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Int. J. Med. Sci. 2007, 4 36International Journal of Medical Sciences ISSN 1449-1907 www.medsci.org 2007 4(1):36-44 © Ivyspring International Publisher. All rights reserved Research Paper Proteomic analysis of mechanisms of hypoxia-induced apoptosis in tro-phoblastic cells Shin-ichi Ishioka, Yoshiaki Ezaka, Kota Umemura, Takuhiro Hayashi, Toshiaki Endo, Tsuyoshi Saito Department of Obstetrics and Gynecology, Sapporo Medical University, School of Medicine, Sapporo, Japan Correspondence to: Shin-ichi Ishioka, Department of Obstetrics and Gynecology, Sapporo Medical University, School of Medicine, Mi-nami 1-jo, Nishi 16-chome, Chuou-ku, Sapporo, Japan. E-mail: ishioka@sapmed.ac.jp. Tel: 011-611-2111(ext.3373). Fax: 011-563-0860 Received: 2006.09.13; Accepted: 2006.12.26; Published: 2006.12.29 Preeclampsia is often accompanied by hypoxia of the placenta and this condition induces apoptosis in tro-phoblastic cells. The aim of this study was to characterize global changes of apoptosis-related proteins induced by hypoxia in trophoblastic cells so as to clarify the mechanism of hypoxia-induced apoptosis by using the PoweBlot, an antibody-based Western array. Human choriocarcinoma cell line JAR was cultured for 24 hours under aerobic and hypoxic conditions. Hypoxia induced apoptosis accompanied by increased expression of Bcl-x, Caspase-3 and -9, Hsp70, PTEN, and Bag-1. Bad, pan-JNK/SAPK-1, Bcl-2, Bid, and Caspase-8 showed de-creased expression. Hypoxia-induced apoptosis was increased with the transfection of a bag-1 antisense oligonu-cleotide. The bag-1 antisense oligonucleotide affected the expression of Bid, Bad, Bcl-2, JNK, and phosphorylated JNK, although expression of PTEN and Bcl-X did not change. Bag-1 may inhibit apoptosis by suppressing the expression of Bid and Bad. It may also enhance apoptosis by inhibiting the expression of Bcl-2 and by modulat-ing phosphorylation of JNK. Both mitochondrial and stress-activated apoptosis pathways played important roles in the hypoxia induced cell death of trophoblastic cells. These findings will contribute to establish new ap-proach to detect hypoxic stress of the placenta, which leads to preeclampsia and other hypoxia-related obstetrics complications. Key words: Hypoxia, apoptosis, trophoblast, preeclampsia 1. Introduction Hypoxia of the placenta is a cause of various complications of pregnancy. Clinical conditions such as preeclampsia, anemia, and smoking can be accom-panied by villous hypoxia, characterized by dimin-ished syncytial differentiation, syncytial knots, and prominent cytotrophoblasts [1]. Hypoxia is known to induce apoptosis in various cells, including tro-phoblastic cells [2-4]. A higher degree of apoptosis is found in placentas from pregnancies complicated by intrauterine fetal growth retardation (IUGR) [5]. Simi-larly, apoptosis is more prevalent in cytotrophoblasts from pregnancies complicated by preeclampsia com-pared with similar specimens obtained from uncom-plicated pregnancies [6]. Thus, apoptosis plays an important role in the development of various obstet-rical complications. Apoptosis is a cascade of events that involves ac-tivation of many genes and synthesis of various pro-teins. The importance of several apoptotic pathways such as mitochondrial pathways and death receptor pathways has been reported [7,8]. However, apoptosis is a very complex process, and only a single pathway cannot explain the whole apoptotic network. The bal-ance of the expression of positive and negative regu-lators of apoptosis determines the apoptotic Mechanisms of Evolution Mechanisms of Evolution Bởi: OpenStaxCollege The Hardy-Weinberg equilibrium principle says that allele frequencies in a population will remain constant in the absence of the four factors that could change them Those factors are natural selection, mutation, genetic drift, and migration (gene flow) In fact, we know they are probably always affecting populations Natural Selection Natural selection has already been discussed Alleles are expressed in a phenotype Depending on the environmental conditions, the phenotype confers an advantage or disadvantage to the individual with the phenotype relative to the other phenotypes in the population If it is an advantage, then that individual will likely have more offspring than individuals with the other phenotypes, and this will mean that the allele behind the phenotype will have greater representation in the next generation If conditions remain the same, those offspring, which