Is Overoxidation of Peroxiredoxin Physiologically Significant?

Eukaryotic peroxiredoxins are highly susceptible to sulfinic acid formation. This overoxidation, which is thought to convert peroxiredoxins into chaperones, can be reversed by sulfiredoxins. Several organisms, including Caenorhabditis elegans, lack sulfiredoxins but encode sestrins, proteins proposed to be functionally equivalent. We induced peroxiredoxin overoxidation in C. elegans with a short peroxide pulse. We found that reduction of overoxidized peroxiredoxin 2 (PRDX-2) was extremely slow and sestrin-independent, strongly implying that worms lack an efficient repair system. Analysis of PRDX-2's overoxidation status during C. elegans lifespan revealed no accumulation of overoxidized PRDX-2 at any point, questioning whether PRDX-2 overoxidation in worms is physiologically relevant. Antioxid. Redox Signal. 14, 725-730.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90505/1/ars-2E2010-2E3717.pd

Behavioral Responses to Gold Nanoparticle Exposure and H2O2-Induced Oxidative Stress in Caenorhabditis elegans

Gold nanoparticles (AuNPs) have been utilized in many biomedical disciplines, most notably cancer therapy and drug delivery. Recent research suggests that with specific peptide manipulation, AuNPs can deliver drugs across the blood-brain barrier (BBB), allowing for treatment of neurodegeneration and other neurological afflictions. Neurodegeneration has been shown to be caused by oxidative stress. The present experiment aimed to assess the effects of AuNPs on C. elegans behavior that had undergone H2O2-induced oxidative stress. It was predicted that worms exposed to both H2O2 and AuNPs would have higher survival, mechanosensation, and thrashing rates than worms only exposed to H2O2. After worms were exposed to H2O2 solution and AuNP solution, mortality, mechanosensation, and thrashing data were obtained. Nematodes who were exposed to both AuNPs and H2O2 (μ = 51.1 thrashes/min) did not experience the same decrease in locomotion as the worms only exposed to H2O2 (μ = 30.8 thrashes/min), p = 0.05. This suggests that AuNP exposure may reverse the negative effects of H2O2 on C. elegans movement. Worms exposed to AuNPs by liquid vehicle in the first experiment exhibited significantly less locomotion (μ = 46.3 thrashes/min) than worms exposed to AuNPs through their food in the second experiment (μ = 119.6 thrashes/min), p \u3c 0.001. Results from this study assert that AuNPs may help relieve symptoms of oxidative stress and neurodegeneration, especially in neuromuscular activity in C. elegans

The Effect of Nonassociative Learning on Oxidative Stress in Caenorhabditis elegans: A Potential Application for Alzheimer’s Disease Research

Alzheimer’s disease results in learning and memory deficits due to toxic changes in the brain caused by amyloid-β plaques and oxidative stress. Oxidative stress is caused by the overproduction of free radicals, which are uncharged molecules containing an unpaired valence electron. Nonassociative learning is a type of cognitive processing that only uses one stimulus instead of two related stimuli. Cognitive processing promotes neural growth and learning, while Alzheimer’s inhibits it. The purpose of this study was to test how nonassociative learning impacts oxidative stress and thus, if it might be considered as a potential treatment option for Alzheimer’s disease. It was hypothesized that the application of nonassociative learning would reduce the effects of oxidative stress on C. elegans, resulting in increased mobility and egg-laying. Mechanosensory, chemosensory, and novel environment habituation were used to increase mobility and egg-laying in C. elegans, in opposition to a hydrogen peroxide treatment that induced oxidative stress. The equation F(3,236)=44.73, p\u3c0.0001 was used to run the one-way ANOVA for time to paralysis. The Tukey test demonstrated differences between the control group and all of the experimental groups. The equation F(3,16)=4.72072, p=0.021252 was used to run the one-way repeated measures ANOVA for egg-laying. The Fisher test demonstrated differences between the control group and the mechanosensory and chemosensory groups. It was concluded that the application of nonassociative learning to C. elegans reverses the negative effects of oxidative stress, stimulating mobility and egg-laying

Fluid Dynamics in the HeartMate 3: Influence of the Artificial Pulse Feature and Residual Cardiac Pulsation

