How Changes in the Cost of Living are Measured

Adaptive changes in the expression of nuclear and mitochondrial encoded subunits of cytochrome c oxidase and the catalytic activity during hypoxia C. Vijayasarathy 1, * ,† , Shirish Damle 1, *, Subbuswamy K. Prabu 1, *, Cynthia M. Otto 2 and Narayan G. Avadhani 1 1 Department of Animal Biology and 2 Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA The effects of physiologically relevant hypoxia on the catalytic activity of cytochrome c oxidase (CytOX), mito- chondrial gene expression, and both nuclear and mito- chondrial encoded CytOX mRNA levels were investigated in murine monocyte macrophages, mouse C2C12 skeletal myocytes and rat adrenal pheochromocytoma PC12 cells. Our results suggest a coordinated down regulation of mito- chondrial genome-coded CytOX I and II and nuclear genome-coded CytOX IV and Vb mRNAs during hypoxia. Hypoxia also caused a severe decrease in mitochondrial transcription rates, and associated decrease in mitochondrial transcription factor A. The enzyme from hypoxia exposed cells exhibited altered subunit content as revealed by blue native gel electrophoresis. There was a generalized decline in mitochondrial function that led to a decrease in total cellular heme and ATP pools. We also observed a decrease in mitochondrial heme aa 3 content and decreased levels of CytOX subunit I, IV and Vb, though the catalytic efficiency of the enzyme (TN for cytochrome c oxidase) remained nearly the same. Increased glycolytic flux and alterations in the kinetic characteristics of the CytOX might be the two mechanisms by which hypoxic cells maintain adequate ATP levels to sustain life processes. Reoxygenation nearly com- pletely reversed hypoxia-mediated changes in CytOX mRNA contents, rate of mitochondrial transcription, and the catalytic activity of CytOX enzyme. Our results show adaptive changes in CytOX structure and activity during physiological hypoxia. Keywords: hypoxia; cytochrome c oxidase; subunit content; mitochondrial genome transcription. Cytochrome c oxidase (CytOX) is the terminal oxidase of the mitochondrial electron transport chain [1–5], which catalyzes the reduction of the dioxygen (O 2 ) to water and harnesses the free energy of the reaction to phosphorylate ADP to ATP. Heme and Cu, which transfer electrons from ferrocytochrome c to molecular oxygen, constitute the catalytic site of the enzyme complex. The three catalytic subunits, CytOX I, II and III are coded by the mitochon- drial DNA and are synthesized within mitochondria. Heme a, heme a 3 and Cu b are ligated to subunit I, while Cu a is ligated to subunit II which is also the binding site for cytochrome c [4,5]. The remaining 10 subunits of the mammalian enzyme, namely, IV, Vb, VIa, VIb, VIc, VIIa, VIIb and VIII are encoded by the nuclear genome, synthesized in the cytosol and imported into mitochondria [1–3]. Some of the nuclear-encoded subunits in the mam- mals are regulated developmentally and occur as tissue specific isoforms [6,7]. Although the nuclear encoded subunits, such as CytOX VIa and VIb, have been shown to enhance the catalytic efficiency of the enzyme [8,9], the precise role of many nuclear-encoded How Changes in the Cost of Living are Measured How Changes in the Cost of Living are Measured By: OpenStaxCollege The most commonly cited measure of inflation in the United States is the Consumer Price Index (CPI) The CPI is calculated by government statisticians at the U.S Bureau of Labor Statistics based on the prices in a fixed basket of goods and services that represents the purchases of the average family of four In recent years, the statisticians have paid considerable attention to a subtle problem: that the change in the total cost of buying a fixed basket of goods and services over time is conceptually not quite the same as the change in the cost of living, because the cost of living represents how much it costs for a person to feel that his or her consumption provides an equal level of satisfaction or utility To understand the distinction, imagine that over the past 10 years, the cost of purchasing a fixed basket of goods increased by 25% and your salary also increased by 25% Has your personal standard of living held constant? If you not necessarily purchase an identical fixed basket of goods every year, then an inflation calculation based on the cost of a fixed basket of goods may be a misleading measure of how your cost of living has changed Two problems arise here: substitution bias and quality/new goods bias When the price of a good rises, consumers tend to purchase less of it and to seek out substitutes instead Conversely, as the price of a good falls, people will tend to purchase more of it This pattern implies that goods with generally rising prices should tend over time to become less important in the overall basket of goods used to calculate inflation, while goods with falling prices should tend to become more important Consider, as an example, a rise in the price of peaches by $100 per pound If consumers were utterly inflexible in their demand for peaches, this would lead to a big rise in the price of food for consumers Alternatively, imagine that people are utterly indifferent to whether they have peaches or other types of fruit Now, if peach prices rise, people completely switch to other fruit choices and the average price of food does not change at all A fixed and unchanging basket of goods assumes that consumers are locked into buying exactly the same goods, regardless of price changes—not a very likely assumption Thus, substitution bias—the rise in the price of a fixed basket of goods over time—tends 1/8 How Changes in the Cost of Living are Measured to overstate the rise in a consumer’s true cost of living, because it does not take into account that the person can substitute away from goods whose relative prices have risen The other major problem in using a fixed basket of goods as the basis for calculating inflation is how to deal with the arrival of improved versions of older goods or altogether new goods Consider the problem that arises if a cereal is improved by adding 12 essential vitamins and minerals—and also if a box of the cereal costs 5% more It would clearly be misleading to count the entire resulting higher price as inflation, because the new price is being charged for a product of higher (or at least different) quality