CaIn2S475/C3N4photoanode exhibits a photocurrent density of 4.5 mA cm-2, which is 5.2 and 51.1-fold higher than that of TiO2/CaIn2S475 and pristine TiO2photoanode, respectively. Moreover, the applied bias photo-to-current efficiency (ABPE) of the TiO2/CaIn2S475/C3N4photoanode reaches 3.5% at 0.36 V (versus reversible hydrogen electrode). These results are helpful for fabricating more efficient heterostructure photoelectrodes.

A novel proxy to examine interspecific phosphorus facilitation between plant species.

Resource complementarity can contribute to enhanced ecosystem functioning in diverse plant communities, but the role of facilitation in the enhanced complementarity is poorly understood. Here, we use leaf manganese concentration ([Mn]) as a proxy for rhizosheath carboxylate concentration to explore novel mechanisms of complementarity mediated by phosphorus (P) facilitation. In pot experiments, we showed that mixtures involving Carex korshinskyi, an efficient P-mobilizing species, exhibited greater biomass and relative complementarity effect than combinations without C. korshinskyi on P-deficient soils. Compared with monocultures, leaf [Mn] and [P] of species that are inefficient at P mobilization increased by 27% and 21% when grown with C. korshinskyi (i.e. interspecific P facilitation via carboxylates) rather than next to another inefficient P-mobilizing species. This experimental result was supported by a meta-analysis including a range of efficient P-mobilizing species. Phosphorus facilitation enhanced the relative complementarity effect in low-P environments, related to a greater change in several facilitated species of their root morphological traits relative to those in monoculture. Using leaf [Mn] as a proxy, we highlight a vital mechanism of interspecific P facilitation via belowground processes and provide evidence for the pivotal role of P facilitation mediated by the plasticity of root traits in biodiversity research.

Histone demethylase LSD2 acts as an E3 ubiquitin ligase and inhibits cancer cell growth through promoting proteasomal degradation of OGT.

Histone demethylases play important roles in various biological processes in a manner dependent on their demethylase activities. However, little is known about their demethylase-independent activities. Here, we report that LSD2, a well-known histone H3K4me1/me2 demethylase, possesses an unexpected E3 ubiquitin ligase activity. LSD2 directly ubiquitylates and promotes proteasome-dependent degradation of O-GlcNAc transferase (OGT), and inhibits A549 lung cancer cell growth in a manner dependent on its E3 ligase activity, but not demethylase activity. The depletion of LSD2 stabilizes OGT and promotes colony formation of 293T cells. LSD2 regulates distinct groups of target genes through histone demethylase and E3 ligase activities, respectively. Such regulation suggests a mechanism through which LSD2 suppresses tumorigenesis by promoting the degradation of OGT and other substrates yet to be discovered. Our study reveals an antigrowth function of LSD2 dependent on its E3 ligase activity and establishes a connection between histone demethylase and ubiquitin-dependent pathway.

Erythromycin Attenuates Hyperoxia Induced Lung Injury by Enhancing GSH Expression and Inhibiting Expression of Inflammatory Cytokines.

Introduction: Oxidative stress and inflammation have proven to be key factors contributing to the occurrence of BPD. Erythromycin has been shown to be effective in treating the redox imbalance seen in many non-bacterial infectious chronic inflammatory diseases. Methods: Ninety-six premature rats were randomly divided into air + saline chloride group, air + erythromycin group, hyperoxia + saline chloride group and hyperoxia + erythromycin group. Lung tissue specimens were collected from 8 premature rats in each group on days 1, 7 and 14, respectively. Results: Pulmonary pathological changes in premature rats after hyperoxia exposure were similar to those of BPD. Hyperoxia exposure induced high expression of GSH, TNF-α, and IL-1ß. Erythromycin intervention caused a further increase in GSH expression and a decrease in TNF-α and IL-1ß expression. Conclusion: GSH, TNF-α and IL-1ß are all involved in the development of BPD. Erythromycin may alleviate BPD by enhancing the expression of GSH and inhibiting the release of inflammatory mediators.

AtHD2D, a plant-specific histone deacetylase involved in abscisic acid response and lateral root development.

