Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 426
Filtrar
Más filtros

País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Genome Res ; 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37993136

RESUMEN

Traditional evolutionary biology research mainly relies on sequence information to infer evolutionary relationships between genes or proteins. In contrast, protein structural information has long been overlooked, although structures are more conserved and closely linked to the functions than the sequences. To address this gap, we conducted a proteome-wide structural analysis using experimental and computed protein structures for organisms from the three distinct domains, including Homo sapiens (eukarya), Escherichia coli (bacteria), and Methanocaldococcus jannaschii (archaea). We reveal the distribution of structural similarity and sequence identity at the genomic level and characterize the twilight zone, where signals obtained from sequence alignment are blurred and evolutionary relationships cannot be inferred unambiguously. We find that structurally similar homologous protein pairs in the twilight zone account for ∼0.004%-0.021% of all possible protein pair combinations, which translates to ∼8%-32% of the protein-coding genes, depending on the species under comparison. In addition, by comparing the structural homologs, we show that human proteins involved in the energy supply are more similar to their E. coli homologs, whereas proteins relating to the central dogma are more similar to their M. jannaschii homologs. We also identify a bacterial GPCR homolog in the E. coli proteome that displays distinctive domain architecture. Our results shed light on the characteristics of the twilight zone and the origin of different pathways from a protein structure perspective, highlighting an exciting new frontier in evolutionary biology.

2.
Proc Biol Sci ; 291(2025): 20240500, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38889790

RESUMEN

Gene drive alleles that can bias their own inheritance could engineer populations for control of disease vectors, invasive species and agricultural pests. There are successful examples of suppression drives and confined modification drives, but developing confined suppression drives has proven more difficult. However, CRISPR-based toxin-antidote dominant embryo (TADE) suppression drive may fill this niche. It works by targeting and disrupting a haplolethal target gene in the germline with its gRNAs while rescuing this target. It also disrupts a female fertility gene by driving insertion or additional gRNAs. Here, we used a reaction-diffusion model to assess drive performance in continuous space, where outcomes can be substantially different from those in panmictic populations. We measured drive wave speed and found that moderate fitness costs or target gene disruption in the early embryo from maternally deposited nuclease can eliminate the drive's ability to form a wave of advance. We assessed the required release size, and finally we investigated migration corridor scenarios. It is often possible for the drive to suppress one population and then persist in the corridor without invading the second population, a potentially desirable outcome. Thus, even imperfect variants of TADE suppression drive may be excellent candidates for confined population suppression.


Asunto(s)
Sistemas CRISPR-Cas , Tecnología de Genética Dirigida , Animales , Modelos Genéticos , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas
3.
Opt Express ; 32(3): 4639-4649, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38297660

RESUMEN

Dynamic tuning metasurfaces represent a significant advancement in optical encryption techniques, enabling highly secure multichannel responses. This paper proposes a liquid crystal (LC) tunable dual-layered metasurface to establish a thermal-encrypted optical platform for information storage. Through the screening of unit cells and coupling of characteristics, a dynamic polarization-dependent beam-steering metasurface is vertically cascaded with an angular multiplexing nanoprinting metasurface, separated by a dielectric layer. By integrating high-birefringence LCs into dual-layered metasurfaces, the cascaded meta-system can achieve dynamic thermal-switching for pre-encoded nanoprinting images. This work provides a promising solution for developing compact dynamic meta-systems for customized optical storage and information encryption.

