Multiple roles for hypoxia inducible factor 1-alpha in airway epithelial cells during mucormycosis.

During pulmonary mucormycosis, inhaled sporangiospores adhere to, germinate, and invade airway epithelial cells to establish infection. We provide evidence that HIF1α plays dual roles in airway epithelial cells during Mucorales infection. We observed an increase in HIF1α protein accumulation and increased expression of many known HIF1α-responsive genes during in vitro infection, indicating that HIF1α signaling is activated by Mucorales infection. Inhibition of HIF1α signaling led to a substantial decrease in the ability of R. delemar to invade cultured airway epithelial cells. Transcriptome analysis revealed that R. delemar infection induces the expression of many pro-inflammatory genes whose expression was significantly reduced by HIF1α inhibition. Importantly, pharmacological inhibition of HIF1α increased survival in a mouse model of pulmonary mucormycosis without reducing fungal burden. These results suggest that HIF1α plays two opposing roles during mucormycosis: one that facilitates the ability of Mucorales to invade the host cells and one that facilitates the ability of the host to mount an innate immune response.

A Contemporary Framework Update for Today's School Nursing Landscape: Introducing the School Nursing Practice Framework™.

School nursing is a unique nursing specialty that benefits from a practice framework that aids school nurses in explaining and accomplishing their role. In 2016, the NASN debuted its Framework for 21st Century School Nursing Practice™, which has shaped school nursing practice as well as education, leadership, research, and collaboration with stakeholders. However, practice frameworks are not meant to remain the same indefinitely. Therefore, NASN evaluated and updated the Framework to ensure its continued alignment with the education and healthcare landscape. The purpose of this article is to share the history of the Framework for 21st Century School Nursing Practice™ development, provide the rationale for the update, and discuss the strategic process NASN used to update its Framework now entitled the School Nursing Practice Framework™.

Common analysis of direct RNA sequencinG CUrrently leads to misidentification of m5C at GCU motifs.

RNA modifications, such as methylation, can be detected with Oxford Nanopore Technologies direct RNA sequencing. One commonly used tool for detecting 5-methylcytosine (m5C) modifications is Tombo, which uses an "Alternative Model" to detect putative modifications from a single sample. We examined direct RNA sequencing data from diverse taxa including viruses, bacteria, fungi, and animals. The algorithm consistently identified a m5C at the central position of a GCU motif. However, it also identified a m5C in the same motif in fully unmodified in vitro transcribed RNA, suggesting that this is a frequent false prediction. In the absence of further validation, several published predictions of m5C in a GCU context should be reconsidered, including those from human coronavirus and human cerebral organoid samples.