bluuebunny/crossref_metadata_2025 huggingface dataset:
U.S. INCOME, SAVING, AND WEALTH, 1929—1969
Authors: Christensen Lurits R. , Jorgenson Dale W.
Published: April 2005

The objective of this paper is to present income and expenditure accounts, accumulation accounts, and the asset side of the wealth accounts for the U.S. private national economy in current and constant prices. These accounts are integrated with the production and factor outlay accounts for the U.S. private domestic economy in current and constant prices given in our earlier papers. Taken together, these accounts constitute a complete accounting system in current and constant prices for the private sector of the U.S. economy.

Our complete accounting system incorporates a new concept of the standard of living, defined as the ratio of the quantity index of gross private national expenditures to the quantity index of gross private national consumer receipts. Our concept of the standard of living is similar but not identical to our concept of total factor productivity. Changes in the private standard of living reflect both changes in total factor productivity and changes in the proportion of the total product consumed in the public sector.
THE EFFECTS OF MACROECONOMIC FLUCTUATIONS ON THE DISTRIBUTION OF INCOME*
Authors: Mirer Thad W.
Published: April 2005

This study develops a microanalytic simulation model to examine the effects of macroeconomic fluctuations on the distribution on the distribution of income. A representational sample of the population of the United States is linked with equations determining the variability of various types of factor income. Each family's income experience is simulated under alternative aggregate conditions, and the income distributions arising under these conditions are compared. The main results are similar for alternative specifications of the model. The incidence of a downturn in economic activity, whether accompanied by changes in the rate of inflation or not, and measured in terms of the loss of factor income, leaves the upper middle class relatively better off than before and leaves most others relatively worse off. The very rich bear the heaviest burden.
THE TREATMENT OF STOCK APPRECIATION IN THE MEASUREMENT OF NATIONAL INCOME*
Authors: Haig Bryan
Published: April 2005

In the latest official national income publication the Australian Commonwealth Statistician has altered the treatment of stock appreciation in the measurement of national income at current prices. Previously, stock appreciation had been included in both national expenditure and national product. Now the amount of stock appreciation (the difference between the change in the value of stocks and the value of the change in stocks) has been deducted from investment in stocks, and consequently national expenditure, and from trading incomes, and consequently national income. The former procedure (including stock appreciation in national expenditure and national product) had been advocated by the present author, when editor of the first official national income publications issued by the Commonwealth Statistician. In this note an attempt is made to set out the reasons for this view. A new approach is also suggested for handling the item of stock appreciation in national income accounts, which does not rest on the assumption that stock appreciation is a capital gain which should be excluded from trading incomes and national product.
RELIABILITY OF THE QUARTERLY NATIONAL INCOME AND PRODUCT ACCOUNTS OF THE UNITED STATES, 1947–1971*
Authors: Young Allan H.
Published: April 2005

The reliability of the quarterly national income and product (NIP) accounts of the United States is examined from several standpoints. First, possible sources of error in the quarterly NIP accounts are explored, the most important being the lack of appropriate data, seasonal adjustment errors, sampling errors and biases, and the nature of the U.S. statistical system. Next, four ways of assessing the reliability of the accounts are considered. The most weight is given to measures of revisions in early estimates of the quarterly NIP aggregates. Results of previous studies of revisions are reviewed, and a summary of a major study of revisions for the period 1947–71 is given. The other ways of assessing reliability which are examined are the effect of errors on economic policy making, analysis of the statistical discrepancy, and expert judgment on sources and methodology.

The degree of accuracy is judged to be generally sufficient for the policy decisions for which the NIP estimates are used. The early estimates of a quarter's change in GNP almost always distinguish whether the ultimate estimate will be large or small and will usually distinguish whether the ultimate estimate will be larger or smaller than the preceding quarter. While the accuracy of the estimates has generally been sufficient, the accuracy for 1965 was judged insufficient by policymakers. There is some evidence that errors have been reduced over time.
PROBLEMS OF DETERMINING AND MEASURING THE RELIABILITY OF NATIONAL ACCOUNTS IN DEVELOPING COUNTRIES
Authors: Webster S. J.
Published: April 2005

