Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.721
Filtrar
2.
J Virol ; : e0168422, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36651747

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is becoming a dominant circulator and has several mutations in the spike glycoprotein, which may cause shifts of immunogenicity, so as to result in immune escape and breakthrough infection among the already infected or vaccinated populations. It is unclear whether infection with Omicron could generate adequate cross-variant protection. To investigate this possibility, we used Syrian hamsters as an animal model for infection of SARS-CoV-2. The serum from Omicron BA.1 variant-infected hamsters showed a significantly lower neutralization effect against infection of the same or different SARS-CoV-2 variants than the serum from Beta variant-infected hamsters. Furthermore, the serum from Omicron BA.1 variant-infected hamsters were insufficient to protect against rechallenge of SARS-CoV-2 Prototype, Beta and Delta variants and itself. Importantly, we found that rechallenge with different SARS-CoV-2 lineages elevated cross-variant serum neutralization titers. Overall, our findings indicate a weakened immunogenicity feature of Omicron BA.1 variant that can be overcome by rechallenge of a different SARS-CoV-2 lineages. Our results may lead to a new guideline in generation and use of the vaccinations to combat the pandemic of SARS-CoV-2 Omicron variant and possible new variants. IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant causes breakthrough infections among convalescent patients and vaccinated populations. However, Omicron does not generate robust cross-protective responses. Here, we investigate whether heterologous SARS-CoV-2 challenge is able to enhance antibody response in a sensitive animal model, namely, Syrian hamster. Of note, a heterologous challenge of Beta and Omicron BA.1 variant significantly broadens the breadth of SARS-CoV-2 neutralizing responses against the prototype, Beta, Delta, and Omicron BA.1 variants. Our findings confirm that vaccination strategy with heterologous antigens might be a good option to protect against the evolving SARS-CoV-2.

3.
J Control Release ; 354: 713-725, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702258

RESUMO

Open fractures and internal fixation implants are often accompanied by bacterial infection, leading to osteomyelitis, characterized by intractable bone infection and sequestrum formation, and can result in lifelong disability or fatal sepsis. As common clinical treatment strategies, high-dose antibiotic application and autologous bone transplantation face the risk of recurrence and donor site injury. Herein, we designed and prepared a novel drug delivery system by rational selection of the antibacterial single-chain amphiphile (cetylpyridinium chloride, CPC) and osteoinductive sterol (20S-hydroxycholesterol, Oxy) to formulate CPC/Oxy sterosomes. We demonstrate their excellent biocompatibility and antibacterial ability through 2D and 3D settings in vitro. In addition, the osteogenic differentiation of bone marrow mesenchymal stem cells was investigated in cell monolayers and a hydrogel environment. Moreover, a rat infected critical-sized calvarial defect model was employed to illustrate the effects of antibacterial and osteogenic CPC/Oxy sterosomes in vivo. Our results showed that CPC/Oxy sterosomes not only exterminated bacterial infections, but also enhanced calvarial healing without additional antibiotics, bone formation promoters or exogenous cells. This research provides a promising and effective multifunctional sterosomal platform for the treatment of infected bone defects, with the potential to be combined with therapeutic genes, and small molecule drugs.

4.
Mol Oncol ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703611

RESUMO

The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole-exome sequencing (WES) and T-cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunologic levels in LP tumors were compared with multiple cancers previously reported. The lymphocyte infiltration was further assessed by immunohistochemistry (IHC) in LP tumors. In total, we identified 6,339 non-silent mutations from multi-samples, with a median tumor mutation burden (TMB) of 3.30 mutations/Mb, comparable to gastric adenocarcinoma from the Cancer Genome Atlas (TCGA) cohort (P=0.53). An extremely high level of genomic ITH was observed, with only 12.42, 5.37, 5.35 and 30.67% of mutations detectable across 10 regions within the same tumors of each patient, respectively. TCR sequencing revealed that TCR clonality was substantially lower in LP than in multi-cancers. IHC using antibodies against CD4, CD8 and PD-L1 demonstrated scant T-cell infiltration in the four LP tumors. Furthermore, profound TCR ITH was observed in all LP tumors, with no T-cell clones shared across tumor regions in any of the patients, while over 94% of T-cell clones were restricted to individual tumor regions. The Morisita overlap index (MOI) ranged from 0.21 to 0.66 among multi-regions within the same tumors, significantly lower than that of lung cancer (P=0.002). Our results show that LP harbored extremely high genomic and TCR ITH and suppressed T-cell infiltration, suggesting a potential contribution to the frequent recurrence and poor therapeutic response of this adenocarcinoma.

