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1.
Mol Cell ; 80(5): 764-778.e7, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33207182

RESUMO

Autophagy eliminates cytoplasmic content selected by autophagy receptors, which link cargo to the membrane-bound autophagosomal ubiquitin-like protein Atg8/LC3. Here, we report a selective autophagy pathway for protein condensates formed by endocytic proteins in yeast. In this pathway, the endocytic protein Ede1 functions as a selective autophagy receptor. Distinct domains within Ede1 bind Atg8 and mediate phase separation into condensates. Both properties are necessary for an Ede1-dependent autophagy pathway for endocytic proteins, which differs from regular endocytosis and does not involve other known selective autophagy receptors but requires the core autophagy machinery. Cryo-electron tomography of Ede1-containing condensates, at the plasma membrane and in autophagic bodies, shows a phase-separated compartment at the beginning and end of the Ede1-mediated selective autophagy route. Our data suggest a model for autophagic degradation of macromolecular protein complexes by the action of intrinsic autophagy receptors.


Assuntos
Família da Proteína 8 Relacionada à Autofagia , Autofagia , Endocitose , Modelos Biológicos , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Família da Proteína 8 Relacionada à Autofagia/química , Família da Proteína 8 Relacionada à Autofagia/metabolismo , Microscopia Crioeletrônica , Ligação Proteica , Proteólise , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/ultraestrutura , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo
2.
J Allergy Clin Immunol ; 152(1): 182-194.e7, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36758835

RESUMO

BACKGROUND: Inborn errors of immunity have been implicated in causing immune dysregulation, including allergic diseases. STAT6 is a key regulator of allergic responses. OBJECTIVES: This study sought to characterize a novel gain-of-function STAT6 mutation identified in a child with severe allergic manifestations. METHODS: Whole-exome and targeted gene sequencing, lymphocyte characterization, and molecular and functional analyses of mutated STAT6 were performed. RESULTS: This study reports a child with a missense mutation in the DNA binding domain of STAT6 (c.1114G>A, p.E372K) who presented with severe atopic dermatitis, eosinophilia, and elevated IgE. Naive lymphocytes from the affected patient displayed increased TH2- and suppressed TH1- and TH17-cell responses. The mutation augmented both basal and cytokine-induced STAT6 phosphorylation without affecting dephosphorylation kinetics. Treatment with the Janus kinase 1/2 inhibitor ruxolitinib reversed STAT6 hyperresponsiveness to IL-4, normalized TH1 and TH17 cells, suppressed the eosinophilia, and improved the patient's atopic dermatitis. CONCLUSIONS: This study identified a novel inborn error of immunity due to a STAT6 gain-of-function mutation that gave rise to severe allergic dysregulation. Janus kinase inhibitor therapy could represent an effective targeted treatment for this disorder.


Assuntos
Dermatite Atópica , Eosinofilia , Hipersensibilidade , Criança , Humanos , Fatores de Transcrição/genética , Mutação com Ganho de Função , Dermatite Atópica/genética , Hipersensibilidade/genética , Eosinofilia/genética , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Células Th2
3.
J Allergy Clin Immunol ; 147(6): 2021-2029, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34092352

RESUMO

Inflammasomes are molecular machines that carry out inflammatory responses on challenges by pathogens and endogenous dangers. Dysregulation of inflammasome assembly and regulation is associated with numerous human diseases from autoimmunity to cancer. In recent years, significant advances have been made in understanding the mechanism of inflammasome signaling using structural approaches. Here, we review inflammasomes formed by the NLRP1, NLRP3, and NLRC4 sensors, which are well characterized structurally, and discuss the structural and functional diversity among them.