4.
Opt Lett ; 49(8): 2053-2056, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38621074

RESUMEN

Plasmonic nanosensors and the dynamic control of light fields are of the utmost significance in the field of micro- and nano-optics. Here, our study successfully demonstrates a plasmonic nanosensor in a compact coupled resonator system and obtains the pressure-induced transparency phenomenon for the first time to our knowledge. The proposed structure consists of a groove and slot cavity coupled in the metal-insulator-metal waveguide, whose mechanical and optical characteristics are investigated in detail using the finite element method. Simulation results show that we construct a quantitative relationship among the resonator deformation quantity, the applied pressure variation, and the resonant wavelength offset by combining the mechanical and optical properties of the proposed system. The physical features contribute to highly efficient plasmonic nanosensors for refractive index and optical pressure sensing with sensitivity of 1800 nm/RIU and 7.4 nm/MPa, respectively. Furthermore, the light waves are coupled to each other in the resonators, which are detuned due to the presence of pressure, resulting in the pressure-induced transparency phenomenon. It is noteworthy to emphasize that, unlike previously published works, our numerical results take structural deformation-induced changes in optical properties into account, making them trustworthy and practical. The proposed structure introduces a novel, to the best of our knowledge, approach for the dynamic control of light fields and has special properties that can be utilized for the realization of various integrated components.

5.
Haematologica ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38961734

RESUMEN

Generation of mammalian red blood cells requires the expulsion of polarized nuclei late in terminal erythroid differentiation. However, the mechanisms by which spherical erythroblasts determine the direction of nuclear polarization and maintain asymmetry during nuclear expulsion are poorly understood. Given the analogy of erythroblast enucleation to asymmetric cell division and the key role of Aurora kinases in mitosis, we sought to investigate the function of Aurora kinases in erythroblast enucleation. We found that AURKA (Aurora kinase A) is abundantly expressed in orthochromatic erythroblasts. Intriguingly, high-resolution confocal microscopy analyses revealed that AURKA co-localized with the centrosome on the side of the nucleus opposite its membrane contact point during polarization and subsequently translocated to the anterior end of the protrusive nucleus upon nuclear exit. Mechanistically, AURKA regulated centrosome maturation and localization via interaction with i-tubulin to provide polarization orientation for the nucleus. Furthermore, we identified ECT2 (epithelial cell transforming 2), a guanine nucleotide exchange factor, as a new interacting protein and ubiquitination substrate of AURKA. After forming the nuclear protrusion, AURKA translocated to the anterior end of the protrusive nucleus to directly degrade ECT2, which is partly dependent on kinase activity of AURKA. Moreover, knockdown of ECT2 rescued impaired enucleation caused by AURKA inhibition. Our findings have uncovered a previously unrecognized role of Aurora kinases in the establishment of nuclear polarization and eventual nuclear extrusion and provide new mechanistic insights into erythroblast enucleation.

6.
J Magn Reson Imaging ; 59(5): 1710-1722, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37497811

RESUMEN

BACKGROUND: Accurate diagnosis of breast lesions and discrimination of axillary lymph node (ALN) metastases largely depend on radiologist experience. PURPOSE: To develop a deep learning-based whole-process system (DLWPS) for segmentation and diagnosis of breast lesions and discrimination of ALN metastasis. STUDY TYPE: Retrospective. POPULATION: 1760 breast patients, who were divided into training and validation sets (1110 patients), internal (476 patients), and external (174 patients) test sets. FIELD STRENGTH/SEQUENCE: 3.0T/dynamic contrast-enhanced (DCE)-MRI sequence. ASSESSMENT: DLWPS was developed using segmentation and classification models. The DLWPS-based segmentation model was developed by the U-Net framework, which combined the attention module and the edge feature extraction module. The average score of the output scores of three networks was used as the result of the DLWPS-based classification model. Moreover, the radiologists' diagnosis without and with the DLWPS-assistance was explored. To reveal the underlying biological basis of DLWPS, genetic analysis was performed based on RNA-sequencing data. STATISTICAL TESTS: Dice similarity coefficient (DI), area under receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and kappa value. RESULTS: The segmentation model reached a DI of 0.828 and 0.813 in the internal and external test sets, respectively. Within the breast lesions diagnosis, the DLWPS achieved AUCs of 0.973 in internal test set and 0.936 in external test set. For ALN metastasis discrimination, the DLWPS achieved AUCs of 0.927 in internal test set and 0.917 in external test set. The agreement of radiologists improved with the DLWPS-assistance from 0.547 to 0.794, and from 0.848 to 0.892 in breast lesions diagnosis and ALN metastasis discrimination, respectively. Additionally, 10 breast cancers with ALN metastasis were associated with pathways of aerobic electron transport chain and cytoplasmic translation. DATA CONCLUSION: The performance of DLWPS indicates that it can promote radiologists in the judgment of breast lesions and ALN metastasis and nonmetastasis. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.


