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1.
Cell ; 185(23): 4376-4393.e18, 2022 11 10.
Article in English | MEDLINE | ID: mdl-36318920

ABSTRACT

The function of biomolecular condensates is often restricted by condensate dissolution. Whether condensates can be suppressed without condensate dissolution is unclear. Here, we show that upstream regulators of the Hippo signaling pathway form functionally antagonizing condensates, and their coalescence into a common phase provides a mode of counteracting the function of biomolecular condensates without condensate dissolution. Specifically, the negative regulator SLMAP forms Hippo-inactivating condensates to facilitate pathway inhibition by the STRIPAK complex. In response to cell-cell contact or osmotic stress, the positive regulators AMOT and KIBRA form Hippo-activating condensates to facilitate pathway activation. The functionally antagonizing SLMAP and AMOT/KIBRA condensates further coalesce into a common phase to inhibit STRIPAK function. These findings provide a paradigm for restricting the activity of biomolecular condensates without condensate dissolution, shed light on the molecular principles of multiphase organization, and offer a conceptual framework for understanding upstream regulation of the Hippo signaling pathway.


Subject(s)
Hippo Signaling Pathway , Protein Serine-Threonine Kinases , Signal Transduction
2.
J Biol Chem ; 300(1): 105538, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38072046

ABSTRACT

Histone chaperone FACT (facilitates chromatin transcription) is well known to promote chromatin recovery during transcription. However, the mechanism how FACT regulates genome-wide chromatin accessibility and transcription factor binding has not been fully elucidated. Through loss-of-function studies, we show here that FACT component Ssrp1 is required for DNA replication and DNA damage repair and is also essential for progression of cell phase transition and cell proliferation in mouse embryonic fibroblast cells. On the molecular level, absence of the Ssrp1 leads to increased chromatin accessibility, enhanced CTCF binding, and a remarkable change in dynamic range of gene expression. Our study thus unequivocally uncovers a unique mechanism by which FACT complex regulates transcription by coordinating genome-wide chromatin accessibility and CTCF binding.


Subject(s)
CCCTC-Binding Factor , Chromatin , DNA-Binding Proteins , Gene Expression Regulation , High Mobility Group Proteins , Histone Chaperones , Animals , Mice , CCCTC-Binding Factor/genetics , CCCTC-Binding Factor/metabolism , Chromatin/genetics , DNA Replication , Histone Chaperones/genetics , DNA-Binding Proteins/genetics , High Mobility Group Proteins/genetics , NIH 3T3 Cells , DNA Repair
3.
BMC Cancer ; 24(1): 453, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605291

ABSTRACT

BACKGROUND: Evidence from observational studies suggests an association between chronic obstructive pulmonary disease (COPD) and lung cancer. The potential interactions between the immune system and the lungs may play a causative role in COPD and lung cancer and offer therapeutic prospects. However, the causal association and the immune-mediated mechanisms between COPD and lung cancer remain to be determined. METHODS: We employed a two-sample Mendelian randomization (MR) approach to investigate the causal association between COPD and lung cancer. Additionally, we examined whether immune cell signals were causally related to lung cancer, as well as whether COPD was causally associated with immune cell signals. Furthermore, through two-step Mendelian randomization, we investigated the mediating effects of immune cell signals in the causal association between COPD and lung cancer. Leveraging publicly available genetic data, our analysis included 468,475 individuals of European ancestry with COPD, 492,803 individuals of European ancestry with lung cancer, and 731 immune cell signatures of European ancestry. Additionally, we conducted single-cell transcriptome sequencing analysis on COPD, lung cancer, and control samples to validate our findings. FINDINGS: We found a causal association between COPD and lung cancer (odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.31-2.02, P-value < 0.001). We also observed a causal association between COPD and regulatory T cells (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.01-1.40, P-value < 0.05), as well as a causal association between regulatory T cells and lung cancer (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 1.002-1.045, P-value < 0.05). Furthermore, our two-step Mendelian randomization analysis demonstrated that COPD is associated with lung cancer through the mediation of regulatory T cells. These findings were further validated through single-cell sequencing analysis, confirming the mediating role of regulatory T cells in the association between COPD and lung cancer. INTERPRETATION: As far as we are aware, we are the first to combine single-celled immune cell data with two-sample Mendelian randomization. Our analysis indicates a causal association between COPD and lung cancer, with regulatory T cells playing an intermediary role.