In eukaryotes, histone acetylation levels directly regulate downstream gene expression. As a plant-specific histone deacetylase (HDAC), HD2D is involved in plant development and abiotic stress. However, the response of HD2D to drought stress and its interacting proteins, is still unclear. In this study, we analysed HD2D gene expression patterns in Arabidopsis, revealing that HD2D gene was highly expressed in roots and rosette leaves, but poorly expressed in other tissues such as stems, flowers, and young siliques. The HD2D gene expression was induced by d-mannitol. We investigated the responses to drought stress in the wild-type plant, HD2D overexpression lines, and hd2d mutants. HD2D-overexpressing lines showed abscisic acid (ABA) hypersensitivity and drought tolerance, and these phenotypes were not present in hd2d mutants. RNA-seq analysis revealed the transcriptome changes caused by HD2D under drought stress, and showed that HD2D responded to drought stress via the ABA signalling pathway. In addition, we demonstrated that CASEIN KINASE II (CKA4) directly interacted with HD2D. The phosphorylation of Ser residues on HD2D by CKA4 enhanced HD2D enzymatic activity. Furthermore, the phosphorylation of HD2D was shown to contribute to lateral root development and ABA sensing in Arabidopsis, but, these phenotypes could not be reproduced by the overexpression of Ser-phospho-null HD2D lines. Collectively, this study suggests that HD2D responded to drought stress by regulating the ABA signalling pathway, and the expression of drought stress-related genes. The regulatory mechanism of HD2D mediated by CKII phosphorylation provides new insights into the ABA response and lateral root development in Arabidopsis.

Structure and Function of TET Enzymes.

Mammalian DNA methylation mainly occurs at the carbon-C5 position of cytosine (5mC). TET enzymes were discovered to successively oxidize 5mC to 5-hydromethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Ten-eleven translocation (TET) enzymes and oxidized 5mC derivatives play important roles in various biological and pathological processes, including regulation of DNA demethylation, gene transcription, embryonic development, and oncogenesis. In this chapter, we will discuss the discovery of TET-mediated 5mC oxidation and the structure, function, and regulation of TET enzymes. We start with brief descriptions of the mechanisms of TET-mediated 5mC oxidation and TET-dependent DNA demethylation. We then discuss the TET-mediated epigenetic reprogramming in pluripotency maintenance and embryogenesis, as well as in tumorigenesis and neural system. We further describe the structural basis for substrate recognition and preference in TET-mediated 5mC oxidation. Finally, we summarize the chemical molecules and interacting proteins that regulate TET's activity.

Structural insight into autoinhibition and histone H3-induced activation of DNMT3A.

DNA methylation is an important epigenetic modification that is essential for various developmental processes through regulating gene expression, genomic imprinting, and epigenetic inheritance. Mammalian genomic DNA methylation is established during embryogenesis by de novo DNA methyltransferases, DNMT3A and DNMT3B, and the methylation patterns vary with developmental stages and cell types. DNA methyltransferase 3-like protein (DNMT3L) is a catalytically inactive paralogue of DNMT3 enzymes, which stimulates the enzymatic activity of Dnmt3a. Recent studies have established a connection between DNA methylation and histone modifications, and revealed a histone-guided mechanism for the establishment of DNA methylation. The ATRX-DNMT3-DNMT3L (ADD) domain of Dnmt3a recognizes unmethylated histone H3 (H3K4me0). The histone H3 tail stimulates the enzymatic activity of Dnmt3a in vitro, whereas the molecular mechanism remains elusive. Here we show that DNMT3A exists in an autoinhibitory form and that the histone H3 tail stimulates its activity in a DNMT3L-independent manner. We determine the crystal structures of DNMT3A-DNMT3L (autoinhibitory form) and DNMT3A-DNMT3L-H3 (active form) complexes at 3.82 and 2.90 Å resolution, respectively. Structural and biochemical analyses indicate that the ADD domain of DNMT3A interacts with and inhibits enzymatic activity of the catalytic domain (CD) through blocking its DNA-binding affinity. Histone H3 (but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. The finding adds another layer of regulation of DNA methylation to ensure that the enzyme is mainly activated at proper targeting loci when unmethylated H3K4 is present, and strongly supports a negative correlation between H3K4me3 and DNA methylation across the mammalian genome. Our study provides a new insight into an unexpected autoinhibition and histone H3-induced activation of the de novo DNA methyltransferase after its initial genomic positioning.