Asunto(s)
Neoplasias de la Mama , Aprendizaje Profundo , Humanos , Femenino , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Estudios Retrospectivos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Imagen por Resonancia Magnética
7.
Cell Commun Signal ; 22(1): 166, 2024 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-38454449

RESUMEN

BACKGROUND: Clinical and experimental studies have shown that the myocardial inflammatory response during pathological events varies between males and females. However, the cellular and molecular mechanisms of these sex differences remain elusive. CD73/adenosine axis has been linked to anti-inflammatory responses, but its sex-specific cardioprotective role is unclear. The present study aimed to investigate whether the CD73/adenosine axis elicits sex-dependent cardioprotection during metabolic changes and myocarditis induced by hypobaric hypoxia. METHODS: For 7 days, male and female mice received daily injections of the CD73 inhibitor adenosine 5'- (α, ß-methylene) diphosphate (APCP) 10 mg/kg/day while they were kept under normobaric normoxic and hypobaric hypoxic conditions. We evaluated the effects of hypobaric hypoxia on the CD73/adenosine axis, myocardial hypertrophy, and cardiac electrical activity and function. In addition, metabolic homeostasis and immunoregulation were investigated to clarify the sex-dependent cardioprotection of the CD73/adenosine axis. RESULTS: Hypobaric hypoxia-induced cardiac dysfunction and adverse remodeling were more pronounced in male mice. Also, male mice had hyperactivity of the CD73/adenosine axis, which aggravated myocarditis and metabolic shift compared to female mice. In addition, CD73 inhibition triggered prostatic acid phosphatase ectonucleotidase enzymatic activity to sustain adenosine overproduction in male mice but not in female mice. Moreover, dual inhibition prostatic acid phosphatase and CD73 enzymatic activities in male mice moderated adenosine content, alleviating glycolytic shift and proinflammatory response. CONCLUSION: The CD73/adenosine axis confers a sex-dependent cardioprotection. In addition, extracellular adenosine production in the hearts of male mice is influenced by prostatic acid phosphatase and tissue nonspecific alkaline phosphatase.


Asunto(s)
Adenosina , Miocarditis , Femenino , Masculino , Ratones , Animales , Miocarditis/metabolismo , Miocarditis/patología , Hipoxia/metabolismo , Miocardio/metabolismo , Corazón , 5'-Nucleotidasa/metabolismo
8.
BMC Pregnancy Childbirth ; 24(1): 13, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166871

RESUMEN

BACKGROUND: Healthy parturients may experience pulmonary edema and disturbed cardiac function during labor. We aimed to evaluate the extravascular lung water (EVLW), intravascular volume, and cardiac function of normal parturients during spontaneous vaginal delivery by bedside ultrasound. And to explore the correlation between EVLW and intravascular volume, cardiac function. METHODS: This was a prospective observational study including 30 singleton-term pregnant women undergoing spontaneous vaginal delivery. Bedside ultrasound was performed at the early labor, the end of the second stage of labor, 2 and 24 h postpartum, and 120 scanning results were recorded. EVLW was evaluated by the echo comet score (ECS) obtained by the 28-rib interspaces technique. Inferior vena cava collapsibility index (IVC-CI), left ventricle ejection fraction, right ventricle fractional area change, left and right ventricular E/A ratio, and left and right ventricular index of myocardial performance (LIMP and RIMP) were measured. Measurements among different time points were compared, and the correlations between ECS and other measurements were analyzed. RESULTS: During the spontaneous vaginal delivery of healthy pregnant women, 2 had a mild EVLW increase at the early labor, 8 at the end of the second stage of labor, 13 at 2 h postpartum, and 4 at 24 h postpartum (P < 0.001). From the early labor to 24 h postpartum, ECS first increased and then decreased, reaching its peak at 2 h postpartum (P < 0.001). IVC-CI first decreased and then increased, reaching its minimum at the end of the second stage of labor (P < 0.001). RIMP exceeded the cut-off value of 0.43 at the end of the second stage of labor. ECS was weakly correlated with IVC-CI (r=-0.373, P < 0.001), LIMP (r = 0.298, P = 0.022) and RIMP (r = 0.211, P = 0.021). CONCLUSIONS: During spontaneous vaginal delivery, the most vital period of perinatal care is between the end of the second stage of labor and 2 h postpartum, because the risk of pulmonary edema is higher and the right ventricle function may decline. IVC-CI can be used to evaluate maternal intravascular volume. The increase in EVLW may be related to the increase in intravascular volume and the decrease in ventricular function.