Most developing countries have compiled national accounts on a regular basis only for the last few years. It has not yet been possible for them to collect many of the statistics necessary to obtain good coverage of their economic activities by methods which would generally be accepted as reliable. Consequently the checks on reliability imposed by the framework of the national accounts are often absent, and the accounts prepared contain many estimates of doubtful quality. These doubts can usually only be removed as statistics collected by better methods become available. This is proving to be a slow process, partly because of the shortage of trained statistical staff and the competing demands of social and demographic statistics and partly because of the inherent difficulties in collecting good statistics from small businesses and traditional households. The need to define traditional households as producers as well as consumers leads to our demanding extra information from this difficult sector. In addition it is often difficult for the national accounts statistician, and even more so for the user, to find out in the time available exactly how some of the statistics with which he is presented were obtained. When this cannot be done it is impossible to assess their reliability. Thus assessing the overall reliability of national accounts in developing countries for even a limited range of uses is at present largely a matter of personal judgment. The information necessary to make more objective assessments rarely exists and hence the problems which developed countries face in using such information are not yet within the experience of most developing countries.
COMMENT
Authors: Ward Michael
Published: April 2005

The basic theme of Mr. Webster's practical and uncontentious paper is that unreliability undermines credibility. In the following comment specific issues he mentions will be considered in more detail to illustrate some of the principal general points made in his paper.
PROBLEMS OF DETERMINING AND MEASURING THE RELIABILITY OF THE NATIONAL ACCOUNTS: HUNGARY'S EXPERIENCES
Authors: ÁRVAY J.
Published: April 2005

Economic realities can be described in national accounting only by certain approximative means and presumptions; therefore they cannot be measured with absolute accuracy. However, because of their great importance these investigations must fulfil as far as possible the reliability required for the economic control and planning of the national economy, in accordance with predetermined concepts and methods.

The reliability of national accounting is favourable in Hungary, as they are based mostly (92 percent) on the bookkeeping data of enterprises, cooperatives and institutions. The bookkeeping system is uniform in all economic organizations, in conformity with central regulations, and it takes into account the demand of computations for national accounting.

Despite these favourable conditions lesser or greater contradictions can be found in the national accounts every year. The absolute measure of the differences is not significant; however, if compared to the annual increase it results in uncertainty of 15 percent. The uncertainty is reduced by the fact that the sign of differences is the same every year.

The author classifies the causes of uncertainty in national accounts into four groups: 1. problems of the time shift of the connected economic processes and of their accounting; 2. effect of the enterprise interests; 3. inadequacy of methodological regulation; 4. inaccuracy of data surveys and processing. The study deals with the special factors of inaccuracy occurring in constant price accounting. Inaccuracy of the most important aggregates, for instance that of the volume index of the national income, comes to 0.5‐0.7 percent which results, in the case of a yearly 5 percent “real” increase in the index, in reliability limits of 10 to 15 percent.

In the concluding part of the study the author points out that in Hungary the unexplored contradictions are not shown as “statistical discrepancy” but they are included in the various aggregates on the basis of considerations discussed in the study.
DISTRIBUTION OF LABOR INCOMES IN URBAN ZAIRE
Authors: McCabe James L.
Published: April 2005

The author addresses himself first to the problem that summary measures of wage income inequality, computed for Kinshasa, the main urban area in Zaire, tend to overstate the degree of total labor income inequality among sharing units of comparable size. It is argued that this is true for two main reasons: (1) earnings from female commercial activity are not recorded in the available statistics; and (2) the 1960 UN definition of household upon which the measures of inequality are based understates the size of the actual sharing unit. Data taken from the 1967 Socio‐Demographic Survey of Kinshasa and the 1970 household budget study are used to test these hypotheses regarding short‐run income inequality.

