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1.
Genes (Basel) ; 15(4)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38674345

ABSTRACT

Integrated networks have become a new interest in genome-scale network research due to their ability to comprehensively reflect and analyze the molecular processes in cells. Currently, none of the integrated networks have been reported for higher organisms. Eriocheir sinensis is a typical aquatic animal that grows through ecdysis. Ecdysone has been identified to be a crucial regulator of ecdysis, but the influence factors and regulatory mechanisms of ecdysone synthesis in E. sinensis are still unclear. In this work, the genome-scale metabolic network and protein-protein interaction network of E. sinensis were integrated to reconstruct a metabolic-protein interaction integrated network (MPIN). The MPIN was used to analyze the influence factors of ecdysone synthesis through flux variation analysis. In total, 236 integrated reactions (IRs) were found to influence the ecdysone synthesis of which 16 IRs had a significant impact. These IRs constitute three ecdysone synthesis routes. It is found that there might be alternative pathways to obtain cholesterol for ecdysone synthesis in E. sinensis instead of absorbing it directly from the feeds. The MPIN reconstructed in this work is the first integrated network for higher organisms. The analysis based on the MPIN supplies important information for the mechanism analysis of ecdysone synthesis in E. sinensis.


Subject(s)
Brachyura , Ecdysone , Protein Interaction Maps , Ecdysone/metabolism , Animals , Brachyura/metabolism , Brachyura/genetics , Metabolic Networks and Pathways
2.
Curr Issues Mol Biol ; 46(4): 3676-3693, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38666959

ABSTRACT

Artemia is a widely distributed small aquatic crustacean, renowned for its ability to enter a state of embryonic diapause. The embryonic diapause termination (EDT) is closely linked to environmental cues, but the precise underlying mechanisms remain elusive. In this study, ATAC-seq and RNA-seq sequencing techniques were employed to explore the gene expression profiles in Artemia cysts 30 min after EDT. These profiles were compared with those during diapause and 5 h after EDT. The regulatory mechanisms governing the EDT process were analyzed through Gene Ontology (GO) enrichment analysis of differentially expressed genes. Furthermore, the active G-protein-coupled receptors (GPCRs) were identified through structural analysis. The results unveiled that the signaling transduction during EDT primarily hinges on GPCRs and the cell surface receptor signaling pathway, but distinct genes are involved across different stages. Hormone-mediated signaling pathways and the tachykinin receptor signaling pathway exhibited heightened activity in the '0-30 min' group, whereas the Wnt signaling pathway manifested its function solely in the '30 min-5 h' group. These results imply a complete divergence in the mechanisms of signal regulation during these two stages. Moreover, through structural analysis, five GPCRs operating at different stages of EDT were identified. These findings provide valuable insights into the signal regulation mechanisms governing Artemia diapause.

3.
Nature ; 627(8005): 797-804, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38480894

ABSTRACT

Evidence shows a continuing increase in the frequency and severity of global heatwaves1,2, raising concerns about the future impacts of climate change and the associated socioeconomic costs3,4. Here we develop a disaster footprint analytical framework by integrating climate, epidemiological and hybrid input-output and computable general equilibrium global trade models to estimate the midcentury socioeconomic impacts of heat stress. We consider health costs related to heat exposure, the value of heat-induced labour productivity loss and indirect losses due to economic disruptions cascading through supply chains. Here we show that the global annual incremental gross domestic product loss increases exponentially from 0.03 ± 0.01 (SSP 245)-0.05 ± 0.03 (SSP 585) percentage points during 2030-2040 to 0.05 ± 0.01-0.15 ± 0.04 percentage points during 2050-2060. By 2060, the expected global economic losses reach a total of 0.6-4.6% with losses attributed to health loss (37-45%), labour productivity loss (18-37%) and indirect loss (12-43%) under different shared socioeconomic pathways. Small- and medium-sized developing countries suffer disproportionately from higher health loss in South-Central Africa (2.1 to 4.0 times above global average) and labour productivity loss in West Africa and Southeast Asia (2.0-3.3 times above global average). The supply-chain disruption effects are much more widespread with strong hit to those manufacturing-heavy countries such as China and the USA, leading to soaring economic losses of 2.7 ± 0.7% and 1.8 ± 0.5%, respectively.