Asunto(s)
Agua Pulmonar Extravascular , Edema Pulmonar , Femenino , Humanos , Embarazo , Parto Obstétrico , Agua Pulmonar Extravascular/diagnóstico por imagen , Edema Pulmonar/diagnóstico por imagen , Edema Pulmonar/etiología , Volumen Sistólico , Ultrasonografía , Estudios Prospectivos
9.
PLoS Genet ; 17(2): e1009363, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33630843

RESUMEN

Genome-wide association studies (GWASs) have identified multiple susceptibility loci for Alzheimer's disease (AD), which is characterized by early and progressive damage to the hippocampus. However, the association of hippocampal gene expression with AD and the underlying neurobiological pathways remain largely unknown. Based on the genomic and transcriptomic data of 111 hippocampal samples and the summary data of two large-scale meta-analyses of GWASs, a transcriptome-wide association study (TWAS) was performed to identify genes with significant associations between hippocampal expression and AD. We identified 54 significantly associated genes using an AD-GWAS meta-analysis of 455,258 individuals; 36 of the genes were confirmed in another AD-GWAS meta-analysis of 63,926 individuals. Fine-mapping models further prioritized 24 AD-related genes whose effects on AD were mediated by hippocampal expression, including APOE and two novel genes (PTPN9 and PCDHA4). These genes are functionally related to amyloid-beta formation, phosphorylation/dephosphorylation, neuronal apoptosis, neurogenesis and telomerase-related processes. By integrating the predicted hippocampal expression and neuroimaging data, we found that the hippocampal expression of QPCTL and ERCC2 showed significant difference between AD patients and cognitively normal elderly individuals as well as correlated with hippocampal volume. Mediation analysis further demonstrated that hippocampal volume mediated the effect of hippocampal gene expression (QPCTL and ERCC2) on AD. This study identifies two novel genes associated with AD by integrating hippocampal gene expression and genome-wide association data and reveals candidate hippocampus-mediated neurobiological pathways from gene expression to AD.


Asunto(s)
Enfermedad de Alzheimer/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Hipocampo/metabolismo , Polimorfismo de Nucleótido Simple , Transcriptoma/genética , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Femenino , Redes Reguladoras de Genes/genética , Genómica/métodos , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Secuenciación Completa del Genoma/métodos
10.
J Environ Manage ; 352: 120004, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38218170

