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1.
Genes Dev ; 36(3-4): 225-240, 2022 02 01.
Article in English | MEDLINE | ID: mdl-35144965

ABSTRACT

The BEN domain is a recently recognized DNA binding module that is present in diverse metazoans and certain viruses. Several BEN domain factors are known as transcriptional repressors, but, overall, relatively little is known of how BEN factors identify their targets in humans. In particular, X-ray structures of BEN domain:DNA complexes are only known for Drosophila factors bearing a single BEN domain, which lack direct vertebrate orthologs. Here, we characterize several mammalian BEN domain (BD) factors, including from two NACC family BTB-BEN proteins and from BEND3, which has four BDs. In vitro selection data revealed sequence-specific binding activities of isolated BEN domains from all of these factors. We conducted detailed functional, genomic, and structural studies of BEND3. We show that BD4 is a major determinant for in vivo association and repression of endogenous BEND3 targets. We obtained a high-resolution structure of BEND3-BD4 bound to its preferred binding site, which reveals how BEND3 identifies cognate DNA targets and shows differences with one of its non-DNA-binding BEN domains (BD1). Finally, comparison with our previous invertebrate BEN structures, along with additional structural predictions using AlphaFold2 and RoseTTAFold, reveal distinct strategies for target DNA recognition by different types of BEN domain proteins. Together, these studies expand the DNA recognition activities of BEN factors and provide structural insights into sequence-specific DNA binding by mammalian BEN proteins.


Subject(s)
Repressor Proteins , Transcription Factors , Animals , Binding Sites , Drosophila/metabolism , Mammals , Protein Binding , Protein Domains , Repressor Proteins/genetics , Transcription Factors/metabolism
2.
BMC Genomics ; 25(1): 423, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684946

ABSTRACT

BACKGROUND: Single-cell clustering has played an important role in exploring the molecular mechanisms about cell differentiation and human diseases. Due to highly-stochastic transcriptomics data, accurate detection of cell types is still challenged, especially for RNA-sequencing data from human beings. In this case, deep neural networks have been increasingly employed to mine cell type specific patterns and have outperformed statistic approaches in cell clustering. RESULTS: Using cross-correlation to capture gene-gene interactions, this study proposes the scCompressSA method to integrate topological patterns from scRNA-seq data, with support of self-attention (SA) based coefficient compression (CC) block. This SA-based CC block is able to extract and employ static gene-gene interactions from scRNA-seq data. This proposed scCompressSA method has enhanced clustering accuracy in multiple benchmark scRNA-seq datasets by integrating topological and temporal features. CONCLUSION: Static gene-gene interactions have been extracted as temporal features to boost clustering performance in single-cell clustering For the scCompressSA method, dual-channel SA based CC block is able to integrate topological features and has exhibited extraordinary detection accuracy compared with previous clustering approaches that only employ temporal patterns.


Subject(s)
Single-Cell Analysis , Single-Cell Analysis/methods , Cluster Analysis , Humans , Epistasis, Genetic , Sequence Analysis, RNA/methods , Gene Regulatory Networks , Computational Biology/methods , Gene Expression Profiling/methods , Algorithms , Deep Learning , Neural Networks, Computer
3.
Drug Metab Rev ; 56(1): 62-79, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38226647

ABSTRACT

Melatonin, historically recognized for its primary role in regulating circadian rhythms, has expanded its influence particularly due to its wide range of biological activities. It has firmly established itself in cancer research. To highlight its versatility, we delved into how melatonin interacts with key signaling pathways, such as the Wnt/ß-Catenin, PI3K, and NF-κB pathways, which play foundational roles in tumor development and progression. Notably, melatonin can intricately modulate these pathways, potentially affecting various cellular functions such as apoptosis, metastasis, and immunity. Additionally, a comprehensive review of current clinical studies provides a dual perspective. These studies confirm melatonin's potential in cancer management but also underscore its inherent limitations, particularly its limited bioavailability, which often relegates it to a supplementary role in treatments. Despite this limitation, there is an ongoing quest for innovative solutions and current advancements include the development of melatonin derivatives and cutting-edge delivery systems. By synthesizing the past, present, and future, this review provides a detailed overview of melatonin's evolving role in oncology, positioning it as a potential cornerstone in future cancer therapeutics.