are carrying the same allele, will also benefit Over time, the allele will increase in frequency in the population Mutation Mutation is a source of new alleles in a population Mutation is a change in the DNA sequence of the gene A mutation can change one allele into another, but the net effect is a change in frequency The change in frequency resulting from mutation is small, so its effect on evolution is small unless it interacts with one of the other factors, such as selection A mutation may produce an allele that is selected against, selected for, or selectively neutral Harmful mutations are removed from the population by selection and will generally only be found in very low frequencies equal to the mutation rate Beneficial mutations will spread through the population through selection, although that initial spread is slow Whether or not a mutation is beneficial or harmful is determined by whether it helps an organism survive to sexual maturity and reproduce It should be noted that mutation is the ultimate source of genetic variation in all populations—new alleles, and, therefore, new genetic variations arise through mutation 1/6 Mechanisms of Evolution Genetic Drift Another way a population’s allele frequencies can change is genetic drift ([link]), which is simply the effect of chance Genetic drift is most important in small populations Drift would be completely absent in a population with infinite individuals, but, of course, no population is this large Genetic drift occurs because the alleles in an offspring generation are a random sample of the alleles in the parent generation Alleles may or may not make it into the next generation due to chance events including mortality of an individual, events affecting finding a mate, and even the events affecting which gametes end up in fertilizations If one individual in a population of ten individuals happens to die before it leaves any offspring to the next generation, all of its genes—a tenth of the population’s gene pool—will be suddenly lost In a population of 100, that individual represents only percent of the overall gene pool; therefore, it has much less impact on the population’s genetic structure and is unlikely to remove all copies of even a relatively rare allele Imagine a population of ten individuals, half with allele A and half with allele a (the individuals are haploid) In a stable population, the next generation will also have ten individuals Choose that generation randomly by flipping a coin ten times and let heads be A and tails be a It is unlikely that the next generation will have exactly half of each allele There might be six of one and four of the other, or some different set of frequencies Thus, the allele frequencies have changed and evolution has occurred A coin will no longer work to choose the next generation (because the odds are no longer one half for each allele) The frequency in each generation will drift up and down on what is known as a random walk until at one point either all A or all a are chosen and that allele is fixed from that point on This could take a very long time for a large population This simplification is not very biological, but it can be shown that real populations behave this way The effect of drift on frequencies is greater the smaller a population is Its effect is also greater on an allele with a frequency far from one half Drift will influence every allele, even those that are being naturally selected Art Connection 2/6 Mechanisms of Evolution Genetic drift in a population can lead to the elimination of an allele from a population by chance In each generation, a random set of individuals reproduces to produce the next generation The frequency of alleles in the next generation is equal to the frequency of alleles among the individuals reproducing Do you think genetic drift would happen more quickly on an island or on the mainland? Genetic drift can also be magnified by natural or human-caused events, such as a disaster that randomly kills a large portion of the population, ... Journal of Water and Environment Technology, Vol.3, No.1, 2005 - 19 - Study on the Photolytic Mechanisms of Red 141 Dye Wastewaters with an 185nm Vacuum-UV lamp Yung-Shuen Shen Department of Environmental Engineering, Da-Yeh University, 112 Shan-Jeau Rd., Chang-Hwa, 515, Taiwan, Republic of China, Tel : 886-4-851-1888 ext : 2363, Fax : 886-4-851-1330, (E-mail : ysshen@mail.dyu.edu.tw) ABSTRACT The decomposition of Reactive Red 141 dye wastewaters by photolysis and VUV/H 2 O 2 process with a 185nm Vacuum-UV