RESUMEN

Soil loss is an environmental concern of global importance. Accurate simulation of soil loss in small watersheds is crucial for protecting the environment and implementing soil and water conservation measures. However, predicting soil loss while meeting the criteria of high precision, efficiency, and generalizability remains a challenge. Therefore, this study first used three machine learning (ML) algorithms, namely, random forest (RF), support vector machine (SVM), and artificial neural network (ANN) to develop soil loss models and predict soil loss rates (SLRs). These soil loss models were constructed using field observation data with an average SLR of 1756.48 t/km2 from rainfall events and small watersheds in the hilly-gully region of the Loess Plateau, China. During training, testing and generalizability stages, the average coefficients of determination from the RF, SVM, and ANN models were 0.903, 0.860, and 0.836, respectively. Similarly, the average Nash-Sutcliffe coefficients of efficiency from the RF, SVM and ANN models were 0.893, 0.791 and 0.814, respectively. These results indicated that MLs have superior predictive performance and generalizability, and broad prospects for predicting SLRs. This study also demonstrated that the RF model outperformed better than the SVM and ANN models. Therefore, the RF model was used to simulate the SLR of each small watershed in the Chabagou watershed. Our results showed the four-year (2017-2020) average annual SLR of the small watersheds ranged from 0.73 to 1.63 × 104 t/(km2∙a) in the Chabagou watershed. Additionally, the results also indicated the SLR of small watersheds under the rainstorm event with a 100-year recurrence interval was 4.4-51.3 times that of other rainfall events.Furthermore, this study confirmed that bare land was the predominant source of soil loss in the Chabagou watershed, followed by cropland land and grassland. This study helps to provide the theoretical basis for deploying soil and water conservation measures to realize the sustainable utilization of soil resources in the future.


Asunto(s)
Conservación de los Recursos Hídricos , Suelo , Algoritmos , China , Aprendizaje Automático
11.
Hum Brain Mapp ; 44(15): 5139-5152, 2023 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-37578386

RESUMEN

Florbetapir 18 F (AV45), a highly sensitive and specific positron emission tomographic (PET) molecular biomarker binding to the amyloid-ß of Alzheimer's disease (AD), is constrained by radiation and cost. We sought to combat it by combining multimodal magnetic resonance imaging (MRI) images and a collaborative generative adversarial networks model (CollaGAN) to develop a multimodal MRI-derived Amyloid-ß (MRAß) biomarker. We collected multimodal MRI and PET AV45 data of 380 qualified participants from the ADNI dataset and 64 subjects from OASIS3 dataset. A five-fold cross-validation CollaGAN were applied to generate MRAß. In the ADNI dataset, we found MRAß could characterize the subject-level AV45 spatial variations in both AD and mild cognitive impairment (MCI). Voxel-wise two-sample t-tests demonstrated amyloid-ß depositions identified by MRAß in AD and MCI were significantly higher than healthy controls (HCs) in widespread cortices (p < .05, corrected) and were much similar to those by AV45 (r > .92, p < .001). Moreover, a 3D ResNet classifier demonstrated that MRAß was comparable to AV45 in discriminating AD from HC in both the ADNI and OASIS3 datasets, and in discriminate MCI from HC in ADNI. Finally, we found MRAß could mimic cortical hyper-AV45 in HCs who later converted to MCI (r = .79, p < .001) and was comparable to AV45 in discriminating them from stable HC (p > .05). In summary, our work illustrates that MRAß synthesized by multimodal MRI could mimic the cerebral amyloid-ß depositions like AV45 and lends credence to the feasibility of advancing MRI toward molecular-explainable biomarkers.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones/métodos , Disfunción Cognitiva/patología , Biomarcadores
12.
Genome Res ; 30(12): 1789-1801, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33060171

RESUMEN

The advances of large-scale genomics studies have enabled compilation of cell type-specific, genome-wide DNA functional elements at high resolution. With the growing volume of functional annotation data and sequencing variants, existing variant annotation algorithms lack the efficiency and scalability to process big genomic data, particularly when annotating whole-genome sequencing variants against a huge database with billions of genomic features. Here, we develop VarNote to rapidly annotate genome-scale variants in large and complex functional annotation resources. Equipped with a novel index system and a parallel random-sweep searching algorithm, VarNote shows substantial performance improvements (two to three orders of magnitude) over existing algorithms at different scales. It supports both region-based and allele-specific annotations and introduces advanced functions for the flexible extraction of annotations. By integrating massive base-wise and context-dependent annotations in the VarNote framework, we introduce three efficient and accurate pipelines to prioritize the causal regulatory variants for common diseases, Mendelian disorders, and cancers.


