ABSTRACT
BACKGROUND: We have previously identified auto-antibody (Ab) to collapsin response mediator protein 2 (CRMP2) in patients with encephalitis. The present study aims to evaluate the pathogenic effects of anti-CRMP2 Ab. METHODS: Recombinant CRMP2 protein was injected subcutaneously into mice to establish an active immune mouse model with anti-CRMP2 Ab. Behavioral assessments, histopathological staining, and electrophysiological testing were performed to identify any pathogenic changes. RESULTS: The mice exhibited signs of impaired motor coordination four weeks post-immunization of CRMP2 protein. Moreover, CRMP2 immunized mice for eight weeks showed anxiety-like behaviors indicating by tests of open field and the elevated plus maze. After incubating the CA1 region of hippocampal brain section with the sera from CRMP2 immunized mice, the whole-cell path-clamp recordings showed increased excitability of pyramidal neurons. However, no obvious inflammation and infiltration of immune cells were observed by histopathological analysis. Western blot showed that the phosphorylation levels of CRMP2-Thr514 and -Ser522 were not affected. CONCLUSION: In an active immunization model with CRMP2 protein, impaired coordination and anxiety-like behaviors were observed. Also, anti-CRMP2 Abs containing sera heightened the excitability of hippocampal pyramidal neurons in vitro, which imply the pathogenic effects of anti-CRMP2 Ab.
Subject(s)
Anxiety , Intercellular Signaling Peptides and Proteins , Nerve Tissue Proteins , Pyramidal Cells , Animals , Pyramidal Cells/pathology , Pyramidal Cells/metabolism , Pyramidal Cells/immunology , Anxiety/immunology , Anxiety/pathology , Mice , Nerve Tissue Proteins/immunology , Intercellular Signaling Peptides and Proteins/immunology , Male , Autoantibodies/immunology , Behavior, Animal/drug effects , Disease Models, Animal , Phosphorylation , Hippocampus/pathology , Hippocampus/immunology , Hippocampus/metabolismABSTRACT
Multi-omic data, i.e., genomics, epigenomics, transcriptomics, proteomics, characterize cellular complex signaling systems from multi-level and multi-view and provide a holistic view of complex cellular signaling pathways. However, it remains challenging to integrate and interpret multi-omics data. Graph neural network (GNN) AI models have been widely used to analyze graph-structure datasets and are ideal for integrative multi-omics data analysis because they can naturally integrate and represent multi-omics data as a biologically meaningful multi-level signaling graph and interpret multi-omics data by node and edge ranking analysis for signaling flow/cascade inference. However, it is non-trivial for graph-AI model developers to pre-analyze multi-omics data and convert them into graph-structure data for individual samples, which can be directly fed into graph-AI models. To resolve this challenge, we developed mosGraphGen (multi-omics signaling graph generator), a novel computational tool that generates multi-omics signaling graphs of individual samples by mapping the multi-omics data onto a biologically meaningful multi-level background signaling network. With mosGraphGen, AI model developers can directly apply and evaluate their models using these mos-graphs. We evaluated the mosGraphGen using both multi-omics datasets of cancer and Alzheimer's disease (AD) samples. The code of mosGraphGen is open-source and publicly available via GitHub: https://github.com/Multi-OmicGraphBuilder/mosGraphGen.
ABSTRACT
In pressurized water reactors, LiOH may be concentrated in some areas, leading to the accelerated corrosion of fuel claddings. Injecting boric acid into primary coolants can mitigate the accelerated corrosion effect of LiOH on Zircaloys, but the effects of boron content on the corrosion behavior of the Zr-Sn-Nb alloy are still unknown. This work focused on the corrosion and hydrogen absorption behavior at 360 °C/18.6 MPa in 100 mg/kg LiOH solutions with 0 mg/kg, 50 mg/kg, and 200 mg/kg boron contents for up to 510 days, aiming to study the effect of boron content on corrosion resistance in LiOH solutions. Corrosion kinetics, microstructures of oxide films, hydrogen absorption concentrations and hydride morphology were obtained after the test. The results show that injecting boron in LiOH solutions can significantly reduce the corrosion weight gain, hydrogen concentration, and hydrogen length of Zr-Sn-Nb alloys, that is, improving corrosion resistance effectively. During the oxidation of the Zr-Sn-Nb alloy, B3+ and Li+ incorporate in oxide films. The incorporation of Li+ may lead to the generation of oxygen vacancies, which can carry oxygen from the solutions to O/M interface, accelerating corrosion. The incorporation of B3+ in oxide films will slow down the oxidation of Zr-Sn-Nb alloys by reducing the oxygen vacancies caused by Li+ aggregation.