Subject(s)
Melatonin , Neoplasms , Humans , Melatonin/therapeutic use , Melatonin/metabolism , Signal Transduction , Biology , Neoplasms/drug therapy
4.
Development ; 148(6)2021 03 17.
Article in English | MEDLINE | ID: mdl-33597191

ABSTRACT

Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here, we reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early to late phase of neurogenesis in the mouse neocortex. Loss of Prdm16 delays the timely progression of RG, leading to defective cortical laminar organization. Our genomic analyses demonstrate that PRDM16 regulates a subset of genes that are dynamically expressed between early and late neurogenesis. We show that PRDM16 suppresses target gene expression through limiting chromatin accessibility of permissive enhancers. We further confirm that crucial target genes regulated by PRDM16 are neuronal specification genes, cell cycle regulators and molecules required for neuronal migration. These findings provide evidence to support the finding that neural progenitors temporally shift the gene expression program to achieve neural cell diversity.


Subject(s)
Cell Differentiation/genetics , DNA-Binding Proteins/genetics , Neurogenesis/genetics , Neurons/metabolism , Transcription Factors/genetics , Animals , Cell Movement/genetics , Chromatin/genetics , Ependymoglial Cells/metabolism , Gene Expression Regulation, Developmental/genetics , Mice , Neocortex/growth & development , Neocortex/metabolism , Neural Stem Cells/metabolism , Neuroglia/metabolism , Signal Transduction/genetics
5.
J Cardiovasc Electrophysiol ; 35(5): 1007-1016, 2024 May.
Article in English | MEDLINE | ID: mdl-38468346

ABSTRACT

INTRODUCTION: Cather ablation (CA) is a well-recognized treatment alternative for atrial fibrillation (AF) patients despite more than 20% ablation-treated patients suffering from AF recurrence. The underlying mechanism of AF recurrence postablation is probably associated with high cardiac parasympathetic activity, which can be assessed with deceleration capacity (DC) of heart rate. Given that the relationship between DC and AF recurrence is still controversial, this systematic review and meta-analysis was performed to investigate the characteristics of DC in patients with and without AF recurrence, evaluating the prognostic value of DC in AF patients after CA. METHODS: A literature search was systematically performed in the Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases until October 01, 2023. The observational studies reporting either the pre- and postablation DC in both recurrence and non-recurrence groups or the ratios based on DC for predicting AF recurrence were mainly included. Weighted mean differences (WMD) or odds ratios (OR) based on DC would be calculated with a random-effect model, if heterogeneity estimated with the I2 index and Q statistic was significant (I2 > 50% or p < .05); otherwise, a fixed-effect model would be utilized. RESULTS: A total of eight observational studies involving 914 AF patients treated with radiofrequency or cryoballoon ablation were included in this study. Ablation-treated patients with AF recurrence had the higher DC postablation in relation to those without recurrence (WMD, 1.00; 95% confidence interval [CI], 0.33-1.67; p < .01), which was present up to 3 months of follow-up (WMD, 1.54; 95% CI, 1.11-1.96; p < .01), whereas there was no statistical significance in DC before ablation between recurrence and non-recurrence groups (WMD, 0.34; 95% CI, -0.12 to 0.79; p = .15). The high DC postablation was a risk factor for AF recurrence in ablation-treated patients (OR, 2.17; 95% CI, 1.44-3.25; p < .01). CONCLUSION: The high DC postablation was associated with the risk of AF recurrence, suggesting that DC may act as a prognostic indicator in AF patients treated with CA.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Deceleration , Heart Rate , Predictive Value of Tests , Recurrence , Adult , Aged , Female , Humans , Male , Middle Aged , Action Potentials , Atrial Fibrillation/physiopathology , Atrial Fibrillation/surgery , Atrial Fibrillation/diagnosis , Catheter Ablation/adverse effects , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
6.
Cytokine ; 180: 156663, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38815522