Assuntos
Inflamassomos/metabolismo , Inflamassomos/ultraestrutura , Animais , Biomarcadores , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Suscetibilidade a Doenças , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo , Piroptose , Transdução de Sinais
4.
Exp Dermatol ; 30(10): 1366-1374, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32347582

RESUMO

BACKGROUND: Skin microbiota are involved in the skin physiological functions and are also affected by the skin physiological characteristics. OBJECTIVE: To better understand the skin microbial characteristics of facial cheek skin and the relationship with skin physiological characteristics. METHODS: By bacterial 16S rRNA gene sequencing, the authors studied the facial cheek skin microbial characteristics of 85 cases of young women aged 18-25 years. RESULTS: Healthy young woman's cheek skin bacterial composition was relatively stable. Dry skin has high bacterial diversity and richness, and oily skin has low bacterial diversity and richness. Cutibacterium was significantly enriched in oily skin and was significantly negatively correlated with other genera such as Streptococcus (r > 0.5). There were significant positive correlations among other genera of enrichment in dry and neutral skin such as Streptococcus and Rothia (r > 0.8). Skin sebum level was significantly negatively correlated with bacterial alpha diversity index. The combined abundance of Cutibacterium acnes and Staphylococcus epidermidis was significantly positively correlated with sebum secretion (r > 0.5). CONCLUSIONS: The skin sebum secretion and bacterial interaction were the important factors driving the young females' cheek skin bacterial community structure.


Assuntos
Estruturas Bacterianas/fisiologia , Bochecha/microbiologia , Microbiota/fisiologia , Pele/microbiologia , Adolescente , Adulto , China , Feminino , Voluntários Saudáveis , Humanos , Sebo/metabolismo , Adulto Jovem
5.
Arch Microbiol ; 203(8): 5215-5224, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34351458

RESUMO

Magnolia bark is an edible traditional Chinese medicine that has antibacterial activity against Staphylococcus aureus. In the present study, interactions between S. aureus DNA and raw magnolia bark (RMB) and ginger mix-fried magnolia bark (GMB) aqueous extracts were determined via spectroscopic methods. Fluorescence spectroscopy and Stern-Volmer constants showed that S. aureus DNA quenched the fluorescence of the extracts by static quenching. UV-Vis spectroscopy and iodide quenching experiments indicated that the interactions between S. aureus DNA and the fluorescent substances might involve groove binding or electrostatic interactions. In 4', 6-diamidino-2-phenylindole competitive assays, the fluorescence intensity at decreased as the extract amount was increased. This indicates that groove binding is responsible for the fluorescence quenching. The antibacterial activity of GMB aqueous extract treated under light, cold, heat and cycling hot-cold conditions decreased by 13.99, 9.31, 10.89 and 14.40%, respectively, whereas that of RMB aqueous extract treated under the same conditions decreased by 8.91, 14.99, 14.99 and 13.70%, respectively. The results indicate that S. aureus DNA quenches the fluorescence of GMB and RMB aqueous extracts by grooving interactions. Additionally, the antibacterial activities of GMB and RMB extracts are sensitive to light and temperature, respectively.


Assuntos
Magnolia , Staphylococcus aureus , Antibacterianos/farmacologia , DNA , Casca de Planta , Extratos Vegetais/farmacologia
6.
Dermatology ; 236(2): 160-169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31553991

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a chronic, recurrent skin condition with recently increased incidence in younger children. AD development has been correlated with the skin microbiome, and Staphylococcus aureus enrichment causes significant increases in skin lesions. OBJECTIVE: Our objectives were to compare the microbial diversity of the cheek skin of children with or without AD aged 0-1 years in China, and to determine whether 4 types of skin-isolated bacteria could inhibit S. aureus in vitro. METHODS: The skin microbial samples of cheek skin of children were sequenced by 16S rRNA V1-V2 region. Four skin isolated bacterial fermentation supernatants were tested for effects on S. aureus growth, membrane formation, and induction of cytokine secretion from HaCaT cells. RESULTS: Bacterial diversity decreased significantly in skin with severe AD compared to healthy skin (p < 0.01). Seven phyla had content >1%, 4 of which differed in AD (p < 0.05). 38 genera had content >1%, 15 differed (p < 0.05). Differences in 8 species were observed (p < 0.05). In vitro antibacterial and cellular experiments showed that S. aureus growth, biofilm formation, and induction of interleukin (IL)-1α and IL-6 secretion from HaCaT cells were significantly inhibited by Klebsiella oxytoca, Kocuria rhizophila, and Staphylococcus epidermidis culture supernatants (p < 0.05). CONCLUSION: Skin microbiome changes in children varied with age and with AD. There were complex interactions between skin isolated bacteria and S. aureus which could inhibit S. aureus growth and biofilm formation in vitro, suggesting that these microorganisms could be used in AD treatment.


