198,503 research outputs found
Selenium cytotoxicity in cancer
No full textSelenium is an essential trace element, present in the 21st amino acid selenocysteine, which is specifically incorporated into selenoproteins. Today, there are 25 identified selenoproteins in humans, whereof many comprises redox active functions to uphold the intracellular redox balance. The redox activity is dependent on the location of selenocysteine within their active sites. It is also therefore selenium is recognized as an antioxidant.There are increasing number of studies with supporting evidences of redox active selenium compounds as anti-tumor metabolites, both in prevention and treatment of cancers, depending on the concentration. At lower doses selenium supplementation supports the synthesis and function of selenoproteins, while at higher concentration, selenium becomes a prooxidant and may cause reactive oxygen speices (ROS) formation, and induces cell death. Still, the selenium induced cytotoxic mechanisms in cancer are not fully characterized. The aim of this thesis was therefore undertaken to study the cytotoxic mechanism induced by some redox active selenium species in tumor cells, and their interaction with the thioredoxin and the glutaredoxin system.We found selenium compounds to be substrates of the glutaredoxin system, and that elevated Grx1 also increases the cytotoxicity of selenite, selenodiglutathione and seleno-DL-cystine. Moreover, selenite induced a redox shift within cells by increased cysteinylation and glutathionylation of proteins, which might be an important mechanism in selenium induced cytotoxicity. Methylselenol is considered to be the most reactive selenium metabolite to induce cell death in cancer cells. We showed the occurrence of a spontaneous methylation of selenide by s-adenosylmethionine (SAM) to form methylselenol. Methylselenol was a superior substrate for the thioredoxin and the glutaredoxin systems, compared to selenide. This newly formed selenium metabolite was also more toxic to tumor cells.Furthermore, selenite, selenodiglutathione and seleno-DL-cystine induce different programmed cell death (PCD) in HeLa cells, which was unexpected, since both selenite and selenodiglutathione are reduced to selenide. Selenodiglutathione was found to glutathionylate free protein thiols, which might be the reason to these diverse cell death mechanisms. Selenite induced a necroptosis-like cell death, while seleno-DL-cystine treatment induced two subgroups of cell death. One group was clearly apoptosis while the other displayed a paraptosis-like cell death, with massive cytoplasmic vacuolation and concomitant ER stress and unfolded protein response (UPR).In a study of selenite to promote all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL), we found selenite to potentiate the effect of ATRA induced maturation of NB4 cells. This was determined by increased expression of CD11b, nuclear morphology changes, and decrease of PML-RARα expression. This 2 differentiation might be redox regulated, since both selenite and ATRA induced changes of redox protein expression both on mRNA and protein level.In this thesis work, we show that selenium compounds are potent anti-tumoral drugs to induce cell death and to potentiate differentiation in leukemic cells. We conclude that the mechanisms are not only caused by ROS formation, but by multiple mechanisms, depending on molecular structure, which is of benefit to overcome drug resistance in tumors.List of scientific papersI. Wallenberg M, Olm E, Hebert C, Björnstedt M, and Fernandes A.P. Selenium compounds are substrates for glutaredoxins: a novel pathway for selenium metabolism and a potential mechanism for selenium-mediated cytotoxicity. Biochem J. (2010) 429, 85-93. https://doi.org/10.1042/BJ20100368 II. Fernandes A.P*, Wallenberg M*, Gandin V, Misra S, Tisato F, Marzano C, Rigobello M.P, Kumar S and Björnstedt M. Methylselenol Formed by Spontaneous Methylation of Selenide Is a Superior Selenium Substrate to the Thioredoxin and Glutaredoxin Systems. PLOS ONE. 2012 Nov. Volume 7, Issue 11, e50727. https://doi.org/10.1371/journal.pone.0050727 III. Wallenberg M, Misra S, M.Wasik A, Marzano C, Björnstedt M, Gandin V and Fernandes A.P. Selenium induces a multi-target cell death process by complex mechanisms beyond ROS formation. [Submitted]IV. Misra S, Wallenberg M, Barsham A, Gandin V, Matolcsy A, Björnstedt M and Fernandes A.P. Selenite potentiates all-trans retinoic acid induced maturation of NB4 cells. [Manuscript]</p
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Dr. Glendon Swarthout
No full textHosted by Roger M. Busfield, MSU Assistant Professor of Speech and Theater, Meet the Author is designed to introduce a general audience to a contemporary author and their work through in-depth interviews. This episode features a conversation between Dr. Glendon Swarthout, prolific author and English professor at MSU, and assistant professors Sam S. Baskett and Theodore B. Strandness
STIAS–Wallenberg Roundtable on mHealth: Towards a roadmap for image-based mobile technologies for health care
No full textCITATION: Galloway, M. 2017. STIAS–Wallenberg Roundtable on mHealth : towards a roadmap for image-based mobile technologies for health care. South African Journal of Science, 113(7/8), Art. #a0218, doi:10.17159/sajs.2017/a0218.The original publication is available at http://sajs.co.zaNo abstract availablehttps://www.sajs.co.za/article/view/3980Publisher's versio
Balance with Memory in Signed Networks via Mittag-Leffler Matrix Functions
