346 research outputs found
Communicating Value: Understanding Adjunct Typology, Job Satisfaction Levels, and Professional Development Interests
Higher education institutions are navigating budget cuts, changing enrollment, and the need to differentiate from the competition. Reductions in government funding and budgetary constraints are prompting universities to reduce the number of full-time, tenure-track faculty and rely more heavily on adjunct faculty to meet their demand for instructors. Therefore it is important to determine the distinct needs and satisfaction levels of this faculty group in order to provide appropriate resources and development opportunities for them. This study sought to determine if adjunct faculty job satisfaction levels differ based on adjunct typology (Gappa & Leslie, 1993) or institutional affiliation, and to determine professional development interests of adjunct faculty. Adjunct faculty from three institutions of higher education participated in the study. Significant differences were identified using analysis of variance tests and the results were discussed. Recommendations for senior academic leaders and department heads were offered, including a recommendation to evaluate their institutions to determine the unique distribution of adjunct types represented therein and customize interventions to address the adjuncts’ distinct interests and needs. This research describes the differences in demographics and job satisfaction needs among the four adjunct types (Gappa & Leslie, 1993), and discusses the faculty development interests of the adjunct participants. Based on the findings, the researcher suggests that academic leaders address a broad spectrum of adjunct needs in order to improve satisfaction levels and attend to professional development interests
Early Cytokine-Induced Transient NOX2 Activity Is ER Stress-Dependent and Impacts β-Cell Function and Survival
In type 1 diabetes (T1D) development, proinflammatory cytokines (PIC) released by
immune cells lead to increased reactive oxygen species (ROS) production in β-cells. Nonetheless, the
temporality of the events triggered and the role of different ROS sources remain unclear. Isolated islets
from C57BL/6J wild-type (WT), NOX1 KO and NOX2 KO mice were exposed to a PIC combination.
We show that cytokines increase O2
•− production after 2 h in WT and NOX1 KO but not in NOX2 KO
islets. Using transgenic mice constitutively expressing a genetically encoded compartment specific
H2O2 sensor, we show, for the first time, a transient increase of cytosolic/nuclear H2O2
in islet cells
between 4 and 5 h during cytokine exposure. The H2O2
increase coincides with the intracellular
NAD(P)H decrease and is absent in NOX2 KO islets. NOX2 KO confers better glucose tolerance and
protects against cytokine-induced islet secretory dysfunction and death. However, NOX2 absence
does not counteract the cytokine effects in ER Ca2+ depletion, Store-Operated Calcium Entry (SOCE)
increase and ER stress. Instead, the activation of ER stress precedes H2O2 production. As early
NOX2-driven ROS production impacts β-cells’ function and survival during insulitis, NOX2 might be
a potential target for designing therapies against early β-cell dysfunction in the context of T1D onset
In Defence of Modest Doxasticism About Delusions
Here I reply to the main points raised by the commentators on the arguments put forward in my Delusions and Other Irrational Beliefs (OUP, 2009). My response is aimed at defending a modest doxastic account of clinical delusions, and is articulated in three sections. First, I consider the view that delusions are in-between perceptual and doxastic states, defended by Jacob Hohwy and Vivek Rajan, and the view that delusions are failed attempts at believing or not-quite-beliefs, proposed by Eric Schwitzgebel and Maura Tumulty. Then, I address the relationship between the doxastic account of delusions and the role, nature, and prospects of folk psychology, which is discussed by Dominic Murphy, Keith Frankish, and Maura Tumulty in their contributions. In the final remarks, I turn to the continuity thesis and suggest that, although there are important differences between clinical delusions and non-pathological beliefs, these differences cannot be characterised satisfactorily in epistemic terms. \u
In-cell NMR characterization of the secondary structure populations of a disordered conformation of α-Synuclein within E. coli cells
α-Synuclein is a small protein strongly implicated in the pathogenesis of Parkinson’s disease and related neurodegenerative disorders. We report here the use of in-cell NMR spectroscopy to observe directly the structure and dynamics of this protein within E. coli cells. To improve the accuracy in the measurement of backbone chemical shifts within crowded in-cell NMR spectra, we have developed a deconvolution method to reduce inhomogeneous line broadening within cellular samples. The resulting chemical shift values were then used to evaluate the distribution of secondary structure populations which, in the absence of stable tertiary contacts, are a most effective way to describe the conformational fluctuations of disordered proteins. The results indicate that, at least within the bacterial cytosol, α-synuclein populates a highly dynamic state that, despite the highly crowded environment, has the same characteristics as the disordered monomeric form observed in aqueous solution
Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection.