Structural insight into substrate preference for TET-mediated oxidation.

DNA methylation is an important epigenetic modification. Ten-eleven translocation (TET) proteins are involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Here we show that human TET1 and TET2 are more active on 5mC-DNA than 5hmC/5fC-DNA substrates. We determine the crystal structures of TET2-5hmC-DNA and TET2-5fC-DNA complexes at 1.80 Å and 1.97 Å resolution, respectively. The cytosine portion of 5hmC/5fC is specifically recognized by TET2 in a manner similar to that of 5mC in the TET2-5mC-DNA structure, and the pyrimidine base of 5mC/5hmC/5fC adopts an almost identical conformation within the catalytic cavity. However, the hydroxyl group of 5hmC and carbonyl group of 5fC face towards the opposite direction because the hydroxymethyl group of 5hmC and formyl group of 5fC adopt restrained conformations through forming hydrogen bonds with the 1-carboxylate of NOG and N4 exocyclic nitrogen of cytosine, respectively. Biochemical analyses indicate that the substrate preference of TET2 results from the different efficiencies of hydrogen abstraction in TET2-mediated oxidation. The restrained conformation of 5hmC and 5fC within the catalytic cavity may prevent their abstractable hydrogen(s) adopting a favourable orientation for hydrogen abstraction and thus result in low catalytic efficiency. Our studies demonstrate that the substrate preference of TET2 results from the intrinsic value of its substrates at their 5mC derivative groups and suggest that 5hmC is relatively stable and less prone to further oxidation by TET proteins. Therefore, TET proteins are evolutionarily tuned to be less reactive towards 5hmC and facilitate the generation of 5hmC as a potentially stable mark for regulatory functions.

Protective effect of adrenomedullin on hyperoxia-induced lung injury. / è‚¾ä¸Šè ºé«“è´¨ç´ å¯¹é«˜æ°§è‚ºæŸä¼¤çš„ä¿æŠ¤ä½œç”¨ç ”ç©¶.

OBJECTIVES: To study the role of adrenomedullin (ADM) in hyperoxia-induced lung injury by examining the effect of ADM on the expression of calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein 2 (RAMP2), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB) in human pulmonary microvascular endothelial cells (HPMECs) under different experimental conditions. METHODS: HPMECs were randomly divided into an air group and a hyperoxia group (n=3 each).The HPMECs in the hyperoxia group were cultured in an atmosphere of 92% O2 (3 L/minute) +5% CO2. RT-qPCR and Western blot were used to measure the mRNA and protein expression levels of ADM, CRLR, RAMP2, ERK1/2, and PKB. Other HPMECs were divided into a non-interference group and an interference group (n=3 each), and the mRNA and protein expression levels of ADM, ERK1/2, and PKB were measured after the HPMECs in the interference group were transfected with ADM siRNA. RESULTS: Compared with the air group, the hyperoxia group had significant increases in the mRNA and protein expression levels of ADM, CRLR, RAMP2, ERK1/2, and PKB (P<0.05). Compared with the non-interference group, the interference group had significant reductions in the mRNA and protein expression levels of ADM, ERK1/2, and PKB (P<0.05). CONCLUSIONS: ERK1/2 and PKB may be the downstream targets of the ADM signaling pathway. ADM mediates the ERK/PKB signaling pathway by regulating CRLR/RAMP2 and participates in the protection of hyperoxia-induced lung injury.

Application of NMR metabolomics to search for human disease biomarkers in blood.

Recently, nuclear magnetic resonance spectroscopy (NMR)-based metabolomics analysis and multivariate statistical techniques have been incorporated into a multidisciplinary approach to profile changes in small molecules associated with the onset and progression of human diseases. The purpose of these efforts is to identify unique metabolite biomarkers in a specific human disease so as to (1) accurately predict and diagnose diseases, including separating distinct disease stages; (2) provide insights into underlying pathways in the pathogenesis and progression of the malady and (3) aid in disease treatment and evaluate the efficacy of drugs. In this review we discuss recent developments in the application of NMR-based metabolomics in searching disease biomarkers in human blood samples in the last 5 years.

The effect of self-referencing on memory for different kinds of source information.