ABSTRACT

BACKGROUND: Glioma represents the predominant malignant brain tumor. This investigation endeavors to elucidate the impact and prospective mechanisms of glycolysis-related lncARSR on glioma. METHODS: LncARSR level was assessed in normal glial cells and glioma cells. Cell proliferation, migration, and invasion measurements were conducted through CCK-8, wound healing, and transwell assay. Flow cytometry was utilized to measure cell apoptosis and cell cycle. Biochemical assay kits and immunoblotting were employed to measure the content of glycolysis-related indicators and protein expression, respectively. We analyzed the impact of both lncARSR knockdown and overexpression of the Signal Transducer and Activator of Transcription 3 (STAT3) on Hexokinase 2 (HK2) using dual luciferase reporter assays and Chromatin Immunoprecipitation (ChIP) experiments. Further assessment of the impact of lncARSR on glioma progression was conducted through animal experiments. RESULTS: LncARSR was expressed at elevated levels in glioma cells compared to normal glial cells. Overexpressing lncARSR enhanced proliferation, migration, invasion, and G2/M phase arrest in glioma cells and also increased glucose, lactate, ATP production, as well as the expression of HK2, PFK1, PKM2, GLUT1, and LDHA. STAT3 binding to the HK2 gene promoter was weakened following the knockdown of lncARSR. Upregulation of STAT3 reversed the suppressed functions of knocking down lncARSR on cell proliferation, migration, invasion, G2/M phase arrest, and glycolysis and counteracted its promotional effect on cell apoptosis. In vivo, knocking down lncARSR inhibits glioma growth and ki67 and PCNA expression. CONCLUSION: LncARSR promotes the development of glioma by enhancing glycolysis through the STAT3-HK2 axis.


Subject(s)
Cell Movement , Cell Proliferation , Glioma , Glycolysis , Hexokinase , RNA, Long Noncoding , STAT3 Transcription Factor , STAT3 Transcription Factor/metabolism , Glioma/metabolism , Glioma/pathology , Glioma/genetics , Hexokinase/metabolism , Hexokinase/genetics , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Cell Line, Tumor , Animals , Cell Movement/genetics , Mice , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Mice, Nude , Apoptosis , Signal Transduction
7.
Gerontology ; 70(2): 134-142, 2024.
Article in English | MEDLINE | ID: mdl-37967546

ABSTRACT

INTRODUCTION: Theoretically, some metabolic traits may predispose older individuals to weight loss during aging, leading to increased all-cause mortality and many serious health issues. Biomarkers to robustly predict progressive weight loss during aging are, however, lacking. We prospectively assessed if urinary levels of F2-isoprostanes and their peroxisomal ß-oxidation metabolite, 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoP-M), were associated with subsequent weight loss in middle-aged and older women. METHODS: Included in the analysis were 2,066 women aged 40-70 years, a subset of a prospective cohort study. F2-isoprostanes (F2-IsoPs) and its ß-oxidation metabolite, F2-IsoP-M, were measured in urine using gas chromatography-mass spectrometry. Measurements of anthropometry and exposures to major determinants of body weight were performed at baseline and repeated thrice over 15-year follow-up. The longitudinal associations of F2-IsoP-M and the F2-IsoP-M to its parent compound, F2-IsoP, ratio (MPR) with repeatedly measured weight changes were examined using linear mixed-effect models. RESULTS: After adjusting for time-varying covariates: energy intake, physical activity, and comorbidity index, among others, levels of F2-IsoP-M and the MPR were both inversely associated with percentage of weight change. Weight in the highest quartile of these two biomarkers was 1.33% (95% CI = -2.41, -0.24) and 1.09% (95% CI = -2.16, -0.02) lower than those in the lowest quartile group, with p for trend of 0.01 and 0.03, respectively. The inverse association was consistently seen across follow-up periods, although appearing stronger with prolonged follow-up. There was no association between the parent compound, F2-IsoPs, and weight change. CONCLUSION: This study demonstrates the first piece of evidence to associate F2-IsoP metabolism, peroxisomal ß-oxidation, with weight loss in older women. Further investigations into the role of lipid peroxidation and peroxisomal ß-oxidation in weight change among older individuals are warranted.