Subject(s)
Lung Neoplasms , Pulmonary Disease, Chronic Obstructive , Humans , Lung Neoplasms/genetics , Mendelian Randomization Analysis , Single-Cell Gene Expression Analysis , T-Lymphocytes, Regulatory , Pulmonary Disease, Chronic Obstructive/genetics , Genome-Wide Association Study
4.
Nanotechnology ; 35(18)2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38271736

ABSTRACT

Tunable composition of perovskite micro/nanostructures are perfect candidate for the designing of multifunctional optoelectronic circuits. Especially, integrated polychromatic luminescence based on the perovskite materials along a single substrate or chip is essential to the integrated photonic devices and multicolor displays. Here, we reported a synthesis of composition tunable CsPbI3(1-x)Br3x(X = 0.65-0.9) perovskite microstructures on a single substrate via a magnetic-pulling CVD method. The PL emissions can be changed gradually from green (558 nm, 2.23 eV) to red (610 nm, 2.03 eV) under a focused 375 nm laser illumination. Furthermore, these composition-graded alloyed perovskite microcrystals show stable emissions after six months in air, which may find applications in multicolor display and broad band light sources in the future.

5.
Environ Res ; 258: 119411, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38876423

ABSTRACT

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.

6.
Article in English | MEDLINE | ID: mdl-38708780

ABSTRACT

BACKGROUND: Large to giant congenital melanocytic nevi (LGCMN) significantly decrease patients' quality of life, but the inaccuracy of current classification system makes their clinical management challenging. OBJECTIVES: To improve and extend the existing LGCMN 6B/7B classification systems by developing a novel LGCMN classification system based on a new phenotypic approach to clinical tool development. METHODS: Three hundred and sixty-one LGCMN cases were categorized into four subtypes based on anatomic site: bonce (25.48%), extremity (17.73%), shawl (19.67%) and trunks (37.12%) LGCMN. A 'BEST' classification system of LGCMN was established and validated by a support vector machine classifier combined with the 7B system. RESULTS: The most common LGCMN distributions were on bonce and trunks (bathing trunk), whereas breast/belly and body LGCMN were exceptionally rare. Sexual dimorphism characterized distribution, with females showing a wider range of lesions in the genital area. Nearly half of the patients with bathing trunk LGCMN exhibited a butterfly-like distribution. Approximately half of the LGCMN with chest involvement did not have nipple-areola complex involvement. Abdomen, back and buttock involvement was associated with the presence of satellite nevi (r = 0.558), and back and buttock involvement was associated with the presence of nodules (r = 0.364). CONCLUSIONS: The effective quantification of a standardized anatomical site provides data support for the accuracy of the 6B/7B classification systems. The simplified BEST classification system can help establish a LGCMN clinical database for exploration of LGCMN aetiology, disease management and prognosis prediction.

7.
Sensors (Basel) ; 24(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38475045

ABSTRACT

Some fusion criteria in multisensor and multitarget motion tracking cannot be directly applied to nonlinear motion models, as the fusion accuracy applied in nonlinear systems is relatively low. In response to the above issue, this study proposes a distributed Gaussian mixture cardinality jumping Markov-cardinalized probability hypothesis density (GM-JMNS-CPHD) filter based on a generalized inverse covariance intersection. The state estimation of the JMNS-CPHD filter combines the state evaluation of traditional CPHD filters with the state estimation of jump Markov systems, estimating the target state of multiple motion models without knowing the current motion models. The performances of the generalized covariance intersection (GCI)GCI-GM-JMNS-CPHD and generalized inverse covariance intersection (GICI)GICI-GM-JMNS-CPHD methods are evaluated via simulation results. The simulation results show that, compared with algorithms such as Sensor1, Sensor2, GCI-GM-CPHD, and GICI-GM-CPHD, this algorithm has smaller optimal subpattern assignment (OSPA) errors and a higher fusion accuracy.