Assuntos
Bochecha/microbiologia , Dermatite Atópica/microbiologia , Microbiota , Pele/microbiologia , Infecções Estafilocócicas/fisiopatologia , Staphylococcus aureus , Pré-Escolar , China , Dermatite Atópica/fisiopatologia , Dermatite Atópica/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Higiene da Pele , Infecções Estafilocócicas/microbiologia
7.
Exp Dermatol ; 28(11): 1289-1297, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31472099

RESUMO

BACKGROUND: The microbiological basis of diaper dermatitis has not been clearly elucidated; however, a better understanding of microbial colonization may be vital for developing appropriate therapies. METHODS: Using 16S-rRNA gene sequencing technology, we characterized and compared the bacterial communities obtained from the buttock skin sites of children with diaper dermatitis and from healthy controls. Bacterial diversity in the buttock lesion area and subsequent recovery after emollient treatment have been discussed herein. RESULTS: In buttock skin of children with or without diaper dermatitis, Staphylococcus and Anaerococcus were predominant in the total skin microbiome. Compared with the healthy group, the overall skin bacterial richness and diversity were higher in children with diaper dermatitis, with the abundance of Proteobacteria being significantly higher. In the diaper dermatitis group, the richness of Enterococcus, Erwinia and Pseudomonas was significantly higher, and the levels of Clostridium and Actinomyces were significantly lower than those in healthy children. Richness of Staphylococcus aureus was significantly higher in the diaper dermatitis group, whereas that of Staphylococcus epidermidis and Bifidobacterium longum was lower. Staphylococcus epidermidis and Staphylococcus haemolyticus, the dominant species found in buttock skin, were observed to recover earlier after the disease had improved through emollient treatment. CONCLUSION: Staphylococcus epidermidis, as skin probiotic bacterium, and B longum, Clostridium butyricum and Lactobacillus ruminis, which are intestinal probiotic bacteria, are significantly decreased in diaper dermatitis lesions. These changes in the buttock skin microflora indicate an imbalance in the microflora and suggest that the intestinal microflora may be undergoing dynamic changes. The results of this study suggest that probiotic bacterial supplementation may be useful in the treatment and prevention of diaper dermatitis.


Assuntos
Dermatite das Fraldas/microbiologia , Microbiota , Creme para a Pele/uso terapêutico , Pele/microbiologia , Estudos de Casos e Controles , Pré-Escolar , China , Dermatite das Fraldas/tratamento farmacológico , Humanos , Lactente , Microbiota/efeitos dos fármacos , Creme para a Pele/farmacologia
8.
Eur J Clin Microbiol Infect Dis ; 38(9): 1677-1685, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31152265