ABSTRACT
Symbiotic nitrogen fixation (SNF) by rhizobia is not only the main natural bionitrogen-source for organisms but also a green process leveraged to increase the fertility of soil for agricultural production. However, an insufficient understanding of the regulatory mechanism of SNF hinders its practical application. During SNF, nifA-fixA signaling is essential for the biosynthesis of nitrogenases and electron transfer chain proteins. In the present study, the TetR regulator NffT, whose mutation increased fixA expression, was discovered through a fixA-promoter-ß-glucuronidase fusion assay performed with Rhizobium johnstonii. Real-time quantitative PCR analysis showed that nffT deletion increased the expression of symbiotic genes including nifA and fixA in nifA-fixA signaling, and fixL, fixK, fnrN, and fixN9 in fixL-fixN signaling. nffT overexpression resulted in disordered nodules and reduced nitrogen-fixing efficiency. Electrophoretic mobility shift assays revealed that NffT directly regulated the transcription of RL0091-93, which encode an ATP-binding ABC transporter predicted to be involved in carbohydrate transport. Purified His-tagged NffT bound to a 68 bp DNA sequence located -32 to -99 bp upstream of RL0091-93 and NffT deletion significantly increased the expression of RL0091-93. nffT-promoter-ß-glucuronidase fusion assay indicated that nffT expression was regulated by the cobNTS genes and cobalamin. Mutations in cobNTS significantly decreased the expression of nffT, and cobalamin restored its expression. These results revealed that NffT affects nodule development and nitrogen-fixing reaction by participating in a complex regulatory network of symbiotic and carbohydrate metabolic genes and, thus, plays a pivotal regulatory role during symbiosis of R. johnstonii-Pisum sativum.IMPORTANCESymbiotic nitrogen fixation (SNF) by rhizobia is a green way to maintain soil fertility without causing environmental pollution or consuming chemical energy. A detailed understanding of the regulatory mechanism of this complex process is essential for promoting sustainable agriculture. In this study, we discovered the TetR-type regulator NffT, which suppressed the expression of fixA in Rhizobium johnstonii. Furthermore, NffT was confirmed to play pleiotropic roles in R. johnstonii-Pisum sativum symbiosis; specifically, it inhibited rhizobial growth, nodule differentiation, and nitrogen-fixing reactions. We revealed that NffT indirectly affected R. johnstonii-P. sativum symbiosis by participating in a complex regulatory network of symbiotic and carbohydrate metabolic genes. Furthermore, cobalamin, a chemical molecule, was reported for the first time to be involved in TetR-type protein transcription during symbiosis. Thus, NffT identification connects SNF regulation with genetic, metabolic, and chemical signals and provides new insights into the complex regulation of SNF, laying an experimental basis for the targeted construction of rhizobial strains with highly efficient nitrogen-fixing capacity.