8.
Sensors (Basel) ; 24(8)2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38676063

ABSTRACT

In the process of the intelligent inspection of belt conveyor systems, due to problems such as its long duration, the large number of rollers, and the complex working environment, fault diagnosis by acoustic signals is easily affected by signal coupling interference, which poses a great challenge to selecting denoising methods of signal preprocessing. This paper proposes a novel wavelet threshold denoising algorithm by integrating a new biparameter and trisegment threshold function. Firstly, we elaborate on the mutual influence and optimization process of two adjustment parameters and three wavelet coefficient processing intervals in the BT-WTD (the biparameter and trisegment of wavelet threshold denoising, BT-WTD) denoising model. Subsequently, the advantages of the proposed threshold function are theoretically demonstrated. Finally, the BT-WTD algorithm is applied to denoise the simulation signals and the vibration and acoustic signals collected from the belt conveyor experimental platform. The experimental results indicate that this method's denoising effectiveness surpasses that of traditional threshold function denoising algorithms, effectively addressing the denoising preprocessing of idler roller fault signals under strong noise backgrounds while preserving useful signal features and avoiding signal distortion problems. This research lays the theoretical foundation for the non-contact intelligent fault diagnosis of future inspection robots based on acoustic signals.

9.
Nano Lett ; 23(4): 1289-1297, 2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36749085

ABSTRACT

Ceramic nanofibrous nanostructure-based sponges have attracted significant attention due to ultrahigh porosity, low thermal conductivity, large specific area, and chemical stability. From the regulation of the fiber itself to the construction method of 3D networks, efforts are being made to improve the mechanical properties of ceramic sponges for practical applications. So far resilient compressibility has been realized in ceramic nanofibrous-based sponges via structural design, but they still show brittle fracture under a more complex stress state. Herein, we introduced a highly aligned and interwoven Si3N4 nanofiber sponge, which exhibits superflexibility, large break elongation (>80%), large-strain reversible stretch (20%), and good resistance to tensile fatigue. The ceramic sponge also displays reversible compressibility up to 60% strain, puncture resistance, high air filtration efficiency (>99.8%), and low pressure drop (38% of cotton fiber), making the ceramic sponge a high-performance wearable respirator to protect us from harm due to PM2.5 pollution and possible microorganisms.

10.
Molecules ; 29(7)2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38611935

ABSTRACT

Immobilized metal ion affinity chromatography (IMAC) adsorbents generally have excellent affinity for histidine-rich proteins. However, the leaching of metal ions from the adsorbent usually affects its adsorption performance, which greatly affects the reusable performance of the adsorbent, resulting in many limitations in practical applications. Herein, a novel IMAC adsorbent, i.e., Cu(II)-loaded polydopamine-coated urchin-like titanate microspheres (Cu-PDA-UTMS), was prepared via metal coordination to make Cu ions uniformly decorate polydopamine-coated titanate microspheres. The as-synthesized microspheres exhibit an urchin-like structure, providing more binding sites for hemoglobin. Cu-PDA-UTMS exhibit favorable selectivity for hemoglobin adsorption and have a desirable adsorption capacity towards hemoglobin up to 2704.6 mg g-1. Using 0.1% CTAB as eluent, the adsorbed hemoglobin was easily eluted with a recovery rate of 86.8%. In addition, Cu-PDA-UTMS shows good reusability up to six cycles. In the end, the adsorption properties by Cu-PDA-UTMS towards hemoglobin from human blood samples were analyzed by SDS-PAGE. The results showed that Cu-PDA-UTMS are a high-performance IMAC adsorbent for hemoglobin separation, which provides a new method for the effective separation and purification of hemoglobin from complex biological samples.