4.
Environ Res ; 251(Pt 2): 118644, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38485074

ABSTRACT

Tetracycline hydrochloride (TC) accumulates in large quantities in the water environment, causing a serious threat to human health and ecological environment safety. This research focused on developing cost-effective catalysts with high 2e- selectivity for electro-Fenton (EF) technology, a green pollution treatment method. Defective nitrogen-doped porous carbon (d-NPC) was prepared using the metal-organic framework as the precursor to achieve in-situ H2O2 production and self-decomposition into high activity ·OH for degradation of TC combined with Co2+/Co3+. The d-NPC produced 172.1 mg L-1 H2O2 within 120 min, and could degrade 96.4% of TC in EF system. The self-doped defects and graphite-nitrogen in d-NPC improved the oxygen reduction performance and increased the H2O2 yield, while pyridine nitrogen could catalyze H2O2 to generate ·OH. The possible pathway of TC degradation was also proposed. In this study, defective carbon materials were prepared by ball milling, which provided a new strategy for efficient in-situ H2O2 production and the degradation of pollutants.


Subject(s)
Carbon , Hydrogen Peroxide , Nitrogen , Tetracycline , Water Pollutants, Chemical , Hydrogen Peroxide/chemistry , Nitrogen/chemistry , Carbon/chemistry , Tetracycline/chemistry , Water Pollutants, Chemical/chemistry , Metal-Organic Frameworks/chemistry , Iron/chemistry
5.
Environ Res ; 249: 118362, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38325787

ABSTRACT

Sulfate radical-based advanced oxidation processes with (SR-AOPs) are widely employed to degrade organic pollutants due to their high efficiency, cost-effectiveness and safety. In this study, a highly active and stable FeNiP was successfully prepared by reduction and heat treatment. FeNiP exhibited high performance of peroxymonosulfate (PMS) activation for tetracycline hydrochloride (TC) removal. Over a wide pH range, an impressive TC degaradation efficiency 97.86% was achieved within 60 min employing 0.1 g/L FeNiP and 0.2 g/L PMS at room temperature. Both free radicals of SO4·-, ·OH, ·O2- and non-free radicals of 1O2 participated the TC degradation in the FeNiP/PMS system. The PMS activation ability was greatly enhanced by the cycling between Ni and Fe bimetal, and the active site regeneration was achieved due to the existence of the negatively charged Pn-. Moreover, the FeNiP/PMS system exhibited substantial TC degradation levels in both simulated real-world disturbance scenarios and practical water tests. Cycling experiments further affirmed the robust stability of FeNiP catalyst, demonstrating sustained degradation efficiency of approximately 80% even after four cycles. These findings illuminate its promising potential across natural water bodies, presenting an innovative catalyst construction approach for PMS activation in the degradation of antibiotic pollutants.


Subject(s)
Iron , Peroxides , Tetracycline , Water Pollutants, Chemical , Tetracycline/chemistry , Water Pollutants, Chemical/chemistry , Peroxides/chemistry , Iron/chemistry , Nickel/chemistry , Anti-Bacterial Agents/chemistry , Oxidation-Reduction , Water Purification/methods
6.
Front Psychiatry ; 15: 1292877, 2024.
Article in English | MEDLINE | ID: mdl-38419907