Subject(s)
Rhizobium , Rhizobium/genetics , Rhizobium/metabolism , Nitrogen Fixation/genetics , Pisum sativum , Glucuronidase/metabolism , Carbohydrates , Nitrogen/metabolism , Soil , Vitamin B 12/metabolism , Symbiosis/geneticsABSTRACT
To investigate the responses of crop production and soil profile nutrient status to biochar (BC) application, we conducted a soil column experiment considering two BC addition rates (0.5 and 1.5 wt% of the weight of 0-20 cm topsoil) combined with two nitrogen (N) input levels (low N: 144 kg ha-1, LN; high N: 240 kg ha-1, HN). The results showed that BC application increased the soil pH. The soil pH of the 0-10 cm profile under LN and the 20-40 cm profile under HN were both significantly increased by 0.1-0.2 units after BC addition. Under LN, BC addition significantly increased NH4+-N (17.8-46.9%), total N (15.4-38.4%), and soil organic carbon (19.9-24.0%) in the 0-10 cm profile, but decreased NH4+-N in the 20-30 cm soil profile and NO3--N in the 10-30 cm profile by 13.8-28.5% and 13.0-34.9%, respectively. BC had an increasing effect on the available phosphorus, the contents of which in the 10-20 and 30-40 cm soil profiles under LN and 20-30 cm profile under HN were significantly elevated by 14.1%, 24.0%, and 23.27%, respectively. However, BC exerted no effect on the available potassium in the soil profile. BC had a strong improving effect (15.3%) on the wheat yield, especially the N144 + BC0.5% treatment, which could be compared to the HN treatment, but there was no yield-increasing effect when high N fertilizer was supplied. In summary, BC improved the fertility of agriculture soil (0-20 cm) with wheat. In particular, low N inputs together with an appropriate rate of BC (0.5 wt%) could not only achieve the low inputs but also the high outputs in wheat production. In future study, we will compare the effects of multiple doses of N and BC on soil fertility and crop production.
ABSTRACT
BACKGROUND: The NAC TF family is widely involved in plant responses to various types of stress. Red clover (Trifolium pratense) is a high-quality legume, and the study of NAC genes in red clover has not been comprehensive. The aim of this study was to analyze the NAC gene family of red clover at the whole-genome level and explore its potential role in the Pb stress response. RESULTS: In this study, 72 TpNAC genes were identified from red clover; collinearity analysis showed that there were 5 pairs of large fragment replicators of TpNAC genes, and red clover was found to be closely related to Medicago truncatula. Interestingly, the TpNAC genes have more homologs in Arabidopsis thaliana than in soybean (Glycine max). There are many elements in the TpNAC genes promoters that respond to stress. Gene expression analysis showed that all the TpNAC genes responded to Pb stress. qRT-PCR showed that the expression levels of TpNAC29 and TpNAC42 were significantly decreased after Pb stress. Protein interaction network analysis showed that 21 TpNACs and 23 other genes participated in the interaction. In addition, the TpNAC proteins had three possible 3D structures, and the secondary structure of these proteins were mainly of other types. These results indicated that most TpNAC members were involved in the regulation of Pb stress in red clover. CONCLUSION: These results suggest that most TpNAC members are involved in the regulation of Pb stress in red clover. TpNAC members play an important role in the response of red clover to Pb stress.
Subject(s)
Genome, Plant , Trifolium , Trifolium/genetics , Transcription Factors/genetics , Lead , Gene Expression ProfilingABSTRACT
Phenol-amine coatings have attracted significant attention in recent years owing to their adjustable composition and multifaceted biological functionalities. The current preparation of phenol-amine coatings, however, involves a chemical reaction within the solution or interface, resulting in lengthy preparation times and necessitating specific reaction conditions, such as alkaline environments and oxygen presence. The facile, rapid, and eco-friendly preparation of phenol-amine coatings under mild conditions continues to pose a challenge. In this study, we use a macromolecular phenol-amine, Tanfloc, to form a stable colloid under neutral conditions, which was then rapidly adsorbed on the titanium surface by electrostatic action and then spread and fused to form a continuous coating within several minutes. This nonchemical preparation process was rapid, mild, and free of chemical additives. The in vitro and in vivo results showed that the Tanfloc colloid fusion coating inhibited destructive inflammation, promoted osteogenesis, and enhanced osteointegration. These remarkable advantages of the colloidal phenol-amine fusion coating highlight the suitability of its future application in clinical practice.
