3,232 research outputs found
Multifunctional Structural Supercapacitor Composites Based on Carbon Aerogel Modified High Performance Carbon Fiber Fabric
It is well documented that bedrest has adverse outcomes for hospitalized patients. This is especially true for critically ill patients due to life support measures, invasive catheters, and mechanical ventilation. Consequences associated with bedrest in critical care patients include venous thromboembolism, ventilator associated pneumonia, pressure ulcer development, and muscle weakness. Respiratory muscle weakness is associated with prolonged ventilator support and delayed extubation. The Awakening and Breathing Coordination, Delirium Monitoring and Management, and Early Mobility (ABCDE) bundle uses evidence based practice to prevent and treat ICU acquired delirium and weakness. The bundle aims to do this by standardizing care processes in collaboration with the ICU team to promote early mobility in ventilated patients. The purpose of this research study was to determine if the implementation of an early mobility protocol decreased the number of ventilator days for patients who receive mechanical ventilation. A retrospective chart review was conducted at a 16 bed ICU. Group A included 30 subjects (n=30) who were treated pre implementation of the ABCDE bundle and Group B included 39 (n=39) subjects who were treated post implementation of the ABCDE bundle. There were less average ventilator days found in Group A in comparison to Group B. Additionally, there was a significant difference found in the ICU length of stay pre implementation (M=9.4, SD=4.4) and post implementation (M=5.7, SD=2.6) of the ABCDE bundle for early mobility, t (65) =4.3, p = 0.00005. The APRN can use the evidence in the ABCDE bundle to guide care to critically ill patients that are mechanically ventilated. Utilizing the ABCDE bundle additionally allows the APRN to be instrumental in improving patient outcomes through interdisciplinary collaboration
Ceramide synthase TLCD3B is a novel gene associated with human recessive retinal dystrophy
PURPOSE: Previous studies suggest that ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. However, no pathogenic variant in ceramide synthases has been identified in human patients and knockout of various ceramide synthases in mice has not led to photoreceptor degeneration. METHODS: Exome sequencing was used to identify candidate disease genes in patients with vision loss as confirmed by standard evaluation methods, including electroretinography (ERG) and optical coherence tomography. The vision loss phenotype in mice was evaluated by ERG and histological analyses. RESULTS: Here we have identified four patients with cone-rod dystrophy or maculopathy from three families carrying pathogenic variants in TLCD3B. Consistent with the phenotype observed in patients, the Tlcd3bKO/KO mice exhibited a significant reduction of the cone photoreceptor light responses, thinning of the outer nuclear layer, and loss of cone photoreceptors across the retina. CONCLUSION: Our results provide a link between loss-of-function variants in a ceramide synthase gene and human retinal dystrophy. Establishment of the Tlcd3b knockout murine model, an in vivo photoreceptor cell degeneration model due to loss of a ceramide synthase, will provide a unique opportunity in probing the role of ceramide in survival and function of photoreceptor cells
A novel class of microRNA-recognition elements that function only within open reading frames.
MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells
Nature of protein family signatures: Insights from singular value analysis of position-specific scoring matrices
Position-specific scoring matrices (PSSMs) are useful for detecting weak
homology in protein sequence analysis, and they are thought to contain some
essential signatures of the protein families. In order to elucidate what kind
of ingredients constitute such family-specific signatures, we apply singular
value decomposition to a set of PSSMs and examine the properties of dominant
right and left singular vectors. The first right singular vectors were
correlated with various amino acid indices including relative mutability, amino
acid composition in protein interior, hydropathy, or turn propensity, depending
on proteins. A significant correlation between the first left singular vector
and a measure of site conservation was observed. It is shown that the
contribution of the first singular component to the PSSMs act to disfavor
potentially but falsely functionally important residues at conserved sites. The
second right singular vectors were highly correlated with hydrophobicity
scales, and the corresponding left singular vectors with contact numbers of
protein structures. It is suggested that sequence alignment with a PSSM is
essentially equivalent to threading supplemented with functional information.