Subject(s)
Hemoglobins , Imidazoles , Indoles , Polymers , Humans , Microspheres , Chromatography, Affinity , Ions
11.
Psychogeriatrics ; 24(2): 433-442, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38337190

ABSTRACT

BACKGROUND: Given the potential harms of dysphagia after stroke, we noticed the possibility of non-invasive brain stimulation treatments in the management process. METHODS: The meta-analysis search for articles published before May 2023 in databases. We used STATA 12.0 software to compute the standard mean difference (SMD) and 95% confidence intervals (CI). RESULTS: The study showed a greater improvement in swallowing function in post-stroke dysphagia given transcranial direct current stimulation (tDCS) immediately after treatment, compared to those given sham tDCS (SMD = 2.99, 95% CI = 1.86-4.11). The study showed a greater improvement in swallowing function in post-stroke dysphagia given tDCS some days after treatment, compared to those given sham tDCS (SMD = 2.01, 95% CI = 0.87-3.16). The study showed a greater improvement in swallowing function in post-stroke dysphagia given repetitive transcranial magnetic stimulation (rTMS) immediately after treatment, compared to those given sham rTMS (SMD = 4.17, 95% CI = 3.11-5.23). The study showed a greater improvement in swallowing function in post-stroke dysphagia given rTMS some days after treatment, compared to those given sham rTMS (SMD = 1.77, 95% CI = 0.94-2.60). CONCLUSIONS: In conclusion, our study showed the beneficial effects of non-invasive brain stimulation on difficulty swallowing for stroke patients and speculated about the potential application of non-invasive brain stimulation on post-stroke dysphagia improvement.


Subject(s)
Deglutition Disorders , Stroke , Transcranial Direct Current Stimulation , Humans , Deglutition Disorders/etiology , Deglutition Disorders/therapy , Stroke/complications , Stroke/therapy , Brain
12.
Proc Biol Sci ; 290(1990): 20221658, 2023 01 11.
Article in English | MEDLINE | ID: mdl-36629113

ABSTRACT

Human-induced biodiversity loss negatively affects ecosystem function, but the interactive effects of biodiversity change across trophic levels remain insufficiently understood. We sampled arboreal spiders and lepidopteran larvae across seasons in 2 years in a subtropical tree diversity experiment, and then disentangled the links between tree diversity and arthropod predator diversity by deconstructing the pathways among multiple components of diversity (taxonomic, phylogenetic and functional) with structural equation models. We found that herbivores were major mediators of plant species richness effects on abundance, species richness, functional and phylogenetic diversity of predators, while phylogenetic, functional and structural diversity of trees were also important mediators of this process. However, the strength and direction differed between functional, structural and phylogenetic diversity effects, indicating different underlying mechanisms for predator community assembly. Abundance and multiple diversity components of predators were consistently affected by tree functional diversity, indicating that the variation in structure and environment caused by plant functional composition might play key roles in predator community assembly. Our study highlights the importance of an integrated approach based on multiple biodiversity components in understanding the consequences of biodiversity loss in multitrophic communities.


Subject(s)
Arthropods , Spiders , Animals , Humans , Ecosystem , Phylogeny , Biodiversity , Plants
13.
NMR Biomed ; 36(1): e4824, 2023 01.
Article in English | MEDLINE | ID: mdl-36057449