5.
J Mol Biol ; : 167955, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36642156

RESUMO

An emerging set of results suggests that liquid-liquid phase separation (LLPS) is the basis for the formation of membrane-less compartments in cells. Evidence is now mounting that various types of virus-induced membrane-less compartments and organelles are also assembled via LLPS. Specifically, viruses appear to use intracellular phase transitions to form subcellular microenvironments known as viral factories, inclusion bodies, or viroplasms. These compartments - collectively referred to as viral biomolecular condensates - can be used to concentrate replicase proteins, viral genomes, and host proteins that are required for virus replication. They can also be used to subvert or avoid the intracellular immune response. This review examines how certain DNA or RNA viruses drive the formation of viral condensates, the possible biological functions of those condensates, and the biophysical and biochemical basis for their assembly.

6.
J Fungi (Basel) ; 9(1)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36675928

RESUMO

Plant debris are habitats favoring survival and multiplication of various microbial species. During continuing mycological surveys of saprobic microfungi from plant debris in Yunnan Province, China, several Corynespora-like and Dendryphiopsis-like isolates were collected from dead branches of unidentified perennial dicotyledonous plants. Four barcodes, i.e., ITS, LSU, SSU and tef1-α, were amplified and sequenced. Morphological studies and multigene phylogenetic analyses by maximum likelihood and Bayesian inference revealed three new Corynespora species (C. mengsongensis sp. nov., C. nabanheensis sp. nov. and C. yunnanensis sp. nov.) and a new Kirschsteiniothelia species (K. nabanheensis sp. nov.) within Dothideomycetes, Ascomycota. A list of identified and accepted species of Corynespora with major morphological features, host information and locality was compiled. This work improves the knowledge of species diversity of Corynespora and Kirschsteiniothelia in Yunnan Province, China.

7.
ChemSusChem ; 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36588092

RESUMO

The widespread use of chemicals has brought serious water pollution threatening human health and environment, which requires green, fast and low-cost purification urgently. Here we build up a novel material family of sky-parking like 3D structured graphene oxides (SP-GOs) with adjustable interlayer-space of 0.8~1.7 nm via the insertion of different sized diamine compounds as support pillars between GO layers. The assembled 3D SP-GOs exhibit superior adsorption capacity and short removal time for various aromatic organic compounds in water, achieving record-breaking maximum adsorption capacity of 535.79 mg/g toward the most common water-pollutant bisphenol A (BPA) at ambient conditions as well as significantly improved removal of other organic pollutants including sulfapyridine, carbamazepine, ketoprofen and 2-naphthol. The construction of SP-GO provides a simple approach for evolving the GO material from 2D to 3D and a new avenue for the decontamination of pollutants in environmental remediation.

8.
Int J Biol Macromol ; 230: 123255, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36639088

RESUMO

Despite their essential and multiple roles in biological processes, the molecular mechanism of Dof transcription factors (TFs) for responding to abiotic stresses is rarely reported in plants. We identified a soybean Dof gene GmDof41 which was involved in the responses to drought, salt, and exogenous ABA stresses. Overexpression of GmDof41 in soybean transgenic hairy roots attenuated H2O2 accumulation and regulated proline homeostasis, resulting in the drought and salt tolerance. Yeast one-hybrid and electrophoretic mobility shift assay (EMSA) illustrated that GmDof41 was regulated by the DREB1-type protein GmDREB1B;1 that could improve drought and salt tolerance in plants. Further studies illustrated GmDof41 can directly bind to the promoter of GmDREB2A which encodes a DREB2-type protein and affects abiotic stress tolerance in plants. Collectively, our results suggested that GmDof41 positively regulated drought and salt tolerance by correlating with GmDREB1B;1 and GmDREB2A. This study provides an important basis for further exploring the abiotic stress-tolerance mechanism of Dof TFs in soybean.