Asunto(s)
Biología Computacional/métodos , Predisposición Genética a la Enfermedad/genética , Algoritmos , Bases de Datos Genéticas , Variación Genética , Genoma Humano , Humanos , Anotación de Secuencia Molecular , Secuenciación Completa del Genoma
13.
Small ; 19(43): e2302380, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37357155

RESUMEN

There are enormous yet largely underexplored exotic phenomena and properties emerging from interfaces constructed by diverse types of components that may differ in composition, shape, or crystal structure. It remains poorly understood the unique properties a coherent interface between crystalline and amorphous materials may evoke, and there lacks a general strategy to fabricate such interfaces. It is demonstrated that by topotactic partial oxidation heterostructures composed of coherently registered crystalline and amorphous materials can be constructed. As a proof-of-concept study, heterostructures consisting of crystalline P3 N5 and amorphous P3 N5 Ox can be synthesized by creating amorphous P3 N5 Ox from crystalline P3 N5 without interrupting the covalent bonding across the coherent interface. The heterostructure is dictated by nanometer-sized short-range-ordered P3 N5 domains enclosed by amorphous P3 N5 Ox matrix, which entails simultaneously fast charge transfer across the interface and bicomponent synergistic effect in catalysis. Such a P3 N5 /P3 N5 Ox heterostructure attains an optimal adsorption energy for *OOH intermediates and exhibits superior electrocatalytic performance toward H2 O2 production by adopting a selectivity of 96.68% at 0.4 VRHE and a production rate of 321.5 mmol h-1 gcatalyst -1 at -0.3 VRHE . The current study provides new insights into the synthetic strategy, chemical structure, and catalytic property of a sub-nanometer coherent interface formed between crystalline and amorphous materials.

14.
J Transl Med ; 21(1): 34, 2023 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-36670462

RESUMEN

BACKGROUND: The disruption of blood-brain barrier (BBB), predominantly made up by brain microvascular endothelial cells (BMECs), is one of the characteristics of Alzheimer's disease (AD). Thus, improving BMEC function may be beneficial for AD treatment. Tanshinone IIA (Tan IIA) has been proved to ameliorate the cognitive dysfunction of AD. Herein, we explored how Tan IIA affected the function of BMECs in AD. METHODS: Aß1-42-treated brain-derived endothelium cells.3 (bEnd.3 cells) was employed for in vitro experiments. And we performed molecular docking and qPCR to determine the targeting molecule of Tan IIA on Sirtuins family. The APPswe/PSdE9 (APP/PS1) mice were applied to perform the in vivo experiments. Following the behavioral tests, protein expression was determined through western blot and immunofluorescence. The activities of oxidative stress-related enzymes were analyzed by biochemically kits. Nissl staining and thioflavin T staining were conducted to reflect the neurodegeneration and Aß deposition respectively. RESULTS: Molecular docking and qPCR results showed that Tan IIA mainly acted on Sirtuin1 (SIRT1) in Sirtuins family. The inhibitor of SIRT1 (EX527) was employed to further substantiate that Tan IIA could attenuate SIRT1-mediated endoplasmic reticulum stress (ER stress) in BMECs. Behavioral tests suggested that Tan IIA could improve the cognitive deficits in APP/PS1 mice. Tan IIA administration increased SIRT1 expression and alleviated ER stress in APP/PS1 mice. In addition, LRP1 expression was increased and RAGE expression was decreased after Tan IIA administration in both animals and cells. CONCLUSION: Tan IIA could promote Aß transportation by alleviating SIRT1-mediated ER stress in BMECs, which ameliorated cognitive deficits in APP/PS1 mice.