Self-referential processing has been proven to be effective in improving source memory. However, it is unclear whether different types of source information would be consistently enhanced when an item is self-referentially processed. In two experiments, the authors examined the influence of the self (compared with other-referencing and semantic processing) as well as learning intention (incidental/intentional learning) on memory for two types of source information (spatial location and colour) that differ in the amount of cognitive resources they require to be encoded in memory. Results show that self-referencing has enhanced memory for spatial location of words whatever this information is learned intentionally or incidentally, whereas it cannot facilitate memory for the colour of words under the intentional learning condition, nor can it under the incidental condition. These findings suggest that self-referential processing is beneficial in memory improvement but not all-powerful, a source self-reference effect is subject to source information type.

Structure and Function of TET Enzymes.

Mammalian DNA methylation mainly occurs at the carbon-C5 position of cytosine (5mC). TET enzymes were discovered to successively oxidize 5mC to 5-hydromethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). TET enzymes and oxidized 5mC derivatives play important roles in various biological and pathological processes, including regulation of DNA demethylation, gene transcription, embryonic development, and oncogenesis. In this chapter, we will discuss the discovery of TET-mediated 5mC oxidation and the structure, function, and regulation of TET enzymes.

Ascorbic Acid Reprograms Epigenome and Epitranscriptome by Reducing Fe(III) in the Catalytic Cycle of Dioxygenases.

Ascorbic acid (ASC) has been reported to stimulate DNA iterative oxidase ten-eleven translocation (TET) enzymes, Jumonji C-domain-containing histone demethylases, and potentially RNA m6A demethylases FTO and ALKBH5 as a cofactor. Although ascorbic acid has been widely investigated in reprogramming DNA and histone methylation status in vitro, in cultured cells and mouse models, its specific role in the catalytic cycle of dioxygenases remains enigmatic. Here, we systematically investigated the stimulation of ASC toward TET2, ALKBH3, histone demethylases, and FTO. We find that ASC reprograms epitranscriptome by erasing the hypermethylated m6A sites in mRNA. Biochemistry and electron spin resonance assays demonstrate that ASC enters the active pocket of dioxygenases and reduces Fe(III), either incorporated upon protein synthesis or generated upon rebounding the hydroxyl radical during oxidation, into Fe(II). Finally, we propose a remedied model for the catalytic cycle of dioxygenases by adding in the essential cofactor, ASC, which refreshes and regenerates inactive dioxygenase through recycling Fe(III) into Fe(II) in a dynamic "hit-and-run" manner.

AtHD2D is involved in regulating lateral root development and participates in abiotic stress response in Arabidopsis.

Roots are essential to terrestrial plants, as their growth and morphology are crucial for plant development. The growth of the roots is affected and regulated by several internal and external environmental signals and metabolic pathways. Among them, chromatin modification plays an important regulatory role. In this study, we explore the potential roles of the histone deacetylase AtHD2D in root development and lay the foundation for further research on the biological processes and molecular mechanisms of AtHD2D in the future. Our study indicates that AtHD2D affects the root tip microenvironment homeostasis by affecting the gene transcription levels required to maintain the root tip microenvironment. In addition, we confirmed that AtHD2D is involved in regulating Arabidopsis lateral root development and further explained the possible role of AtHD2D in auxin-mediated lateral root development. AtHD2D can effectively enhance the resistance of Arabidopsis thaliana to abiotic stress. We believe that AtHD2D is involved in coping with abiotic stress by promoting the development of lateral roots. Overexpression of AtHD2D promotes the accumulation of reactive oxygen species (ROS) in roots, indicating that AtHD2D is also involved in developing lateral roots mediated by ROS. Previous studies have shown that the overexpression of AtHD2D can effectively enhance the resistance of Arabidopsis thaliana to abiotic stress. Based on our data, we believe that AtHD2D participates in the response to abiotic stress by promoting the development of lateral roots. AtHD2D-mediated lateral root development provides new ideas for studying the mechanism of HDAC protein in regulating root development.

Mediating role of anxiety and impulsivity in the association between child maltreatment and lifetime non-suicidal self-injury with and without suicidal self-injury.