9.
Cancer Res ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36637424

RESUMO

Retinoblastoma (RB) protein can exert tumor suppressor functions even when it becomes phosphorylated. It is thus essential to understand how phosphorylated RB (p-RB) expression and function are regulated. Here we demonstrated that RING finger domain protein TRIM28 bound and promoted ubiquitination and degradation of CDK4/6-phosphorylated RB protein. SETDB1, a known TRIM28 binding partner, protected p-RB from degradation through the binding of methylated RB by its Tudor domain independent of its methyltransferase activity. SETDB1 was found to be frequently overexpressed due to gene amplification and positively correlated with p-RB in prostate cancer patient specimens. Inhibition of SETDB1 expression using a gene-specific antisense oligonucleotide (ASO) reduced tumor growth but accelerated RB protein degradation, limiting the therapeutic efficacy. However, co-administration of CDK4/6 inhibitor palbociclib blocked ASO-induced RB degradation and resulted in a much greater cancer-inhibitory effect than each inhibitor alone both in vitro and in vivo. This study identified CDK4/6-dependent, TRIM28-mediated proteasomal degradation as a mechanism of RB inactivation and reveals SETDB1 as a key inhibitor of this process. Our findings suggest that combined targeting of SETDB1 and CDK4/6 represents a viable approach for treatment of cancers with SETDB1 gene amplification or overexpression.

10.
Huan Jing Ke Xue ; 44(1): 356-366, 2023 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-36635823

RESUMO

The farmland environment is directly related to the quality and safety of agricultural products. In order to understand the characteristics and main influencing factors of heavy metals in farmland soil in the Yellow River irrigation area of Ningxia, sampling and monitoring were conducted for five consecutive years from 2017 to 2021, and the distribution characteristics and correlation of heavy metals were analyzed. The pollution status and potential ecological risks of heavy metals were evaluated, and the main sources of heavy metals in farmland were analyzed. The results showed that the average values of Pb, As, Zn, Ni, Cu, Hg, Cr, and Cd in the soil of the Ningxia Yellow River irrigation area were 19.74, 11.67, 66.88, 29.09, 22.55, 0.03, 62.27, and 0.19 mg·kg-1, respectively, which were enriched to some extent compared with the background values of the soil environment in Ningxia. Among them, Hg and Cd had middle- and high-grade ecological risk points; however, none of them exceeded the control value of agricultural land soil pollution risk, and all sampling sites had no high-risk or extremely high-risk levels. The results of source analysis based on positive matrix factorization (PMF) and correlation analysis showed that there were five main sources of heavy metals in farmland soil in the study area: natural sources, mixed sources of industrial and mining activities and the production and life of residents, transportation sources, agricultural production activities sources, and industrial sources, with contribution rates of 26.54%, 25.59%, 22.52%, 15.63%, and 9.72%, respectively. On the whole, the heavy metals in farmland soil in the Ningxia Yellow River irrigation area did not exceed the standard, and there was no high-level ecological risk. The production environment of the farmland soil was good, but the contribution rate of human activities to soil heavy metals was large.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Humanos , Solo , Fazendas , Cádmio/análise , Rios , Monitoramento Ambiental/métodos , Poluentes do Solo/análise , Metais Pesados/análise , Mercúrio/análise , Medição de Risco , China
11.
Nat Genet ; 55(1): 78-88, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36624346

