Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 404.802
Filtrar
1.
Parasitol Int ; 86: 102468, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34520840

RESUMO

Parastrigea brasiliana (Szidat, 1928) Dubois, 1964, was described from (Cochlearius cochlearius) in South America. The taxonomy of this species has been unstable due that it was described as a member of Strigea Abildgaard, 1790. However, the same author one year later transferred it to Apharyngostrigea Ciurea, 1927 and since then, it has been alternatively placed in the genus Apharyngostrigea or Parastrigea Szidat, 1928 from Strigeidae. In the current research, specimens identified as P. brasiliana were collected from type host in southeastern Mexico. We sequenced three molecular markers: the internal transcribed spacers ITS1 and ITS2 including the 5.8S gene (ITS region), the D1-D3 domains of the large subunit (LSU) from nuclear DNA and cytochrome c oxidase subunit I (cox 1) from mitochondrial DNA. These sequences were aligned with other sequences available in the GenBank dataset from Strigeidae. Maximum likelihood and Bayesian analyses inferred with three molecular markers consistently showed that P. brasiliana is not closely related to other members of the genus Parastrigea and are placed in a reciprocal monophyletic clade inside Apharyngostrigea, with very low genetic divergence, varying from 0 to 0.09% for the ITS, from 0 to 0.08% for the LSU and from 0.21 to 0.43% for cox 1. Consequently, we proposed to reallocate it to A. brasiliana. The phylogenetic analyses obtained are key and very useful for re-evaluate the morphology of A. brasiliana because this species share morphological characters with the genera Parastrigea (concentration of vitelline follicles distributed in two lateral expansions on the forebody) and Apharyngostrigea (absence of pharynx). Finally, the current record of A. brasiliana expands its distribution range in four countries, namely, the USA, Mexico, Venezuela and Brazil, in the Neotropical region.


Assuntos
Doenças das Aves/parasitologia , Aves , Trematódeos , Infecções por Trematódeos/veterinária , Animais , DNA de Helmintos/análise , DNA Mitocondrial/análise , Proteínas de Helminto/análise , México , Microscopia Eletrônica de Varredura/veterinária , Trematódeos/anatomia & histologia , Trematódeos/classificação , Trematódeos/genética , Trematódeos/ultraestrutura , Infecções por Trematódeos/parasitologia
2.
Parasitol Int ; 86: 102472, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34597759

RESUMO

Kudoa ocellatus n. sp. was found in the musculature of Astronotus ocelattus (Agassiz, 1831) from the Arari River on Marajó Island in Pará, Brazil. The new species forms pseudocysts in the epaxial and hypaxial musculature composed of various spores that are pseudoquadrate in the apical view. In the lateral view, the spores were triangular or pyramidal. In the lateral view, the spores were 46 ± 0.11 µm (4.5-4.8) in length and 6.6 ± 0.3 µm (6.2-7.2) in width, with four pyriform polar capsules of equal size that measured 2.0 ± 0.16 µm (1.8-2.2) in length and 1.5 ± 0.18 µm (1.3-1.8) in width. Based on the partial (1418 bps) sequence of the SSU rDNA gene, Kudoa ocellatus n. sp. was distinct from all the other Kudoa species deposited in GenBank. The phylogenetic Bayesian Inference and P distance placed the new species together with the other Kudoa species that parasitize freshwater Amazonian fish. The morphological evidence, together with the SSU rDNA gene sequence, supported the description of Kudoa ocellatus n. sp., a distinct new species of the genus, which parasitizes a freshwater Amazonian cichlid.