Subject(s)
Coated Materials, Biocompatible , Osteogenesis , Coated Materials, Biocompatible/pharmacology , Coated Materials, Biocompatible/chemistry , Prostheses and Implants , Titanium/chemistry , Titanium/pharmacology , ColloidsABSTRACT
In a rice-wheat rotation system, biochar (BC) applied in different crop seasons undergoes contrast property changes in the soil. However, it is unclear how aged BC affects the production and quality of wheat and the nutrent status in a soil profile. In the present soil column experiment, the effects of no nitrogen (N) fertilizer and BC addition (control), N fertilizer (N420) and BC (5 t ha-1) applied at rice [N420 + BC(R)], or wheat [N420 + BC(W)] seasons at a same rate of N fertilizer (420 kg ha-1 yr-1) on yield and quality of wheat as well as the nutrient contents of soil profiles (0-5, 5-10, 10-20, 20-30, 30-40, and 40-50 cm) were observed. The results showed that N420 + BC(W) significantly reduced NH4+-N content in 5-10 and 10-20 cm soils by 62.1% and 36.2%, respectively, compared with N420. In addition, N420 + BC(W) significantly reduced NO3--N contents by 17.8% and 40.4% in 0-5 and 20-30 cm profiles, respectively, but N420 + BC(R) slightly increased them. The BC applied in wheat season significantly increased the 0-5 and 40-50 cm soil total N contents (24.0% and 48.1%), and enhanced the 30-40 and 40-50 cm soil-available phosphorus contents (48.2 and 35.75%) as well as improved the 10-20 and 20-30 cm soil-available potassium content (38.1% and 57.5%). Overall, our results suggest that N420 + BC(W) had stronger improving effects on soil fertility than N420 + BC(R). Compared to N420, there was a significant 5.9% increase in wheat grain yield, but no change in total amino acids in wheat kernels in N420 + BC(W). Considering the responses of soil profile nutrient contents as well as wheat yield and quality to BC application in different crop seasons, it is more appropriate to apply BC in wheat season. Our results could provide a scientific basis for the ideal time to amend BC into the rice-wheat rotation system, in order to achieve more benefits of BC on crop production and soil fertility.
ABSTRACT
Caucasian clover (Trifolium ambiguum M. Bieb.) is an excellent perennial plant in the legume family Fabaceae, with a well-developed rhizome and strong clonal growth. Auxin is one of the most important phytohormones in plants and plays an important role in plant growth and development. Auxin response factor (ARF) can regulate the expression of auxin-responsive genes, thus participating in multiple pathways of auxin transduction signaling in a synergistic manner. No genomic database has been established for Caucasian clover. In this study, 71 TaARF genes were identified through a transcriptomic database of Caucasian clover rhizome development. Phylogenetic analysis grouped the TaARFs into six (1-6) clades. Thirty TaARFs contained a complete ARF structure, including three relatively conserved regions. Physical and chemical property analysis revealed that TaARFs are unstable and hydrophilic proteins. We also analyzed the expression pattern of TaARFs in different tissues (taproot, horizontal rhizome, swelling of taproot, rhizome bud and rhizome bud tip). Quantitative real-time RT-PCR revealed that all TaARFs were responsive to phytohormones (indole-3-acetic acid, gibberellic acid, abscisic acid and methyl jasmonate) in roots, stems and leaves. These results helped elucidate the role of ARFs in responses to different hormone treatments in Caucasian clover.
Subject(s)
Plant Growth Regulators , Trifolium , Plant Growth Regulators/pharmacology , Transcriptome , Phylogeny , Trifolium/genetics , Trifolium/metabolism , Medicago/genetics , Medicago/metabolism , Transcription Factors/metabolism , Plant Proteins/metabolism , Multigene Family , Indoleacetic Acids/metabolism , Gene Expression Profiling , Hormones , Gene Expression Regulation, PlantABSTRACT
An Et3N-catalyzed cascade [3 + 2]-annulation of ß-oxo-acrylamides with cyclic N-sulfonyl ketimines or sulfamate-derived imines is developed under mild reaction conditions, which provides a concise and efficient route to access valuable sultam- or sulfamidate-fused imidazolidinone derivatives in good to excellent yields (80-95% yields) with excellent diastereoselectivities (>20:1 drs). The current protocol features atom economy, a transition-metal-free process, and broad functional group tolerance. Moreover, the asymmetric variant of the [3 + 2]-cycloaddition reaction was achieved in the presence of diphenylethanediamine or quinine-based bifunctional squaramide organocatalysts C-1 and C-11, giving the corresponding chiral polycyclic imidazolidinones in 68-90% yields with 25-94% ees and >20:1 drs in all cases.