RESUMO

Atopic dermatitis (AD), a chronic relapsing inflammatory pruritic skin disorder with a unique pathophysiology, has a high incidence in the perioral zone among infants. This study aimed to analyze the association of skin microfloral dynamics with disease severity and treatment of AD in 0-1-year-old infants. Based on the eczema area and severity index, subjects were divided into five groups, i.e., mild, moderate, severe, and severe post-treatment, with a healthy control group, and bacterial density at the perioral lesion, disease severity, and treatment were assessed in 0-1-year-old infants with AD. The perioral lesions were colonized predominantly by Firmicutes, followed in abundance by Proteobacteria, Actinobacteria, and Bacteroidetes. In the phylum Firmicutes, Streptococcus was the most predominant genus. In AD infants, the abundance of Bacteroidetes and Fusobacterium decreased significantly with an increase in disease severity (p < 0.01). The abundance of 6 genera, including Prevotella, decreased significantly with an increase in disease severity (p < 0.05). The abundance of Prevotella melaninogenica decreased gradually with an increase in disease severity and increased after treatment; this trend was reversed for Corynebacterium simulans. A reduction in the abundance of Staphylococcus and an increase in that of skin microflora including Prevotella spp., Staphylococcus epidermidis, and Erwinia dispersa were associated with treatment and clinical improvement. Skin bacterial composition varies with AD severity, and Corynebacterium simulans and Prevotella melaninogenica are positively and negatively correlated with AD severity, respectively. This study provides a theoretical basis to identify potential biomarkers AD occurrence and pathogenesis.


Assuntos
Bactérias/efeitos dos fármacos , Dermatite Atópica/microbiologia , Dermatite Perioral/microbiologia , Microbiota , Pele/microbiologia , Bactérias/classificação , Dermatite Atópica/tratamento farmacológico , Dermatite Perioral/tratamento farmacológico , Eczema , Humanos , Lactente , Recém-Nascido , RNA Ribossômico 16S , Índice de Gravidade de Doença
9.
Clin Oral Investig ; 23(12): 4223-4231, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30820823

RESUMO

OBJECTIVES: We investigated the incidence of tuberculosis (TB) in patients with newly diagnosed oral cancer and analyzed the risk factors for TB development and mortality in oral cancer patients. MATERIALS AND METHODS: We used Taiwan's National Health Insurance Database to determine the incidence of TB and to analyze the risk factors for TB in patients newly diagnosed with oral cancer. From 2000 to 2011, we identified 40,327 oral cancer patients and the same number of subjects from the general population matched for sex, age, and comorbidities at a 1:1 ratio. RESULTS: Compared with the matched cohort, oral cancer patients exhibited a higher risk for TB (adjusted hazard ratio (aHR) 2.36, 95% confidence interval (CI) 2.06-2.71). Age ≥ 50 (aHR 1.90, 95% CI 1.57-2.29), being male (aHR 1.98, 95% CI 1.36-2.89), having diabetes mellitus (aHR 1.31, 95% CI 1.05-1.64), alcohol use disorder (aHR 1.42, 95% CI 1.06-1.89), human immunodeficiency virus (HIV) (aHR 8.24, 95% CI 2.05-33.14), chemotherapy (aHR 1.41, 95% CI 1.15-1.72), and radiotherapy for oral cancer (aHR 1.92, 95% CI 1.57-2.36) were identified as independent risk factors for TB in oral cancer patients. Hyperlipidemia was an independent protective factor for TB in oral cancer patients. CONCLUSION: Old age, male sex, diabetes mellitus, alcohol use disorder, and HIV were independent risk factors for TB in patients with oral cancer. CLINICAL RELEVANCE: High-risk oral cancer patients should be regularly screened for TB, especially those in endemic areas.


Assuntos
Neoplasias Bucais/epidemiologia , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Endêmicas , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Vigilância da População , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
10.
New Phytol ; 213(1): 250-263, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27513887