The policy observation is made that, while modernization of the commodity distribution system may provide a disincentive for sharing and a reduction in opportunities for female employment, investment in non‐service sectors may equalize the secular income distribution for a given migration cohort. Evidence of unskilled migrants moving from service to non‐service sector employment in response to increased labor demand is presented. This is accomplished by supplementing sample survey data with time series on aggregate employment by sector for Kinshasa.
HOME OWNERSHIP AND THE WEALTH POSITION OF BLACK AND WHITE AMERICANS*
Authors: Birnbaum Howard , Weston Rafael
Published: April 2005

This paper examines the wealth position of blacks relative to whites, on the basis of data in the Survey of Economic Opportunity. The analysis indicates that at the same levels of both income and wealth blacks consistently invest more in consumer durables, especially housing, than do whites. The paper then explores possible explanations for this finding, suggesting that these investment differences are not solely due to the income and wealth position of blacks, but may be due to a smaller set of investment opportunities institutionally fostered by discriminatory forces.
WEALTH DISTRIBUTION AND INVESTMENT INCOME IN BRITAIN*
Authors: Atkinson A. B. , Harrison A. J.
Published: April 2005

This paper examines two different approaches to the estimation of the size distribution of wealth. The first section describes new estimates for the distribution in Britain in 1968 using the estate method and discusses the sensitivity of the results to the main assumptions. The second section presents preliminary estimates using the investment data, a method which has not been widely used. In the final section the results obtained for the upper tail of the distribution from the two methods are compared.
THE SIZE DISTRIBUTION OF PERSONAL WEALTH IN THE REPUBLIC OF IRELAND1
Authors: Lyons Patrick M.
Published: April 2005

This paper presents the results of applying the mortality multiplier approach to estate duty statistics in order to estimate the size distribution of personal wealth in the Republic of Ireland. It commences with an examination of the limitations of the estate duty statistics, a discussion of the problems involved in collecting the data, and a short consideration of the mortality multipliers used.

Estimates are presented for the size distribution of personal wealth, and the distribution of wealth between age groups. Some comparisons are given with wealth in Northern Ireland, Great Britain and the U.S.A. Estimates of the components of personal capital were not found possible.

Finally, preliminary estimates are made for the distribution of wealth among married and single persons, in order to provide the basis for an analysis of wealth possessed by wealth‐owning units (defined as single males, single females and married couples). By making extreme assumptions, upper and lower limits are placed on the actual pattern of the size distribution of wealth by wealth‐owning units.
MEASUREMENT OF THE DISTRIBUTION OF WEALTH IN CANADA
Authors: Podoluk J. R.
Published: April 2005

The only periodic data available in Canada on the asset holdings and net worth of the household sector are data collected through a series of household surveys originally initiated in 1954. Some limited data on the holdings of financial claims by the personal and unincorporated business sector are available from flow of funds work. Data are unavailable for estimation from estate tax returns.

The scope of the surveys has been expanded substantially so that the most recent survey obtained a very comprehensive list of asset holdings. The experience with Canadian surveys has been similar to that of other countries; surveys appear to underestimate asset holdings although the estimates are more reliable for widely held assets than for assets with a very skewed distribution. Nevertheless, the surveys appear to trace the accumulated distribution of personal savings over time to a considerable degree and provide useful cross‐sectional trend data.

Canadian data show that wealth is more unequally distributed among family units than is income although wealth appears to be more equally distributed between income groups than is income. Wealth is also very unequally distributed within the same income group. Over time, there appears to have been some movement towards a more equal distribution of asset holdings between income groups.
THE SUITABILITY OF THE DIVISIA INDEX FOR THE MEASUREMENT OF ECONOMIC AGGREGATES
Authors: Usher D.
Published: April 2005

This paper considers the properties of the Divisia, or chain‐link, index, as they relate to the argument that this is the most appropriate index for use in studying the sources of economic growth. The great advantage of the Divisia index is alleged to be its “accuracy”, that is, its capacity to combine time series of prices and quantities to give a true reflection of the height of a utility or production function over time. The paper shows that there are circumstances where the confidence in the accuracy of the Divisia index is justified, but that the conditions required are very restrictive and typically do not obtain in the contexts where the Divisia index is used. Misplaced confidence in the Divisia index has led to errors of interpretation that might otherwise have been avoided, and has given rise to a distorted view of the process of economic growth.
CHANGING INCOME DISTRIBUTION UNDER DEVELOPMENT: COLOMBIA
Authors: Berry A.
Published: April 2005