Assuntos
Ciclídeos , Doenças dos Peixes/epidemiologia , Myxozoa/classificação , Doenças Parasitárias em Animais/epidemiologia , Animais , Brasil/epidemiologia , Doenças dos Peixes/parasitologia , Interações Hospedeiro-Parasita , Myxozoa/genética , Myxozoa/ultraestrutura , Doenças Parasitárias em Animais/parasitologia , Prevalência
5.
PLoS One ; 16(11): e0259732, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34780505

RESUMO

Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) are bioactive particles that evoke beneficial responses in recipient cells. We identified a role for MSC-EV in immune modulation and cellular salvage in a model of SARS-CoV-2 induced acute lung injury (ALI) using pulmonary epithelial cells and exposure to cytokines or the SARS-CoV-2 receptor binding domain (RBD). Whereas RBD or cytokine exposure caused a pro-inflammatory cellular environment and injurious signaling, impairing alveolar-capillary barrier function, and inducing cell death, MSC-EVs reduced inflammation and reestablished target cell health. Importantly, MSC-EV treatment increased active ACE2 surface protein compared to RBD injury, identifying a previously unknown role for MSC-EV treatment in COVID-19 signaling and pathogenesis. The beneficial effect of MSC-EV treatment was confirmed in an LPS-induced rat model of ALI wherein MSC-EVs reduced pro-inflammatory cytokine secretion and respiratory dysfunction associated with disease. MSC-EV administration was dose-responsive, demonstrating a large effective dose range for clinical translation. These data provide direct evidence of an MSC-EV-mediated improvement in ALI and contribute new insights into the therapeutic potential of MSC-EVs in COVID-19 or similar pathologies of respiratory distress.


Assuntos
Lesão Pulmonar Aguda/complicações , Lesão Pulmonar Aguda/virologia , COVID-19/patologia , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Pneumonia/complicações , Pneumonia/virologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Modelos Animais de Doenças , Vesículas Extracelulares/ultraestrutura , Humanos , Imunomodulação , Masculino , Modelos Biológicos , Pneumonia/patologia , Ratos Sprague-Dawley , SARS-CoV-2/fisiologia , Transdução de Sinais , Células THP-1
8.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639010

RESUMO

Chloroplasts of higher plants are semi-autonomous organelles that perform photosynthesis and produce hormones and metabolites. They play crucial roles in plant growth and development. Although many seedling-lethal nuclear genes or regulators required for chloroplast development have been characterized, the understanding of chloroplast development is still limited. Using a genetic screen, we isolated a mutant named ell1, with etiolated leaves and a seedling-lethal phenotype. Analysis by BN-PAGE and transmission electron microscopy revealed drastic morphological defects of chloroplasts in ell1 mutants. Genetic mapping of the mutant gene revealed a single mutation (G-to-A) at the 5' splice site of intron 5 in CRS1, resulting in an exon skipping in CRS1, indicating that this mutation in CRS1 is responsible for the observed phenotype, which was further confirmed by genetic analysis. The incorrectly spliced CRS1 failed to mediate the splicing of atpF intron. Moreover, the quantitative analysis suggested that ZmCRS1 may participate in chloroplast transcription to regulate the development of chloroplast. Taken together, these findings improve our understanding of the ZmCRS1 protein and shed new light on the regulation of chloroplast development in maize.


Assuntos
Cloroplastos/genética , Éxons , Regulação da Expressão Gênica de Plantas , Splicing de RNA , Zea mays/genética , Cloroplastos/ultraestrutura , Clonagem Molecular , Genes de Plantas , Mutação , Fenótipo , Fotossíntese/genética , Desenvolvimento Vegetal
9.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639013

RESUMO

The electron density of a nanoparticle is a very important characteristic of the properties of a material. This paper describes the formation of silver nanoparticles (NPs) and the variation in the electronic state of an NP's surface upon the reduction in Ag+ ions with oxalate ions, induced by UV irradiation. The calculations were based on optical spectrophotometry data. The NPs were characterized using Transmission electron microscopy and Dynamic light scattering. As ~10 nm nanoparticles are formed, the localized surface plasmon resonance (LSPR) band increases in intensity, decreases in width, and shifts to the UV region from 402 to 383 nm. The interband transitions (IBT) band (≤250 nm) increases in intensity, with the band shape and position remaining unchanged. The change in the shape and position of the LSPR band of silver nanoparticles in the course of their formation is attributable to an increasing concentration of free electrons in the particles as a result of a reduction in Ag+ ions on the surface and electron injection by CO2- radicals. The ζ-potential of colloids increases with an increase in electron density in silver nuclei. A quantitative relationship between this shift and electron density on the surface was derived on the basis of the Mie-Drude theory. The observed blue shift (19 nm) corresponds to an approximately 10% increase in the concentration of electrons in silver nanoparticles.