ABSTRACT

The purpose of this study was to evaluate the value of amide proton transfer-weighted (APTw) MRI radiomic features for the differentiation of tumor recurrence from treatment effect in malignant gliomas. Eighty-six patients who had suspected tumor recurrence after completion of chemoradiation or radiotherapy, and who had APTw-MRI data acquired at 3 T, were retrospectively analyzed. Using a fluid-attenuated inversion recovery (FLAIR) image-based mask, radiomics analysis was applied to the processed APTw and structural MR images. A chi-square automatic interaction detector decision tree was used for classification analysis. Models with and without APTw features were built using the same strategy. Tenfold cross-validation was applied to obtain the overall classification performance of each model. Sixty patients were confirmed as having tumor recurrence, and the remainder were confirmed as having treatment effect, at median time points of 190 and 171 days after therapy, respectively. There were 525 radiomic features extracted from each of the processed APTw and structural MR images. Based on these, the APTw-based model yielded the highest accuracy (86.0%) for the differentiation of tumor recurrence from treatment effect, compared with 74.4%, 76.7%, 83.7%, and 76.7% for T1 w, T2 w, FLAIR, and Gd-T1 w, respectively. Model classification accuracy was 82.6% when using the combined structural MR images (T1 w, T2 w, FLAIR, Gd-T1 w), and increased to 89.5% when using these structural plus APTw images. The corresponding sensitivity and specificity were 85.0% and 76.9% for the combination of structural MR images, and 85.0% and 100% after adding APTw image features. Adding APTw-based radiomic features increased MRI accuracy in the assessment of the treatment response in post-treatment malignant gliomas.


Subject(s)
Glioma , Protons , Humans , Amides , Neoplasm Recurrence, Local/diagnostic imaging , Retrospective Studies , Glioma/diagnostic imaging , Glioma/therapy
14.
Opt Lett ; 48(7): 1846-1849, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37221781

ABSTRACT

In this Letter, we report a bridge-connected three-electrode germanium-on-silicon (Ge-on-Si) avalanche photodiode (APD) array compatible with the complementary metal-oxide semiconductor (CMOS) process. In addition to the two electrodes on the Si substrate, a third electrode is designed for Ge. A single three-electrode APD was tested and analyzed. By applying a positive voltage on the Ge electrode, the dark current of the device can be reduced, and yet the response of the device can be increased. Under a dark current of 100 nA, as the voltage on Ge increases from 0 V to 15 V, the light responsivity is increased from 0.6 A/W to 1.17 A/W. We report, for the first time to the best of our knowledge, the near-infrared imaging properties of an array of three-electrode Ge-on-Si APDs. Experiments show that the device can be used for LiDAR imaging and low-light detection.

15.
J Anim Ecol ; 92(2): 442-453, 2023 02.
Article in English | MEDLINE | ID: mdl-36507573

ABSTRACT

Global biodiversity decline and its cascading effects through trophic interactions pose a severe threat to human society. Establishing the impacts of biodiversity decline requires a more thorough understanding of multi-trophic interactions and, more specifically, the effects that loss of diversity in primary producers has on multi-trophic community assembly. Within a synthetic conceptual framework for multi-trophic beta-diversity, we tested a series of hypotheses on neutral and niche-based bottom-up processes in assembling herbivore and carnivore communities in a subtropical forest using linear models, hieratical variance partitioning based on linear mixed-effects models (LMMs) and simulation. We found that the observed taxonomic, phylogenetic and functional beta-diversity of both herbivorous caterpillars and carnivorous spiders were significantly and positively related to tree dissimilarity. Linear models and variance partitioning for LMMs jointly suggested that as a result of bottom-up effects, producer dissimilarities were predominant in structuring consumer dissimilarity, the strength of which highly depended on the trophic dependencies on producers, the diversity facet examined, and data quality. Importantly, linear models for standardized beta-diversities against producer dissimilarities implied a transition between niche-based processes such as environmental filtering and competitive exclusion, which supports the role of bottom-up effect in determining consumer community assembly. These findings enrich our mechanistic understanding of the 'Diversity Begets Diversity' hypothesis and the complexity of higher-trophic community assembly, which is fundamental for sustainable biodiversity conservation and ecosystem management.


