The Arf-GEF GBF1 undergoes multi-domain structural shifts to activate Arf at the Golgi

Golgi homeostasis require the activation of Arf GTPases by the guanine-nucleotide exchange factor requires GBF1, whose recruitment to the Golgi represents a rate limiting step in the process. GBF1 contains a conserved, catalytic, Sec7 domain (Sec7d) and five additional (DCB, HUS, HDS1-3) domains. Herein, we identify the HDS3 domain as essential for GBF1 membrane association in mammalian cells and document the critical role of HDS3 during the development of Drosophila melanogaster. We show that upon binding to Golgi membranes, GBF1 undergoes conformational changes in regions bracketing the catalytic Sec7d. We illuminate GBF1 interdomain arrangements by negative staining electron microscopy of full-length human GBF1 to show that GBF1 forms an anti-parallel dimer held together by the paired central DCB-HUS core, with two sets of HDS1-3 arms extending outward in opposite directions. The catalytic Sec7d protrudes from the central core as a largely independent domain, but is closely opposed to a previously unassigned α-helix from the HDS1 domain. Based on our data, we propose models of GBF1 engagement on the membrane to provide a paradigm for understanding GBF1-mediated Arf activation required for cellular and organismal function

Nurses and Midwives in the Digital Age

This follow-up survey on trends in Nursing Informatics (NI) was conducted by the International Medical Informatics Association (IMIA) Student and Emerging Professionals (SEP) group as a cross-sectional study in 2019. There were 455 responses from 24 countries. Based on the findings NI research is evolving rapidly. Current ten most common trends include: clinical quality measures, clinical decision support, big data, artificial intelligence, care coordination, education and competencies, patient safety, mobile health, description of nursing practices and evaluation of patient outcomes. The findings help support the efforts to efficiently use resources in the promotion of health care activities, to support the development of informatics education and to grow NI as a profession.</p

Identification and comparison of missed nursing care in the United States of America and South Korea

Aims and objectivesThis study aimed to identify and compare missed nursing care types and reasons between South Korea and the United States of America.BackgroundPatient safety has become a significant task of the healthcare delivery systems worldwide. The omission of nursing care constitutes a growing concern because it threatens both patient safety and nursing care quality.DesignThis study used a cross‐sectional, descriptive and comparative design.MethodsData were collected from registered nurses working in two university‐affiliated tertiary hospitals and a general hospital in Korea and a Midwest United States tertiary hospital. In addition, the STROBE checklist was used in this study.ResultsWhile substantial, the level of missed nursing care reported by Korean nurses was lower than that of United States nurses. Only three nursing care activities, setting up meals, patient assessment and skin/wound care, did not significantly differed between two countries. More basic nursing care types such as ambulation, feeding and mouth care were missed more than others in both countries. The reasons for missed care differed between two countries. However, both Korean and US nurses reported labour resource problems as reasons for missed care.ConclusionsAlthough the types of missed nursing care differed significantly between countries, both Korean and US nurses reported labour resource problems for the top reasons for missed care. Thus, comparing missed nursing care could assist nursing administrators in developing strategies to improve care quality and patient safety.Relevance to clinical practiceThe level and reasons for missed nursing care are very influential factors for patient outcomes and patient safety. Appropriate skill mix and staffing are needed to decrease extent of missed care, so that enhancing patient safety and quality of nursing care.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167810/1/jocn15712_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167810/2/jocn15712.pd

18F-FDG PET findings in frontotemporal dementia: an SPM analysis of 29 patients

Frontotemporal dementia (FTD) is a common cause of presenile dementia. The aim of the current study was 2-fold: (a) to delineate the brain regions with reduction of glucose metabolism, and (b) to investigate the hemispheric asymmetry of glucose metabolism in FTD using (18)F-FDG PET. METHODS: We compared the regional metabolic patterns on (18)F-FDG PET images obtained from 29 patients with FTD and 11 healthy subjects using a voxel-wise analysis (statistical parametric mapping [SPM]). The hemispheric asymmetry of glucose metabolism was computed based on 2 different measures: one (AI(ROI)) by counting the (18)F-FDG activity of each hemisphere on the normalized and spatially smoothed PET images and the other (AI(SPM)) by counting the number of voxels with significant hypometabolism based on SPM results. RESULTS: Significant hypometabolism was identified in extensive prefrontal areas, cingulate gyri, anterior temporal regions, and the left inferior parietal lobule. Hypometabolism was also found in the bilateral insula and uncus, left putamen and globus pallidus, and medial thalamic structures. Frontal hypometabolism was more prominent in the left hemisphere than in the right. Twenty-six (90%) of the 29 patients with FTD had AI(ROI) values indicating significant lateralization of glucose metabolism; 18 patients had hypometabolism more severe on the left than right side, and only 8 patients had the opposite pattern. Results from AI(SPM) showed similar patterns. CONCLUSION: The voxel-wise analysis of (18)F-FDG PET images of patients with FTD revealed hypometabolism in extensive cortical regions, such as frontal and anterior temporal areas, cingulate gyri, uncus, and insula and subcortical areas, including basal ganglia (putamen and globus pallidus) and medial thalamic regions. The hemispheric asymmetry of hypometabolism (more frequently lateralized to the left) was common in patients with FTD, which may be another metabolic feature that helps to differentiate FTD from Alzheimer's disease or other causes of dementia

Site-specific phosphorylations of the Arf activator GBF1 differentially regulate GBF1 function in Golgi homeostasis and secretion versus cytokinesis

Abstract Diverse cellular processes, including membrane traffic, lipid homeostasis, cytokinesis, mitochondrial positioning, and cell motility are critically dependent on the Sec7 domain guanine nucleotide exchange factor GBF1. Yet, how the participation of GBF1 in a particular cellular function is regulated is unknown. Here, we show that the phosphorylation of specific highly conserved serine and tyrosine residues within the N-terminal domain of GBF1 differentially regulates its function in maintaining Golgi homeostasis and facilitating secretion versus its role in cytokinesis. Specifically, GBF1 mutants containing single amino acid substitutions that mimic a stably phosphorylated S233, S371, Y377, and Y515 or the S233A mutant that can’t be phosphorylated are fully able to maintain Golgi architecture and support cargo traffic through the secretory pathway when assessed in multiple functional assays. However, the same mutants cause multi-nucleation when expressed in cells, and appear to inhibit the progression through mitosis and the resolution of cytokinetic bridges. Thus, GBF1 participates in distinct interactive networks when mediating Golgi homeostasis and secretion versus facilitating cytokinesis, and GBF1 integration into such networks is differentially regulated by the phosphorylation of specific GBF1 residues

Determinants of nurse absenteeism and intent to leave: An international study.

To access publisher's full text version of this article click on the hyperlink belowTo determine factors associated with nurses' intent to leave their positions and absenteeism. There is a recognized global shortage of nurses but limited data describing and determining factors associated with nurse absenteeism and intent to leave. This study involved a secondary analysis of the results from direct-care registered nurses' responses to the MISSCARE Survey, with data from seven countries included. Multi-level modelling was used to determine nurse characteristics and working environment factors associated with nurse absenteeism and intent to leave. The level of absenteeism and intent to leave varied significantly across countries, with registered nurses in Lebanon reporting the highest intention to leave within 12 months (43%) and registered nurses in Iceland and Australia the highest level of absenteeism (74% and 73%, respectively). Factors associated with outcomes included perceived staffing adequacy of unit, job satisfaction, and age of the nurse