Assuntos
Eletricidade , Elétrons , Nanopartículas Metálicas/química , Prata/química , Soluções/química , Fenômenos Químicos , Eletroquímica , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Transmissão , Modelos Teóricos , Tamanho da Partícula , Ressonância de Plasmônio de Superfície
10.
Immunity ; 54(10): 2218-2230.e5, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34644557

RESUMO

The RNA sensor MDA5 recruits the signaling adaptor MAVS to initiate type I interferon signaling and downstream antiviral responses, a process that requires K63-linked polyubiquitin chains. Here, we examined the mechanisms whereby K63-polyUb chain regulate MDA5 activation. Only long unanchored K63-polyUbn (n ≥ 8) could mediate tetramerization of the caspase activation and recruitment domains of MDA5 (MDA5CARDs). Cryoelectron microscopy structures of a polyUb13-bound MDA5CARDs tetramer and a polyUb11-bound MDA5CARDs-MAVSCARD assembly revealed a tower-like formation, wherein eight Ubs tethered along the outer rim of the helical shell, bridging MDA5CARDs and MAVSCARD tetramers into proximity. ATP binding and hydrolysis promoted the stabilization of RNA-bound MDA5 prior to MAVS activation via allosteric effects on CARDs-polyUb complex. Abundant ATP prevented basal activation of apo MDA5. Our findings reveal the ordered assembly of a MDA5 signaling complex competent to recruit and activate MAVS and highlight differences with RIG-I in terms of CARD orientation and Ub sensing that suggest different abilities to induce antiviral responses.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Helicase IFIH1 Induzida por Interferon/metabolismo , Transdução de Sinais/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/química , Microscopia Crioeletrônica , Células HEK293 , Humanos , Imunidade Inata/fisiologia , Helicase IFIH1 Induzida por Interferon/química , Helicase IFIH1 Induzida por Interferon/ultraestrutura , Poliubiquitina/química , Poliubiquitina/metabolismo , Ligação Proteica
11.
J Gen Virol ; 102(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34704922

RESUMO

Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125-241 kbp contain 70-170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae.


Assuntos
Genoma Viral , Herpesviridae , Animais , Evolução Molecular , Herpesviridae/classificação , Herpesviridae/genética , Herpesviridae/fisiologia , Herpesviridae/ultraestrutura , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/virologia , Adaptação ao Hospedeiro , Vírion/química , Vírion/ultraestrutura , Latência Viral , Replicação Viral
12.
PLoS One ; 16(10): e0258208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34614009

RESUMO

Islet transplantation is being considered as an alternative treatment for type 1 diabetes. Despite recent progress, transplant recipients continue to experience progressive loss of insulin independence. Cyanidin-3-O-Glucoside (C3G) has shown to be protective against damage that may lead to post-transplant islet loss. In this study, human islets cultured with or without C3G were treated with human amylin, Aß1-42, H2O2, or rapamycin to mimic stresses encountered in the post-transplant environment. Samples of these islets were collected and assayed to determine C3G's effect on cell viability and function, reactive oxygen species (ROS), oxidative stress, amyloid formation, and the presence of inflammatory as well as autophagic markers. C3G treatment of human islets exposed to either amylin or Aß1-42 increased cell viability (p<0.01) and inhibited amyloid formation (p<0.01). A reduction in ROS and an increase in HO-1 gene expression as well as in vitro islet function were also observed in C3G-treated islets exposed to amylin or Aß1-42, although not significantly. Additionally, treatment with C3G resulted in a significant reduction in the protein expression of inflammatory markers IL-1ß and NLRP3 (p<0.01) as well as an increase in LC3 autophagic marker (p<0.05) in human islets treated with amylin, Aß1-42, rapamycin, or H2O2. Thus, C3G appears to have a multi-faceted protective effect on human islets in vitro, possibly through its anti-oxidant property and alteration of inflammatory as well as autophagic pathways.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Antocianinas/farmacologia , Glucosídeos/farmacologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/toxicidade , Ilhotas Pancreáticas/citologia , Fragmentos de Peptídeos/toxicidade , Adulto , Idoso , Autofagia/efeitos dos fármacos , Biomarcadores/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Inflamação/patologia , Secreção de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/ultraestrutura , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Adulto Jovem
13.
Eur J Endocrinol ; 185(6): 841-854, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34643546