ABSTRACT
As the prevailing non-volatile memory (NVM), flash memory offers mass data storage at high integration density and low cost. However, due to the 'speed-retention-endurance' dilemma, their typical speed is limited to ~microseconds to milliseconds for program and erase operations, restricting their application in scenarios with high-speed data throughput. Here, by adopting metallic 1T-LixMoS2 as edge contact, we show that ultrafast (10-100 ns) and robust (endurance>106 cycles, retention>10 years) memory operation can be simultaneously achieved in a two-dimensional van der Waals heterostructure flash memory with 2H-MoS2 as semiconductor channel. We attribute the superior performance to the gate tunable Schottky barrier at the edge contact, which can facilitate hot carrier injection to the semiconductor channel and subsequent tunneling when compared to a conventional top contact with high density of defects at the metal interface. Our results suggest that contact engineering can become a strategy to further improve the performance of 2D flash memory devices and meet the increasing demands of high speed and reliable data storage.
ABSTRACT
Osteogenesis surrounding dental implants is initiated by a series of early physiological events, including the inflammatory response. However, the persistence of an anti-infection surface often results in compromised histocompatibility and osseointegration. Here, we presented a programmed surface containing both silver nanoparticles (AgNPs) and silver ions (Ag+) with a heterogeneous structure and time-dependent functionalities. The AgNPs were located at the surface of the heparin-chitosan polyelectrolyte coating (PEM), whereas Ag+ was distributed at both the surface and inside of the coating under optimized conditions (pH=4). The optimized coating (Ag-4) exhibited potent bactericidal activity at the early stage (12 and 24 h after inoculation) and a sustained antibacterial efficacy in the subsequent stage (one or two weeks), as it gradually depleted. Furthermore, compared to coatings with sustained high silver concentrations in bacteria-cell coculture experiments, the degradable Ag-4 coating demonstrated improved cytocompatibility, better cell viability, and morphology over time. At a later stage (within one month), the in vivo test revealed that Ag-4-coated titanium had superior histocompatibility and osteogenesis outcomes compared to bare titanium in a bacteria-exposed environment. The programmed surface of dental implants presented in this study offers innovative ideas for sequential antibacterial effects and osseointegration.
Subject(s)
Dental Implants , Metal Nanoparticles , Osseointegration , Metal Nanoparticles/chemistry , Silver/pharmacology , Silver/chemistry , Titanium/pharmacology , Titanium/chemistry , Coated Materials, Biocompatible/pharmacology , Coated Materials, Biocompatible/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Surface PropertiesABSTRACT
Amending soil with biochar can reduce the toxic effects of heavy metals (HM) on plants and the soil. However, the effects of different concentrations of biochar on the properties and microbial activities in lead (Pb)-contaminated soils are unclear. In this study, two Pb concentrations were set (low, 1000 mg/kg; high, 5000 mg/kg), and five corn straw biochar (CSB) concentrations (0, 2.5, 5, 10 and 15%) were used to determine the response of the growth and rhizosphere of red clover (Trifolium pretense L.) (in terms of soil properties and bacteria) to CSB and Pb application. The results showed that 5% CSB better alleviated the toxicity of Pb on the shoot length of red clover, the biomass increased by 74.55 and 197.76% respectively and reduced the enrichment factor (BCF) and transport factor (TF) of red clover. Pb toxicity reduced soil nutrients, catalase (CAT), acid phosphatase (ACP) and urease activity, while the addition of CSB increased soil pH, soil organic matter (SOM) content and soil enzyme activity. 16S rDNA amplicon sequencing analysis showed that Pb toxicity reduced the diversity of rhizosphere bacteria in red clover and reduced the relative abundance of plant growth-promoting rhizobacteria such as Gemmatimonas, Devosia and Bryobacter. Spearman correlation analysis showed that the addition of alkaline CSB restored the relative abundance of rhizobacteria positively correlated with pH, such as Chitinophaga, Sphingomonas, Devosia and Pseudomonas, and thus restored the rhizosphere soil environment. This study demonstrates that 5% CSB can better alleviate the toxicity of Pb to red clover and soil. We also provide a theoretical basis for the subsequent use of beneficial bacteria to regulate the repair efficiency of red clover.