ABSTRACT

Introduction: Internet addiction disorder (IAD) has grown into public health concern of global proportions. Previous studies have indicated that individuals with IAD may exhibit altered levels of serotonin and dopamine, which are known to play crucial roles in depression, anxiety, impulsivity, and addiction. Therefore, polymorphisms in the receptors that mediate the effects of serotonin and dopamine and affect their functional states as well as their activities are suspect. In this study, we aimed to investigate the association between IAD and rs6313 (T102C) polymorphism in the serotonin 2A receptor (5-HT2A) gene, (HTR2A). Methods: Twenty patients with IAD and twenty healthy controls (HCs) were included in this study. Young's Internet Addiction Test (IAT), Self-Rating Anxiety Scale, Self-Rating Depression Scale, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Barratt Impulse Scale, Pittsburgh Sleep Quality Index (PSQI), and Social Support Rating Scale (SSRS) were used to assess the severity of internet addiction, mental status, impulsive traits, sleep quality, and social support. Genotyping was performed to identify rs6313 polymorphisms in the HTR2A gene of all participants. Results: The frequencies of the C and T alleles of HTR2A T102C were 28% and 72% in the IAD group and 53% and 47% in the HCs group, respectively, indicating that the differences between these two groups were significant. No significant difference was observed in the distribution of the CC, CT, and TT genotypes of HTR2A gene T102C between the IAD and the HCs groups. Additionally, there was no difference in the distribution of the frequencies of the HTR2A gene T102C CC and CT+TT genotypes between the two groups. However, the distribution between the TT and CC+CT genotypes showed an apparent statistical difference in the HTR2A gene T102C between the two groups. Correlation analysis indicated that the IAT score was positively correlated with the Y-BOCS and BIS scores for the CC+CT genotype in patients with IAD. Moreover, the IAT score was positively correlated with the PSQI score in patients with IAD carrying the TT genotype. Conclusion: The present study demonstrates that rs6313 in HTR2A is associated with IAD, and that the T allele of rs6313 in HTR2A may be a risk factor for IAD.

7.
Environ Res ; 248: 118264, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38266894

ABSTRACT

Oil/water separation has become a global concern due to the increasing discharge of multi-component harmful oily wastewater. Super wetting membranes have been shown to be an effective material for oil/water separation. Ultra-high flux stainless-steel meshes (SSM) with superhydrophilicity and underwater superoleophobicity were fabricated by tannic acid (TA) modified ZIF-8 nanoparticles (TZIF-8) and two-dimensional MXene materials for oil/water separation. The TZIF-8 increased the interlayer space of MXene, enhancing the flux permeation (69,093 L m-2h-1) and rejection of the composite membrane (TZIF-8@MXene/SSM). The TZIF-8@MXene/SSM membrane showed an underwater oil contact angle of 154.2°. The membrane maintained underwater superoleophobic after stability and durability tests, including various pH solutions, organic solvents, reusability, etc. In addition, the oil/water separation efficiency of TZIF-8@MXene/SSM membranes was higher than 99% after treatment in harsh conditions and recycling. The outstanding anti-fouling, stability, durability, and recyclability properties of TZIF-8@MXene/SSM membrane highlight the remarkable potential of membranes for complex oil/water separation process.


Subject(s)
Nanoparticles , Polyphenols , Transition Elements , Membranes , Nitrites , Stainless Steel
8.
Stress Biol ; 3(1): 37, 2023 Sep 06.
Article in English | MEDLINE | ID: mdl-37981586

ABSTRACT

Among the plant molecular mechanisms capable of effectively mitigating the effects of adverse weather conditions, the heat shock proteins (HSPs), a group of chaperones with multiple functions, stand out. At a time of full progress on the omic sciences, they look very promising in the genetic engineering field, especially in order to conceive superior genotypes, potentially tolerant to abiotic stresses (AbSts). Recently, some works concerning certain families of maize HSPs (ZmHSPs) were published. However, there was still a lack of a study that, with a high degree of criteria, would fully conglomerate them. Using distinct but complementary strategies, we have prospected as many ZmHSPs candidates as possible, gathering more than a thousand accessions. After detailed data mining, we accounted for 182 validated ones, belonging to seven families, which were subcategorized into classes with potential for functional parity. In them, we identified dozens of motifs with some degree of similarity with proteins from different kingdoms, which may help explain some of their still poorly understood means of action. Through in silico and in vitro approaches, we compared their expression levels after controlled exposure to several AbSts' sources, applied at diverse tissues, on varied phenological stages. Based on gene ontology concepts, we still analyzed them from different perspectives of term enrichment. We have also searched, in model plants and close species, for potentially orthologous genes. With all these new insights, which culminated in a plentiful supplementary material, rich in tables, we aim to constitute a fertile consultation source for those maize researchers attracted by these interesting stress proteins.