RESUMO

Objective: CAV1 encodes caveolin-1, a major protein of plasma membrane microdomains called caveolae, involved in several signaling pathways. Caveolin-1 is also located at the adipocyte lipid droplet. Heterozygous pathogenic variants of CAV1 induce rare heterogeneous disorders including pulmonary arterial hypertension and neonatal progeroid syndrome. Only one patient was previously reported with a CAV1 homozygous pathogenic variant, associated with congenital generalized lipodystrophy (CGL3). We aimed to further delineate genetic transmission, clinical, metabolic, and cellular characteristics of CGL3. Design/Methods: In a large consanguineous kindred referred for CGL, we performed next-generation sequencing, as well as clinical, imagery, and metabolic investigations. We studied skin fibroblasts from the index case and the previously reported patient with CGL3. Results: Four patients, aged 8 months to 18 years, carried a new homozygous p.(His79Glnfs*3) CAV1 variant. They all displayed generalized lipodystrophy since infancy, insulin resistance, low HDL-cholesterol, and/or high triglycerides, but no pulmonary hypertension. Two patients also presented at the age of 15 and 18 years with dysphagia due to achalasia, and one patient had retinitis pigmentosa. Heterozygous parents and relatives (n = 9) were asymptomatic, without any metabolic abnormality. Patients' fibroblasts showed a complete loss of caveolae and no protein expression of caveolin-1 and its caveolin-2 and cavin-1 partners. Patients' fibroblasts also displayed insulin resistance, increased oxidative stress, and premature senescence. Conclusions: The CAV1 null variant investigated herein leads to an autosomal recessive congenital lipodystrophy syndrome. Loss of caveolin-1 and/or caveolae induces specific manifestations including achalasia which requires specific management. Overlapping phenotypic traits between the different CAV1-related diseases require further studies.


Assuntos
Caveolina 1/genética , Acalasia Esofágica/genética , Lipodistrofia Generalizada Congênita/genética , Adolescente , Cavéolas/patologia , Cavéolas/ultraestrutura , Caveolina 1/metabolismo , Caveolina 2/metabolismo , Senescência Celular , Criança , Pré-Escolar , Consanguinidade , Dislipidemias/metabolismo , Acalasia Esofágica/patologia , Feminino , Fibroblastos/patologia , Fibroblastos/ultraestrutura , Homozigoto , Humanos , Lactente , Lipodistrofia Generalizada Congênita/metabolismo , Lipodistrofia Generalizada Congênita/patologia , Masculino , Microscopia Eletrônica de Transmissão , Estresse Oxidativo , Linhagem , Proteínas de Ligação a RNA/metabolismo
14.
PLoS One ; 16(10): e0257368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34613997

RESUMO

Cremation 168 from the second half of the 8th century BCE (Pithekoussai's necropolis, Ischia Island, Italy), better known as the Tomb of Nestor's Cup, is widely considered as one of the most intriguing discoveries in the Mediterranean Pre-Classic archaeology. A drinking cup, from which the Tomb's name derives, bears one of the earliest surviving examples of written Greek, representing the oldest Homeric poetry ever recovered. According to previous osteological analyses, the Cup is associated with the cremated remains of a juvenile, aged approximately 10-14 years at death. Since then, a vast body of literature has attempted to explain the unique association between the exceptionality of the grave good complex, the symposiac and erotic evocation of the Nestor's Cup inscription with the young age of the individual buried with it. This paper reconsiders previous assessments of the remains by combining gross morphology with qualitative histology and histomorphometric analyses of the burnt bone fragments. This work reveals the commingled nature of the bone assemblage, identifying for the first time, more than one human individual mixed with faunal remains. These outcomes dramatically change previous reconstructions of the cremation deposit, rewriting the answer to the question: who was buried with Nestor's Cup?.


Assuntos
Cremação/história , Adolescente , Arqueologia/história , Restos Mortais/anatomia & histologia , Restos Mortais/ultraestrutura , Osso e Ossos/anatomia & histologia , Osso e Ossos/ultraestrutura , Criança , História Antiga , Humanos , Itália
15.
Nutrients ; 13(10)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34684660

RESUMO

Decreased energy expenditure and chronically positive energy balance contribute to the prevalence of obesity and associated metabolic dysfunctions, such as dyslipidemia, hepatic fat accumulation, inflammation, and muscle mitochondrial defects. We investigated the effects of Chrysanthemum morifolium Ramat flower extract (CE) on obesity-induced inflammation and muscle mitochondria changes. Sprague-Dawley rats were randomly divided into four groups and fed either a normal diet, 45% high-fat diet (HF), HF containing 0.2% CE, or 0.4% CE for 13 weeks. CE alleviated HF-increased adipose tissue mass and size, dyslipidemia, hepatic fat deposition, and systematic inflammation, and increased energy expenditure. CE significantly decreased gene expression involved in adipogenesis, pro-inflammation, and the M1 macrophage phenotype, as well as glycerol-3-phosphate dehydrogenase (GPDH) and nuclear factor-kappa B (NF-kB) activities in epididymal adipose tissue. Moreover, CE supplementation improved hepatic fat accumulation and modulated gene expression related to fat synthesis and oxidation with an increase in adenosine monophosphate-activated protein kinase (AMPK) activity in the liver. Furthermore, CE increased muscle mitochondrial size, mitochondrial DNA (mtDNA) content, and gene expression related to mitochondrial biogenesis and function, including sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and PGC-1α-target genes, along with AMPK-SIRT1 activities in the skeletal muscle. These results suggest that CE attenuates obesity-associated inflammation by modulating the muscle AMPK-SIRT1 pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Chrysanthemum/química , Flores/química , Inflamação/tratamento farmacológico , Mitocôndrias Musculares/metabolismo , Obesidade/complicações , Extratos Vegetais/uso terapêutico , Sirtuína 1/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/patologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Tecido Adiposo Branco/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Dieta Hiperlipídica , Dislipidemias/complicações , Metabolismo Energético/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertrofia , Inflamação/etiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Mitocôndrias Musculares/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/ultraestrutura , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley
16.
BMC Plant Biol ; 21(1): 477, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670492

RESUMO

BACKGROUND: Both underground rhizomes/buds and above-ground Moso bamboo (Phyllostachys heterocycla) shoots/culms/branches are connected together into a close inter-connecting system in which nutrients are transported and shared among each organ. However, the starch storage and utilization mechanisms during bamboo shoot growth remain unclear. This study aimed to reveal in which organs starch was stored, how carbohydrates were transformed among each organ, and how the expression of key genes was regulated during bamboo shoot growth and developmental stages which should lay a foundation for developing new theoretical techniques for bamboo cultivation. RESULTS: Based on changes of the NSC content, starch metabolism-related enzyme activity and gene expression from S0 to S3, we observed that starch grains were mainly elliptical in shape and proliferated through budding and constriction. Content of both soluble sugar and starch in bamboo shoot peaked at S0, in which the former decreased gradually, and the latter initially decreased and then increased as shoots grew. Starch synthesis-related enzymes (AGPase, GBSS and SBE) and starch hydrolase (α-amylase and ß-amylase) activities exhibited the same dynamic change patterns as those of the starch content. From S0 to S3, the activity of starch synthesis-related enzyme and starch amylase in bamboo rhizome was significantly higher than that in bamboo shoot, while the NSC content in rhizomes was obviously lower than that in bamboo shoots. It was revealed by the comparative transcriptome analysis that the expression of starch synthesis-related enzyme-encoding genes were increased at S0, but reduced thereafter, with almost the same dynamic change tendency as the starch content and metabolism-related enzymes, especially during S0 and S1. It was revealed by the gene interaction analysis that AGPase and SBE were core genes for the starch and sucrose metabolism pathway. CONCLUSIONS: Bamboo shoots were the main organ in which starch was stored, while bamboo rhizome should be mainly functioned as a carbohydrate transportation channel and the second carbohydrate sink. Starch metabolism-related genes were expressed at the transcriptional level during underground growth, but at the post-transcriptional level during above-ground growth. It may be possible to enhance edible bamboo shoot quality for an alternative starch source through genetic engineering.