Subject(s)
F2-Isoprostanes , Oxidative Stress , Female , Humans , Middle Aged , Aged , F2-Isoprostanes/metabolism , Prospective Studies , Biomarkers/metabolism , Weight Loss
8.
Graefes Arch Clin Exp Ophthalmol ; 262(7): 2329-2336, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38376562

ABSTRACT

PURPOSE: This study aims to assess the accuracy of three parameters (white-to-white distance [WTW], angle-to-angle [ATA], and sulcus-to-sulcus [STS]) in predicting postoperative vault and to formulate an optimized predictive model. METHODS: In this retrospective study, a cohort of 465 patients (comprising 769 eyes) who underwent the implantation of the V4c implantable Collamer lens with a central port (ICL) for myopia correction was examined. Least absolute shrinkage and selection operator (LASSO) regression and classification models were used to predict postoperative vault. The influences of WTW, ATA, and STS on predicting the postoperative vault and ICL size were analyzed and compared. RESULTS: The dataset was randomly divided into training (80%) and test (20%) sets, with no significant differences observed between them. The screened variables included only seven variables which conferred the largest signal in the model, namely, lens thickness (LT, estimated coefficients for logistic least absolute shrinkage of -0.20), STS (-0.04), size (0.08), flat K (-0.006), anterior chamber depth (0.15), spherical error (-0.006), and cylindrical error (-0.0008). The optimal prediction model depended on STS (R2=0.419, RMSE=0.139), whereas the least effective prediction model relied on WTW (R2=0.395, RMSE=0.142). In the classified prediction models of the vault, classification prediction of the vault based on STS exhibited superior accuracy compared to ATA or WTW. CONCLUSIONS: This study compared the capabilities of WTW, ATA, and STS in predicting postoperative vault, demonstrating that STS exhibits a stronger correlation than the other two parameters.


Subject(s)
Lens Implantation, Intraocular , Myopia , Phakic Intraocular Lenses , Refraction, Ocular , Visual Acuity , Humans , Retrospective Studies , Myopia/surgery , Myopia/physiopathology , Male , Female , Adult , Postoperative Period , Refraction, Ocular/physiology , Young Adult , Anterior Chamber/pathology , Anterior Chamber/diagnostic imaging , Biometry/methods , Follow-Up Studies , Middle Aged
9.
BMC Oral Health ; 24(1): 48, 2024 01 08.
Article in English | MEDLINE | ID: mdl-38191341

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the condylar morphological changes after orthodontic treatment in adult patients with Class II malocclusion using a Cone-beam computed tomography (CBCT). METHODS: Images of twenty-eight adult patients with Class II malocclusion who have no temporomandibular symptoms were involved in this study. To analyze the post-treatment changes in condylar morphology, mimics 17.0 software was used to measure several values and reconstruct the three-dimensional condyle, including height of the condyle, area and bone mineral density of the maximum axial and sagittal section, volume and bone mineral density of the three-dimensional condyle and condylar head before and after orthodontic treatment. Using SPSS 19.0 software package Paired t-test was applied for comparison of condylar morphology analysis between pre-treatment and post-treatment. RESULTS: Height of condylar head increase significant (P < .05). Bone mineral density showed a decrease in the maximum axial and sagittal section, three-dimensional condyle and condylar head (P < .01). Evaluation of volume revealed that volume of both condyle and condylar head decrease considerably (P < .05). No significant difference was detected in other values ((P > .05). CONCLUSION: Condylar volume decreased and height of condylar head have changed, so we speculated that adaptive bone remodeling of the condyle occurs.