RESUMO

Several physiological functions have been attributed to class III peroxidases (PRXs) in plants, but the in planta role of most members of this family still remains undetermined. Here, we report the first functional characterization of PRX17 (At2g22420), one of the 73 members of this family in Arabidopsis thaliana. Localization of PRX17 was examined by transient expression in Nicotiana benthamiana. Loss- and gain-of-function mutants in A. thaliana were studied. Regulation at the gene and protein levels was analyzed using ß-glucuronidase (GUS) activity, quantitative reverse transcriptase (qRT)-PCR, zymography, and chromatin immunoprecipitation. Phenotypes were characterized including lignin and xylan contents. PRX17 was expressed in various tissues, including vascular tissues, and PRX17 was localized to the cell wall. In prx17, the lignin content was reduced in the stem and siliques and bolting was delayed, while the opposite phenotype was observed in 35S:PRX17 plants, together with a significant increase of lignin and xylan immunofluorescence signal. Finally, we demonstrated that the transcription factor AGAMOUS-LIKE15 (AGL15) binds to the PRX17 promoter and regulates PRX17 expression level. This converging set of structural, transcriptomic and physiological data suggests that PRX17, under the control of AGL15, contributes to developmental programs by playing an essential role in regulating age-dependent lignified tissue formation, including changes in cell wall properties.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Parede Celular/metabolismo , Lignina/metabolismo , Proteínas de Domínio MADS/metabolismo , Peroxidase/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Sequência de Bases , DNA Bacteriano/genética , Flores/fisiologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Proteínas de Domínio MADS/genética , Mutação/genética , Peroxidases , Filogenia , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Frações Subcelulares/metabolismo
11.
Plant Physiol ; 172(4): 2374-2387, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27794101

RESUMO

The MADS box transcription factor Arabidopsis (Arabidopsis thaliana) AGAMOUS-LIKE15 (AGL15) and a putative ortholog from soybean (Glycine max), GmAGL15, are able to promote somatic embryogenesis (SE) in these plants when ectopically expressed. SE is an important means of plant regeneration, but many plants, or even particular cultivars, are recalcitrant for this process. Understanding how (Gm)AGL15 promotes SE by identifying and characterizing direct and indirect downstream regulated genes can provide means to improve regeneration by SE for crop improvement and to perform molecular tests of genes. Conserved transcription factors and the genes they regulate in common between species may provide the most promising avenue to identify targets for SE improvement. We show that (Gm)AGL15 negatively regulates auxin signaling in both Arabidopsis and soybean at many levels of the pathway, including the repression of AUXIN RESPONSE FACTOR6 (ARF6) and ARF8 and TRANSPORT INHIBITOR RESPONSE1 as well as the indirect control of components via direct expression of a microRNA-encoding gene. We demonstrate interaction between auxin and gibberellic acid in the promotion of SE and document an inverse correlation between bioactive gibberellic acid and SE in soybean, a difficult crop to transform. Finally, we relate hormone accumulation to transcript accumulation of important soybean embryo regulatory factors such as ABSCISIC ACID INSENSITIVE3 and FUSCA3 and provide a working model of hormone and transcription factor interaction in the control of SE.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/embriologia , Arabidopsis/genética , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glycine max/embriologia , Proteínas de Domínio MADS/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/metabolismo , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Proteínas F-Box/metabolismo , Genes de Plantas , Giberelinas/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Domínio MADS/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/metabolismo , Proteínas Repressoras/metabolismo , Glycine max/efeitos dos fármacos , Glycine max/genética
12.
Plant Physiol ; 165(4): 1591-1603, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24948837

RESUMO

Multiple factors, including the MADS-domain proteins AGAMOUS-LIKE15 (AGL15) and AGL18, contribute to the regulation of the transition from vegetative to reproductive growth. AGL15 and AGL18 were previously shown to act redundantly as floral repressors and upstream of FLOWERING LOCUS T (FT) in Arabidopsis (Arabidopsis thaliana). A series of genetic and molecular experiments, primarily focused on AGL15, was performed to more clearly define their role. agl15 agl18 mutations fail to suppress ft mutations but show additive interactions with short vegetative phase (svp) mutations in ft and suppressor of constans1 (soc1) backgrounds. Chromatin immunoprecipitation analyses with AGL15-specific antibodies indicate that AGL15 binds directly to the FT locus at sites that partially overlap those bound by SVP and FLOWERING LOCUS C. In addition, expression of AGL15 in the phloem effectively restores wild-type flowering times in agl15 agl18 mutants. When agl15 agl18 mutations are combined with agl24 svp mutations, the plants show upward curling of rosette and cauline leaves, in addition to early flowering. The change in leaf morphology is associated with elevated levels of FT and ectopic expression of SEPALLATA3 (SEP3), leading to ectopic expression of floral genes. Leaf curling is suppressed by sep3 and ft mutations and enhanced by soc1 mutations. Thus, AGL15 and AGL18, along with SVP and AGL24, are necessary to block initiation of floral programs in vegetative organs.