BACKGROUND: Child maltreatment can increase the risk of lifetime non-suicidal self-injury (NSSI) and suicidal self-injury (SSI), but there is limited knowledge regarding the differences of potentially psychological mechanisms between NSSI with and without SSI. METHODS: Participants, 3918 community-based Chinese young men aged 18-34 years in Chengdu, were included in this study. We investigated the association between depression, anxiety, psychosis, child maltreatment, adulthood traumatic events, impulsivity, alcohol dependence, drug abuse, and lifetime of NSSI among participants with and without SSI. Parallel mediation analysis was utilized to explore the mediators for the relation between child maltreatment and NSSI. RESULTS: The prevalence of lifetime NSSI was 6.1 % (95 % CI: 5.4 %-6.9 %) among young men. Anxiety and impulsivity partially mediated the effect of child maltreatment on NSSI either with (indirect effect: 51.2 %) or without SSI (indirect effect: 34.3 %). Depression was independently and significantly associated with only NSSI but not with NSSI+SSI. Alcohol dependence and psychosis were independently and significantly associated with NSSI+SSI and mediated the effect of child maltreatment on NSSI+SSI. LIMITATIONS: The cross-sectional survey data limits the robustness of the proof to the causal relationships. CONCLUSIONS: Anxiety and impulsivity are associated with NSSI either with or without SSI and partially mediate the effect of child maltreatment on NSSI. Depression is associated with only NSSI, while alcohol dependence and psychosis are only associated with NSSI+SSI. It could be crucial to improve treatment and recovery of alcohol dependence and psychosis for preventing young men engaged in NSSI from attempting SSI.

Status of mandatory treatment of mentally ill offenders without criminal responsibility in China: Information from 5,262 mandatory treatment judgments.

Background: To avoid public health risks, all governments ensure monitoring and treatment of mentally ill persons if they offend and assess their level of criminal responsibility. The Criminal Procedure Law of the People's Republic of China (2013) instituted special procedures. However, there are few articles in English which explain the implementation of mandatory treatment procedures in China. Methods: We collected 5,262 qualified documents from 2013 to 2021 from the China Judgments Documents Online. We analyzed social demographic characteristics, trial-related information as well as the mandatory treatment-related content, to investigate the mandatory treatment of China's mentally ill offenders without criminal responsibility, from 2013 to 2021. Simple descriptive statistics and chi-square tests were used to compare differences among several types of documents. Results: There was an overall change trend of the number of documents: increasing year by year from 2013 to 2019 after the implementation of the new law, but with sharp decrease in 2020 and 2021 during covid-19 pandemic. From 2013 to 2021, a total of 3,854 people had applications made for mandatory treatment, of whom 3,747 (97.2%) were given mandatory treatment, 107 (2.8%) had applications rejected. "Schizophrenia and other psychotic disorders" was the most common diagnosis in both groups and all offenders receiving mandatory treatment (3,747, 100.0%) were considered to have no criminal responsibility. A total of 1,294 patients had applications made for relief of mandatory treatment, of whom 827 (63.9%) were subsequently approved for relief, 467 (36.1%) were rejected. A total of 118 patients had applications for relief two or more times, and 56 (47.5%) were finally relieved. Conclusion: Our study presents the Chinese model of a criminal mandatory treatment system to the international community which has been in operation since the implementation of the new law. Legislatory changes and covid-19 pandemic can have effect on the number of mandatory treatment cases. Patients, their close relatives and mandatory treatment institutions have the right to apply for relief from mandatory treatment, but the final decision in China is taken by the court.

NM23 Is a CP-Binding Protein Involved in Infectious Hypodermal and Hematopoietic Necrosis Virus Infection in Shrimp.

The aim of this study was to identify the putative host cell receptor for Infectious Hypodermal and Hematopoietic Necrosis Virus (IHHNV) CP in the gill membrane of L. vannamei. Putative CP binding partners were screened first using a 2-dimensional Virus Overlay Protein Blot Assay (VOPBA) to probe isolated gill membrane proteins using recombinant CP. Putative binding partners were identified using mass spectrometry. A Phage Display Random Dodecapeptide Library was used to screen for dodecapeptides and motifs that bound to CP. Finally, putative binding pairs were confirmed using GST(glutathione-S-transferase) pulldown assays. 2-Dimensional VOPBA identified NM23 as a putative binding partner for IHHNV CP. GST pulldown experiments confirmed the direct interaction of NM23 and IHHNV CP. The phage display library was used to identify six groups of dodecapeptides that bound to CP. From these peptides, three characteristic binding motifs were identified, SW*Y, SKWV, and PQR. Interestingly, the SW*Y motif was also found in NM23. We are the first to implicate NM23 in IHHNV infection and postulate that it may bind to the CP using the SW*Y motif, although this remains to be confirmed.