Assuntos
Metabolismo dos Carboidratos/genética , Proteínas de Plantas/metabolismo , Poaceae/genética , Amido/metabolismo , Transcriptoma , Enzima Ramificadora de 1,4-alfa-Glucana/genética , Enzima Ramificadora de 1,4-alfa-Glucana/metabolismo , Amilases/genética , Amilases/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/fisiologia , Brotos de Planta/ultraestrutura , Poaceae/crescimento & desenvolvimento , Poaceae/fisiologia , Poaceae/ultraestrutura , Rizoma/genética , Rizoma/crescimento & desenvolvimento , Rizoma/fisiologia , Rizoma/ultraestrutura
17.
Sci Rep ; 11(1): 20295, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645849

RESUMO

Novel SARS-CoV-2, an etiological factor of Coronavirus disease 2019 (COVID-19), poses a great challenge to the public health care system. Among other druggable targets of SARS-Cov-2, the main protease (Mpro) is regarded as a prominent enzyme target for drug developments owing to its crucial role in virus replication and transcription. We pursued a computational investigation to identify Mpro inhibitors from a compiled library of natural compounds with proven antiviral activities using a hierarchical workflow of molecular docking, ADMET assessment, dynamic simulations and binding free-energy calculations. Five natural compounds, Withanosides V and VI, Racemosides A and B, and Shatavarin IX, obtained better binding affinity and attained stable interactions with Mpro key pocket residues. These intermolecular key interactions were also retained profoundly in the simulation trajectory of 100 ns time scale indicating tight receptor binding. Free energy calculations prioritized Withanosides V and VI as the top candidates that can act as effective SARS-CoV-2 Mpro inhibitors.


Assuntos
COVID-19/tratamento farmacológico , Proteases 3C de Coronavírus/metabolismo , Compostos Fitoquímicos/farmacologia , Antivirais/farmacologia , Biologia Computacional/métodos , Proteases 3C de Coronavírus/efeitos dos fármacos , Proteases 3C de Coronavírus/ultraestrutura , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Simulação de Acoplamento Molecular/métodos , Simulação de Dinâmica Molecular , Peptídeo Hidrolases/efeitos dos fármacos , Compostos Fitoquímicos/metabolismo , Inibidores de Proteases/farmacologia , Ligação Proteica/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade
18.
Nat Commun ; 12(1): 6042, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654813

RESUMO

Centriole biogenesis and maintenance are crucial for cells to generate cilia and assemble centrosomes that function as microtubule organizing centers (MTOCs). Centriole biogenesis and MTOC function both require the microtubule nucleator γ-tubulin ring complex (γTuRC). It is widely accepted that γTuRC nucleates microtubules from the pericentriolar material that is associated with the proximal part of centrioles. However, γTuRC also localizes more distally and in the centriole lumen, but the significance of these findings is unclear. Here we identify spatially and functionally distinct subpopulations of centrosomal γTuRC. Luminal localization is mediated by augmin, which is linked to the centriole inner scaffold through POC5. Disruption of luminal localization impairs centriole integrity and interferes with cilium assembly. Defective ciliogenesis is also observed in γTuRC mutant fibroblasts from a patient suffering from microcephaly with chorioretinopathy. These results identify a non-canonical role of augmin-γTuRC in the centriole lumen that is linked to human disease.