9.
Cell Rep ; 42(12): 113460, 2023 12 26.
Article in English | MEDLINE | ID: mdl-37979168

ABSTRACT

The recruitment of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors underlies the strengthening of neuronal connectivity during learning and memory. This process is triggered by N-methyl-D-aspartate (NMDA) receptor-dependent postsynaptic Ca2+ influx. Synaptotagmin (Syt)-1 and -7 have been proposed as Ca2+ sensors for AMPA receptor exocytosis but are functionally redundant. Here, we identify a cytosolic C2 domain-containing Ca2+-binding protein, Copine-6, that forms a complex with AMPA receptors. Loss of Copine-6 expression impairs activity-induced exocytosis of AMPA receptors in primary neurons, which is rescued by wild-type Copine-6 but not Ca2+-binding mutants. In contrast, Copine-6 loss of function does not affect steady-state expression or tetrodotoxin-induced synaptic upscaling of surface AMPA receptors. Loss of Syt-1/Syt-7 significantly reduces Copine-6 protein expression. Interestingly, overexpression of wild-type Copine-6, but not the Ca2+-binding mutants, restores activity-dependent exocytosis of AMPA receptors in Syt-1/Syt-7 double-knockdown neurons. We conclude that Copine-6 is a postsynaptic Ca2+ sensor that mediates AMPA receptor exocytosis during synaptic potentiation.


Subject(s)
Exocytosis , Receptors, AMPA , Receptors, AMPA/metabolism , Exocytosis/physiology , Neurons/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Calcium/metabolism
10.
Brain Behav ; 13(11): e3241, 2023 11.
Article in English | MEDLINE | ID: mdl-37721727

ABSTRACT

BACKGROUND: Internet addiction (IA), recognized as a behavioral addiction, is emerging as a global public health problem. Acupuncture has been demonstrated to be effective in alleviating IA; however, the mechanism is not yet clear. To fill this knowledge gap, our study aimed to investigate the modulatory effects of acupuncture on the functional interactions among the addiction-related networks in adolescents with IA. METHODS: Thirty individuals with IA and thirty age- and sex-matched healthy control subjects (HCs) were recruited. Subjects with IA were given a 40-day acupuncture treatment, and resting-state functional magnetic resonance imaging (fMRI) data were collected before and after acupuncture sessions. HCs received no treatment and underwent one fMRI scan after enrollment. The intergroup differences in functional connectivity (FC) among the subcortical nucleus (SN) and fronto-parietal network (FPN) were compared between HCs and subjects with IA at baseline. Then, the intragroup FC differences between the pre- and post-treatment were analyzed in the IA group. A multiple linear regression model was further employed to fit the FC changes to symptom relief in the IA group. RESULTS: In comparison to HCs, subjects with IA exhibited significantly heightened FC within and between the SN and FPN at baseline. After 40 days of acupuncture treatment, the FC within the FPN and between the SN and FPN were significantly decreased in individuals with IA. Symptom improvement in subjects with IA was well fitted by the decrease in FC between the left midbrain and ventral prefrontal cortex and between the left thalamus and ventral anterior prefrontal cortex. CONCLUSION: These findings confirmed the modulatory effects of acupuncture on the aberrant functional interactions among the SN and FPN, which may partly reflect the neurophysiological mechanism of acupuncture for IA.


Subject(s)
Acupuncture Therapy , Internet Addiction Disorder , Humans , Adolescent , Magnetic Resonance Imaging/methods , Prefrontal Cortex , Acupuncture Therapy/methods , Thalamus , Seizures , Brain , Brain Mapping/methods
11.
J Neurosci ; 43(30): 5448-5457, 2023 07 26.
Article in English | MEDLINE | ID: mdl-37419688