Pharmacokinetic changes for newer antiepileptic drugs and seizure control during pregnancy.

OBJECTIVE: To investigate pharmacokinetic changes in newer antiepileptic drugs (AEDs) and assess seizure frequencies and risk factors of increased seizures during pregnancy in women with epilepsy (WWE). METHODS: A total of 56 pregnancies in 53 WWE who received newer antiepileptic drugs (AEDs) were enrolled. Data on seizure activity and types, daily dose, and AEDs blood levels were derived from routine clinical follow-up. Changes in AEDs clearance were compared between each trimester and nonpregnant baseline. The ratio of AED levels of each trimester to their targets (nonpregnant baseline) concentrations (RTC) was compared between patients with and without an increased seizure. A binary logistic regression was used to investigate the risk factors contributing to seizure worsening during pregnancy. RESULTS: Increased clearances of LTG, LEV, and OXC were observed in all trimesters versus nonpregnant baseline. The peak changes in the clearance of LTG (3.42-fold baseline clearance) (p < 0.001) and LEV (2.78-fold) (p < 0.001) occurred in the second trimester during pregnancy, followed by oxcarbazepine (2.11-fold) in the third trimester (p < 0.03). Plasma concentrations of LTG and LEV during pregnancy were significantly decreased compared to baseline levels, except for OXC. However, no significant differences in RTC values were observed between patients with and without seizure worsening. Some risk factors as seizures for the prior nine months could significantly affect seizure frequency during pregnancy. CONCLUSION: We found substantial changes in the pharmacokinetics of multiple newer AEDs in WWE, reinforcing the need for therapeutic drug monitoring (TDM) during pregnancy. We would encourage at least one monitoring every trimester and probably more frequently for women with poorly seizure control before pregnancy, and AEDs dose adjustment should keep up with clearance changes. In addition, a well-controlled seizure nine months before pregnancy could lower the risks of seizure during pregnancy, highlighting the importance of pre-pregnancy counseling and seizure management before pregnancy.

Structures of +1 nucleosome-bound PIC-Mediator complex.

RNA polymerase II-mediated eukaryotic transcription starts with the assembly of the preinitiation complex (PIC) on core promoters. The +1 nucleosome is well positioned about 40 base pairs downstream of the transcription start site (TSS) and is commonly known as a barrier of transcription. The +1 nucleosome-bound PIC-Mediator structures show that PIC-Mediator prefers binding to T40N nucleosome located 40 base pairs downstream of TSS and contacts T50N but not the T70N nucleosome. The nucleosome facilitates the organization of PIC-Mediator on the promoter by binding TFIIH subunit p52 and Mediator subunits MED19 and MED26 and may contribute to transcription initiation. PIC-Mediator exhibits multiple nucleosome-binding patterns, supporting a structural role of the +1 nucleosome in the coordination of PIC-Mediator assembly. Our study reveals the molecular mechanism of PIC-Mediator organization on chromatin and underscores the significance of the +1 nucleosome in regulating transcription initiation.

The effect of value on long-term associative memory.

Items with high value are often remembered better than those with low value. It is not clear, however, whether this value effect extends to the binding of associative details (e.g., word colour) in episodic memory. Here, we explored whether value enhances memory for associative information in two different scenarios that might support a more effective process of binding between identity and colour. Experiment 1 examined incidental binding between item and colour using coloured images of familiar objects, whereas Experiment 2 examined intentional learning of word colour. In both experiments, increasing value led to improvements in memory for both item and colour, and these effects persisted after approximately 24 hr. Experiment 3a and Experiment 3b replicated the value effect on intentional word-colour memory from Experiment 2 while also demonstrating this effect to be less reliable when word colour is incidental to the encoding phase. Thus, value-directed prioritisation can facilitate episodic associative memory when conditions for binding are optimised through the use of appropriate to-be remembered materials and encoding conditions.