Subject(s)
Ecosystem , Herbivory , Humans , Animals , Phylogeny , Biodiversity , Forests
16.
Environ Res ; 237(Pt 2): 117092, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37683785

ABSTRACT

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that induce oxidative inflammatory responses and disrupt the endocrine and central nervous systems, all of which can influence sleep. OBJECTIVE: To investigate the association between PFAS exposure and sleep health measures in U.S. adults. METHODS: We analyzed serum concentration data of four PFAS [perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)] reported for 8913 adults in NHANES 2005-2014. Sleep outcomes, including trouble sleeping, having a diagnosis of sleep disorder, and recent daily sleep duration classified as insufficient or excessive sleep (<6 or >9 h/day) were examined. Weighted logistic regression was used to estimate the association between the sleep outcomes and each PFAS modeled continuously (log2) or in exposure tertiles. We applied quantile g-computation to estimate the effect of the four PFAS as a mixture on the sleep outcomes. We conducted a quantitative bias analysis to assess the potential influence of self-selection and uncontrolled confounding. RESULTS: We observed some inverse associations between serum PFAS and trouble sleeping or sleep disorder, which were more consistent for PFOS (e.g., per log2-PFOS (ng/ml) and trouble sleeping OR = 0.93, 95%CI: 0.89, 0.98; sleep disorder OR = 0.89, 95%CI: 0.83, 0.95). Per quartile increase of the PFAS mixture was inversely associated with trouble sleeping and sleep disorder. No consistent associations were found for sleep duration across analyses. Our bias analysis suggests that the finding on sleep disorder could be explained by a moderate level of self-selection and negative confounding effects. CONCLUSIONS: We found no evidence to suggest exposure to four legacy PFAS worsened self-reported sleep health among U.S. adults. While some inverse associations between specific PFAS and sleep disorder were observed, self-selection and uncontrolled confounding biases may play a role in these findings.

17.
Appl Opt ; 62(21): 5652-5659, 2023 Jul 20.
Article in English | MEDLINE | ID: mdl-37707181

ABSTRACT

To eliminate the time shift of code edges on a single-sideband (SSB) modulation signal transmission in a radio-over-fiber (RoF) system, a new, to the best of our knowledge, SSB modulation scheme based on an optimal transmission point for a double-parallel Mach-Zehnder modulator (DP-MZM) is proposed. The scheme is based on DP-MZM to realize the separation of the carrier and the +1st-order sideband at the optimal transmission point, and the baseband signal modulates the 2.5 Gb/s data signal to the +1st-order sideband of the SSB signal; then, the carrier and the +1st-order sideband are transmitted with a carrier-to-sideband ratio of 0 dB. Theoretical analysis shows that compared to the traditional SSB-modulated optical millimeter-wave signal generation scheme this scheme completely solves the problem of the time shift of code edges caused by dispersion. The simulation results show that the improved SSB modulation scheme has a Q factor of 23.362, the minimum bit error rate is 4.207×10-127 at 73.453 km, and the eye diagram is still very clear. Under the premise of meeting the basic requirements of communications, the maximum communications distance can reach 135 km, which is 270% of the transmission distance of a traditional SSB modulation model. Thus, the system performance has been greatly improved.

18.
Proc Natl Acad Sci U S A ; 117(8): 4078-4087, 2020 02 25.
Article in English | MEDLINE | ID: mdl-32041890

ABSTRACT

Anthrax lethal toxin (LT) is a protease virulence factor produced by Bacillus anthracis that is required for its pathogenicity. LT treatment causes a rapid degradation of c-Jun protein that follows inactivation of the MEK1/2-Erk1/2 signaling pathway. Here we identify COP1 as the ubiquitin E3 ligase that is essential for LT-induced c-Jun degradation. COP1 knockdown using siRNA prevents degradation of c-Jun, ETV4, and ETV5 in cells treated with either LT or the MEK1/2 inhibitor, U0126. Immunofluorescence staining reveals that COP1 preferentially localizes to the nuclear envelope, but it is released from the nuclear envelope into the nucleoplasm following Erk1/2 inactivation. At baseline, COP1 attaches to the nuclear envelope via interaction with translocated promoter region (TPR), a component of the nuclear pore complex. Disruption of this COP1-TPR interaction, through Erk1/2 inactivation or TPR knockdown, leads to rapid COP1 release from the nuclear envelope into the nucleoplasm where it degrades COP1 substrates. COP1-mediated degradation of c-Jun protein, combined with LT-mediated blockade of the JNK1/2 signaling pathway, inhibits cellular proliferation. This effect on proliferation is reversed by COP1 knockdown and ectopic expression of an LT-resistant MKK7-4 fusion protein. Taken together, this study reveals that the nuclear envelope acts as a reservoir, maintaining COP1 poised for action. Upon Erk1/2 inactivation, COP1 is rapidly released from the nuclear envelope, promoting the degradation of its nuclear substrates, including c-Jun, a critical transcription factor that promotes cellular proliferation. This regulation allows mammalian cells to respond rapidly to changes in extracellular cues and mediates pathogenic mechanisms in disease states.


