293 research outputs found
The state of the science of nurse work environments in the United States: A systematic review
A healthy nurse work environment is a workplace that is safe, empowering, and satisfying. Many research studies were conducted on nurse work environments in the last decade; however, it lacks an overview of these research studies. The purpose of this review is to identify, evaluate, and summarize the major foci of studies about nurse work environments in the United States published between January 2005 and December 2017 and provide strategies to improve nurse work environments. Databases searched included MEDLINE via PubMed, CINAHL, PsycINFO, Nursing and Allied Health, and the Cochrane Library. The literature search followed the PRISMA guideline. Fifty-four articles were reviewed. Five major themes emerged: 1) Impacts of healthy work environments on nurses' outcomes such as psy- chological health, emotional strains, job satisfaction, and retention; 2) Associations between healthy work environments and nurse interpersonal relationships at workplaces, job performance, and pro- ductivity; 3) Effects of healthy work environments on patient care quality; 4) Influences of healthy work environments on hospital accidental safety; and 5) Relationships between nurse leadership and healthy work environments. This review shows that nurses, as frontline patient care providers, are the foun- dation for patient safety and care quality. Promoting nurse empowerment, engagement, and interper- sonal relationships at work is rudimental to achieve a healthy work environment and quality patient care. Healthier work environments lead to more satisfied nurses who will result in better job perfor- mance and higher quality of patient care, which will subsequently improve healthcare organizations' financial viability. Fostering a healthy work environment is a continuous effort
Caenorhabditis elegans RIG-I Homolog Mediates Antiviral RNA Interference Downstream of Dicer-Dependent Biogenesis of Viral Small Interfering RNAs.
Dicer enzymes process virus-specific double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) to initiate specific antiviral defense by related RNA interference (RNAi) pathways in plants, insects, nematodes, and mammals. Antiviral RNAi in Caenorhabditis elegans requires Dicer-related helicase 1 (DRH-1), not found in plants and insects but highly homologous to mammalian retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), intracellular viral RNA sensors that trigger innate immunity against RNA virus infection. However, it remains unclear if DRH-1 acts analogously to initiate antiviral RNAi in C. elegans Here, we performed a forward genetic screen to characterize antiviral RNAi in C. elegans Using a mapping-by-sequencing strategy, we uncovered four loss-of-function alleles of drh-1, three of which caused mutations in the helicase and C-terminal domains conserved in RLRs. Deep sequencing of small RNAs revealed an abundant population of Dicer-dependent virus-derived small interfering RNAs (vsiRNAs) in drh-1 single and double mutant animals after infection with Orsay virus, a positive-strand RNA virus. These findings provide further genetic evidence for the antiviral function of DRH-1 and illustrate that DRH-1 is not essential for the sensing and Dicer-mediated processing of the viral dsRNA replicative intermediates. Interestingly, vsiRNAs produced by drh-1 mutants were mapped overwhelmingly to the terminal regions of the viral genomic RNAs, in contrast to random distribution of vsiRNA hot spots when DRH-1 is functional. As RIG-I translocates on long dsRNA and DRH-1 exists in a complex with Dicer, we propose that DRH-1 facilitates the biogenesis of vsiRNAs in nematodes by catalyzing translocation of the Dicer complex on the viral long dsRNA precursors.IMPORTANCE The helicase and C-terminal domains of mammalian RLRs sense intracellular viral RNAs to initiate the interferon-regulated innate immunity against RNA virus infection. Both of the domains from human RIG-I can substitute for the corresponding domains of DRH-1 to mediate antiviral RNAi in C. elegans, suggesting an analogous role for DRH-1 as an intracellular dsRNA sensor to initiate antiviral RNAi. Here, we developed a forward genetic screen for the identification of host factors required for antiviral RNAi in C. elegans Characterization of four distinct drh-1 mutants obtained from the screen revealed that DRH-1 did not function to initiate antiviral RNAi. We show that DRH-1 acted in a downstream step to enhance Dicer-dependent biogenesis of viral siRNAs in C. elegans As mammals produce Dicer-dependent viral siRNAs to target RNA viruses, our findings suggest a possible role for mammalian RLRs and interferon signaling in the biogenesis of viral siRNAs
Dynamics of Hydrophobic Core Phenylalanine Residues Probed by Solid-State Deuteron NMR