Asunto(s)
Enfermedad de Alzheimer , Células Endoteliales , Ratones , Animales , Células Endoteliales/metabolismo , Sirtuina 1/metabolismo , Simulación del Acoplamiento Molecular , Estrés del Retículo Endoplásmico , Enfermedad de Alzheimer/tratamiento farmacológico , Modelos Animales de Enfermedad
15.
Blood ; 138(20): 1986-1997, 2021 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-34098576

RESUMEN

The erythropoietin receptor (EpoR) has traditionally been thought of as an erythroid-specific gene. Notably, accumulating evidence suggests that EpoR is expressed well beyond erythroid cells. However, the expression of EpoR in non-erythroid cells has been controversial. In this study, we generated EpoR-tdTomato-Cre mice and used them to examine the expression of EpoR in tissue macrophages and hematopoietic cells. We show that in marked contrast to the previously available EpoR-eGFPcre mice, in which a very weak eGFP signal was detected in erythroid cells, tdTomato was readily detectable in both fetal liver (FL) and bone marrow (BM) erythroid cells at all developmental stages and exhibited dynamic changes during erythropoiesis. Consistent with our recent finding that erythroblastic island (EBI) macrophages are characterized by the expression of EpoR, tdTomato was readily detected in both FL and BM EBI macrophages. Moreover, tdTomato was also detected in subsets of hematopoietic stem cells, progenitors, megakaryocytes, and B cells in BM as well as in spleen red pulp macrophages and liver Kupffer cells. The expression of EpoR was further shown by the EpoR-tdTomato-Cre-mediated excision of the floxed STOP sequence. Importantly, EPO injection selectively promoted proliferation of the EpoR-expressing cells and induced erythroid lineage bias during hematopoiesis. Our findings imply broad roles for EPO/EpoR in hematopoiesis that warrant further investigation. The EpoR-tdTomato-Cre mouse line provides a powerful tool to facilitate future studies on EpoR expression and regulation in various non-hematopoietic cells and to conditionally manipulate gene expression in EpoR-expressing cells for functional studies.


Asunto(s)
Expresión Génica , Células Madre Hematopoyéticas/metabolismo , Macrófagos/metabolismo , Receptores de Eritropoyetina/genética , Animales , Células Madre Hematopoyéticas/citología , Humanos , Integrasas/análisis , Integrasas/genética , Sustancias Luminiscentes/análisis , Sustancias Luminiscentes/metabolismo , Proteínas Luminiscentes/análisis , Proteínas Luminiscentes/genética , Macrófagos/citología , Ratones , Receptores de Eritropoyetina/análisis , Proteína Fluorescente Roja
16.
Blood ; 138(17): 1615-1627, 2021 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-34036344

RESUMEN

Histone deacetylases (HDACs) are a group of enzymes that catalyze the removal of acetyl groups from histone and nonhistone proteins. HDACs have been shown to have diverse functions in a wide range of biological processes. However, their roles in mammalian erythropoiesis remain to be fully defined. This study showed that, of the 11 classic HDAC family members, 6 (HDAC1, -2, -3, and HDAC5, -6, -7) are expressed in human erythroid cells, with HDAC5 most significantly upregulated during terminal erythroid differentiation. Knockdown of HDAC5 by either short hairpin RNA or small interfering RNA in human CD34+ cells followed by erythroid cell culture led to increased apoptosis, decreased chromatin condensation, and impaired enucleation of erythroblasts. Biochemical analyses revealed that HDAC5 deficiency resulted in activation of p53 in association with increased acetylation of p53. Furthermore, although acetylation of histone 4 (H4) is decreased during normal terminal erythroid differentiation, HDAC5 deficiency led to increased acetylation of H4 (K12) in late-stage erythroblasts. This increased acetylation was accompanied by decreased chromatin condensation, implying a role for H4 (K12) deacetylation in chromatin condensation. ATAC-seq and RNA sequencing analyses revealed that HDAC5 knockdown leads to increased chromatin accessibility genome-wide and global changes in gene expression. Moreover, pharmacological inhibition of HDAC5 by the inhibitor LMK235 also led to increased H4 acetylation, impaired chromatin condensation, and enucleation. Taken together, our findings have uncovered previously unrecognized roles and molecular mechanisms of action for HDAC5 in human erythropoiesis. These results may provide insights into understanding the anemia associated with HDAC inhibitor treatment.