This paper examines the available evidence relative to the distribution of income in a developing country, Colombia, over a relatively long span of years, roughly from the mid‐30s to the mid‐60s, especially in the context of the argument that recent growth has been characterized by worsening distribution and stable or declining incomes for lower income groups. The basic conclusions are that income distribution within agriculture worsened throughout the period, while non‐agricultural income probably worsened from the mid‐30s to the early 50s, improved from then to the mid‐60s, and then leveled off. During the period of improvement in non‐agricultural income, it appears that the overall distribution also improved somewhat. Over the period as a whole, the main gainers have been the second and third deciles from the top; the top decile appears to have lost. The bottom two deciles also appear to have lost.
AN ANALYSIS OF REVISIONS OF NATIONAL ACCOUNTS DATA FOR 40 COUNTRIES
Authors: Glejser H. , Schavey P.
Published: April 2005

The paper analyzes annual revisions of figures for G.N.P. and 8 of its components in 40 countries. It arrives at the conclusion that first estimates are very often significantly biased downwards, especially Private Consumption, Fixed Investment, G.D.P. and G.N.P. Also successive revisions are sometimes correlated (negatively in most cases). The distribution of revisions differ as between developed and developing countries.
THE PRELIMINARY AND FINAL FIGURES OF THE DANISH NATIONAL ACCOUNTS
Authors: Bjerke Kjeld
Published: April 2005

This paper compares preliminary estimates (available about four months after the close of the period to which they refer) with final estimates (available three years after the close of the period) for certain national accounting aggregates and some of their major components. It concludes that preliminary estimates are consistently low for gross domestic product, exports, and public consumption, whereas imports, private consumption, and gross capital formation may be either low or high. The best early estimates, in the sense of closest to the final figures, are those for gross domestic product, imports, and exports.
THE EFFICIENCY OF REAL AND HUMAN RESOURCES IN HUNGARIAN INDUSTRY
Authors: Nyilas András
Published: April 2005

The author attributes economic growth in Hungary to three factors: structural change, increase of employment, and productivity. On the basis of this he points out that in the 1950's the first two factors were responsible for nearly half of the economic growth. From the 1960's this tendency has changed; more and more importance has been taken by the increase of productivity. As the main source of economic growth is the increase of industrial productivity, in the further part of the study the author makes an attempt to break down the development of Hungarian industry into its components and to analyse their efficiency. Starting from the present conditions of industrial development he investigates what further increase of industry the resources accumulated till now and their probable growth will allow in the future.

Taking into account the role of material and human resources the author draws the following conclusions.

Industrial production will increase in the future at the same rate as productivity.

The increase of industrial investment will probably be lessened, which postulates the greater increase of capital productivity as well as that productivity will increase at a higher rate than the capital‐labour ratio.

These conclusions assume an increase in the efficiency of industrial investment and an above average increase in the high‐productivity branches.

A further source of increasing productivity is accumulated human capital. The higher educational level is one of the guarantees for the ever‐increasing role of productivity in economic growth in the future.
SUGGESTIONS FOR TREATMENT OF HUMAN CAPITAL IN NATIONAL ACCOUNTS—WITH ILLUSTRATIONS FROM INDIAN DATA*
Authors: Sharma Devindra , Ram Rati
Published: April 2005

After giving a brief discussion of the biases that exist in the conventional estimation procedures followed in the construction of national accounts, this paper argues for restructuring of national accounts so as to treat human capital formation as investment rather than consumption and suggests that a beginning should be made in respect of schooling. The argument is based on the notion that “investment” or “capital” is that which yields future income streams and also on the rather obvious point that treating as consumption large outlays that really constitute investment distorts analyses of resource allocation, growth and income distribution, and obscures intersectoral relations. It is pointed out that the proposed restructuring of national accounts is more relevant and important for developing countries, many of which are embarked on investment planning. Another major point emphasized is that the input of students’time should be properly measured and included in the estimates of capital formation by schooling.

To illustrate what these proposals imply, revision has been attempted of the estimates of (a) educational outlay (or activity in the education sector), (b) gross capital formation, and (c) gross national product, pertaining to the national accounts of a major developing country, namely India, for the years 1960–61 through 1965–66. The modified estimates, though first approximations and covering only a part of the human capital formation and having a systematically downward bias, nevertheless indicate an upward revision of the estimate of activity in the education sector by about 200 to 300 percent, of gross capital formation by about 50 percent and of the gross national product by 4 to 7 percent. These magnitudes show the substantial order of distortion involved in the conventional procedures.
GROWTH, POVERTY, AND INEQUALITY IN LATIN AMERICA: A CAUSAL ANALYSIS, 1970–94
Authors: Janvry Alain de , Sadoulet Elisabeth
Published: April 2005

