ABSTRACT
RAS proteins are peripheral membrane GTPases that activate multiple downstream effectors for cell proliferation and differentiation. The formation of a signaling RAS-RAF complex at the plasma membrane is implicated in a quarter of all human cancers; however, the underlying mechanism remains unclear. In this work, nanodisc platforms and paramagnetic relaxation enhancement (PRE) analyses to determine the structure of a hetero-tetrameric complex comprising KRAS and the RAS-binding domain (RBD) and cysteine-rich domain (CRD) of activated RAF1 are employed. The binding of the RBD or RBD-CRD differentially alters the dimerization modes of KRAS on both anionic and neutral membranes, validated by interface-specific mutagenesis. Notably, the RBD binding allosterically generated two distinct KRAS dimer interfaces in equilibrium, favored by KRAS free and in complex with the RBD-CRD, respectively. Additional interactions of the CRD with both KRAS protomers are mutually cooperative to stabilize a new dimer configuration of KRAS bound to the RBD-CRD. The RAF binding sequentially alters KRAS dimerization, providing new insights into RAF activation, including a configurational transition of the KRAS dimer to provide an interaction site for the CRD and release the autoinhibited RAF complex. These methods are applicable to many other signaling protein complexes on the membrane.
ABSTRACT
The addition of plant-growth-promoting bacteria (PGPB) to heavy-metal-contaminated soils can significantly improve plant growth and productivity. This study isolated heavy-metal-tolerant bacteria with growth-promoting traits and investigated their inoculation effects on the germination rates and growth of millet (Panicum miliaceum) and mustard (Brassica juncea) in Cd- and Zn-contaminated soil. Leifsonia sp. ZP3, which is resistant to Cd (0.5 mM) and Zn (1 mM), was isolated from forest soil. The ZP3 strain exhibited plant-growth-promoting activity, including indole-3-acetic acid production, phosphate solubilization, catalase activity, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging. In soil contaminated with low concentrations of Cd (0.232 ± 0.006 mM) and Zn (6.376 ± 0.256 mM), ZP3 inoculation significantly increased the germination rates of millet and mustard 8.35- and 31.60-fold, respectively, compared to the non-inoculated control group, while the shoot and root lengths of millet increased 1.77- and 4.44-fold (p < 0.05). The chlorophyll content and seedling vigor index were also 4.40 and 18.78 times higher in the ZP3-treated group than in the control group (p < 0.05). The shoot length of mustard increased 1.89-fold, and the seedling vigor index improved 53.11-fold with the addition of ZP3 to the contaminated soil (p < 0.05). In soil contaminated with high concentrations of Cd and Zn (0.327 ± 0.016 and 8.448 ± 0.250 mM, respectively), ZP3 inoculation led to a 1.98-fold increase in the shoot length and a 2.07-fold improvement in the seedling vigor index compared to the control (p < 0.05). The heavy-metal-tolerant bacterium ZP3 isolated in this study thus represents a promising microbial resource for improving the efficiency of phytoremediation in Cd- and Zn-contaminated soil.
Subject(s)
Biodegradation, Environmental , Cadmium , Germination , Mustard Plant , Panicum , Soil Microbiology , Soil Pollutants , Zinc , Mustard Plant/microbiology , Mustard Plant/growth & development , Soil Pollutants/metabolism , Cadmium/metabolism , Zinc/metabolism , Panicum/microbiology , Panicum/growth & development , Plant Roots/microbiology , Plant Roots/growth & development , Metals, Heavy/metabolism , Soil/chemistry , Indoleacetic Acids/metabolismABSTRACT
Quantum dots (QDs) have garnered a significant amount of attention as promising memristive materials owing to their size-dependent tunable bandgap, structural stability, and high level of applicability for neuromorphic computing. Despite these advantageous properties, the development of QD-based memristors has been hindered by challenges in understanding and adjusting the resistive switching (RS) behavior of QDs. Herein, we propose three types of InP/ZnSe/ZnS QD-based memristors to elucidate the RS mechanism, employing a thin poly(methyl methacrylate) layer. This approach not only allows us to identify which carriers (electron or hole) are trapped within the QD layer but also successfully demonstrates QD-based synaptic devices. Furthermore, to utilize the QD memristor as a synapse, long-term potentiation/depression (LTP/LTD) characteristics are measured, resulting in a low nonlinearity of LTP/LTD at 0.1/1. On the basis of the LTP/LTD characteristics, single-layer perceptron simulations were performed using the Extended Modified National Institute of Standards and Technology, verifying a maximum recognition rate of 91.46%.
ABSTRACT
Type II toxin-antitoxin (TA) systems are ubiquitously distributed genetic elements in prokaryotes and are crucial for cell maintenance and survival under environmental stresses. The antitoxin is a modular protein consisting of the disordered C-terminal region that physically contacts and neutralizes the cognate toxin and the well-folded N-terminal DNA binding domain responsible for autorepression of TA transcription. However, how the two functional domains communicate is largely unknown. Herein, we determined the crystal structure of the N-terminal domain of the type II antitoxin MazE-mt10 from Mycobacterium tuberculosis, revealing a homodimer of the ribbon-helix-helix (RHH) fold with distinct DNA binding specificity. NMR studies demonstrated that full-length MazE-mt10 forms the helical and coiled states in equilibrium within the C-terminal region, and that helical propensity is allosterically enhanced by the N-terminal binding to the cognate operator DNA. This coil-to-helix transition may promote toxin binding/neutralization of MazE-mt10 and further stabilize the TA-DNA transcription repressor. This is supported by many crystal structures of type II TA complexes in which antitoxins form an α-helical structure at the TA interface. The hidden helical state of free MazE-mt10 in solution, favored by DNA binding, adds a new dimension to the regulatory mechanism of type II TA systems. Furthermore, complementary approaches using X-ray crystallography and NMR allow us to study the allosteric interdomain interplay of many other full-length antitoxins of type II TA systems.
Subject(s)
Antitoxins , Mycobacterium tuberculosis , Mycobacterium tuberculosis/metabolism , Antitoxins/chemistry , Models, Molecular , Transcription Factors/metabolism , DNA/metabolism , Bacterial Proteins/metabolismABSTRACT
Self-assemblies (i.e., nanoclusters) of the RAS GTPase on the membrane act as scaffolds that activate downstream RAF kinases and drive MAPK signaling for cell proliferation and tumorigenesis. However, the mechanistic details of nanoclustering remain largely unknown. Here, size-tunable nanodisc platforms and paramagnetic relaxation enhancement (PRE) analyses revealed the structural basis of the cooperative assembly processes of fully processed KRAS, mutated in a quarter of human cancers. The cooperativity is modulated by the mutation and nucleotide states of KRAS and the lipid composition of the membrane. Notably, the oncogenic mutants assemble in nonsequential pathways with two mutually cooperative 'α/α' and 'α/ß' interfaces, while α/α dimerization of wild-type KRAS promotes the secondary α/ß interaction sequentially. Mutation-based interface engineering was used to selectively trap the oligomeric intermediates of KRAS and probe their favorable interface interactions. Transiently exposed interfaces were available for the assembly. Real-time NMR demonstrated that higher-order oligomers retain higher numbers of active GTP-bound protomers in KRAS GTPase cycling. These data provide a deeper understanding of the nanocluster-enhanced signaling in response to the environment. Furthermore, our methodology is applicable to assemblies of many other membrane GTPases and lipid nanoparticle-based formulations of stable protein oligomers with enhanced cooperativity.
Subject(s)
Proto-Oncogene Proteins p21(ras) , Signal Transduction , Humans , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , ras Proteins/chemistry , raf Kinases/metabolism , DimerizationABSTRACT
The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.
ABSTRACT
Although peptides notoriously have poor intrinsic pharmacokinetic properties, it is well-known that nanostructures with excellent pharmacokinetic properties can be designed. Noticing that peptide inhibitors are generally nonpolar, here, we consolidate the peptide inhibitor targeting intracellular protein-protein interactions (PPIs) as an integral part of biodegradable self-assembled depsipeptide nanostructures (SdPNs). Because the peptide inhibitor has the dual role of PPI inhibition and self-assembly in this design, problems associated with the poor pharmacokinetics of peptides and encapsulation/entrapment processes can be overcome. Optimized SdPNs displayed better tumor targeting and PPI inhibition properties than the comparable small molecule inhibitor in vivo. Kinetics of PPI inhibition for SdPNs were gradual and controllable in contrast to the rapid inhibition kinetics of the small molecule. Because SdPN is modular, any appropriate peptide inhibitor can be incorporated into the platform without concern for the poor pharmacokinetic properties of the peptide.
