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1.
Int J Surg Pathol ; : 10668969231213983, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38018140

RESUMO

Testicular sex cord-stromal tumors are clonal neoplasms, with the majority being of Leydig cell followed by Sertoli cell origins. In Leydig cell tumors, adipocytic differentiation has been previously reported as a possible distinguishing feature, which has not been reported in other sex cord-stromal tumors. Herein, we report a case of a 48-year-old man who presented with an incidentally discovered 1.1 cm testicular mass, for which he underwent partial orchiectomy. Microscopically, the tumor showed features consistent with sex cord-stromal tumor with strong and diffuse nuclear and cytoplasmic reaction for B-catenin immunohistochemistry, supporting the diagnosis of Sertoli cell tumor. A novel adipocytic differentiation, reported previously in Leydig cell tumors, was present in this tumor.

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.
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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