Taking advantage of consistent poverty and income inequality data for 12 Latin American countries between 1970 and 1994, we analyze the determinants of changes in the incidence of urban and rural poverty and in Gini coefficients over spells of years, stressing in particular the role of aggregate income growth. We find that income growth reduces urban and rural poverty but not inequality. We also find that income growth is more effective in reducing urban poverty if the levels of inequality and poverty are lower, and the levels of secondary education higher. We show that there is an asymmetry in the impact of growth on poverty and inequality, with recession having strong negative effects on both poverty and inequality. Since growth does not reduce inequality, economic cycles create ratchet effects on the level of inequality. However, post‐structural adjustment growth is quite effective at reducing poverty, particularly if inequality is low.
ACCOUNTING FOR NONMARKET HOUSEHOLD PRODUCTION WITHIN A NATIONAL ACCOUNTS FRAMEWORK
Authors: Landefeld J. Steven , McCulla Stephanie H.
Published: April 2005

The satellite accounts illustrated in this paper reflect the household's role as a producer and an investor in durables as well as a consumer by modifying the NIPA's to (1) incorporate the value of nonmarket (unpaid) household work into GDP; and (2) treat expenditures on consumer durables as investment and measure the value of the services those durables provide. Additionally, an Input–Output (I–O) model highlights the household's functions as a producer and investor in much greater detail for the year 1992 by incorporating a household industry for each time‐use activity and by showing the inputs to and outputs from each household industry's production.
DOMINANCE TESTING OF TRANSFERS IN ROMANIA
Authors: Sahn David E. , Younger Stephen D. , Simler Kenneth R.
Published: April 2005

In this paper we compare the progressivity of different government transfers made to households in Romania. We use distribution free standard errors to examine the difference between concentration curves that may be correlated, and thereafter employ statistical tests that take into account the covariance matrix for the ordinate estimates. In addition, we estimate extended Gini coefficients for the same transfers to check their consistency with the tests of inequality dominance. The results show that almost all transfer payments in Romania are progressive, and that they have an important effect on the distribution of income. Rankings among different transfer payments are, however, not robust. In particular, sensitivity analysis using different household equivalence scales indicates that many results are not consistent across scales, and that lower size elasticities contribute to changes in ranking of Ginis and loss of statistical significance in dominance tests.
NATIONAL ACCOUNTS ESTIMATION USING INDICATOR RATIOS
Authors: Magnus Jan R. , Tongeren Jan W. van , Vos Aart F. de
Published: April 2005

We propose a new approach to national accounts compilation, which also serves as a formalization of current compilation practices. When formalizing the procedure, a distinction is made between (basic) data, national accounts identities and so‐called indicator ratios. The latter are ratios of or percentage relations between national accounts variables, such as the relation between output and value added. Indicator ratios are currently used in national accounts compilation practices in order to make adjustments to the basic data or to fill in missing data. The latter use is particularly relevant when basic data are scarce, which is the case not only in many developing countries, but also in developed countries when annual accounts are compiled for recent periods. The (basic) data, indicator ratios and identities together are used in a Bayesian approach to estimate the values of national accounts variables and analytical indicator ratios based thereon. The amendment of the current practices consists in introducing reliability intervals of basic data and indicator ratios, which allows for the use of a much larger number of indicator ratios in the compilation and checking of national accounts data. The Bayesian compilation approach makes it possible–in contrast to current practices–to use indicator ratios both as priors and as analytical indicators.
MEASURING NEW ZEALAND'S GDP 1865–1933: A COINTEGRATION‐BASED APPROACH
Authors: Greasley David , Oxley Les
Published: April 2005

Official and semi‐official estimates of New Zealand's national income are available on an annual basis for the years since 1932. Retrospective, non‐official, estimates are available from 1859. Chiefly these are constructed following Doblin's (1951) pioneering use of money stock data, velocity, and the implications of the Quantity Theory of Money, and include the estimates of Hawke (1975), Rankin (1992) and Cashin (1995).