Subject(s)
Depsipeptides , Nanostructures , KineticsABSTRACT
BACKGROUND: Data regarding the clinical effects of bacteremia on severe community-acquired pneumonia (CAP) are limited. Thus, we investigated clinical characteristics and outcomes of severe CAP patients with bacteremia compared with those of subjects without bacteremia. In addition, we evaluated clinical factors associated with bacteremia at the time of sepsis awareness. METHODS: We enrolled sepsis patients diagnosed with CAP at emergency departments (EDs) from an ongoing nationwide multicenter observational registry, the Korean Sepsis Alliance, between September 2019 and December 2020. For evaluation of clinical factors associated with bacteremia, we divided eligible patients into bacteremia and non-bacteremia groups, and logistic regression analysis was performed using the clinical characteristics at the time of sepsis awareness. RESULT: During the study period, 1,510 (47.9%) sepsis patients were caused by CAP, and bacteremia was identified in 212 (14.0%) patients. Septic shock occurred more frequently in the bacteremia group than in the non-bacteremia group (27.4% vs. 14.8%; p < 0.001). In multivariable analysis, hematologic malignancies and septic shock were associated with an increased risk of bacteremia. However, chronic lung disease was associated with a decreased risk of bacteremia. Hospital mortality was significantly higher in the bacteremia group than in the non-bacteremia group (27.3% vs. 40.6%, p < 0.001). The most prevalent pathogen in blood culture was Klebsiella pneumoniae followed by Escherichia coli in gram-negative pathogens. CONCLUSION: The incidence of bacteremia in severe CAP was low at 14.0%, but the occurrence of bacteremia was associated with increased hospital mortality. In severe CAP, hematologic malignancies and septic shock were associated with an increased risk of bacteremia.
Subject(s)
Bacteremia , Community-Acquired Infections , Hematologic Neoplasms , Pneumonia , Sepsis , Shock, Septic , Humans , Bacteremia/epidemiology , Community-Acquired Infections/epidemiology , Escherichia coli , Hematologic Neoplasms/complications , Pneumonia/epidemiology , Pneumonia/complications , Retrospective Studies , Risk Factors , Sepsis/complications , Multicenter Studies as Topic , Observational Studies as TopicABSTRACT
The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.
Subject(s)
Oncogene Proteins, Viral , Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Humans , Female , Animals , Mice , Human Papillomavirus Viruses , Oncogene Proteins, Viral/genetics , Papillomavirus Infections/prevention & control , RNA, Messenger/genetics , Papillomavirus E7 Proteins/genetics , Mice, Inbred C57BL , Vaccination/methods , Immunization , Uterine Cervical Neoplasms/prevention & controlABSTRACT
We developed a promising mRNA vaccine against severe fever with thrombocytopenia syndrome (SFTS), an infectious disease caused by the SFTS virus that is primarily transmitted through tick bites. Administration of lipid nanoparticle-encapsulated mRNA-Gn successfully induced neutralizing antibodies and T-cell responses in mice. The vaccinated mice were protected against a lethal SFTS virus challenge, suggesting that this mRNA vaccine may be an effective and successful SFTS vaccine candidate.
ABSTRACT
We propose that the post-deposition oxidation of the IGZO surface is essential for improving the interface quality, with Al2O3 prepared by atomic layer deposition (ALD) employing a common metal precursor trimethylaluminum (TMA). Here, the ALD-Al2O3 process was conducted using H2O as an oxidant at a substrate temperature of 150 °C after IGZO deposition. The depth-resolved X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) data reveal the defect-rich and poor interface of the standard Al2O3/IGZO stack due to the redox reaction between the IGZO surface and TMA. The anion character of the IGZO was modified by introducing fluorine, which is known as a stability enhancer for oxide semiconductors. We highlight that the presence of the fluorine also improves the interface quality with ALD-Al2O3. As a consequence of the fluorine incorporation prior to the ALD-Al2O3 process, the chemical reduction reaction of the IGZO surface was effectively alleviated, resulting in a defect-passivated and sharp interface owing to the strong oxidizing nature of the fluorine.