ABSTRACT

Activity-dependent changes in the number of AMPA-type glutamate receptors (AMPARs) at the synapse underpin the expression of LTP and LTD, cellular correlates of learning and memory. Post-translational ubiquitination has emerged as a key regulator of the trafficking and surface expression of AMPARs, with ubiquitination of the GluA1 subunit at Lys-868 controlling the post-endocytic sorting of the receptors into the late endosome for degradation, thereby regulating their stability at synapses. However, the physiological significance of GluA1 ubiquitination remains unknown. In this study, we generated mice with a knock-in mutation in the major GluA1 ubiquitination site (K868R) to investigate the role of GluA1 ubiquitination in synaptic plasticity, learning, and memory. Our results reveal that these male mice have normal basal synaptic transmission but exhibit enhanced LTP and deficits in LTD. They also display deficits in short-term spatial memory and cognitive flexibility. These findings underscore the critical roles of GluA1 ubiquitination in bidirectional synaptic plasticity and cognition in male mice.SIGNIFICANCE STATEMENT Subcellular targeting and membrane trafficking determine the precise number of AMPA-type glutamate receptors at synapses, processes that are essential for synaptic plasticity, learning, and memory. Post-translational ubiquitination of the GluA1 subunit marks AMPARs for degradation, but its functional role in vivo remains unknown. Here we demonstrate that the GluA1 ubiquitin-deficient mice exhibit an altered threshold for synaptic plasticity accompanied by deficits in short-term memory and cognitive flexibility. Our findings suggest that activity-dependent ubiquitination of GluA1 fine-tunes the optimal number of synaptic AMPARs required for bidirectional synaptic plasticity and cognition in male mice. Given that increases in amyloid-ß cause excessive ubiquitination of GluA1, inhibiting that GluA1 ubiquitination may have the potential to ameliorate amyloid-ß-induced synaptic depression in Alzheimer's disease.


Subject(s)
Neuronal Plasticity , Receptors, AMPA , Mice , Male , Animals , Receptors, AMPA/metabolism , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism , Neuronal Plasticity/physiology , Synapses/physiology , Receptors, Glutamate/metabolism , Ubiquitination , Cognition , Hippocampus/metabolism
12.
Front Psychiatry ; 13: 918729, 2022.
Article in English | MEDLINE | ID: mdl-36032227

ABSTRACT

Objective: The aim of this study was to observe the efficacy of electroacupuncture (EA) and psychotherapy (PT) effect on the mental status, sleep quality and impulsive trait in patients with pathological internet use, and to observe the changes of Monoamine oxidase type A (MAOA) messenger Ribonucleic acid (mRNA) levels in each group. Methods: A total of 60 PIU patients were included for the present study. These patients were randomly divided into two groups: EA group and PT group. Baihui, Sishencong, Hegu, Neiguan, Shenmen, Taichong, Sanyinjiao and Xuanzhong were selected for acupuncture in the EA group, while group psychotherapy combined with individual psychotherapy was used for intervention in patients in the PT group. Young's Internet addiction Test (IAT), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Barratt Impulse Scale (BIS-11) and Pittsburgh Sleep Quality Index (PSQI) were used to observe the severity of Internet addiction, mental status, sleep quality and impulsive trait of all patients at baseline and 40th days of treatment; and MAOA mRNA data were collected at baseline and 40th days of treatment. Results: Electroacupuncture and psychological intervention effectively reduced IAT, SAS, SDS, Y-BOCS, BIS and PSQI scores of PIU patients. After 40 days treatment, the MAOA expression of the PT group was increased, and there was no significant change in EA group. The correlation analysis indicated that IAT scores were positively correlated with SAS, SDS, Y-BOCS, BIS and PSQI at baseline. In addition, after treatment the EA group showed that the change in IAT scores was positively correlated with the change in Y-BOCS and BIS scores, and the PT group showed that the change in IAT scores was positively correlated with the change in SDS, BIS and PSQI scores. Conclusion: The present study showed that electroacupuncture and psychological intervention can improve severity of Internet addiction, mental status, sleep quality and impulsive trait of PIU patients. Simultaneously, neurobiological changes may be the underlying mechanisms of psychotherapy for internet additcion.