RESUMO

Spatial transcriptomics can reveal spatially resolved gene expression of diverse cells in complex tissues. However, the development of computational methods that can use the unique properties of spatial transcriptome data to unveil cell identities remains a challenge. Here we introduce SPICEMIX, an interpretable method based on probabilistic, latent variable modeling for joint analysis of spatial information and gene expression from spatial transcriptome data. Both simulation and real data evaluations demonstrate that SPICEMIX markedly improves on the inference of cell types and their spatial patterns compared with existing approaches. By applying to spatial transcriptome data of brain regions in human and mouse acquired by seqFISH+, STARmap and Visium, we show that SPICEMIX can enhance the inference of complex cell identities, reveal interpretable spatial metagenes and uncover differentiation trajectories. SPICEMIX is a generalizable analysis framework for spatial transcriptome data to investigate cell-type composition and spatial organization of cells in complex tissues.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Humanos , Animais , Camundongos , Diferenciação Celular/genética , Simulação por Computador , Transcriptoma/genética , Análise de Célula Única
12.
J Obstet Gynaecol ; 43(1): 2151356, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36476308

RESUMO

Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer.Impact statementWhat is already known on this subject? The occurrence of cervical cancer is related to Septin9 methylation. In fresh specimens and cervical scrapings, we found the degrees of methylated Septin9 increased with growing severity of cervical lesions. Compared with HPV16/18 genotyping and cytological detection, Septin9 methylation had a better specificity and AUC in detecting ≥ HSIL. Furthermore, plasma-based Septin9 methylation also had a high specificity for pelvic lymphatic metastasis prediction.What the results of this study add? Methylation analysis of Septin9 indicated a similar sensitivity, specificity and AUC in detecting ≥ HSIL, relative to HPV16/18 genotyping. Compared with cytological method, Septin9 methylation also yielded a higher specificity and AUC in detecting ≥ HSIL. And we also found plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with SCCAg.What the implications are of these findings for clinical practice and/or further research? This study aimed to evaluate the relationship between Septin9 methylation and cervical cancer, and to explore the value of methylated Septin9 in the detection of cervical (pre)cancerous lesions. Moreover, we would explore plasma-based ctDNA biomarkers for pelvic lymphatic metastasis prediction of cervical cancer, to improve non-invasive predictive accuracy of pelvic nodal metastasis and reduce the complications caused by pelvic lymphadenectomy.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Metilação de DNA , Papillomavirus Humano 16/genética , Metástase Linfática , Papillomavirus Humano 18 , Biomarcadores Tumorais/genética , Displasia do Colo do Útero/patologia , Sensibilidade e Especificidade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética
14.
J Sci Food Agric ; 103(4): 1668-1675, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36541584

RESUMO

BACKGROUND: Eighteen wheat (Triticum aestivum-Aegilops sharonensis) introgression lines were generated in the previous study. These lines possessed four types of high molecular weight glutenin subunit (HMW-GS) combinations consisting of one glutenin from Ae. sharonensis (Glu-1Ssh ) plus one or more HMW-GSs from common wheat (Glu-A1, Glu-B1, or Glu-D1). RESULTS: In this study, we conducted quality tests to explore the effects of 1Ssh x2.3 and 1Ssh y2.9 on the processing quality of 18 wheat-Aegilops sharonensis introgression lines. Our data showed that the 1Ssh x2.3 and 1Ssh y2.9 subunits had a positive effect on gluten and baking quality. The bread volume of all these lines was higher than that of the parental wheat line LM3. In these lines, the HMW-GS content and the HMW/LMW ratio of 66-36-11 were higher than those of LM3, and the 66-36-11 line exhibited greatly improved quality parameters in comparison with the parent LM3. CONCLUSION: These results demonstrated that the 1Ssh x2.3 and 1Ssh y2.9 subunits from Ae. sharonensis contributed immensely to gluten strength and bread-baking quality, and proved a positive relationship between the HMW-GS sizes and their effects on dough strength in vivo. The materials developed could be used by breeding programs aiming to increase bread-making quality. © 2022 Society of Chemical Industry.