lamp in a batch photoreactor was studied under various initial concentrations of organics, solution pH values, dosages of H 2 O 2 , and purging gases (N 2 , O 2 , and air). The photolytic properties of Red 141 were found to be highly dependent on the solution pH. For the VUV/H 2 O 2 system, the individual contribution to the decomposition of Red 141 by direct photolysis, and free hydroxyl radicals destruction generated from the excitement of O 2 , H 2 O, and H 2 O 2 by an 185nm VUV lamp, respectively was differentiated by the proposed assumption. Experimental results for the VUV-only system revealed that photolytic rates of organics by purging O 2 were apparently larger than those by purging N 2 and the removal of Red 141 was found to be above 90%. For the VUV/H 2 O 2 process, the reaction rates were significantly raised compared with those by direct photolysis. The individual contribution on the decomposition of Red 141 by OH . destruction generated from the excitement of H 2 O 2 molecules was found to be higher than 50% at low pH range (pH=3) in VUV/H 2 O 2 system, however, only 30% at high pH range (pH=11) probably because of the production of hydroxyl radicals from the H 2 O 2 excitement was hampered by the alkaline catalytic reaction between the molecules of H 2 O 2 and HO 2 - . Keywords Red 141, Photolysis, VUV/H 2 O 2 Process, Vacuum-UV lamp INTRODUCTION Dyeing and finishing of textile goods is a major concern to the environmentalist because of large quantities of color, chemical oxygen demand (COD), nonbiodegradable organics, and other hazardous chemicals into the process effluents. Due to the large degree of aromatics present in these molecules and the stability of modern dyes, conventional biological treatment methods are ineffective for decolorization and degradation (Ganesh et al., 1994). The development status of light-induced Advanced oxidation processes (AOPs) for water and wastewaters treatment has gained industrial scales for the UV-oxidation of various refractory and hazardous organics in the presence of oxidants like hydrogen peroxide and/or ozone (UV/H 2 O 2 , UV/O 3 , UV/ O 3 /H 2 O 2 ) (Chemviron Carbon, 1997). The basic concept behind these technologies relies on the photolysis of the added oxidants with powerful medium-pressure mercury lamps to generate very powerful oxidizing species, well known as hydroxyl radicals, then to decompose and even mineralize organic compounds. Formation of OH . radicals by the decomposition of hydrogen peroxide can be initiated by ultraviolet (UV) light irradiation and ozone (O 3 ). The decomposition of various organic pollutants using UV/H 2 O 2 oxidation process has been proved to be very effective (Stefan et al., 1996). On the other hand, Journal of Water and Environment Technology, Vol.3, No.2, 2005 - 243 - ISOTOPE HYDROGRAPH SEPARATION FOR MODELING OF RUNOFF MECHANISMS OF ATMOSPHERICALLY DERIVED CHEMICAL AND RADIOACTIVE POLLUTANTS T. Matsunaga*, N. Yanase*, Y. Hanzawa*, K. Tsuduki* and H. Naganawa* *Department of Environmental Sciences, Tokai Research Establishment, Japan Atomic Energy Research Institute, Tokai-mura, Naka-gun, Ibaraki-ken, 319-1195, Japan ABSTRACT In a tributary watershed of the Kuji River of Japan, the hydrological components of runoff associated with a precipitation event were investigated using isotope tracers of hydrogen ( 2 H) and oxygen ( 18 O) in precipitations and stream water. The runoff was separated into "old water" (pre-existing in the ground before the precipitation event) and "new water"(from the precipitation). It was found that the discharge of several hazardous trace elements (Sb, Cu, Cr) was largely (24-54%) attributable to that of the new water in spite of its small contribution to the total water discharge. These investigations suggest that the new water may play an important role in the migration of atmospherically derived, hazardous trace elements to streams during precipitation events. The present findings will contribute to current necessity of assessment of a risk of long-term exposure to pollutants at low concentrations by providing information on their transport among different environmental media. KEYWORDS deuterium; isotope hydrograph; oxygen-18; pollutants; runoff INTRODUCTION Since the 1980s, non-point source contamination has been one of the central issues in water quality management, particularly with regard to the contamination of fresh water bodies with sources distributed over a catchment. Some of these sources can be considered to originate from the atmosphere. The