Subject(s)
Antigens, Bacterial/pharmacology , Bacterial Toxins/pharmacology , Mitogen-Activated Protein Kinase 3/metabolism , Mitogen-Activated Protein Kinase 6/metabolism , Nuclear Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , Cell Line , Cell Proliferation , Humans , Mice , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 6/genetics , Nuclear Proteins/genetics , Ubiquitin-Protein Ligases/genetics
19.
J Basic Microbiol ; 63(1): 26-38, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36316240

ABSTRACT

This study identified the antifungal metabolites produced by Bacillus altitudinis Q7 against Alternaria alternata and investigated the antifungal activity and antifungal action. Lipopeptide, the important secondary metabolites were identified by Fourier transform infrared (FTIR) and liquid chromatography-mass spectrometry as lichenysin. The antifungal activity of lipopeptide on A. alternata was determined by microdilution technique, and its minimum inhibitory concentration was 1.2 mg/ml. Stability test showed that lipopeptide had excellent temperature and pH resistance. To investigate whether lichenysin acted on the cell membrane and changed its permeability, the ultra-violet absorption of protein and nucleic acid were measured using a colorimetric method. The antifungal metabolites produced by B. altitudinis Q7 was lichenysin, which showed stable antifungal activity in the extreme environments. Lichenysin could inhibit A. alternata by altering the permeability of cell membrane, leading to the outflow of proteins and nucleic acids from the cytoplasm. This research suggests the lipopeptide from B. altitudinis Q7 is a potential biological control agent against A. alternata.


Subject(s)
Antifungal Agents , Bacillus , Antifungal Agents/chemistry , Lipopeptides/pharmacology , Lipopeptides/chemistry , Lipopeptides/metabolism , Bacillus/metabolism , Alternaria
20.
J Integr Plant Biol ; 65(7): 1734-1752, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36916709

ABSTRACT

Although seed weight has increased following domestication from wild soybean (Glycine soja) to cultivated soybean (Glycine max), the genetic basis underlying this change is unclear. Using mapping populations derived from chromosome segment substitution lines of wild soybean, we identified SW16.1 as the causative gene underlying a major quantitative trait locus controlling seed weight. SW16.1 encodes a nucleus-localized LIM domain-containing protein. Importantly, the GsSW16.1 allele from wild soybean accession N24852 had a negative effect on seed weight, whereas the GmSW16.1 allele from cultivar NN1138-2 had a positive effect. Gene expression network analysis, reverse-transcription quantitative polymerase chain reaction, and promoter-luciferase reporter transient expression assays suggested that SW16.1 regulates the transcription of MT4, a positive regulator of seed weight. The natural variations in SW16.1 and other known seed weight genes were analyzed in soybean germplasm. The SW16.1 polymorphism was associated with seed weight in 247 soybean accessions, showing much higher frequency of positive-effect alleles in cultivated soybean than in wild soybean. Interestingly, gene allele matrix analysis of the known seed weight genes revealed that G. max has lost 38.5% of the G. soja alleles and that most of the lost alleles had negative effects on seed weight. Our results suggest that eliminating negative alleles from G. soja led to a higher frequency of positive alleles and changed genetic backgrounds in G. max, which contributed to larger seeds in cultivated soybean after domestication from wild soybean. Our findings provide new insights regarding soybean domestication and should assist current soybean breeding programs.


Subject(s)
Fabaceae , Glycine max , Glycine max/genetics , Alleles , Domestication , Plant Breeding , Seeds/genetics
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