Assuntos
Aegilops , Triticum , Triticum/genética , Triticum/química , Pão , Peso Molecular , Melhoramento Vegetal , Glutens/química
15.
Mol Plant Microbe Interact ; : MPMI09220182R, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36515967

RESUMO

Most bacteria use type II fatty acid synthesis (FAS) systems for synthesizing fatty acids, of which the conserved FabA-FabB pathway is considered to be crucial for unsaturated fatty acid (UFA) synthesis in gram-negative bacteria. Xanthomonas campestris pv. campestris, the phytopathogen of black rot disease in crucifers, produces higher quantities of UFAs under low-temperature conditions for increasing membrane fluidity. The fabA and fabB genes were identified in the X. campestris pv. campestris genome by BLAST analysis; however, the growth of the X. campestris pv. campestris fabA and fabB deletion mutants was comparable to that of the wild-type strain in nutrient and minimal media. The X. campestris pv. campestris ΔfabA and ΔfabB strains produced large quantities of UFAs and, altogether, these results indicated that the FabA-FabB pathway is not essential for growth or UFA synthesis in X. campestris pv. campestris. We also observed that the expression of X. campestris pv. campestris fabA and fabB restored the growth of the temperature-sensitive Escherichia coli fabA and fabB mutants CL104 and CY242, respectively, under non-permissive conditions. The in-vitro assays demonstrated that the FabA and FabB proteins of X. campestris pv. campestris catalyzed FAS. Our study also demonstrated that the production of diffusible signal factor family signals that mediate quorum sensing was higher in the X. campestris pv. campestris ΔfabA and ΔfabB strains and greatly reduced in the complementary strains, which exhibited reduced swimming motility and attenuated host-plant pathogenicity. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

16.
Plant Biotechnol J ; 20(1): 75-88, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34487615

RESUMO

The AGAMOUS-LIKE6 (AGL6)-like genes are ancient MADS-box genes and are functionally studied in a few model plants. The knowledge of these genes in wheat remains limited. Here, by studying a 'double homoeolog mutant' of the AGL6 gene in tetraploid wheat, we showed that AGL6 was required for the development of all four whorls of floral organs with dosage-dependent effect on floret fertility. Yeast two-hybrid analyses detected interactions of AGL6 with all classes of MADS-box proteins in the ABCDE model for floral organ development. AGL6 was found to interact with several additional proteins, including the G protein ß and γ (DEP1) subunits. Analysis of the DEP1-B mutant showed a significant reduction in spikelet number per spike in tetraploid wheat, while overexpression of AGL6 in common wheat increased the spikelet number per spike and hence the grain number per spike. RNA-seq analysis identified the regulation of several meristem activity genes by AGL6, such as FUL2 and TaMADS55. Our work therefore extensively updated the wheat ABCDE model and proposed an alternative approach to improve wheat grain yield by manipulating the AGL6 gene.


Assuntos
Proteínas de Domínio MADS , Triticum , Flores , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Meristema , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Triticum/metabolismo
17.
Front Endocrinol (Lausanne) ; 13: 1056327, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465639

RESUMO

Since Costello et al. proposed the concept of pseudocapsule of pituitary neuroendocrine tumors (PitNETs) in 1936, many studies have been published on its occurrence, development process, histopathology, and morphology. Pseudocapsule has been proposed as the anatomical interface between PitNETs and normal pituitary gland, therefore the so-called pseudocapsule-based extracapsular resection (ER) technique was developed as an extracapsular surgery method for PitNETs,which differs from the conventional intracapsular resection (IR). In recent years, ER has also been widely used in patients of different tumor types, sizes, and age groups, because the pseudocapsule can be identified more clearly under the endoscopy. Endoscopic transsphenoidal resection for PitNETs has become the preferred surgical method. We reviewed relevant literatures in the past 10 years, showing that ER could achieve better rate of gross total resection (GTR) and biochemical remission, and reduce tumor recurrence than IR, without increasing postoperative complications. Therefore, the pseudocapsule and ER should be valued by neurosurgeons and actively promoted clinically.