widespread use of metals and their strict controls at point-sources (relevant firms of smelting, fabrication, etc.) have now raised concerns about spreading of atmospheric depositions of anthropogenic heavy metals at trace levels (NIES, 1991). While a number of related studies have been carried out, the process of inflow of contaminants to water bodies such as streams or impoundments has not been studied enough to allow quantification of its impact. An understanding of the discharge of trace elements will serve to predict migration of hazardous elements in the environment. Even radionuclides that may be released to the atmosphere in a nuclear accident can contribute to the concern of atmospherically derived, broadly spread contamination (Cooper et al., 2002). There are such instances, the Windscale and the Chernobyl accidents. Other than these instances, it is hardly possible to track those radionuclides in the actual environment, because an accidental release seldom occurs. Instead, mathematical modeling has been considered as a useful tool as for tracking those radionuclides (e.g. Monte et al., 2000). Thus, findings about the migration of stable trace elements will be also suggestive in providing a scientific basis for a migration model of those radionuclides by a similarity in their pathways including the atmosphere and the hydrosphere. We have discussed fluvial elemental loads in particulate and dissolved forms in relation with the discharge rate (Nagano et al., 2003). The present study focuses on the hydrological components of runoff after a precipitation event and on their relation to the load of dissolved elements. The Oda River and its Journal of Water and Environment Technology, Vol. 6, No.1, 2008 - 65 - Mechanisms of Unstable Nitrite Inhibition of Aerobic Phosphate Uptake Toshiaki Saito*, Kohei Takahashi**, Senta Tsuboi*, Kouta Yumoto*, Yukihito Yoshida* * Department of Civil Engineering, College of Science and Technology, Nihon University, 1-8 Kanda-surugadai, Chiyoda-ku, Tokyo, 101-8308, Japan ** present affiliation Organo Corporation, 2-8, Shinsuna 1-chome, Koto-ku, Tokyo, 136-8631, Japan ABSTRACT Recently, nitrite has been recognized as one of the considerable inhibitors of biological phosphorus removal. In fact, there are several reports on inhibitory effect of nitrite. While unfortunately, the reported critical levels of nitrite widely spread. So the real effect of nitrite has not yet been well understood. In this study, several batch tests were conducted to obtain stable and quantitative relation between the size of nitrite exposure and the size of inhibition. The obtained results are as follows; 1) Nitrite inhibits aerobic phosphate uptake of PAOs, but the inhibition is not direct inhibition by nitrite but indirect inhibition caused by reduced respiration, 2) PAOs with higher anoxic activity can reduce the inhibitory effect of nitrite, possibly because of aerobic nitrite denitrification, 3) Nitrite inhibition of aerobic phosphate uptake is successfully expressed by the model including aerobic nitrite denitrification rates. These results strongly suggest that unstable nitrite inhibition of aerobic phosphate uptake is caused by widely distributed anoxic activities of PAOs. Keywords: polyphosphate-accumulating organisms (PAOs), nitrite, inhibition, aerobic denitrification, biological phosphorus removal, anoxic phosphate uptake, activated sludge INTRODUCTION Eutrophication of closed water bodies has been one of the most serious water pollution problems all over the world. To solve this problem, nitrogen and phosphorus have to be removed from wastewater. Especially, phosphorus is often a limiting element for eutrophication so that stable performance of phosphorus removal is eagerly required. However, it is well known that biological phosphorus removal (BPR) process often becomes unstable. Therefore, it is an urgent subject to clarify the mechanism of BPR instability. Although several researchers have revealed the influencing factors (Hascoet and Florents, 1985; Kuba et al., 1994; Cech and Hartman, 1993; Liu et al., 1996), it is supposed to be other unknown factors. This study focuses on nitrite that is known as a strong inhibitor for bacteria (Rowe et al., 1979; Almeida et al., 1994; Weon et al., 2002). Since nitrite is often present in full-scale wastewater treatment plants as an intermediate both of nitrification and denitrification, nitrite could be one of the factors deteriorating biological phosphorus removal. Actually, it has been reported that nitrite