14.
Front Psychiatry ; 12: 667699, 2021.
Article in English | MEDLINE | ID: mdl-34335325

ABSTRACT

Objective: Uncontrolled internet use may lead to the emergence of pathological internet use (PIU). PIU has become a global public health concern that can cause a range of psychotic symptoms, including anxiety, depression, and impulse control disorder. To date, we know very little about the principal biological factors related to PIU. Monoamine oxidase type A (MAOA) and serotonin (5-HT) 5-HT2A receptor (5-HT2AR) play critical roles in the development of behavioural and drug addictions. Thus, the aim of this study was to measure the relative expression of mRNA of MAOA and 5-HT2AR in peripheral blood mononuclear cells (PBMCs) of patients with PIU and to determine the correlations between these biological indicators and the comorbid symptoms of patients with PIU. Methods: In this study, the mRNA of MAOA and 5-HT2AR was detected using real-time PCR in PBMCs of the patients with PIU (n = 24) and healthy controls (HCs, n = 25). The relationship between the mRNA levels of MAOA and 5-HT2AR and clinical symptoms in patients with PIU was further investigated. Results: MAOA mRNA in PBMCs was significantly upregulated in patients with PIU compared with that in HCs. mRNA levels of 5-HT2AR were not found to differ significantly between HCs and patients with PIU. Correlation analyses further revealed a significant positive correlation between the relative expression of MAOA mRNA in PBMCs of patients with PIU and the Young's Internet Addiction Test and Self-Rating Depression Scale scores. Conclusion: The present study revealed upregulated expression of MAOA mRNA in patients with PIU and an association between the expression of MAOA mRNA and clinical symptoms of PIU, suggesting that the neurobiological changes may be similar between PIU and substance addiction. Additionally, this study demonstrated a potential association between comorbid symptoms and mRNA levels of MAOA.

15.
Front Neurosci ; 15: 665578, 2021.
Article in English | MEDLINE | ID: mdl-34220426

ABSTRACT

Although mounting neuroimaging studies have greatly improved our understanding of the neurobiological mechanism underlying internet addiction (IA), the results based on traditional group-level comparisons are insufficient in guiding individual clinical practice directly. Specific neuroimaging biomarkers are urgently needed for IA diagnosis and the evaluation of therapy efficacy. Therefore, this study aimed to develop support vector machine (SVM) models to identify IA and assess the efficacy of cognitive behavior therapy (CBT) based on unbiased functional connectivity density (FCD). Resting-state fMRI data were acquired from 27 individuals with IA before and after 8-week CBT sessions and 30 demographically matched healthy controls (HCs). The discriminative FCDs were computed as the features of the support vector classification (SVC) model to identify individuals with IA from HCs, and the changes in these discriminative FCDs after treatment were further used as features of the support vector regression (SVR) model to evaluate the efficacy of CBT. Based on the informative FCDs, our SVC model successfully differentiated individuals with IA from HCs with an accuracy of 82.5% and an area under the curve (AUC) of 0.91. Our SVR model successfully evaluated the efficacy of CBT using the FCD change ratio with a correlation efficient of 0.59. The brain regions contributing to IA classification and CBT efficacy assessment were the left inferior frontal cortex (IFC), middle frontal cortex (MFC) and angular gyrus (AG), the right premotor cortex (PMC) and middle cingulate cortex (MCC), and the bilateral cerebellum, orbitofrontal cortex (OFC) and superior frontal cortex (SFC). These findings confirmed the FCDs of hyperactive impulsive habit system, hypoactive reflecting system and sensitive interoceptive reward awareness system as potential neuroimaging biomarkers for IA, which might provide objective indexes for the diagnosis and efficacy evaluation of IA.