Ventricular assist devices (VADs), among which the HeartMate 3 (HM3) is the latest clinically approved representative, are often the therapy of choice for patients with end‐stage heart failure. Despite advances in the prevention of pump thrombosis, rates of stroke and bleeding remain high. These complications are attributed to the flow field within the VAD, among other factors. One of the HM3’s characteristic features is an artificial pulse that changes the rotor speed periodically by 4000 rpm, which is meant to reduce zones of recirculation and stasis. In this study, we investigated the effect of this speed modulation on the flow fields and stresses using high‐resolution computational fluid dynamics. To this end, we compared Eulerian and Lagrangian features of the flow fields during constant pump operation, during operation with the artificial pulse feature, and with the effect of the residual native cardiac cycle. We observed good washout in all investigated situations, which may explain the low incidence rates of pump thrombosis. The artificial pulse had no additional benefit on scalar washout performance, but it induced rapid variations in the flow velocity and its gradients. This may be relevant for the removal of deposits in the pump. Overall, we found that viscous stresses in the HM3 were lower than in other current VADs. However, the artificial pulse substantially increased turbulence, and thereby also total stresses, which may contribute to clinically observed issues related to hemocompatibility

Influence of Professional Expertise on Dividend Policy among Listed Firms in Nairobi Securities Exchange in Kenya

Management of corporations has been faced by challenges emerging from internal managers not being able to effectively offer stewardship. The organizations owners therefore have to improvise means of ensuring that their interests are protected. In modern corporation’s owners embrace mechanisms like board diversity to mitigate against managers failures to act in their interests. The purpose of this study was to examine the influence o professional expertise on Dividend Policy among listed firms in Nairobi Securities Exchange. In the recent past, most corporations in developing economies experience unstable dividend payment hence the need to determine whether professional expertise can remedy dividend payment situation prevailing. The study examined how professional expertise can influence dividend policy in companies listed on the NSE. The study was guided by agency, signaling, resource dependency and power circulation theories. The study used the explanatory research design. Document analysis was used to collect secondary data from annual reports of firms. Data was analyzed using descriptive statistics such as the mean, median, and standard deviation and fixed effect multiple regression analysis was done to examine the effects between professional expertise and dividend policy in annual reports of firms. The study was also expected to contribute new knowledge on the relationship between professional expertise and dividend policy. The regression results showed that professional expertise (β = .226, p = .490) exhibit a strong direct relationship with dividend policy. The study recommends that policy makers to ensure development of regulations to enhance professional expertise among firms since professional expertise brings about overwhelming benefits to corporate owners by minimizing agency problems related to free cash flows hence enhance payout to shareholder and reduce risk of misallocation of excess resources by firm managers. The study also recommends further studies to be carried out on the relationship between professional expertise and dividend policy on privately owned, SME’s, both listed and unlisted firms using similar study variables and a longer period for the same study to determine whether optimal results would be achieved. Keywords: Professional Expertise, Dividend, Policy, Resource dependency, securities exchang

Heterogeneity in the population response of a human cell line to hydrogen peroxide as measured by a genetically encoded sensor

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 22-26).Genetically encoded ratiometric sensors can provide valuable mechanistic understanding of biological systems. Characterization of cellular response of these sensors is the first step in validating their use. Here, we characterize the response of a genetically encoded H₂O₂ sensor, HyPer, expressed in HeLa cells. Using quantitative fluorescence microscopy, we found significant heterogeneity in HyPer response among the cell population. Further analysis showed that the variation in HyPer response was dependent on expression of HyPer protein as well as on cell cycle phase. Cells with higher levels of expressed HyPer protein showed a stronger HyPer response to H₂O₂. Cells synchronized in S-phase showed a weaker HyPer response than unsynchronized cells. It was determined that this weaker response could be a function of higher antioxidant capacity in S-phase cells. The dependence of HyPer response on these factors needs to be accounted for to avoid experimental artifacts.by Sohail Feroz Ali.S.M

Post-translational modifications and mass spectrometry detection

In this review, we provide a comprehensive bibliographic overview of the role of mass spectrometry and the recent technical developments in the detection of post-translational modifications (PTMs). We briefly describe the principles of mass spectrometry for detecting PTMs and the protein and peptide enrichment strategies for PTM analysis, including phosphorylation, acetylation and oxidation. This review presents a bibliographic overview of the scientific achievements and the recent technical development in the detection of PTMs is provided. In order to ascertain the state of the art in mass spectrometry and proteomics methodologies for the study of PTMs, we analyzed all the PTM data introduced in the Universal Protein Resource (UniProt) and the literature published in the last three years. The evolution of curated data in UniProt for proteins annotated as being post-translationally modified is also analyzed. Additionally, we have undertaken a careful analysis of the research articles published in the years 2010 to 2012 reporting the detection of PTMs in biological samples by mass spectrometry. © 2013 Elsevier Inc