Ideally, one would like to know how much of the higher price is due to the quality change, and how much of it is just a higher price The Bureau of Labor Statistics, which is responsible for the computation of the Consumer Price Index, must deal with these difficulties in adjusting for quality changes Visit this website to view a list of Ford car prices between 1909 and 1927 Consider how these prices compare to today’s models Is the product today of a different quality? A new product can be thought of as an extreme improvement in quality—from something that did not exist to something that does However, the basket of goods that was fixed in the past obviously does not include new goods created since then The basket of goods and services used in the Consumer Price Index (CPI) is revised and updated over time, and so new products are gradually included But the process takes some time For example, room air conditioners were widely sold in the early 1950s, but were not introduced into the basket of goods behind the Consumer Price Index until 1964 The VCR and personal computer were available in the late 1970s and widely sold by the early 1980s, but did not enter the CPI basket of goods until 1987 By 1996, there were more than 40 million cellular phone subscribers in the United States—but cell phones were not yet part of the CPI basket of goods The parade of inventions has continued, with the CPI inevitably lagging a few years behind The arrival of new goods creates problems with respect to the accuracy of measuring inflation The reason people buy new goods, presumably, is that the new goods offer better value for money than existing goods Thus, if the price index leaves out new goods, it overlooks one of the ways in which the cost of living is improving In ... 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Here are some suggestions to help you: First, make sure you’ve got the most recent edition of this book. To learn whether a later edition is available, check the edition number on the book’s spine and then go to Nolo’s online Law Store at www.nolo.com or call RESEARC H Open Access Inflammatory changes in the airways of mice caused by cigarette smoke exposure are only partially reversed after smoking cessation Saskia Braber * , Paul AJ Henricks, Frans P Nijkamp, Aletta D Kraneveld, Gert Folkerts Abstract Background: Tobacco smoking irritates and damages the respiratory tract and contributes to a higher risk of developing lung emphysema. At present, smoking cessation is the only effective treatment for reducing the progression of lung emphysema, however, there is hardly anything known about the effects of smoking cessation on cytokine and chemokine levels in the airways. To the best of our knowledge, this is the first reported in vivo study in which cytokine profiles were determined after cessation of cigarette smoke exposure. Methods: The severity of airway remodeling and inflammation was studied by analyzing alveolar enlargement, heart hypertrophy, inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung tissue and by determining the cytokine and chemokine profiles in the BALF of A/J mice exposed to cigarette smoke for 20 weeks and 8 weeks after smoking cessation. Results: The alveolar enlargement and right ventricle heart hypertrophy found in smoke-exposed mice remained unchanged after smoking cessation. Although the neutrophilic inflammation in the BALF of cigarette smoke- exposed animals was reduced after smoking cessation, a sustained inflammation in the lung tissue was observed. The elevated cytokine (IL-1a and TNF-a) and chemokine (CCL2 and CCL3) levels in the BALF of smoke-exposed mice returned to basal levels after smoking cessation, while the increased IL-12 levels did not return to its basal level. The cigarette smoke-enhanced VEGF levels did not significantly change after smoking cessation. Moreover, IL- 10 levels were reduced in the BALF of smoke-exposed mice and these levels were still significantly decreased after smoking cessation compared to the control animals. Conclusion: The inflammatory changes in the airways caused by cigarette smoke exposure were only partially reversed after smoking cessation. Although smoking cessation should be the first step in reducing the progression of lung emphysema, additional medication could be provided to tackle the sustained airway inflammation. Introduction There are currently more than 1.3 billion tobacco smo- kers worldwide accord ing to the World Health Organi- zation (WHO) [1]. Cigarette smoke contains more than 4000 hazardous chemical compounds, of which 200 are highly toxic [2]. It is generally accepted that cigarette smoking is the most important risk factor for the devel- opment and progression of chronic obstructive pulmon- ary disease (COPD) and accounts for about 80% of COPD cases [3,4]. COPD, a term referring to two lung diseases: chronic bronchitis and emphysema, is charac- terized by an airflow limitation that is not fully reversi- ble. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases [5]. Pulmonary hypertension and right ventricular failure are also often associated with COPD [6,7]. Since a chronic airway inflammation with alveolar wall destruction and airw ay remodeling is central to the pathogenesis of COPD, it is not surprising that several types of inflammatory cells play a role in this condition [8]. Increased numbers of macrophages and neutrophils are observed in sputum andbronchoalveolarlavagefluid(BALF)ofCOPD patients [9-11]. In addition, COPD patients have * Correspondence: s.braber@uu.nl Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands Braber et al. Respiratory Research 2010, 11:99 http://respiratory-research.com/content/11/1/99 © 2010 Braber et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ ... were eating and the places you were staying In other words, the company manager would be paying attention to the production of the firm, while 4/8 How Changes in the Cost of Living are Measured. .. one of the ways in which the cost of living is improving In addition, the price of a new good is often higher when it is first introduced and then declines over time If the new good is not included... included in the CPI for some years, until its price is 2/8 How Changes in the Cost of Living are Measured already lower, the CPI may miss counting this price decline altogether Taking these arguments