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor neurons in the spinal cord. Although the disease's pathophysiological mechanism remains poorly understood, multifactorial mechanisms affecting motor neuron loss converge to worsen the disease. Although two FDA-approved drugs, riluzole and edaravone, targeting excitotoxicity and oxidative stress, respectively, are available, their efficacies are limited to extending survival by only a few months. Here, we developed combinatorial drugs targeting multifactorial mechanisms underlying key components in ALS disease progression. Using data analysis based on the genetic information of patients with ALS-derived cells and pharmacogenomic data of the drugs, a combination of nebivolol and donepezil (nebivolol-donepezil) was identified for ALS therapy. Here, nebivolol-donepezil markedly reduced the levels of cytokines in the microglial cell line, inhibited nuclear factor-κB (NF-κB) nucleus translocation in the HeLa cell and substantially protected against excitotoxicity-induced neuronal loss by regulating the PI3K-Akt pathway. Nebivolol-donepezil significantly promoted the differentiation of neural progenitor cells (NPC) into motor neurons. Furthermore, we verified the low dose efficacy of nebivolol-donepezil on multiple indices corresponding to the quality of life of patients with ALS in vivo using SOD1G93A mice. Nebivolol-donepezil delayed motor function deterioration and halted motor neuronal loss in the spinal cord. Drug administration effectively suppressed muscle atrophy by mitigating the proportion of smaller myofibers and substantially reducing phospho-neurofilament heavy chain (pNF-H) levels in the serum, a promising ALS biomarker. High-dose nebivolol-donepezil significantly prolonged survival and delayed disease onset compared with vehicle-treated mice. These results indicate that the combination of nebivolol-donepezil efficiently prevents ALS disease progression, benefiting the patients' quality of life and life expectancy.
Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Mice , Animals , Amyotrophic Lateral Sclerosis/drug therapy , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/metabolism , Donepezil/therapeutic use , Nebivolol/therapeutic use , Nebivolol/metabolism , Phosphatidylinositol 3-Kinases/metabolism , HeLa Cells , Quality of Life , Spinal Cord/metabolism , Disease Progression , Disease Models, Animal , Mice, Transgenic , Superoxide Dismutase/genetics , Superoxide Dismutase-1/geneticsABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal, fibrotic, interstitial lung disease of unknown cause. Despite extensive studies, the underlying mechanisms of IPF development remain unknown. Here, we found that p300 was upregulated in multiple epithelial cells in lung samples from patients with IPF and mouse models of lung fibrosis. Lung fibrosis was significantly diminished by the alveolar type II (ATII) cell-specific deletion of the p300 gene. Moreover, we found that ubiquitin C-terminal hydrolase L3 (UCHL3)-mediated deubiquitination of p300 led to the transcriptional activation of the chemokines Ccl2, Ccl7, and Ccl12 through the cooperative action of p300 and C/EBPß, which consequently promoted M2 macrophage polarization. Selective blockade of p300 activity in ATII cells resulted in the reprogramming of M2 macrophages into antifibrotic macrophages. These findings demonstrate a pivotal role for p300 in the development of lung fibrosis and suggest that p300 could serve as a promising target for IPF treatment.
