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1.
J Neurosurg ; : 1-14, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39241254

RESUMO

OBJECTIVE: An anatomical taxonomy has been established to guide surgical approach selection for resecting brainstem and deep and superficial cerebral cavernous malformations (CMs). The authors propose a novel taxonomy for cerebellar CMs, introduce 6 distinct neuroanatomical subtypes, and assess their clinical outcomes. METHODS: This bi-institutional, 2-surgeon cohort study included 143 cerebellar CMs that were microsurgically treated over a 25-year period. The proposed taxonomy classifies cerebellar CMs into 6 subtypes on the basis of anatomical location as identified on preoperative MR imaging. Neurological outcomes were assessed using the modified Rankin Scale (mRS), and outcomes were compared among the subtypes, with favorable outcomes defined as mRS scores ≤ 2. RESULTS: A total of 143 cerebellar CMs were resected in 140 patients. The mean (SD) age was 42.3 (15.2) years; 86 (60%) of the cerebellar CMs were in women, and 57 (40%) were in men. Cerebellar subtypes were suboccipital (17%, 25/143); tentorial (9%, 13/143); petrosal (43%, 62/143); vermian (13%, 18/143); tonsillar (2%, 3/143); and deep nuclear (15%, 22/143). Overall, 78 of 143 (55%) cerebellar CMs presenting to a cerebellar surface were resected without tissue transgression, and the remaining CMs (65/143, 45%) required translobular or transsulcal approaches. Complete resection was achieved in 134 of 143 cases (94%). Favorable outcomes were achieved in 91% (129/141) of cases with follow-up at a mean (SD) follow-up duration of 37.4 (53.8) months. Relative outcomes were unchanged or improved relative to the preoperative baseline in 93% (131/141) of cases with follow-up, without differences between subtypes. CONCLUSIONS: Most cerebellar CMs are convexity lesions that do not require deep dissection. However, transsulcal and fissural approaches are used for those beneath the cerebellar surface to minimize tissue transgression and preserve associated function. Complete resection without any new deficit is accomplished in most patients. The proposed taxonomy for cerebellar CMs (suboccipital, tentorial, petrosal, vermian, tonsillar, and deep nuclear) guides the selection of craniotomy and approach to enhance patient safety and optimize neurological outcomes.

2.
Cell Rep ; 38(7): 110361, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35172143

RESUMO

Many lncRNAs have been discovered using transcriptomic data; however, it is unclear what fraction of lncRNAs is functional and what structural properties affect their phenotype. MUNC lncRNA (also known as DRReRNA) acts as an enhancer RNA for the Myod1 gene in cis and stimulates the expression of other promyogenic genes in trans by recruiting the cohesin complex. Here, experimental probing of the RNA structure revealed that MUNC contains multiple structural domains not detected by prediction algorithms in the absence of experimental information. We show that these specific and structurally distinct domains are required for induction of promyogenic genes, for binding genomic sites and gene expression regulation, and for binding the cohesin complex. Myod1 induction and cohesin interaction comprise only a subset of MUNC phenotype. Our study reveals unexpectedly complex, structure-driven functions for the MUNC lncRNA and emphasizes the importance of experimentally determined structures for understanding structure-function relationships in lncRNAs.


Assuntos
Desenvolvimento Muscular/genética , RNA Longo não Codificante/metabolismo , Transcrição Gênica , Animais , Sequência de Bases , Diferenciação Celular/genética , Linhagem Celular , Feminino , Genoma , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Conformação de Ácido Nucleico , Fenótipo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Longo não Codificante/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Deleção de Sequência
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