Subject(s)
Bone Density , Malocclusion, Angle Class II , Adult , Humans , Cone-Beam Computed Tomography , Dental Care , Malocclusion, Angle Class II/diagnostic imaging , Malocclusion, Angle Class II/therapy , Bone and Bones
10.
Development ; 147(5)2020 03 11.
Article in English | MEDLINE | ID: mdl-32041791

ABSTRACT

Orderly division of radial glial progenitors (RGPs) in the developing mammalian cerebral cortex generates deep and superficial layer neurons progressively. However, the mechanisms that control RGP behavior and precise neuronal output remain elusive. Here, we show that the oxidative stress level progressively increases in the developing mouse cortex and regulates RGP behavior and neurogenesis. As development proceeds, numerous gene pathways linked to reactive oxygen species (ROS) and oxidative stress exhibit drastic changes in RGPs. Selective removal of PRDM16, a transcriptional regulator highly expressed in RGPs, elevates ROS level and induces expression of oxidative stress-responsive genes. Coinciding with an enhanced level of oxidative stress, RGP behavior was altered, leading to abnormal deep and superficial layer neuron generation. Simultaneous expression of mitochondrially targeted catalase to reduce cellular ROS levels significantly suppresses cortical defects caused by PRDM16 removal. Together, these findings suggest that oxidative stress actively regulates RGP behavior to ensure proper neurogenesis in the mammalian cortex.


Subject(s)
Cerebral Cortex/growth & development , DNA-Binding Proteins/genetics , Neural Stem Cells/cytology , Neurogenesis/physiology , Oxidative Stress/physiology , Transcription Factors/genetics , Animals , Cells, Cultured , Cerebral Cortex/cytology , Mice , Mice, Knockout , Neural Stem Cells/metabolism , Reactive Oxygen Species/metabolism
11.
Opt Express ; 31(2): 997-1013, 2023 Jan 16.
Article in English | MEDLINE | ID: mdl-36785146

ABSTRACT

Quantitative evaluation of spatial brightness has been difficult, mainly due to the lack of a metric that is both highly related to subjective evaluation and convenient to measure in the field. This work investigated the applicability of using indirect corneal illuminance to evaluate spatial brightness for a visual field in interior spaces. Three lighting scenes with different patterns of lighting distribution, which all delivered indirect light to the subjects, were compared against each other in pairs for spatial brightness. The corresponding indirect corneal illuminance required for each test scene to match the spatial brightness of the reference scene with a fixed corneal illuminance was obtained. The results showed that our proposed metric had a high correlation with subjective evaluation of spatial brightness even under very different patterns of lighting distribution. Furthermore, the proposed metric was compared with the prior metrics of MRSE and Lav,B40 in spatial brightness evaluation, and the former showed the best correlation with subjective judgments. Since the spatial brightness assessment for various visual fields together compose people's overall impression of an illuminated space, the proposed metric of indirect corneal illuminance, which combines both accuracy and convenience in measurement, could serve as a preferred metric for spatial brightness evaluation.

12.
Opt Express ; 31(6): 9543-9553, 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-37157522

ABSTRACT

Due to the unprecedented wavefront shaping capability, the metasurface has demonstrated state-of-the-art performances in various applications, especially in printing and holography. Recently, these two functions have been combined into a single metasurface chip to achieve a capability expansion. Despite the progress, current dual-mode metasurfaces are realized at the expense of an increase in the difficulty of the fabrication, reduction of the pixel resolution, or strict limitation in the illumination conditions. Inspired by the Jacobi-Anger expansion, a phase-assisted paradigm, called Bessel metasurface, has been proposed for simultaneous printing and holography. By elaborately arranging the orientations of the single-sized nanostructures with geometric phase modulation, the Bessel metasurface can not only encode a greyscale printing image in real space but can reconstruct a holographic image in k-space. With the merits of compactness, easy fabrication, convenient observation, and liberation of the illumination conditions, the design paradigm of the Bessel metasurface would have promising prospects in practical applications, including optical information storage, 3D stereoscopic displays, multifunctional optical devices, etc.

