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1.
J Bone Jt Infect ; 7(4): 163-167, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032800

RESUMO

We present the rare case of a 61-year-old female with Mycobacterium fortuitum osteomyelitis of the cuboid bone following penetrating plantar trauma. The patient underwent a single-stage surgery for the condition, including lesion debridement and bone defect filling with absorbable, gentamicin-/vancomycin-loaded, calcium sulfate-hydroxyapatite biocomposites, that resolved favorably 5 months after intervention.

2.
Nat Cell Biol ; 24(6): 896-905, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35681009

RESUMO

Mechanical force controls fundamental cellular processes in health and disease, and increasing evidence shows that the nucleus both experiences and senses applied forces. Such forces can lead to the nuclear translocation of proteins, but whether force controls nucleocytoplasmic transport, and how, remains unknown. Here we show that nuclear forces differentially control passive and facilitated nucleocytoplasmic transport, setting the rules for the mechanosensitivity of shuttling proteins. We demonstrate that nuclear force increases permeability across nuclear pore complexes, with a dependence on molecular weight that is stronger for passive than for facilitated diffusion. Owing to this differential effect, force leads to the translocation of cargoes into or out of the nucleus within a given range of molecular weight and affinity for nuclear transport receptors. Further, we show that the mechanosensitivity of several transcriptional regulators can be both explained by this mechanism and engineered exogenously by introducing appropriate nuclear localization signals. Our work unveils a mechanism of mechanically induced signalling, probably operating in parallel with others, with potential applicability across signalling pathways.


Assuntos
Núcleo Celular , Poro Nuclear , Transporte Ativo do Núcleo Celular/fisiologia , Núcleo Celular/metabolismo , Poro Nuclear/genética , Poro Nuclear/metabolismo , Transporte Proteico , Receptores Citoplasmáticos e Nucleares/metabolismo
3.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281276

RESUMO

Extracellular vesicles (EVs) are membranous, rounded vesicles released by prokaryotic and eukaryotic cells in their normal and pathophysiological states. These vesicles form a network of intercellular communication as they can transfer cell- and function-specific information (lipids, proteins and nucleic acids) to different cells and thus alter their function. Fungi are not an exception; they also release EVs to the extracellular space. The vesicles can also be retained in the periplasm as periplasmic vesicles (PVs) and the cell wall. Such fungal vesicles play various specific roles in the lives of these organisms. They are involved in creating wall architecture and maintaining its integrity, supporting cell isolation and defence against the environment. In the case of pathogenic strains, they might take part in the interactions with the host and affect the infection outcomes. The economic importance of fungi in manufacturing high-quality nutritional and pharmaceutical products and in remediation is considerable. The analysis of fungal EVs opens new horizons for diagnosing fungal infections and developing vaccines against mycoses and novel applications of nanotherapy and sensors in industrial processes.


Assuntos
Vesículas Extracelulares/fisiologia , Fungos/fisiologia , Transporte Biológico Ativo , Vesículas Extracelulares/genética , Vesículas Extracelulares/imunologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Fungos/genética , Fungos/patogenicidade , Genes Fúngicos , Interações entre Hospedeiro e Microrganismos/imunologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Modelos Biológicos , Micoses/diagnóstico , Micoses/microbiologia , RNA Fúngico/genética , RNA Fúngico/metabolismo
4.
Biochemistry ; 56(31): 4029-4038, 2017 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-28703578

RESUMO

Transfer RNAs (tRNAs) are among the most heavily modified RNA species. Posttranscriptional tRNA modifications (ptRMs) play fundamental roles in modulating tRNA structure and function and are being increasingly linked to human physiology and disease. Detection of ptRMs is often challenging, expensive, and laborious. Restriction fragment length polymorphism (RFLP) analyses study the patterns of DNA cleavage after restriction enzyme treatment and have been used for the qualitative detection of modified bases on mRNAs. It is known that some ptRMs induce specific and reproducible base "mutations" when tRNAs are reverse transcribed. For example, inosine, which derives from the deamination of adenosine, is detected as a guanosine when an inosine-containing tRNA is reverse transcribed, amplified via polymerase chain reaction (PCR), and sequenced. ptRM-dependent base changes on reverse transcription PCR amplicons generated as a consequence of the reverse transcription reaction might create or abolish endonuclease restriction sites. The suitability of RFLP for the detection and/or quantification of ptRMs has not been studied thus far. Here we show that different ptRMs can be detected at specific sites of different tRNA types by RFLP. For the examples studied, we show that this approach can reliably estimate the modification status of the sample, a feature that can be useful in the study of the regulatory role of tRNA modifications in gene expression.


Assuntos
Adenosina Desaminase/metabolismo , Modelos Biológicos , Polimorfismo de Fragmento de Restrição , Processamento Pós-Transcricional do RNA , RNA de Transferência de Alanina/metabolismo , RNA de Transferência de Treonina/metabolismo , Adenosina/metabolismo , Adenosina Desaminase/química , Adenosina Desaminase/genética , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Pareamento de Bases , Biologia Computacional , Desaminação , Sistemas Inteligentes , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Inosina/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , RNA de Transferência de Alanina/antagonistas & inibidores , RNA de Transferência de Treonina/antagonistas & inibidores , RNA de Transferência de Valina/antagonistas & inibidores , RNA de Transferência de Valina/metabolismo , Transcrição Reversa , Especificidade por Substrato
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