Subject(s)
Alveolar Epithelial Cells , Idiopathic Pulmonary Fibrosis , Ubiquitin Thiolesterase , Animals , Mice , Chemokine CCL2/genetics , Deubiquitinating Enzymes , Idiopathic Pulmonary Fibrosis/genetics , Lung , Humans , Ubiquitin Thiolesterase/metabolism , E1A-Associated p300 ProteinABSTRACT
The long-term remediation performance under the natural conditions is required to establish the appropriate remediation strategy for contaminated soil. The objective of this study was to compare the long-term remediation efficiency of biostimulation and phytoextraction in contaminated soil containing petroleum hydrocarbons (PHs) and heavy metals. Two types of contaminated soil (soil contaminated with diesel only and co-contaminated with diesel and heavy metals) were prepared. For the biostimulation treatments, the soil was amended with compost, whereas maize, a representative phytoremediation plant, was cultivated for the phytoextraction treatments. There was no significant difference in remediation performance of biostimulation and phytoextraction in the diesel-contaminated soil, in which the maximum total petroleum hydrocarbon (TPH) removability was 94-96% (p < 0.05). However, phytoextraction exhibited the higher removability for TPH and heavy metals than biostimulation in the co-contaminated soil. There was no considerable change in the TPH removal in biostimulation (16-25%), while phytoextraction showed a 75% of TPH removal rate in the co-contaminated soil. Additionally, no significant changes were observed in heavy metals concentration of biostimulation, whereas the removability of heavy metals was 33-63% in phytoextraction. Meanwhile, maize, which is a suitable plant for phytoextraction, showed a translocation factor (translocating efficiency from roots to shoots) value of >1. Correlation analysis revealed that soil properties (pH, water content, and organic content) negatively correlated with pollutants removal. Additionally, the soil bacterial communities were changed over the investigated period, and the types of pollutants exerted a significant influence on the bacterial community dynamics. This study performed a pilot-scale comparison of two types of biological remediation technologies under natural environmental conditions and provided information on changes in the bacterial community structures. This study can be useful for establishing appropriate biological remediation methods to restore soil contaminated with PHs and heavy metals.
Subject(s)
Environmental Pollutants , Metals, Heavy , Petroleum , Soil Pollutants , Soil/chemistry , Biodegradation, Environmental , Metals, Heavy/analysis , Petroleum/analysis , Environmental Pollutants/analysis , Soil Pollutants/analysis , Soil Microbiology , Hydrocarbons/analysisABSTRACT
Chd8+/N2373K mice with a human C-terminal-truncating mutation (N2373K) display autistic-like behaviors in juvenile and adult males but not in females. In contrast, Chd8+/S62X mice with a human N-terminal-truncating mutation (S62X) display behavioral deficits in juvenile males (not females) and adult males and females, indicative of age-differential sexually dimorphic behaviors. Excitatory synaptic transmission is suppressed and enhanced in male and female Chd8+/S62X juveniles, respectively, but similarly enhanced in adult male and female mutants. ASD-like transcriptomic changes are stronger in newborn and juvenile (but not adult) Chd8+/S62X males but in newborn and adult (not juvenile) Chd8+/S62X females. These results point to age-differential sexual dimorphisms in Chd8+/S62X mice at synaptic and transcriptomic levels, in addition to the behavioral level.
ABSTRACT
Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis. [BMB Reports 2023; 56(2): 114-119].
Subject(s)
Histones , Liver Cirrhosis , Mice , Animals , Histones/metabolism , Liver/metabolism , Disease Models, Animal , Diet, High-FatABSTRACT
With the prolongation of non-ordinary situations such as school closures due to the coronavirus disease 2019 (COVID-19) pandemic, high school students have experienced irregular sleep-wake cycles and elevated academic stress resulting from reduced academic achievement and widened gaps in academic performance. This cross-sectional study aimed to investigate the associations among chronotype, social jetlag, lifelong learning competency, and academic stress in high school students during the COVID-19 pandemic. Data were collected through an online survey from May-June 2021. The mean social jetlag was found to be 2 h and 9 min, and multiple regression analysis revealed that social jetlag and lifelong competency affected academic stress. Thus, measures to minimize social jetlag and improve lifelong learning competencies should be implemented to reduce academic stress among high school students. School nurses should identify students with severe social jetlag and provide guidance and interventions to promote sleep hygiene and regular lifestyles.