13.
Mol Pharm ; 20(2): 1025-1038, 2023 02 06.
Article in English | MEDLINE | ID: mdl-36571795

ABSTRACT

Boron neutron capture therapy (BNCT) is becoming a promising radiation treatment technique dealing with tumors due to its cellular targeting specificity. In this article, based on the biocompatible chitosan oligosaccharide (COS), we designed a boron delivery system using carborane (CB) as a boron drug with cRGD peptide modification and paclitaxel (PTX) loaded in the hydrophobic core. The nanoparticles (cRGD-COS-CB/PTX) realized the boron delivery into tumor sites with an enhanced permeability and retention (EPR) effect and an active targeting effect achieved by the cRGD-integrin interaction on the surface of tumor cells. The uniform spherical nanoparticles can be selectively taken by hepatoma cells rather than normal hepatocytes. In vivo experiments showed that the nanoparticles had a targeting effect on tumor sites in both subcutaneous and orthotopic tumor models, which was an encouraging result for radiotherapy for liver cancer. To sum up, the nanoparticles we produced proved to be promising dual-functionalized nanoparticles for radiotherapy and chemotherapy.


Subject(s)
Boranes , Boron Neutron Capture Therapy , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/radiotherapy , Boron Neutron Capture Therapy/methods , Boron , Liver Neoplasms/drug therapy , Liver Neoplasms/radiotherapy , Oligosaccharides , Cell Line, Tumor
14.
Org Biomol Chem ; 21(34): 7005-7017, 2023 08 30.
Article in English | MEDLINE | ID: mdl-37593934

ABSTRACT

A series of novel erianin analogues were designed and synthesized based on the bioisosterism principle by altering the two aromatic rings of erianin, the substituents on the rings and the linker between them. The analogues were evaluated as pyruvate carboxylase (PC) inhibitors in hepatocellular carcinoma cells. It was found that compounds 35 and 36, where fluorine replaces a hydroxyl group, exhibited higher activity than erianin (IC50 value of 17.30 nM) in liver cancer cells with IC50 values of 15.15 nM and 10.05 nM, respectively. Additionally, at a concentration of 10 nM, compounds 35 and 36 inhibited PC with inhibitory rates of 39.10% and 40.15%, respectively, exhibiting nearly identical inhibitory activity to erianin (inhibitory rate of 40.07%). Additionally, a computer simulation docking study demonstrated the basis for better interactions between the receptors and ligands. The fluorine atom of 35 can not only form hydrogen bonds with Lys-1043 (NH⋯F, 2.04 Å), but also form fluorine bonds with the carbonyl groups of Lys-1043 (3.67 Å) and Glu-1046 (3.70 Å), due to the different orientations of the halogens on the B ring warhead. Conversely, the chlorine atom of 34 can only form alkyl hydrophobic interactions with the alkane chain in Lys-1043. Fluorinated compounds 35 and 36 also show better chemical stability and higher log P (clog P = 3.89 for 35 and 36) values than that of erianin (clog P = 3.07), and may be used as candidate compounds for further drug development.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Pyruvate Carboxylase , Humans , Carcinoma, Hepatocellular/drug therapy , Computer Simulation , Fluorine , Halogens , Liver Neoplasms/drug therapy , Pyruvate Carboxylase/antagonists & inhibitors , Structure-Activity Relationship
15.
Genes Dev ; 29(1): 48-62, 2015 Jan 01.
Article in English | MEDLINE | ID: mdl-25561495