Assuntos
Tumores Neuroendócrinos , Doenças da Hipófise , Neoplasias Hipofisárias , Humanos , Tumores Neuroendócrinos/cirurgia , Hipófise , Neoplasias Hipofisárias/cirurgia , Sistemas Neurossecretores
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(12): 1393-1397, 2022 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-36453966

RESUMO

OBJECTIVE: To explore the genetic etiology for an infant featuring convulsive status epilepticus, developmental delay and elevated plasma lactate. METHODS: Whole exome sequencing and mitochondrial D-loop sequencing were carried out for the infant. Candidate variants were verified by Sanger sequencing. Previously reported FARS2 gene variants were searched from the PubMed, Wanfang and CNKI databases. RESULTS: The infant was found to harbor compound heterozygous variants of the FARS2 gene, namely c.925G>A (p.G309S) and c.405C>A (p.H135Q), which were inherited from its mother and father, respectively. The former has been recorded by the HGMD as a pathogenic variant, whilst the latter was predicted to be likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics. A total of 30 COXPD14 cases were retrieved from the literature, with common mutations including missense variants, in-frame deletions, splice-site variants and large deletions. CONCLUSION: The common manifestations of COXPD14 have included developmental delay (96%), status epilepticus (97%) and increased lactic acid (96%). The compound heterozygous variants of the FARS2 gene probably underlay the disorder in this child.


Assuntos
Doenças Mitocondriais , Fenilalanina-tRNA Ligase , Estado Epiléptico , Feminino , Humanos , Lactente , Testes Genéticos , Proteínas Mitocondriais/genética
19.
Elife ; 112022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454214

RESUMO

Amino acid (AA) metabolism in vascular endothelium is important for sprouting angiogenesis. SLC38A5 (solute carrier family 38 member 5), an AA transporter, shuttles neutral AAs across cell membrane, including glutamine, which may serve as metabolic fuel for proliferating endothelial cells (ECs) to promote angiogenesis. Here, we found that Slc38a5 is highly enriched in normal retinal vascular endothelium, and more specifically, in pathological sprouting neovessels. Slc38a5 is suppressed in retinal blood vessels from Lrp5-/- and Ndpy/- mice, both genetic models of defective retinal vascular development with Wnt signaling mutations. Additionally, Slc38a5 transcription is regulated by Wnt/ß-catenin signaling. Genetic deficiency of Slc38a5 in mice substantially delays retinal vascular development and suppresses pathological neovascularization in oxygen-induced retinopathy modeling ischemic proliferative retinopathies. Inhibition of SLC38A5 in human retinal vascular ECs impairs EC proliferation and angiogenic function, suppresses glutamine uptake, and dampens vascular endothelial growth factor receptor 2. Together these findings suggest that SLC38A5 is a new metabolic regulator of retinal angiogenesis by controlling AA nutrient uptake and homeostasis in ECs.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros , Células Endoteliais , Humanos , Camundongos , Animais , Glutamina , Fator A de Crescimento do Endotélio Vascular , Neovascularização Patológica/genética , Sistemas de Transporte de Aminoácidos
20.
J Integr Plant Biol ; 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36515424

RESUMO

Cell wall is the first physical barrier to aluminum (Al) toxicity. Modification of cell wall properties to change its binding capacity to Al is one of the major strategies for plant Al resistance; nevertheless, how it is regulated in rice remains largely unknown. In this study, we show that exogenous application of putrescines (Put) could significantly restore the Al resistance of art1, a rice mutant lacking the central regulator Al RESISTANCE TRANSCRIPTION FACTOR 1 (ART1), and reduce its Al accumulation particularly in the cell wall of root tips. Based on RNA-sequencing, yeast-one-hybrid and electrophoresis mobility shift assays, we identified an R2R3 MYB transcription factor OsMYB30 as the novel target in both ART1-dependent and Put-promoted Al resistance. Furthermore, transient dual-luciferase assay showed that ART1 directly inhibited the expression of OsMYB30, and in turn repressed Os4CL5-dependent 4-coumaric acid accumulation, hence reducing the Al-binding capacity of cell wall and enhancing Al resistance. Additionally, Put repressed OsMYB30 expression by eliminating Al-induced H2 O2 accumulation, while exogenous H2 O2 promoted OsMYB30 expression. We concluded that ART1 confers Put-promoted Al resistance via repression of OsMYB30-regulated modification of cell wall properties in rice.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...