Subject(s)
COVID-19 , Sleep , Humans , Circadian Rhythm , Cross-Sectional Studies , Pandemics , Students , Jet Lag Syndrome , Surveys and QuestionnairesABSTRACT
Rhizoremediation is a promising method based on the synergism between plant and rhizobacteria to remediate soil co-contaminated with heavy metals and total petroleum hydrocarbons (TPHs). A plant growth-promoting (PGP) rhizobacterium with diesel-degrading capacity and heavy metal tolerance was isolated from the rhizosphere of tall fescue (Festuca arundinacea L.), after which the effects of its inoculation on rhizoremediation performance were evaluated in heavy metal- and diesel-contaminated soil planted with tall fescue. The bacterial isolate (Novosphingobium sp. CuT1) was characterized by its indole-3-acetic acid (IAA) production, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity, and siderophore productivity as PGP traits. CuT1 was able to grow on 1/10 LB-agar plates containing 5 mM of Cu or 5 mM of Pb. To evaluate the remediation effect of heavy metal- and diesel-contaminated soil by CuT1 inoculation, the experimental conditions were prepared as follows. The soil was artificially contaminated with heavy metals (Cu and Pb) at a final concentration of 500 ppm. The soil was then further contaminated with diesel at final concentrations of 0, 10,000, and 30,000 ppm. Finally, all plots were planted with tall fescue, a representative hyperaccumulating plant. Compared to the rhizoremediation performance of the co-contaminated soil (Cu + Pb + diesel) without inoculation, the bioavailable Cu concentrations in the soil and the tall fescue biomass were significantly increased in CuT1 inoculation. Additionally, the root growth of tall fescue was also promoted in CuT1 inoculation. Correlation analysis showed that Cu bioavailability and bioconcentration factor were positively correlated with CuT1 inoculation. The diesel removal efficiency showed a positive correlation with CuT1 inoculation, although the diesel removal was below 30%. CuT1 inoculation was positively correlated with IAA and dehydrogenase activity in the soil. Moreover, the dry biomass of the tall fescue's roots was highly associated with CuT1 inoculation. Collectively, our findings suggest that Novosphingobium sp. CuT1 can be utilized as an applicable bioresource to enhance rhizoremediation performance in heavy metal- and TPH-contaminated soils.
Subject(s)
Festuca , Metals, Heavy , Soil Pollutants , Biodegradation, Environmental , Lead/pharmacology , Plant Roots , Metals, Heavy/pharmacology , Soil , Soil Pollutants/pharmacology , Soil MicrobiologyABSTRACT
Autism spectrum disorders (ASD) are ~4-times more common in males than females, and CHD8 (a chromatin remodeler)-related ASD shows a strong male bias (~4:1), although the underlying mechanism remains unclear. Chd8-mutant mice with a C-terminal protein-truncating mutation (N2373K) display male-preponderant behavioral deficits as juveniles and adults, although whether this also applies to other Chd8 mutations remains unknown. In addition, it remains unclear whether sexually dimorphic phenotypes in Chd8-mutant mice are differentially observed in males and females across different ages. We here generated new Chd8-mutant (knock-in) mice carrying a patient-derived mutation causing an N-terminal and stronger protein truncation (Chd8+/S62X mice) and characterized the mice by behavioral analyses. Juvenile Chd8+/S62X mice displayed male-preponderant autistic-like behaviors; hypoactivity and enhanced mother-seeking/attachment behavior in males but not in females. Adult male and female Chd8+/S62X mice showed largely similar deficits in repetitive and anxiety-like behavioral domains. Therefore, the CHD8-S62X mutation induces ASD-like behaviors in juvenile male mice and adult male and female mice, pointing to an age-differential sexual dimorphism and also distinct sexual dimorphisms in different Chd8 mutations (N2373K and S62X).
ABSTRACT
The objective of this study was to explore the seasonal characteristics of rhizoremediation and the bacterial community structure over the course of a year in soil contaminated with diesel oil. The soil was contaminated with diesel oil at a total petroleum hydrocarbon (TPH) concentration of 30,000 mg-TPH·kg-soil-1. Tall fescue seedlings were planted in the contaminated soil and rhizoremediation performance was monitored for 317 days. The TPH concentration gradually declined, reaching 75.6% after day 61. However, the TPH removability decreased by up to 30% after re-contamination in the fall and winter. The bacterial community structure exhibited distinct seasonal dynamics. Genus Pseudomonas significantly increased up to 55.7% in the winter, while the genera Immundisolibacter and Lysobacter, well-known petroleum hydrocarbon (PH)-degrading bacteria, were found to be positively linked to the TPH removal rate. Consequently, knowledge of this seasonal variation in rhizoremediation performance and the bacterial community structure is useful for the improvement of rhizoremediation in PH-contaminated environments.