No full textStructural balance is an important characteristic of graphs where edges can be positive or negative, or signed graphs, with a direct impact on the study of real-world complex systems. When a graph is not structurally balanced, it is important to know how much balance still exists. Although several measures have been proposed to characterize the degree of balance, the use of matrix functions of the signed adjacency matrix emerges as an up-and-coming area of research. Here, we take a step forward to use Mittag-Leffler (ML) matrix functions to quantify the notion of balance of signed graphs. We show that the ML balance index can be derived from first principles on the basis of a nonconservative diffusion dynamic and that it accounts for the memory of the system about the past, by diminishing the penalization that long cycles typically receive in other matrix functions. Finally, we demonstrate the important information in the ML balance index with both artificial signed networks and real-world networks in various contexts, ranging from biological and ecological to social ones.The second author acknowledges support from the Maria de Maeztu project CEX2021-001164-M funded by the MCIN/AEI/10.13039/501100011033 and from Agencia Estatal de Investigaci´on (AEI, MCI, Spain) MCIN/AEI/ 10.13039/501100011033 under grant PID2023-149473NB-I00. The first author is funded by the Wallenberg Initiative on Networks and Quantum Information (WINQ).With funding from the Spanish government through the "Maria de Maeztu Centre of Excellence" accreditation (CEX2021-001164-M).Peer reviewe
Simulation of thermal plant optimization and hydraulic aspects of thermal distribution loops for large campuses
No full textFollowing an introduction, the author describes Texas A&M University and its utilities system. After that, the author presents how to construct simulation models for chilled water and heating hot water distribution systems. The simulation model was used in a $2.3 million Ross Street chilled water pipe replacement project at Texas A&M University. A second project conducted at the University of Texas at San Antonio was used as an example to demonstrate how to identify and design an optimal distribution system by using a simulation model. The author found that the minor losses of these closed loop thermal distribution systems are significantly higher than potable water distribution systems. In the second part of the report, the author presents the latest development of software called the Plant Optimization Program, which can simulate cogeneration plant operation, estimate its operation cost and provide optimized operation suggestions. The author also developed detailed simulation models for a gas turbine and heat recovery steam generator and identified significant potential savings. Finally, the author also used a steam turbine as an example to present a multi-regression method on constructing simulation models by using basic statistics and optimization algorithms. This report presents a survey of the author??s working experience at the Energy Systems Laboratory (ESL) at Texas A&M University during the period of January 2002 through March 2004. The purpose of the above work was to allow the author to become familiar with the practice of engineering. The result is that the author knows how to complete a project from start to finish and understands how both technical and nontechnical aspects of a project need to be considered in order to ensure a quality deliverable and bring a project to successful completion. This report concludes that the objectives of the internship were successfully accomplished and that the requirements for the degree of Degree of Engineering have been satisfied
The valvula cerebelli of the spiny eel, Macrognathus aculeatus, receives primary lateral-line afferents from the rostrum of the upper jaw
No full textIn the spiny eel, Macrognathus aculeatus, anterodorsal and (to a lesser degree) anteroventral lateralline nerves project massively to the granular layer of the valvula cerebelli, throughout its rostrocaudal extent. The posterior lateral-line nerve terminates in the corpus cerebelli. Thus, valvula and corpus cerebelli are supplied with mechanosensory input of different peripheral origins. An analysis of the taxonomic distribution of experimentally determined primary lateral-line input to the three parts of the teleostean cerebellum reveals that the eminentia granularis always receives such input, and that the corpus cerebelli is the recipient of primary lateral-line input in many teleosts. The valvula, however, receives primary lateral-line afferents in only two examined species. In M. aculeatus, the massive lateral-line input to the valvula probably originates in mechanoreceptors located in the elongated rostrum of the upper jaw, a characteristic feature of mastacembeloid fishes. This projection to the valvula may therefore represent a unique specialization that arose with the evolution of the peculiar rostrum
Selenium induces a multi-targeted cell death process in addition to ROS formation
No full textSelenium compounds inhibit neoplastic growth. Redox active selenium compounds are evolving as promising chemotherapeutic agents through tumour selectivity and multi-target response, which are of great benefit in preventing development of drug resistance. Generation of reactive oxygen species is implicated in selenium-mediated cytotoxic effects on cancer cells. Recent findings indicate that activation of diverse intracellular signalling leading to cell death depends on the chemical form of selenium applied and/or cell line investigated. In the present study, we aimed at deciphering different modes of cell death in a single cell line (HeLa) upon treatment with three redox active selenium compounds (selenite, selenodiglutathione and seleno-DL-cystine). Both selenite and selenodiglutathione exhibited equipotent toxicity (IC50 5M) in these cells with striking differences in toxicity mechanisms. Morphological and molecular alterations provided evidence of necroptosis-like cell death in selenite treatment, whereas selenodiglutathione induced apoptosis-like cell death. We demonstrate that selenodiglutathione efficiently glutathionylated free protein thiols, which might explain the early differences in cytotoxic effects induced by selenite and selenodiglutathione. In contrast, seleno-DL-cystine treatment at an IC50 concentration of 100M induced morphologically two distinct different types of cell death, one with apoptosis-like phenotype, while the other was reminiscent of paraptosis-like cell death, characterized by induction of unfolded protein response, ER-stress and occurrence of large cytoplasmic vacuoles. Collectively, the current results underline the diverse cytotoxic effects and variable potential of redox active selenium compounds on the survival of HeLa cells and thereby substantiate the potential of chemical species-specific usage of selenium in the treatment of cancers
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