Towards Discovering Inhibitors of cyt c Biosynthesis in Systems, I, II, and III

From the Washington University Office of Undergraduate Research Digest (WUURD), Vol. 12, 05-01-2017. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: Robert Kran

Towards Discovering Inhibitors of Cytochrome c Biogenesis

From the Washington University Senior Honors Thesis Abstracts (WUSHTA), Spring 2018. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: Robert Kranz and Deanna Mende

The Tokar Gap jet : regional circulation, diurnal variability, and moisture transport based on numerical simulations

Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 28 (2015): 5885–5907, doi:10.1175/JCLI-D-14-00635.1.The structure, variability, and regional connectivity of the Tokar Gap jet (TGJ) are described using WRF Model analyses and supporting atmospheric datasets from the East African–Red Sea–Arabian Peninsula (EARSAP) region during summer 2008. Sources of the TGJ’s unique quasi-diurnal nature and association with atypically high atmospheric moisture transport are traced back to larger-scale atmospheric dynamics influencing its forcing. These include seasonal shifts in the intertropical convergence zone (ITCZ), variability of the monsoon and North African wind regimes, and ties to other orographic flow patterns. Strong modulation of the TGJ by regional processes such as the desert heating cycle, wind convergence at the ITCZ surface front, and the local land–sea breeze cycle are described. Two case studies present the interplay of these influences in detail. The first of these was an “extreme” gap wind event on 12 July, in which horizontal velocities in the Tokar Gap exceeded 26 m s−1 and the flow from the jet extended the full width of the Red Sea basin. This event coincided with development of a large mesoscale convective complex (MCC) and precipitation at the entrance of the Tokar Gap as well as smaller gaps downstream along the Arabian Peninsula. More typical behavior of the TGJ during the 2008 summer is discussed using a second case study on 19 July. Downwind impact of the TGJ is evaluated using Lagrangian model trajectories and analysis of the lateral moisture fluxes (LMFs) during jet events. These results suggest means by which TGJ contributes to large LMFs and has potential bearing upon Sahelian rainfall and MCC development.This work was supported by a grant from the King Abdullah University of Science and Technology (KAUST) as well as National Science Foundation Grant OCE0927017 and from DOD (MURI) Grant N000141110087, administered by the Office of Naval Research.2016-02-0

Comment on "Prediction of lattice constant in cubic perovskites"

In a recent work by Jiang et al. [J. Phys. Chem. Solids 67 (2006) 1531-1536], the interrelationship between lattice constant, ionic radii and tolerance factor of cubic perovskites has been established and an empirical equation was obtained. However, the assumption of incorrect ionic coordination led to an incorrect mathematical expression even though the average relative errors between predicted and observed lattice constants of 132 materials were below 1%. Here, corrected coefficients for that empirical expression are obtained, which would likely be useful for investigation of general perovskite materials

The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice

Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP(swe)/PS1(dE9) transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. SIGNIFICANCE STATEMENT The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections between high insulin and extracellular Aβ, but these mechanisms presume that peripheral high insulin elevates brain insulin significantly. We found that physiological hyperinsulinemia in awake, behaving mice does not increase CNS insulin to an appreciable level yet modestly increases extracellular Aβ. We also found that the brain of aged APP/PS1 mice was not insulin resistant, contrary to the current state of the literature. These results further elucidate the relationship between insulin, the brain, and AD and its conflicting roles as both a risk factor and potential treatment