Asunto(s)
Células Eritroides/citología , Eritropoyesis , Histona Desacetilasas/genética , Apoptosis , Eritroblastos/citología , Eritroblastos/metabolismo , Células Eritroides/metabolismo , Humanos , Interferencia de ARN , ARN Interferente Pequeño/genética , Regulación hacia Arriba
17.
Opt Express ; 31(2): 3083-3091, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36785307

RESUMEN

Although structural colors based on nanostructures have attracted many researchers' attentions due to their superior durability and high resolution, most previous reports focused on the static and dynamic structural colors in reflection mode and few researchers focus on the static and dynamic transmission colors for high-saturation RGB models. Here, the hybrid Al-Si3N4 nanogratings with the top SiO2 capping layer and the bottom MgF2 layer that can switch full-hue and high-saturation transmitted structural colors on and off completely by changing the polarization state are theoretically demonstrated. Meanwhile, the hybrid Al-Si3N4 nanogratings with the top capping layer and the bottom layer also achieve the transmittance spectra with the full width at half maximum of ∼58 nm and the transmittance efficiency of over 70% in the on state. The added top capping layer and bottom layer can suppress the sideband of transmittance spectra in the on state and maintain the near-zero transmittance in the off state, thus improving the switching performance between bright and dark states. The realizable high-saturation colors in the on state can take up 125% sRGB space and 80% Adobe sRGB space. More interestingly, with the incident angle varying from 0° to 50°, full-hue color can be also realized in the on state and nearly black color can be also maintained in the off state. The strategy will provide potential applications in advanced color encryption and multichannel imaging.

18.
Opt Express ; 31(7): 11940-11953, 2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37155817

RESUMEN

This study proposed the synergistic merging of twisted-nematic liquid crystals (LCs) and nanograting embedded etalon structures for plasmonic structure color generation, realizing dynamic multifunctional metadevices. Metallic nanogratings and dielectric cavities were designed to provide color selectivity at visible wavelengths. Meanwhile, the polarization for the transmission of light could be actively manipulated by electrically modulating these integrated LCs. Moreover, manufacturing independent metadevices as single storage units with electrically controlled programmability and addressability facilitated secure information encoding and secretive transfer by dynamic high-contrast images. The approaches will pave the way for the development of customized optical storage devices and information encryption.

19.
Opt Express ; 31(2): 1092-1102, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36785151

RESUMEN

We propose a holographic display system for complex amplitude modulation (CAM) using a phase-only spatial light modulator (SLM) and two polarization gratings (PG). The two sub-holograms of the complex-amplitude computed generated hologram (CGH) are loaded in different regions of SLM. Two diffractive components couple in space after longitudinal migration from the double PGs, and finally interfered through the line polarizer. The influence of the system error on the reconstructed image quality is analyzed, which provides a theoretical assessment for adding pre-compensation to CGH to compensate the system error. Moreover, on the base of the proposed system, a large depth of field and enlarged display area display is realized and the real-time display can be achieved because of the analytical complex-amplitude computed generated hologram. The optical experimental results show that the proposed system has high energy efficiency, and can provide high-quality holographic display with a large depth of field and enlarged display area.

20.
Opt Express ; 31(22): 35697-35708, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-38017735

RESUMEN

Electromagnetically induced absorption (EIA) exhibits abnormal dispersion and novel fast-light features, making it a crucial aspect of nanophotonics. Here, the EIA phenomenon is numerically predicted in a compact plasmonic waveguide system by introducing a slot resonator above a square cavity. Simulation results reveal that the EIA response can be easily tuned by altering the structure's parameters, and double EIA valleys can be observed with an additional slot resonator. Furthermore, the investigated structures demonstrate a fast-light effect with an optical delay of ∼ -1.0 ps as a result of aberrant dispersion at the EIA valley, which enable promising applications in the on-chip fast-light area. Finally, a plasmonic nanosensor with a sensitivity of ∼1200 nm/RIU and figure of merit of ∼16600 is achieved based on Fano resonance. The special features of our suggested structure are applicable in realization of various integrated components for the development of multifunctional high-performance nano-photonic devices.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA