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2.
Nature ; 552(7684): 239-243, 2017 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-29186120

RESUMO

The foundations of mammalian development lie in a cluster of embryonic epiblast stem cells. In response to extracellular matrix signalling, these cells undergo epithelialization and create an apical surface in contact with a cavity, a fundamental event for all subsequent development. Concomitantly, epiblast cells transit through distinct pluripotent states, before lineage commitment at gastrulation. These pluripotent states have been characterized at the molecular level, but their biological importance remains unclear. Here we show that exit from an unrestricted naive pluripotent state is required for epiblast epithelialization and generation of the pro-amniotic cavity in mouse embryos. Embryonic stem cells locked in the naive state are able to initiate polarization but fail to undergo lumenogenesis. Mechanistically, exit from naive pluripotency activates an Oct4-governed transcriptional program that results in expression of glycosylated sialomucin proteins and the vesicle tethering and fusion events of lumenogenesis. Similarly, exit of epiblasts from naive pluripotency in cultured human post-implantation embryos triggers amniotic cavity formation and developmental progression. Our results add tissue-level architecture as a new criterion for the characterization of different pluripotent states, and show the relevance of transitions between these states during development of the mammalian embryo.


Assuntos
Embrião de Mamíferos/citologia , Morfogênese , Células-Tronco Pluripotentes/citologia , Âmnio/citologia , Animais , Padronização Corporal , Colágeno , Combinação de Medicamentos , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Camadas Germinativas/citologia , Glicosilação , Células-Tronco Embrionárias Humanas/citologia , Humanos , Laminina , Masculino , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Fator 3 de Transcrição de Octâmero/metabolismo , Proteoglicanas , Sialomucinas/metabolismo , Esferoides Celulares/citologia
3.
J Intensive Care Soc ; 22(4): 319-327, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35154370

RESUMO

BACKGROUND: Using a dextrose-containing solution, instead of normal saline, to maintain the patency of an arterial cannula results in the admixture of glucose in line samples. This can misguide the clinician down an inappropriate treatment pathway for hyperglycaemia. METHODS: Following a near-miss and subsequent educational and training efforts at our institution, we conducted two simulations: (1) to observe whether 20 staff would identify a 5% dextrose/0.9% saline flush solution as the cause for a patient's refractory hyperglycaemia, and (2) to compare different arterial line sampling techniques for glucose contamination. RESULTS: (1) Only 2/20 participants identified the incorrect dextrose-containing flush solution, with the remainder choosing to escalate insulin therapy to levels likely to risk fatality, and (2) glucose contamination occurred regardless of sampling technique. CONCLUSION: Despite national guidance and local educational efforts, this is still an under-recognised error. Operator-focussed preventative strategies have not been effective and an engineered solution is needed.

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