The presented method may be used to separate functionally important sites from
structurally important ones, and thus it may be a useful tool for predicting
protein functions.Comment: 22 pages, 7 figures, 4 table
Application of Inelastic Neutron Scattering to the Methanol-to-Gasoline Reaction Over a ZSM-5 Catalyst
Inelastic neutron scattering (INS) is used to investigate a ZSM-5 catalyst that has been exposed to methanol vapour at elevated temperature. In-line mass spectrometric analysis of the catalyst exit stream confirms methanol-to-gasoline chemistry, whilst ex situ INS measurements detect hydrocarbon species formed in/on the catalyst during methanol conversion. These preliminary studies demonstrate the capability of INS to complement infrared spectroscopic characterisation of the hydrocarbon pool present in/on ZSM-5 during the MTG reaction
Iron and risk of dementia: Mendelian randomisation analysis in UK Biobank
This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData availability statement:
Results are available in a public, open access repository. Access to UK Biobank participant level data requires application. UKB data are available to any bone fide researcher following application (https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access). Summary statistics for these GWAS are available to download from FigShare (DOI 10.6084/m9.figshare.21828498).Background Brain iron deposition is common in dementia, but whether serum iron is a causal risk factor is unknown. We aimed to determine whether genetic predisposition to higher serum iron status biomarkers increased risk of dementia and atrophy of grey matter.
Methods We analysed UK Biobank participants clustered into European (N=451284), African (N=7477) and South Asian (N=9570) groups by genetic similarity to the 1000 genomes project. Using Mendelian randomisation methods, we estimated the association between genetically predicted serum iron (transferrin saturation [TSAT] and ferritin), grey matter volume and genetic liability to clinically defined dementia (including Alzheimer’s disease [AD], non-AD dementia, and vascular dementia) from hospital and primary care records. We also performed time-to-event (competing risks) analysis of the TSAT polygenic score on risk of clinically defined non-AD dementia.
Results In Europeans, higher genetically predicted TSAT increased genetic liability to dementia (Odds Ratio [OR]: 1.15, 95% Confidence Intervals [CI] 1.04 to 1.26, p=0.0051), non-AD dementia (OR: 1.27, 95% CI 1.12 to 1.45, p=0.00018) and vascular dementia (OR: 1.37, 95% CI 1.12 to 1.69, p=0.0023), but not AD (OR: 1.00, 95% CI 0.86 to 1.15, p=0.97). Higher TSAT was also associated with increased risk of non-AD dementia in participants of African, but not South Asian groups. In survival analysis using a TSAT polygenic score, the effect was independent of apolipoprotein-E ε4 genotype (with adjustment subdistribution Hazard Ratio: 1.74, 95% CI 1.33 to 2.28, p=0.00006). Genetically predicted TSAT was associated with lower grey matter volume in caudate, putamen and thalamus, and not in other areas of interest.
Discussion Genetic evidence supports a causal relationship between higher TSAT and risk of clinically defined non-AD and vascular dementia, in European and African groups. This association appears to be independent of apolipoprotein-E ε4.National Institute for Health and Care Research (NIHR
Imaging of ependymomas: MRI and CT
The imaging features of intracranial and spinal ependymoma are reviewed with an emphasis on conventional magnetic resonance imaging (MRI), perfusion MRI and proton magnetic resonance spectroscopy, and computed tomography. Imaging manifestations of leptomeningeal dissemination of disease are described. Finally, salient imaging features obtained in the postoperative period to evaluate completeness of surgical resection, and thereafter for long-term surveillance for disease recurrence, are reviewed
GABAB Receptor Subunit GB1 at the Cell Surface Independently Activates ERK1/2 through IGF-1R Transactivation
BACKGROUND: Functional GABA(B) receptor is believed to require hetero-dimerization between GABA(B1) (GB1) and GABA(B2) (GB2) subunits. The GB1 extracellular domain is required for ligand binding, and the GB2 trans-membrane domain is responsible for coupling to G proteins. Atypical GABA(B) receptor responses observed in GB2-deficient mice suggested that GB1 may have activity in the absence of GB2. However the underlying mechanisms remain poorly characterized. METHODOLOGY/PRINCIPAL FINDINGS: Here, by using cells overexpressing a GB1 mutant (GB1asa) with the ability to translocate to the cell surface in the absence of GB2, we show that GABA(B) receptor agonists, such as GABA and Baclofen, can induce ERK1/2 phosphorylation in the absence of GB2. Furthermore, we demonstrate that GB1asa induces ERK1/2 phosphorylation through Gi/o proteins and PLC dependent IGF-1R transactivation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that GB1 may form a functional receptor at the cell surface in the absence of GB2
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