ABSTRACT

Recently, the BEN (BANP, E5R, and NAC1) domain was recognized as a new class of conserved DNA-binding domain. The fly genome encodes three proteins that bear only a single BEN domain ("BEN-solo" factors); namely, Insensitive (Insv), Bsg25A (Elba1), and CG9883 (Elba2). Insv homodimers preferentially bind CCAATTGG palindromes throughout the genome to mediate transcriptional repression, whereas Bsg25A and Elba2 heterotrimerize with their obligate adaptor, Elba3 (i.e., the ELBA complex), to recognize a CCAATAAG motif in the Fab-7 insulator. While these data suggest distinct DNA-binding properties of BEN-solo proteins, we performed reporter assays that indicate that both Bsg25A and Elba2 can individually recognize Insv consensus sites efficiently. We confirmed this by solving the structure of Bsg25A complexed to the Insv site, which showed that key aspects of the BEN:DNA recognition strategy are similar between these proteins. We next show that both Insv and ELBA proteins are competent to mediate transcriptional repression via Insv consensus sequences but that the ELBA complex appears to be selective for the ELBA site. Reciprocally, genome-wide analysis reveals that Insv exhibits significant cobinding to class I insulator elements, indicating that it may also contribute to insulator function. Indeed, we observed abundant Insv binding within the Hox complexes with substantial overlaps with class I insulators, many of which bear Insv consensus sites. Moreover, Insv coimmunoprecipitates with the class I insulator factor CP190. Finally, we observed that Insv harbors exclusive activity among fly BEN-solo factors with respect to regulation of Notch-mediated cell fate choices in the peripheral nervous system. This in vivo activity is recapitulated by BEND6, a mammalian BEN-solo factor that conserves the Notch corepressor function of Insv but not its capacity to bind Insv consensus sites. Altogether, our data define an array of common and distinct biochemical and functional properties of this new family of transcription factors.


Subject(s)
Drosophila Proteins/genetics , Gene Expression Regulation, Developmental , Transcription Factors/genetics , Transcription Factors/metabolism , Amino Acid Sequence , Animals , Blastoderm/metabolism , Co-Repressor Proteins/chemistry , Co-Repressor Proteins/metabolism , Crystallography , Drosophila Proteins/chemistry , Drosophila Proteins/metabolism , Drosophila melanogaster/embryology , Drosophila melanogaster/genetics , Genome-Wide Association Study , Humans , Mice , Models, Molecular , Protein Binding , Protein Structure, Quaternary , Protein Structure, Tertiary , Sequence Alignment , Signal Transduction , Transcription Factors/chemistry
16.
Int J Mol Sci ; 25(1)2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38203328

ABSTRACT

To explore the function of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) in tomatoes, members of the tomato PIP5K family were identified and characterized using bioinformatic methods, and their expression patterns were also analyzed under salt stress and in different tissues. Twenty-one PIP5K members-namely, SlPIP5K1-SlPIP5K21-were identified from ten chromosomes, and these were divided into three groups according to a phylogenetic analysis. Further bioinformatic analysis showed four pairs of collinear relationships and fragment replication events among the SlPIP5K family members. To understand the possible roles of the SlPIP5Ks, a cis-acting element analysis was conducted, which indicated that tomato PIP5Ks could be associated with plant growth, hormones, and stress responses. We further validated the results of the in silico analysis by integrating RNA-seq and qRT-PCR techniques for salt- and hormone-treated tomato plants. Our results showed that SlPIP5K genes exhibited tissue- and treatment-specific patterns, and some of the SlPIP5Ks exhibited significantly altered expressions after our treatments, suggesting that they might be involved in these stresses. We selected one of the SlPIP5Ks that responded to our treatments, SlPIP5K2, to further understand its subcellular localization. Our results showed that SlPIP5K2 was located on the membrane. This study lays a foundation for the analysis of the biological functions of the tomato SlPIP5K genes and can also provide a theoretical basis for the selection and breeding of new tomato varieties and germplasm innovation, especially under salt stress.


Subject(s)
Solanum lycopersicum , Solanum lycopersicum/genetics , Phosphates , Phylogeny , Plant Breeding , Computational Biology , Plant Growth Regulators
17.
BMC Bioinformatics ; 23(1): 5, 2022 Jan 04.
Article in English | MEDLINE | ID: mdl-34983367