Assuntos
Proteínas de Ciclo Celular/isolamento & purificação , Proteínas de Ciclo Celular/metabolismo , Centríolos/metabolismo , Proteínas Associadas aos Microtúbulos/isolamento & purificação , Proteínas Associadas aos Microtúbulos/metabolismo , Centro Organizador dos Microtúbulos/metabolismo , Animais , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/ultraestrutura , Linhagem Celular , Centríolos/ultraestrutura , Centrossomo/metabolismo , Centrossomo/ultraestrutura , Cílios , Feminino , Humanos , Masculino , Camundongos , Proteínas Associadas aos Microtúbulos/ultraestrutura , Centro Organizador dos Microtúbulos/ultraestrutura , Microtúbulos/metabolismo , Neurônios
19.
Nat Commun ; 12(1): 5922, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635666

RESUMO

Death from acute hemorrhage is a major problem in military conflicts, traffic accidents, and surgical procedures, et al. Achieving rapid effective hemostasis for pre-hospital care is essential to save lives in massive bleeding. An ideal hemostasis material should have those features such as safe, efficient, convenient, economical, which remains challenging and most of them cannot be achieved at the same time. In this work, we report a rapid effective nanoclay-based hemostatic membranes with nanoclay particles incorporate into polyvinylpyrrolidone (PVP) electrospun fibers. The nanoclay electrospun membrane (NEM) with 60 wt% kaolinite (KEM1.5) shows better and faster hemostatic performance in vitro and in vivo with good biocompatibility compared with most other NEMs and clay-based hemostats, benefiting from its enriched hemostatic functional sites, robust fluffy framework, and hydrophilic surface. The robust hemostatic bandages based on nanoclay electrospun membrane is an effective candidate hemostat in practical application.


Assuntos
Bandagens , Hemorragia/tratamento farmacológico , Hemostáticos/farmacologia , Caulim/farmacologia , Nanoestruturas/química , Ferida Cirúrgica/tratamento farmacológico , Animais , Argila/química , Modelos Animais de Doenças , Hemorragia/sangue , Hemorragia/patologia , Hemostasia/efeitos dos fármacos , Hemostáticos/química , Humanos , Caulim/química , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/lesões , Masculino , Nanoestruturas/administração & dosagem , Nanoestruturas/ultraestrutura , Povidona/química , Povidona/farmacologia , Ratos , Ratos Sprague-Dawley , Baço/irrigação sanguínea , Baço/efeitos dos fármacos , Baço/lesões , Ferida Cirúrgica/sangue , Ferida Cirúrgica/patologia
20.
Nat Commun ; 12(1): 5933, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635670

RESUMO

GTPases are regulators of cell signaling acting as molecular switches. The translational GTPase EF-G stands out, as it uses GTP hydrolysis to generate force and promote the movement of the ribosome along the mRNA. The key unresolved question is how GTP hydrolysis drives molecular movement. Here, we visualize the GTPase-powered step of ongoing translocation by time-resolved cryo-EM. EF-G in the active GDP-Pi form stabilizes the rotated conformation of ribosomal subunits and induces twisting of the sarcin-ricin loop of the 23 S rRNA. Refolding of the GTPase switch regions upon Pi release initiates a large-scale rigid-body rotation of EF-G pivoting around the sarcin-ricin loop that facilitates back rotation of the ribosomal subunits and forward swiveling of the head domain of the small subunit, ultimately driving tRNA forward movement. The findings demonstrate how a GTPase orchestrates spontaneous thermal fluctuations of a large RNA-protein complex into force-generating molecular movement.


Assuntos
Escherichia coli/genética , Fator G para Elongação de Peptídeos/química , Biossíntese de Proteínas , RNA Mensageiro/química , RNA Ribossômico 23S/química , RNA de Transferência/química , Ribossomos/metabolismo , Sítios de Ligação , Fenômenos Biomecânicos , Microscopia Crioeletrônica , Escherichia coli/metabolismo , Guanosina Trifosfato/química , Guanosina Trifosfato/metabolismo , Hidrólise , Cinética , Modelos Moleculares , Fator G para Elongação de Peptídeos/genética , Fator G para Elongação de Peptídeos/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Dobramento de Proteína , Domínios e Motivos de Interação entre Proteínas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Ribossômico 23S/genética , RNA Ribossômico 23S/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Ribossomos/ultraestrutura , Termodinâmica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...