13.
Plant Physiol ; 161(4): 2113-27, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23457229

RESUMO

Many of the regulatory processes occurring during plant embryogenesis are still unknown. Relatively few cells are involved, and they are embedded within maternal tissues, making this developmental phase difficult to study. Somatic embryogenesis is a more accessible system, and many important regulatory genes appear to function similar to zygotic development, making somatic embryogenesis a valuable model for the study of zygotic processes. To better understand the role of the Arabidopsis (Arabidopsis thaliana) MADS factor AGAMOUS-Like15 (AGL15) in the promotion of somatic embryogenesis, direct target genes were identified by chromatin immunoprecipitation-tiling arrays and expression arrays. One potential directly up-regulated target was At5g61590, which encodes a member of the ethylene response factor subfamily B-3 of APETALA2/ethylene response factor transcription factors and is related to Medicago truncatula somatic embryo-related factor1 (MtSERF1), which has been shown to be required for somatic embryogenesis in M. truncatula. Here, we report confirmation that At5g61590 is a directly expressed target of AGL15 and that At5g61590 is essential for AGL15's promotion of somatic embryogenesis. Because At5g61590 is a member of the ethylene response factor family, effects of ethylene on somatic embryogenesis were investigated. Precursors to ethylene stimulate somatic embryogenesis, whereas inhibitors of ethylene synthesis or perception reduce somatic embryogenesis. To extend findings to a crop plant, we investigated the effects of ethylene on somatic embryogenesis in soybean (Glycine max). Furthermore, we found that a potential ortholog of AGL15 in soybean (GmAGL15) up-regulates ethylene biosynthesis and response, including direct regulation of soybean orthologs of At5g61590/MtSERF1 named here GmSERF1 and GmSERF2, in concordance with the M. truncatula nomenclature.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/embriologia , Arabidopsis/metabolismo , Etilenos/biossíntese , Glycine max/embriologia , Glycine max/metabolismo , Proteínas de Domínio MADS/metabolismo , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Proteínas de Domínio MADS/genética , Meristema/embriologia , Proteínas de Plantas/genética , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sequências Reguladoras de Ácido Nucleico/genética , Sementes/metabolismo , Homologia de Sequência de Aminoácidos , Glycine max/genética , Regulação para Cima/genética
15.
Mitochondrial DNA B Resour ; 9(3): 411-414, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562438

RESUMO

Hemiboea pterocaulis is a unique species only found in Guilin, Guangxi, China. In this study, we sequenced and assembled the complete chloroplast genome of H. pterocaulis and revealed its phylogenetic relationship with other Hemiboea species. The chloroplast genome sequence of H. pterocaulis is 153,159 bp in length and comprises a large single-copy (LSC) region of 84,178 bp, a small single-copy (SSC) region of 18,087 bp, and a pair of inverted repeat (IR) regions, each with a length of 25,447 bp. It has a total GC content of 37.6% and encodes 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The phylogenetic relationships based on the complete chloroplast genome sequences of Hemiboea taxa indicate that H. pterocaulis is most closely related to H. suiyangensis, indicating that H. pterocaulis is an independent species and is separated from the H. subcapitata complex. These results provide valuable insights into the phylogeny, species divergence, and delimitation of the Hemiboea genus.

16.
Cell Res ; 33(2): 131-146, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36604598

RESUMO

Members of the tumor necrosis factor receptor superfamily (TNFRSF) are important therapeutic targets that can be activated to induce death of cancer cells or stimulate proliferation of immune cells. Although it has long been implicated that these receptors assemble preligand associated states that are required for dominant interference in human disease, such states have so far eluded structural characterization. Here, we find that the ectodomain of death receptor 5 (DR5-ECD), a representative member of TNFRSF, can specifically self-associate when anchored to lipid bilayer, and we report this self-association structure determined by nuclear magnetic resonance (NMR). Unexpectedly, two non-overlapping interaction interfaces are identified that could propagate to higher-order clusters. Structure-guided mutagenesis indicates that the observed preligand association structure is represented on DR5-expressing cells. The DR5 preligand association serves an autoinhibitory role as single-domain antibodies (sdAbs) that partially dissociate the preligand cluster can sensitize the receptor to its ligand TRAIL and even induce substantial receptor signaling in the absence of TRAIL. Unlike most agonistic antibodies that require multivalent binding to aggregate receptors for activation, these agonistic sdAbs are monovalent and act specifically on an oligomeric, autoinhibitory configuration of the receptor. Our data indicate that receptors such as DR5 can form structurally defined preclusters incompatible with signaling and that true agonists should disrupt the preligand cluster while converting it to signaling-productive cluster. This mechanism enhances our understanding of a long-standing question in TNFRSF signaling and suggests a new opportunity for developing agonistic molecules by targeting receptor preligand clustering.


Assuntos
Apoptose , Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Humanos , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/química , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Transdução de Sinais , Proteínas de Transporte/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Linhagem Celular Tumoral
17.
Plant Cell ; 21(9): 2563-77, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19767455

RESUMO

AGAMOUS-Like15 (AGL15) is a MADS domain transcriptional regulator that promotes somatic embryogenesis by binding DNA and regulating gene expression. Chromatin immunoprecipitation (ChIP) analysis previously identified DNA fragments with which AGL15 associates in vivo, and a low-throughput approach revealed a role for AGL15 in gibberellic acid catabolism that is relevant to embryogenesis. However, higher throughput methods are needed to identify targets of AGL15. Here, we mapped AGL15 in vivo binding sites using a ChIP-chip approach and the Affymetrix tiling arrays for Arabidopsis thaliana and found that approximately 2000 sites represented in three biological replicates of the experiment are annotated to nearby genes. These results were combined with high-throughput measurement of gene expression in response to AGL15 accumulation to discriminate responsive direct targets from those further downstream in the network. LEAFY COTYLEDON2, FUSCA3, and ABA INSENSITIVE3, which encode B3 domain transcription factors that are key regulators of embryogenesis, were identified and verified as direct target genes of AGL15. Genes identified as targets of the B3 genes are also targets of AGL15, and we found that INDOLEACETIC ACID-INDUCED PROTEIN30 is involved in promotion of somatic embryo development. The data presented here and elsewhere suggest that much cross-regulation occurs in gene regulatory networks underpinning embryogenesis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Redes Reguladoras de Genes , Proteínas de Domínio MADS/metabolismo , Arabidopsis/embriologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Sítios de Ligação , Imunoprecipitação da Cromatina , DNA de Plantas/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Proteínas de Domínio MADS/genética , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Mol Biol Rep ; 39(2): 1649-57, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21633891

RESUMO

A series of HSP70 promoter deletion constructs was established. Analysis of beta-glucuronidase activities from the promoter deletion constructs in transient expression assays identified a cis-element, located from -493 to -308 bp upstream of the ATG start site. This element was designated as HS185 and has a crucial role in HSP70 promoter activity. HS185 has some characteristics of a miniature inverted-repeat transposable element (MITE), such as terminal inverted repeats (TIRs) (GGTCCCACA) and a putative target site duplication. There are 362 copies of homologous sequences of HS185 in the rice genome, which are preferentially distributed to non-coding regions. Based on these sequence features, we propose that HS185 is an uncharacterized rice MITE, possibly derived from the rice transposon Mutator-like element VIII family. Further transient expression assays showed that HS185 inhibited the enhancer activity of the cauliflower mosaic virus 35S promoter. These results demonstrate that not only is HS185 necessary for HSP70 promoter activity, but it also has a functional role as an insulator. This study explored new regulatory functions of non-coding repeat sequences in rice.