16.
Cell Rep ; 36(1): 109338, 2021 07 06.
Article in English | MEDLINE | ID: mdl-34233182

ABSTRACT

NMDA receptor (NMDAR)-dependent Ca2+ influx underpins multiple forms of synaptic plasticity. Most synaptic NMDAR currents in the adult forebrain are mediated by GluN2A-containing receptors, which are rapidly inserted into synapses during long-term potentiation (LTP); however, the underlying molecular mechanisms remain poorly understood. In this study, we show that GluN2A is phosphorylated at Ser-1459 by Ca2+/calmodulin-dependent kinase IIα (CaMKIIα) in response to glycine stimulation that mimics LTP in primary neurons. Phosphorylation of Ser-1459 promotes GluN2A interaction with the sorting nexin 27 (SNX27)-retromer complex, thereby enhancing the endosomal recycling of NMDARs. Loss of SNX27 or CaMKIIα function blocks the glycine-induced increase in GluN2A-NMDARs on the neuronal membrane. Interestingly, mutations of Ser-1459, including the rare S1459G human epilepsy variant, prolong the decay times of NMDAR-mediated synaptic currents in heterosynapses by increasing the duration of channel opening. These findings not only identify a critical role of Ser-1459 phosphorylation in regulating the function of NMDARs, but they also explain how the S1459G variant dysregulates NMDAR function.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Ion Channel Gating , Protein Subunits/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Amino Acid Sequence , Animals , Female , Glycine , HEK293 Cells , Humans , Models, Biological , Mutation/genetics , Nerve Tissue Proteins , Phosphorylation , Phosphoserine/metabolism , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/chemistry , Receptors, N-Methyl-D-Aspartate/genetics , Synapses/metabolism
17.
J Integr Plant Biol ; 63(8): 1462-1474, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33960113

ABSTRACT

In eukaryotes, histone acetylation is a major modification on histone N-terminal tails that is tightly connected to transcriptional activation. HDA6 is a histone deacetylase involved in the transcriptional regulation of genes and transposable elements (TEs) in Arabidopsis thaliana. HDA6 has been shown to participate in several complexes in plants, including a conserved SIN3 complex. Here, we uncover a novel protein complex containing HDA6, several Harbinger transposon-derived proteins (HHP1, SANT1, SANT2, SANT3, and SANT4), and MBD domain-containing proteins (MBD1, MBD2, and MBD4). We show that mutations of all four SANT genes in the sant-null mutant cause increased expression of the flowering repressors FLC, MAF4, and MAF5, resulting in a late flowering phenotype. Transcriptome deep sequencing reveals that while the SANT proteins and HDA6 regulate the expression of largely overlapping sets of genes, TE silencing is unaffected in sant-null mutants. Our global histone H3 acetylation profiling shows that SANT proteins and HDA6 modulate gene expression through deacetylation. Collectively, our findings suggest that Harbinger transposon-derived SANT domain-containing proteins are required for histone deacetylation and flowering time control in plants.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/genetics , DNA Transposable Elements/genetics , Domestication , Genes, Plant , Histone Deacetylases/metabolism , Histones/metabolism , Transposases/metabolism , Acetylation , Flowers/physiology , Gene Expression Regulation, Plant , Models, Biological , Phenotype , Protein Interaction Maps , Repressor Proteins/metabolism
18.
Medicine (Baltimore) ; 100(12): e24872, 2021 Mar 26.
Article in English | MEDLINE | ID: mdl-33761645

ABSTRACT

BACKGROUND: Internet addiction (IA) has become a global problem characterized by excessive use of the internet, compulsive, and deleterious personal behaviors. Acupuncture has gained more and more attention in the treatment of IA. However, evidence of its effectiveness is lacking. The purpose of this systematic review is to evaluate the efficacy and safety of acupuncture in the treatment of IA. METHODS: The following databases will be searched from the inception to September 30, 2020: the Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wan-fang database, Chinese Biomedical Literature Database, and Chinese Scientific Journal Database. The research on acupuncture and IA meets the screening criteria, and two independent reviewers performed citation screening, data extraction, and risk assessment of bias. We used Cochrane Review Manager 5.3 software for statistical analysis. RESULTS: The findings will be published at scientific conferences or in a peer-reviewed journal. This study is based on the existing research, so there is no need for ethical approval. CONCLUSION: This systematic review provides evidence for the efficacy of acupuncture in treating IA disorder, and it is of great significance for effective clinical routine treatment of IA. TRIAL REGISTRATION NUMBER: INPLASY 2020120099.