We conducted a detailed investigation of the dynamics of two phenylalanine side chains in the hydrophobic core of the villin headpiece subdomain protein (HP36) in the hydrated powder state over the 298-80 K temperature range. Our main tools were static deuteron NMR measurements of longitudinal relaxation and line shapes supplemented with computational modeling. The temperature dependence of the relaxation times reveals the presence of two main mechanisms that can be attributed to the ring-flips, dominating at high temperatures, and small-angle fluctuations, dominating at low temperatures. The relaxation is nonexponential at all temperatures with the extent of nonexponentiality increasing from higher to lower temperatures. This behavior suggests a distribution of conformers with unique values of activation energies. The central values of the activation energies for the ring-flipping motions are among the smallest reported for aromatic residues in peptides and proteins and point to a very mobile hydrophobic core. The analysis of the widths of the distributions, in combination with the earlier results on the dynamics of flanking methyl groups (Vugmeyster et al. J. Phys. Chem. B 2013, 117, 6129-6137), suggests that the hydrophobic core undergoes slow concerted fluctuations. There is a pronounced effect of dehydration on the ring-flipping motions, which shifts the distribution toward more rigid conformers. The crossover temperature between the regions of dominance of the small-angle fluctuations and ring-flips shifts from 195 K in the hydrated protein to 278 K in the dry one. This result points to the role of solvent in softening the core and highlights aromatic residues as markers of the protein dynamical transitions
Fast Motions of Key Methyl Groups in Amyloid-beta Fibrils
Amyloid-beta (A beta) peptide is the major component of plaques found in Alzheimer\u27s disease patients. Using solid-state H-2 NMR relaxation performed on selectively deuterated methyl groups, we probed the dynamics in the threefold symmetric and twofold symmetric polymorphs of native A beta as well as the protofibrils of the D23N mutant. Specifically, we investigated the methyl groups of two leucine residues that belong to the hydrophobic core (L17 and L34) as well as M35 residues belonging to the hydrophobic interface between the cross-beta subunits, which has been previously found to be water-accessible. Relaxation measurements performed over 310-140 K and two magnetic field strengths provide insights into conformational variability within and between polymorphs. Core packing variations within a single polymorph are similar to what is observed for globular proteins for the core residues, whereas M35 exhibits a larger degree of variability. M35 site is also shown to undergo a solvent dependent dynamical transition in which slower amplitude motions of methyl axes are activated at high temperature. The motions, modeled as a diffusion of methyl axis, have activation energy by a factor of 2.7 larger in the twofold compared with the threefold polymorph, whereas D23N protofibrils display a value similar to the threefold polymorph. This suggests enhanced flexibility of the hydrophobic interface in the threefold polymorph. This difference is only observed in the hydrated state and is absent in the dry fibrils, highlighting the role of solvent at the cavity. In contrast, the dynamic behavior of the core is hydration-independent
Risk Indicators for Periodontitis in US Adults: NHANES 2009 to 2012
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142205/1/jper1174.pd
Simultaneous Molecular and Hypoxia Imaging of Brain Tumors In Vivo Using Spectroscopic Photoacoustic Tomography
Noninvasive molecular and functional imaging in vivo is promising for detecting and monitoring various physiological conditions in animals and ultimately humans. To this end, we present a novel noninvasive technology, spectroscopic photoacoustic tomography (SPAT), which offers both strong optical absorption contrast and high ultrasonic spatial resolution. Optical contrast allows spectroscopic separation of signal contributions from multiple optical absorbers (e.g., oxyhemoglobin, deoxyhemoglobin, and a molecular contrast agent), thus enabling simultaneous molecular and functional imaging. SPAT successfully imaged with high resolution the distribution of a molecular contrast agent targeting integrin overexpressed in human U87 glioblastomas in nude mouse brains. Simultaneously, SPAT also imaged the hemoglobin oxygen saturation and the total hemoglobin concentration of the vasculature, which revealed hypoxia in tumor neovasculature. Therefore, SPAT can potentially lead to better understanding of the interrelationships between hemodynamics and specific biomarkers associated with tumor progression
Secretion of Annexin II via Activation of Insulin Receptor and Insulin-like Growth Factor Receptor