Ethical Decision Making in Issues Management Within Activist Groups

Public relations practitioners face many ethical challenges, specifically in issues management (e.g., Bowen & Heath, 2005; J. Grunig & L. Grunig, 1996). By its definition, issues management is concerned with defining issues and problems, manages them through internal and external communication with publics, and often confronts conflicting value systems among publics. Therefore, issues management is on the forefront of ethical decision making in an organization (Heath, 1990). Deontology has been suggested as one of the major theoretical underpinnings for ethics research (e.g., Crawley & Sinclair, 2003; Smudde, 2005). Bowen (2004) proposed a normative theoretical model for ethical decision making in issues management based on Kantian deontology (autonomy, the principle of universality, duty, dignity and respect for others, and the morally good will) and two-way symmetrical communication. Support was found, but more research is warranted to examine the model in different organizational contexts. It is imperative to test the applicability of the normative deontological model (Bowen, 2004) in a new context—that of a non-profit activist coalition. Demands for accountability, ethical transparency, institutionalization concerns, competing values and demands of various publics groups have made it necessary to examine the ethical basis of decision making in non-profit organizations (Dando & Swift, 2003). With its mission of problematizing the fiscal policies of the Word Bank (WB) and the International Monetary Fund (IMF), the participating activist coalition was actually an issues management group engaging thoughtfully in the process of public policies on environmental, labor, development, peace, gender, and social justice issues confronting less developed nations in the world. Through a five-month participant observation in the membership groups of the coalition and 19 in-depth interviews with its issues managers and public relations practitioners, this study attempted to answer the following research questions: (1) What is the process of issues decision making in the coalition?; (2) What is the underlying moral philosophy used in the issues management decisionmaking process?. This study yielded the following findings. Participants argued that decision making should be consensus-oriented and based on equal participation and continuous discussion. Unfortunately, the lack of consistent, dedicated, and enthusiastic input by member groups was a significant impediment to a more inclusive decision making process for the management of issues. Participants’ valued equality – their emphases on being against stereotypes, inequality, and biases was consistent with the deontological paradigm. Moral autonomy was a dominant theme that also emerged through discussion of the sovereign right of each country to decide its own macroeconomic/fiscal policies. Transparency was another ethical consideration that the coalition used in its issues management. Overall, there was a remarkably high degree of congruence between the philosophical approach of deontology and the beliefs espoused by coalition members. The data gathered in this study has far-reaching implications in the positive social role of issues management and public relations. The implications for both businesses and activist coalitions are enormous: more responsive organizations, better policy, and more inclusive and socially responsible private and government initiatives

The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function

This work is licensed under a Creative Commons Attribution 4.0 International License.Methionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide reductase (Msr) system. The Msr type A enzyme (MsrA) plays an important role as a cellular antioxidant and promotes cell survival. The ubiquitin- (Ub) like neddylation pathway, which is controlled by the c-Jun activation domain-binding protein-1 (Jab1), also affects cell survival. Jab1 negatively regulates expression of the cell cycle inhibitor cyclin-dependent kinase inhibitor 1B (P27) through binding and targeting P27 for ubiquitination and degradation. Here we report the finding that MsrA interacts with Jab1 and enhances Jab1′s deneddylase activity (removal of Nedd8). In turn, an increase is observed in the level of deneddylated Cullin-1 (Cul-1, a component of E3 Ub ligase complexes). Furthermore, the action of MsrA increases the binding affinity of Jab1 to P27, while MsrA ablation causes a dramatic increase in P27 expression. Thus, an interaction between MsrA and Jab1 is proposed to have a positive effect on the function of Jab1 and to serve as a means to regulate cellular resistance to oxidative stress and to enhance cell survival.Hedwig Miller Fund for Aging Research of the University of KansasU.S. Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences, Physical Biosciences Program (DOE DE-FG02-05ER15650)NIH R01 GM5749

Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy.

Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention

Black Hole Entropy: From Shannon to Bekenstein

In this note we have applied directly the Shannon formula for information theory entropy to derive the Black Hole (Bekenstein-Hawking) entropy. Our analysis is semi-classical in nature since we use the (recently proposed [8]) quantum mechanical near horizon mode functions to compute the tunneling probability that goes in to the Shannon formula, following the general idea of [5]. Our framework conforms to the information theoretic origin of Black Hole entropy, as originally proposed by Bekenstein.Comment: 9 pages Latex, Comments are welcome; Thoroughly revised version, reference and acknowledgements sections enlarged, numerical error in final result corrected, no major changes, to appear in IJT