Subject(s)
Acupuncture Therapy , Internet Addiction Disorder/therapy , Systematic Reviews as Topic , Acupuncture Therapy/adverse effects , China , Humans , Research Design , Treatment Outcome
19.
Nat Commun ; 11(1): 6212, 2020 12 04.
Article in English | MEDLINE | ID: mdl-33277495

ABSTRACT

Histone 3 Lys 27 trimethylation (H3K27me3)-mediated epigenetic silencing plays a critical role in multiple biological processes. However, the H3K27me3 recognition and transcriptional repression mechanisms are only partially understood. Here, we report a mechanism for H3K27me3 recognition and transcriptional repression. Our structural and biochemical data showed that the BAH domain protein AIPP3 and the PHD proteins AIPP2 and PAIPP2 cooperate to read H3K27me3 and unmodified H3K4 histone marks, respectively, in Arabidopsis. The BAH-PHD bivalent histone reader complex silences a substantial subset of H3K27me3-enriched loci, including a number of development and stress response-related genes such as the RNA silencing effector gene ARGONAUTE 5 (AGO5). We found that the BAH-PHD module associates with CPL2, a plant-specific Pol II carboxyl terminal domain (CTD) phosphatase, to form the BAH-PHD-CPL2 complex (BPC) for transcriptional repression. The BPC complex represses transcription through CPL2-mediated CTD dephosphorylation, thereby causing inhibition of Pol II release from the transcriptional start site. Our work reveals a mechanism coupling H3K27me3 recognition with transcriptional repression through the alteration of Pol II phosphorylation states, thereby contributing to our understanding of the mechanism of H3K27me3-dependent silencing.


Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , Epigenesis, Genetic , Gene Expression Regulation, Plant , Histones/metabolism , Multiprotein Complexes/metabolism , Arabidopsis/metabolism , Arabidopsis Proteins/chemistry , Arabidopsis Proteins/metabolism , Flowers/genetics , Flowers/growth & development , Flowers/metabolism , Gene Expression Regulation, Developmental , Histone Code/genetics , Lysine/metabolism , Methylation , Models, Molecular , Multiprotein Complexes/chemistry , Multiprotein Complexes/genetics , Phosphoprotein Phosphatases/chemistry , Phosphoprotein Phosphatases/genetics , Phosphoprotein Phosphatases/metabolism , Protein Conformation , Time Factors
20.
New Phytol ; 228(2): 622-639, 2020 10.
Article in English | MEDLINE | ID: mdl-32479643

ABSTRACT

Autophagy is an evolutionarily conserved pathway in eukaryotes that delivers unwanted cytoplasmic materials to the lysosome/vacuole for degradation/recycling. Stimulated autophagy emerges as an integral part of plant immunity against intracellular pathogens. In this study, we used turnip mosaic virus (TuMV) as a model to investigate the involvement of autophagy in plant RNA virus infection. The small integral membrane protein 6K2 of TuMV, known as a marker of the virus replication site and an elicitor of the unfolded protein response (UPR), upregulates the selective autophagy receptor gene NBR1 in a UPR-dependent manner. NBR1 interacts with TuMV NIb, the RNA-dependent RNA polymerase of the virus replication complex (VRC), and the autophagy cargo receptor/adaptor protein ATG8f. The NIb/NBR1/ATG8f interaction complexes colocalise with the 6K2-stained VRC. Overexpression of NBR1 or ATG8f enhances TuMV replication, and deficiency of NBR1 or ATG8f inhibits virus infection. In addition, ATG8f interacts with the tonoplast-specific protein TIP1 and the NBR1/ATG8f-containing VRC is enclosed by the TIP1-labelled tonoplast. In TuMV-infected cells, numerous membrane-bound viral particles are evident in the vacuole. Altogether these results suggest that TuMV activates and manipulates UPR-dependent NBR1-ATG8f autophagy to target the VRC to the tonoplast to promote viral replication and virion accumulation.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Potyvirus , Virus Diseases , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Autophagy , Carrier Proteins , Plant Diseases , RNA, Plant , Unfolded Protein Response , Viral Proteins/metabolism
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