ABSTRACT
A visible-light-initiated trifluoromethylation/remote aliphatic C-H alkynylation of α-alkyl-substituted vinyl azides using acetylenic triflones as both the trifluoromethyl and alkyne donors is described. The reaction occurred under environmentally benign and radical initiator-free reaction conditions, affording γ-alkynylated trifluoromethyl ketone derivatives with a broad scope of substituents. Mechanistic studies suggested that the reaction is initiated via a triplet-triplet energy transfer between the 4CzIPN catalyst and acetylenic triflone, followed by fragmentation to generate a trifluoromethyl radical and an alkynyl radical.
ABSTRACT
Human neuroimaging studies have revealed a dedicated cortical system for visual scene processing. But what is a "scene"? Here, we use a stimulus-driven approach to identify a stimulus feature that selectively drives cortical scene processing. Specifically, using fMRI data from BOLD5000, we examined the images that elicited the greatest response in the cortical scene processing system, and found that there is a common "vertical luminance gradient" (VLG), with the top half of a scene image brighter than the bottom half; moreover, across the entire set of images, VLG systematically increases with the neural response in the scene-selective regions (Study 1). Thus, we hypothesized that VLG is a stimulus feature that selectively engages cortical scene processing, and directly tested the role of VLG in driving cortical scene selectivity using tightly controlled VLG stimuli (Study 2). Consistent with our hypothesis, we found that the scene-selective cortical regions-but not an object-selective region or early visual cortex-responded significantly more to images of VLG over control stimuli with minimal VLG. Interestingly, such selectivity was also found for images with an "inverted" VLG, resembling the luminance gradient in night scenes. Finally, we also tested the behavioral relevance of VLG for visual scene recognition (Study 3); we found that participants even categorized tightly controlled stimuli of both upright and inverted VLG to be a place more than an object, indicating that VLG is also used for behavioral scene recognition. Taken together, these results reveal that VLG is a stimulus feature that selectively engages cortical scene processing, and provide evidence for a recent proposal that visual scenes can be characterized by a set of common and unique visual features.
Subject(s)
Magnetic Resonance Imaging , Visual Perception , Humans , Visual Perception/physiology , Magnetic Resonance Imaging/methods , Recognition, Psychology/physiology , Brain Mapping , Pattern Recognition, Visual/physiology , Photic Stimulation/methodsABSTRACT
Silver has been widely used for surface modification to prevent implant-associated infections. However, the inherent cytotoxicity of silver greatly limited the scope of its clinical applications. The construction of surfaces with both good antibacterial properties and favorable cytocompatibility still remains a challenge. In this study, a structurally homogeneous dopamine-silver (DA/Ag) nanocomposite was fabricated on the implant surface to balance the antibacterial activity and cytocompatibility of the implant. The results show that the DA/Ag nanocomposites prepared under the acidic conditions (pH = 4) on the titanium surface are homogeneous with higher Ag+ content, while an obvious core (AgNPs)-shell (PDA) structure is formed under neutral (pH = 7) and alkaline conditions (pH = 10), and the subsequent heat treatment enhanced the stability of PDA-AgNPs nanocomposite coatings on porous titanium. The antibacterial test, cytotoxicity test, hypodermic implantation and osteogenesis test revealed that the homogeneous PDA-AgNPs nanocomposite coating achieved the balance between the antibacterial ability and cytocompatibility, and had the best outcomes for soft tissue healing and bone formation around the implants. This study provides a facile strategy for preparing silver-loaded surfaces with both good antibacterial effect and favorable cytocompatibility, which is expected to further improve the therapeutic efficacy of silver composite-coated dental implants.