The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury and cardioprotection. In the first part, the continued need for cardioprotection beyond that by rapid reperfusion of acute myocardial infarction is emphasized. Then, pathomechanisms of myocardial ischemia/reperfusion to the myocardium and the coronary circulation and the different modes of cell death in myocardial infarction are characterized. Different mechanical and pharmacological interventions to protect the ischemic/reperfused myocardium in elective percutaneous coronary interventions and coronary artery bypass grafting, in acute myocardial infarction and in cardiotoxicity from cancer therapy are detailed. The second part keeps the focus on ROS providing a comprehensive overview of molecular and cellular mechanisms involved in ischemia/reperfusion injury. Starting from mitochondria as the main sources and targets of ROS in ischemic/reperfused myocardium, a complex network of cellular and extracellular processes is discussed, including relationships with Ca2+ homeostasis, thiol group redox balance, hydrogen sulfide modulation, cross-talk with NAPDH oxidases, exosomes, cytokines and growth factors. While mechanistic insights are needed to improve our current therapeutic approaches, advancements in knowledge of ROS-mediated processes indicate that detrimental facets of oxidative stress are opposed by ROS requirement for physiological and protective reactions. This inevitable contrast is likely to underlie unsuccessful clinical trials and limits the development of novel cardioprotective interventions simply based upon ROS removal
Unicompartmental knee arthroplasty in patients aged less than 65: Combined data from the Australian and Swedish Knee Registries
Introduction and purpose: In recent years, there has been renewed interest in using unicompartmental knee arthroplasty (UKA). Several studies have reported increasing numbers of UKAs for osteoarthritis in patients who are less than 65 years of age, with low revision rates. To describe and compare the use and outcome of UKA in this age group, we have combined data from the Australian and Swedish knee registries. Patients and methods: More than 34,000 UKA procedures carried out between 1998 and 2007 were analyzed, and we focused on over 16,000 patients younger than 65 years to determine usage and to determine differences in the revision rate. Survival analysis was used to determine outcomes of revision related to age and sex, using any reason for revision as the endpoint. Results: Both countries showed a decreasing use of UKA in recent years in terms of the proportion of knee replacements and absolute numbers undertaken per year. The 7-year cumulative risk of revision of UKA in patients younger than 65 years was similar in the two countries. Patients younger than 55 years had a statistically significantly higher cumulative risk of revision than patients aged 55 to 64 years (19% and 12%, respectively at 7 years). The risk of revision in patients less than 65 years of age was similar in both sexes. Interpretation: The results of the combined UKA data from the Australian and Swedish registries show a uniformity of outcome between countries with patients aged less than 65 having a higher rate of revision than patients who were 65 or older. Surgeons and patients should be aware of the higher risk of revision in this age group.Annette W-Dahl, Otto Robertsson, Lars Lidgren, Lisa Miller, David Davidson, Stephen Graves
SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation
SUMMARY A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin (HTT) protein, which may be regulated by posttranslational modifications. Here, we define the primary sites of SUMO modification in the amino-terminal domain of HTT, show modification downstream of this domain, and demonstrate that HTT is modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2 modification and that reduction of dPIAS in a mutant HTT Drosophila model is protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa cells in a manner that mimics proteasome inhibition and can be modulated by overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2-modified proteins in the insoluble fraction of HD postmortem striata implicates SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and other cellular proteins that occurs during HD progression
The use of Earth Observation for wetland inventory, assessment and monitoring
The use of Earth Observation (EO) provides Contracting Parties to the Ramsar Convention on Wetlands with new approaches to ensure the wise use and conservation of wetlands at the national and global levels. EO has many applications including the inventory, assessment
and monitoring of wetlands. As technology advances, previous limitations of EO will be reduced, and it is anticipated that the use of EO in the management of wetlands will increase. This Ramsar Technical Report aims to provide practitioners with an overview and illustration,
through case studies, on the use of EO for implementation of the Convention and the wise use of wetlands more broadly
Fluctuations around Bjorken Flow and the onset of turbulent phenomena
We study how fluctuations in fluid dynamic fields can be dissipated or
amplified within the characteristic spatio-temporal structure of a heavy ion
collision. The initial conditions for a fluid dynamic evolution of heavy ion
collisions may contain significant fluctuations in all fluid dynamical fields,
including the velocity field and its vorticity components. We formulate and
analyze the theory of local fluctuations around average fluid fields described
by Bjorken's model. For conditions of laminar flow, when a linearized treatment
of the dynamic evolution applies, we discuss explicitly how fluctuations of
large wave number get dissipated while modes of sufficiently long wave-length
pass almost unattenuated or can even be amplified. In the opposite case of
large Reynold's numbers (which is inverse to viscosity), we establish that
(after suitable coordinate transformations) the dynamics is governed by an
evolution equation of non-relativistic Navier-Stokes type that becomes
essentially two-dimensional at late times. One can then use the theory of
Kolmogorov and Kraichnan for an explicit characterization of turbulent
phenomena in terms of the wave-mode dependence of correlations of fluid dynamic
fields. We note in particular that fluid dynamic correlations introduce
characteristic power-law dependences in two-particle correlation functions.Comment: 40 pages, 5 figures, published versio
Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia
Despite extensive insights into the underlying genetics and biology of acute myeloid leukemia (AML), overall survival remains poor and new therapies are needed. We found that casein kinase 1 α (Csnk1a1), a serine-threonine kinase, is essential for AML cell survival in vivo. Normal hematopoietic stem and progenitor cells (HSPCs) were relatively less affected by shRNA-mediated knockdown of Csnk1a1. To identify downstream mediators of Csnk1a1 critical for leukemia cells, we performed an in vivo pooled shRNA screen and gene expression profiling. We found that Csnk1a1 knockdown results in decreased Rps6 phosphorylation, increased p53 activity, and myeloid differentiation. Consistent with these observations, p53-null leukemias were insensitive to Csnk1a1 knockdown. We further evaluated whether D4476, a casein kinase 1 inhibitor, would exhibit selective antileukemic effects. Treatment of leukemia stem cells (LSCs) with D4476 showed highly selective killing of LSCs over normal HSPCs. In summary, these findings demonstrate that Csnk1a1 inhibition causes reduced Rps6 phosphorylation and activation of p53, resulting in selective elimination of leukemia cells, revealing Csnk1a1 as a potential therapeutic target for the treatment of AML
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