ABSTRACT

BACKGROUND: More and more evidence showed that long non-coding RNAs (lncRNAs) play important roles in the development and progression of human sophisticated diseases. Therefore, predicting human lncRNA-disease associations is a challenging and urgently task in bioinformatics to research of human sophisticated diseases. RESULTS: In the work, a global network-based computational framework called as LRWRHLDA were proposed which is a universal network-based method. Firstly, four isomorphic networks include lncRNA similarity network, disease similarity network, gene similarity network and miRNA similarity network were constructed. And then, six heterogeneous networks include known lncRNA-disease, lncRNA-gene, lncRNA-miRNA, disease-gene, disease-miRNA, and gene-miRNA associations network were applied to design a multi-layer network. Finally, the Laplace normalized random walk with restart algorithm in this global network is suggested to predict the relationship between lncRNAs and diseases. CONCLUSIONS: The ten-fold cross validation is used to evaluate the performance of LRWRHLDA. As a result, LRWRHLDA achieves an AUC of 0.98402, which is higher than other compared methods. Furthermore, LRWRHLDA can predict isolated disease-related lnRNA (isolated lnRNA related disease). The results for colorectal cancer, lung adenocarcinoma, stomach cancer and breast cancer have been verified by other researches. The case studies indicated that our method is effective.


Subject(s)
MicroRNAs , Neoplasms/genetics , RNA, Long Noncoding , Algorithms , Computational Biology , Gene Regulatory Networks , Humans , MicroRNAs/genetics , RNA, Long Noncoding/genetics
18.
Am J Gastroenterol ; 117(9): 1523-1529, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35416798

ABSTRACT

Consistent with previous cross-sectional studies, in the Southern Community Cohort Study, the largest cohort for Black Americans conducted in a predominantly low-income population with 81,694 participants, we found that moderate alcohol drinking was associated with a significantly increased risk of mortality due to liver disease in Black Americans (hazard ratio = 2.06; 95% confidence interval: 1.08-3.94) but not in White Americans (hazard ratio = 0.87; 95% confidence interval: 0.52-1.44). We found that heavy drinking was significantly associated with an increased risk of mortality due to liver disease in both Black and White Americans. Future studies are warranted to understand the mechanism involving such racial disparity.


Subject(s)
Liver Diseases , White People , Alcohol Drinking/epidemiology , Cohort Studies , Humans , Poverty
19.
Opt Express ; 30(19): 33574-33587, 2022 Sep 12.
Article in English | MEDLINE | ID: mdl-36242389

ABSTRACT

Metasurface-based structural-colors are usually implemented by changing the dimensions of nanostructures to produce different spectral responses. Therefore, a single-size nanostructured metasurface usually cannot display structural-colors since it has only one design degree of freedom (DOF), i.e., the orientation angles of nanostructures. Here, we show structural-color nanoprinting images can be generated with a single-size nanostructured metasurface, enabled by designing the anisotropic nanostructure with different spectral responses along its long- and short-axis directions, respectively. More interestingly, the concept of orientation degeneracy of nanostructures can be applied in the metasurface design, which shows two spectral modulations can be implemented under different polarization directions of output light, thus extending the color-nanoprinting from single-channel to dual-channel. The proposed dual-channel metasurface used for anticounterfeiting color-nanoprinting has presented the advantages of ultra-compactness, high information capacity, and vivid colors, which can develop broad applications in fields such as high-end anticounterfeiting, high-density information storage, optical encryption, etc.

20.
Opt Express ; 30(21): 37554-37565, 2022 Oct 10.
Article in English | MEDLINE | ID: mdl-36258342

ABSTRACT

Structural-color nanoprinting, which can generate vivid colors with spatial resolution at subwavelength level, possesses potential market in optical anticounterfeiting and information encryption. Herein, we propose an ultracompact metasurface with a single-cell design strategy to establish three independent information channels for simultaneous watermarked structural-color nanoprinting and holographic imaging. Dual-channel spectrum manipulation and single-channel phase manipulation are combined together by elaborately introducing the orientation degeneracy into the design of variable dielectric nanobricks. Hence, a structural-color nanoprinting image covered with polarization-dependent watermarks and a holographic image can be respectively generated under different decoded environments. The proposed metasurface shows a flexible method for tri-channel image display with high information capacity, and exhibits dual-mode anticounterfeiting with double safeguards, i.e., polarization-controlled watermarks and a far-field holographic image. This study provides a feasible route to develop multifunctional metasurfaces for applications including optical anticounterfeiting, information encryption and security, information multiplexing, etc.

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