ABSTRACT
Silver nanoparticles (AgNPs) are progressively becoming an in-demand material for both medical and life use due to their effective antimicrobial properties. The high surface area-to-volume ratio endows AgNPs with enhanced antibacterial capacity accompanied by inevitable cytotoxicity. Surface coating technique could precisely regulate the particle shape, aggregation, and Ag+ release pattern of AgNPs, by which the cytotoxicity could be significantly reduced. Various coating methods have been explored to shell AgNPs, but it remains a great challenge to precisely control the aggregation state of AgNPs and their shell thickness. Herein, we proposed a simple method to prepare a tunable polydopamine (pDA) coating shell on AgNPs just by tuning the reaction pH and temperature, yet we obtained high antibacterial property and excellent biocompatibility. SEM and TEM revealed that pDA coated AgNPs can form core-shell structures with different aggregation states and shell thickness. Both in vitro and in vivo antibacterial tests show that acid condition and heat-treatment lead to appropriate AgNPs cores and pDA shell structures, which endow Ti with sustained antibacterial properties and preferable cell compatibility. One month of implantation in an infected animal model demonstrated that the obtained surface could promote osteogenesis and inhibit inflammation due to its strong antibacterial properties. Therefore, this study provides a promising approach to fabricate biocompatible antibacterial surface.
ABSTRACT
Background: Deafness-dystonia-optic neuronopathy (DDON) syndrome, a condition that predominantly affects males, is caused by mutations in translocase of mitochondrial inner membrane 8A (TIMM8A)/deafness dystonia protein 1 (DDP1) gene and characterized by progressive deafness coupled with other neurological abnormalities. In a previous study, we demonstrated the phenotype of male mice carrying the hemizygous mutation of Timm8a1-I23fs49X. In a follow-up to that study, this study aimed to observe the behavioral changes in the female mutant (MUT) mice with homologous mutation of Timm8a1 and to elucidate the underlying mechanism for the behavioral changes. Materials and methods: Histological analysis, transmission electron microscopy (EM), Western blotting, hearing measurement by auditory brainstem response (ABR), and behavioral observation were compared between the MUT mice and wild-type (WT) littermates. Results: The weight of the female MUT mice was less than that of the WT mice. Among MUT mice, both male and female mice showed hearing impairment, anxiety-like behavior by the elevated plus maze test, and cognitive deficit by the Morris water maze test. Furthermore, the female MUT mice exhibited coordination problems in the balance beam test. Although the general neuronal loss was not found in the hippocampus of the MUT genotype, EM assessment indicated that the mitochondrial size showing as aspect ratio and form factor in the hippocampus of the MUT strain was significantly reduced compared to that in the WT genotype. More importantly, this phenomenon was correlated with the upregulation of translation of mitochondrial fission process protein 1(Mtfp1)/mitochondrial 18 kDa protein (Mtp18), a key fission factor that is a positive regulator of mitochondrial fission and mitochondrial size. Interestingly, significant reductions in the size of the uterus and ovaries were noted in the female MUT mice, which contributed to significantly lower fertility in the MUT mice. Conclusion: Together, a homologous mutation in the Timm8a1 gene caused the hearing impairment and psychiatric behavioral changes in the MUT mice; the latter phenotype might be related to a reduction in mitochondrial size regulated by MTP18.
ABSTRACT
Lead (Pb) interferes with plant gene expression, alters metabolite contents and affects plant growth. However, the molecular mechanism underlying the plant response to Pb is not completely understood. In the present study, Trifolium pratense L. was exposed to Pb concentrations of 0 (Pb0), 500 (Pb500), 1000 (Pb1000), 2000 (Pb2000) and 3000 (Pb3000) mg/kg in soils. Pb stress affected the ability of T. pratense to accumulate and transport Pb, increased the activity of peroxidase (POD) and the contents of malondialdehyde (MDA) and proline, decreased the amount of photosynthetic pigments and soluble proteins, and led to changes in growth and biomass. Transcriptomic and metabolomic analyses showed that Pb mainly affected eight pathways, and LHC, flavonoids, organic acids, amino acids and carbohydrates were upregulated or downregulated. Moreover, Pb500 induced the upregulation of serA, promoted the synthesis of citric acid, maintained photosynthetic pigment levels, and ultimately promoted an increase in stem length. Pb3000 induced the upregulation of ARF, GH3 and SAUR genes, but the saccharide contents and stem length decreased in response to Pb stress. We used a variety of methods to provide a molecular perspective on the mechanism underlying the response of T. pratense to Pb stress.