Annexin II is secreted into the extracellular environment, where, via interactions with specific proteases and extracellular matrix proteins, it participates in plasminogen activation, cell adhesion, and tumor metastasis and invasion. However, mechanisms regulating annexin II transport across the cellular membrane are unknown. In this study, we used coimmunoprecipitation to show that Annexin-II was bound to insulin and insulin-like growth factor-1 (IGF-1) receptors in PC12 cells and NIH-3T3 cells overexpressing insulin (NIH-3T3(IR)) or IGF-1 receptor (NIH-3T3(IGF-1R)). Stimulation of insulin and IGF-1 receptors by insulin caused a temporary dissociation of annexin II from these receptors, which was accompanied by an increased amount of extracellular annexin II detected in the media of PC12, NIH-3T3(IR), and NIH-3T3(IGF-1R) cells but not in that of untransfected NIH-3T3 cells. Activation of a different growth factor receptor, the platelet-derived growth factor receptor, did not produce such results. Tyrphostin AG1024, a tyrosine kinase inhibitor of insulin and IGF-1 receptor, was shown to inhibit annexin II secretion along with reduced receptor phosphorylation. Inhibitors of a few downstream signaling enzymes including phosphatidylinositol 3-kinase, pp60c-Src, and protein kinase C had no effect on insulin-induced annexin II secretion, suggesting a possible direct link between receptor activation and annexin II secretion. Immunocytochemistry revealed that insulin also induced transport of the membrane-bound form of annexin II to the outside layer of the cell membrane and appeared to promote cell aggregation. These results suggest that the insulin receptor and its signaling pathways may participate in molecular mechanisms mediating annexin II secretion
Women in the Workplace 2022
Women in the Workplace is the largest study on the state of women in corporate America. In 2015, LeanIn.Org and McKinsey & Company launched the study to give companies insights and tools to advance gender diversity in the workplace. Between 2015 and 2022, over 810 companies participated in the study, and more than 400,000 people were surveyed on their workplace experiences. This year, we collected information from 333 participating organizations employing more than 12 million people, surveyed more than 40,000 employees, and conducted interviews with women of diverse identities, including women of color, LGBTQ+ women, and women with disabilities. Our 2022 report focuses on how the pandemic has changed what women want from their companies, including the growing importance of opportunity, flexibility, employee well-being, and diversity, equity, and inclusion
Transport of Mass and Energy in Mercury’s Plasma Sheet
We examined the transport of mass and energy in Mercury’s plasma sheet (PS) using MESSENGER magnetic field and plasma measurements obtained during 759 PS crossings. Regression analysis of proton density and plasma pressure shows a strong linear relationship. We calculated the polytropic index γ for Mercury’s PS to be ~0.687, indicating that the plasma in the tail PS behaves nonadiabatically as it is transported sunward. Using the average magnetic field intensity of Mercury’s tail lobe as a proxy for magnetotail activity level, we demonstrated that γ is lower during active time periods. A minimum in γ was observed at R ~ 1.4 RM, which coincides with previously observed location of Mercury’s substorm current wedge. We suggest that the nonadiabatic behavior of plasma as it is transported into Mercury’s nearâ tail region is primarily driven by particle precipitation and particle scattering due to large loss cone and particle acceleration effect, respectively.Plain Language SummaryThe transport process of mass and energy within Mercury’s magnetotail remains unexplored until now. The availability of in situ magnetic field and plasma measurements from National Aeronautics and Space Administration’s MErcury Surface, Space ENvironment, GEochemistry, and Ranging spacecraft provides us with the first opportunity to study the thermodynamic properties of particles within sunward convecting closed flux tubes in the plasma sheet. In this study, we study how mass and energy are transported in Mercury’s magnetotail by investigating the relationship between the thermal pressure and number density of the plasma in Mercury’s plasma sheet given by the equation of state in magnetohydrodynamics theory. We determined, for the first time, that the plasma behaves nonadiabatically as it is transported sunward toward Mercury. We suggest that precipitation of particles due to Mercury’s large loss cone and demagnetization of particles due to finite gyroradius effect contributes to this nonadiabatic behavior of plasma in the plasma sheet. Our results have major implications in our understanding of particle sources and sinks mechanisms in Mercury’s magnetotail.Key PointsWe calculated the value of polytropic index γ for Mercury’s plasma sheet to be ~0.687, which is smaller than 5/3 (adiabatic)Nonadiabatic plasma behavior is driven by ion precipitation and ion demagnetization due to large loss cone and finite gyroradius effectWe demonstrated that γ is lower during active time and determined a relationship between γ and the location of flow breaking regionPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147033/1/grl58293_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147033/2/grl58293.pd
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