severely inhibits aerobic and anoxic phosphate uptake of Poly-Phosphate Accumulating Organisms (PAOs). However, the reported critical concentration of nitrite has been widely varying (Saito et al., 2004; Kuba et al., 1996;Lee et al., 2001; Meinhold et al., 1999; Ahn et al., 2001). In order to attain stable BPR performance, the mechanism of unstable response of PAOs to nitrite exposure Address correspondence to Toshiaki Saito, Department of Civil Eengineering, College of Science and Technology, Nihon University, Email: saito@civil.cst.nihon-u.ac.jp Received March 11, 2008, Copyright  2011 Pearson Canada Inc. 25 - 1 Chapter 25 Transmission Mechanisms of Monetary Policy: The Evidence Copyright  2011 Pearson Canada Inc. 25 - 2 Structural Model • Examines whether one variable affects another by using data to build a model that explains the channels through which the variable affects the other • Transmission mechanism – The change in the money supply affects interest rates – Interest rates affect investment spending – Investment spending is a component of aggregate spending (output) Copyright  2011 Pearson Canada Inc. 25 - 3 Reduced-Form • Examines whether one variable has an effect on another by looking directly at the relationship between the two • Analyzes the effect of changes in money supply on aggregate output (spending) to see if there is a high correlation • Does not describe the specific path Copyright  2011 Pearson Canada Inc. 25 - 4 Structural Model Advantages and Disadvantages • Possible to gather more evidence ⇒ more confidence on the direction of causation • More accurate predictions • Understand how institutional changes affect the links • Only as good as the model it is based on Copyright  2011 Pearson Canada Inc. 25 - 5 Advantages and Disadvantages of Reduced Form Evidence • No restrictions imposed on the way monetary policy affects the economy • Correlation does not necessarily imply causation – Reverse causation – Outside driving factor Copyright  2011 Pearson Canada Inc. 25 - 6 Early Keynesian Evidence on the Importance of Money • Monetary policy does not matter at all • Three pieces of structural model evidence – Low interest rates during the Great Depression indicated expansionary monetary policy but had no effect on the economy – Empirical studies found no linkage between movement in nominal interest rates and investment spending – Surveys of business people confirmed that investment in physical capital was not based on market interest rates Copyright  2011 Pearson Canada Inc. 25 - 7 Objections to Early Keynesian Evidence • Friedman and Schwartz published a monetary history of the U.S. showing that monetary policy was actually contractionary during the Great Depression • Many different interest rates • During deflation, low nominal interest rates do not necessarily indicate expansionary policy • Weak link between nominal interest rates and investment spending does not rule out a strong link between real interest rates and investment spending • Interest-rate effects are only one of many channels Copyright  2011 Pearson Canada Inc. 25 - 8 Real and Nominal Interest Rates (T-bills) 1931-2009 Copyright  2011 Pearson Canada Inc. 25 - 9 Early Monetarist Evidence on the Importance of Money • Money growth causes business cycle fluctuations but its effect on the business cycle operates with “long and variable lags” • Post hoc, ergo propter hoc – Exogenous event – Reduced form nature leads to possibility of reverse causation – Lag may be a lead Copyright  2011 Pearson Canada Inc. 25 - 10 Hypothetical Example in Which Money Growth Leads Output [...]... in the growth rate of the money supply is soon followed by a decline in output in these episodes, much stronger evidence is presented that money growth is the driving force behind the business cycle • A Monetary History documents several instances in which the change in the ... to run simulations of allele changes caused by drift 4/6 Mechanisms of Evolution Gene Flow Another important evolutionary force is gene flow, or the flow of alleles in and out of a population resulting... will have exactly half of each allele There might be six of one and four of the other, or some different set of frequencies Thus, the allele frequencies have changed and evolution has occurred... Art Connection 2/6 Mechanisms of Evolution Genetic drift in a population can lead to the elimination of an allele from a population by chance In each generation, a random set of individuals reproduces

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