Assuntos
Elementos de DNA Transponíveis/genética , Regulação Viral da Expressão Gênica/genética , Proteínas de Choque Térmico HSP70/genética , Oryza/genética , Elementos Reguladores de Transcrição/genética , Pareamento de Bases , Sequência de Bases , Sítios de Ligação/genética , Caulimovirus/genética , Clonagem Molecular , Biologia Computacional , Vetores Genéticos/genética , Sequências Repetidas Invertidas/genética , Dados de Sequência Molecular , Folhas de Planta/metabolismo , Regiões Promotoras Genéticas/genética , Análise de Sequência de DNA , Nicotiana/metabolismo
19.
Comput Math Methods Med ; 2022: 9150803, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832132

RESUMO

Objective: Ultrasound is a practical imaging modality for screening and identification of anomalies in the organs. This study used ultrasonography to examine the association between body parameters and dimensions of the normal liver, spleen, and kidney in adolescents based on ultrasound examination results. Methods: A total of 300 junior and senior high school teenagers receiving routine health check-ups in our hospital from January 2020 to January 2021 were included. Their height and weight were measured, and their body surface area (BSA) and body mass index (BMI) were calculated. Ultrasound imaging was employed to obtain information such as the length and volume of the liver, gallbladder, spleen, and kidney. Besides, the correlation of body parameters such as gender, age, height, weight, BSA, and BMI with visceral dimension was investigated using the Pearson test and multiple regression analysis, respectively. Results: We observed that the abdominal organs of adolescents were enlarged with age. The span and volume of the liver and the length and volume of the right kidney were significantly larger in boys than in girls. The age, BSA, and BMI were positively correlated with the liver span and spleen length, as well as the left and right kidney lengths. Additionally, age, BSA, and BMI were identified as important predictors for dimensions of the spleen, liver, and kidney. Conclusions: Body parameters are notably associated with the dimensions of the liver, spleen, and kidney and could be utilized as predicting factors for the liver, spleen, and kidney dimensions.


Assuntos
Rim , Baço , Adolescente , Peso Corporal , Feminino , Humanos , Rim/diagnóstico por imagem , Fígado/diagnóstico por imagem , Masculino , Valores de Referência , Baço/diagnóstico por imagem , Ultrassonografia
20.
Environ Sci Pollut Res Int ; 29(26): 39441-39450, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35103946

RESUMO

In this work, two different types of ZnAl-layered double hydroxide (LDH) mixed metal-oxide composites (CeO2 and SnO2) were synthesized and applied for the photodegradation of 4-chlorophenol (4-CP) in wastewater. The fabricated CeO2/ZnAl-LDH and SnO2/ZnAl-LDH were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, UV-visible diffuse reflectance spectroscopy (UV-vis DRS), and theoretical density functional theory (DFT) calculations, suggesting that the band gaps of the synthesized hybrid composites were much lower than those of traditional ZnAl-LDH. In addition, the photocatalytic activity for 4-CP degradation and reaction kinetics were investigated to evaluate the catalytic behavior of the prepared composites. The results indicated that the photocatalytic process in this case followed a pseudo-first-order kinetic model, and SnO2/ZnAl-LDH illustrated the optimum performance for 4-CP degradation with an efficiency of 95.2% due to its stability and recyclability. Additionally, the reaction mechanism of 4-CP photodegradation was studied over SnO2/ZnAl-LDH; it presented that 4-CP could be oxidized by hydroxyl radicals, holes, and superoxide radicals, where hydroxyl radicals were identified as the dominant active species during the degradation process. Finally, decomposition intermediates were measured to deduce the reaction pathway of 4-CP, and three tentative pathways were proposed and discussed.


Assuntos
Clorofenóis , Hidróxidos , Catálise , Hidróxidos/química , Óxidos
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