This paper estimates New Zealand real GDP per capita with monetary data using valid, intervention‐free, cointegration methods. The new measures avoid the ad hoc adjustments found in Rankin (1992), yet unlike Cashin (1995), they incoporate specific New Zealand monetary features. The new time series conform well with independent benchmarks and the historiography of the pre‐1914 period. Alternatively, they suggest an interpretation of New Zealand's growth experience for years around World War One which differs from that of Australia, and from the findings of Rankin (1992) and Cashin (1995).
Short hydrogen bonds in proteins
Authors: Rajagopal Sathyapriya , Vishveshwara Saraswathi
Published: April 2005

Short hydrogen bonds are present in many chemical and biological systems. It is well known that these short hydrogen bonds are found in the active site of enzymes and aid enzyme catalysis. This study aims to systematically characterize all short hydrogen bonds from a nonredundant dataset of protein structures. The study has revealed that short hydrogen bonds are commonly found in proteins and are widely present in different regions of the protein chain, such as the backbone or side chain, and in different secondary structural regions such as helices, strands and turns. The frequency of occurrence of donors and acceptors from the charged side chains as well as from the neutral backbone atoms is equally high. This suggests that short hydrogen bonds in proteins occur either due to increased strength or due to geometrical constraints and this has been illustrated from several examples.
Adhesion properties of adhesion‐regulating molecule 1 protein on endothelial cells
Authors: Lamerant Nathalie , Kieda Claudine
Published: April 2005

Numerous adhesion molecules have been described, and the molecular mechanisms of lymphocyte trafficking across the endothelium is starting to be elucidated. Identification of the molecules involved in the organoselectivity of this process would help in the targeting of drug therapy to specific tissues. Adhesion‐regulating molecule‐1 (ARM‐1) is an adhesion‐regulating molecule previously identified on T cells. It does not belong to any known families of adhesion molecules. In this study, we show the presence of ARM‐1 in endothelial cells, the adhesion partners of lymphocytes. ARM‐1 mRNA was found to be differentially expressed in endothelial cell lines of various tissue origin and lymphocyte cell lines. Interestingly, ARM‐1 is absent from skin endothelial cells. In our assay, skin endothelial cells display a distinct capacity to mediate adhesion of activated T lymphocytes. Overexpression of ARM‐1 in skin endothelial cells increased adhesion of CEMT4 and NK lymphocytes, confirming that ARM‐1 also regulates adhesion in endothelial cells. We also show that ARM‐1 is a cytosolic protein associated with the plasma membrane. However, no cell surface expression of the protein was observed. These results suggest an indirect role of ARM‐1 in adhesion rather than a direct role as an adhesion molecule itself.
14‐3‐3 Proteins regulate glycogen synthase 3β phosphorylation and inhibit cardiomyocyte hypertrophy
Authors: Liao Wenqiang , Wang Shuyi , Han Chide , Zhang Youyi
Published: April 2005

14‐3‐3 Proteins are dimeric phophoserine‐binding molecules that participate in important cellular processes such as cell proliferation, cell‐cycle control and the stress response. In this work, we report that several isoforms of 14‐3‐3s are expressed in neonatal rat cardiomyocytes. To understand their function, we utilized a general 14‐3‐3 peptide inhibitor, R18, to disrupt 14‐3‐3 functions in cardiomyocytes. Cardiomyocytes infected with adenovirus‐expressing YFP‐R18 (AdR18) exhibited markedly increased protein synthesis and atrial natriuretic peptide production and potentiated the responses to norepinephrine stimulation. This response was blocked by the pretreatment with LY294002, a phosphoinositide 3‐kinase (PI3K) inhibitor. Consistent with a role of PI3K in the R18 effect, R18 induced phosphorylation of a protein cloned from the vakt oncogene of retrovirus AKT8 (Akt – also called protein kinase B, PKB) at Ser473 and glycogen synthase 3β (GSK3β) at Ser9, but not extracellular signal‐regulated kinase 1/2 (ERK1/2). AdR18‐induced PKB and GSK3β phosphorylation was completely blocked by LY294002. In addition, a member of the nuclear factor of activated T cells (NFAT) family, NFAT3, was converted into faster mobility forms and translocated into the nucleus upon the treatment of AdR18. These results suggest that 14‐3‐3s inhibits cardiomyocytes hypertrophy through regulation of the PI3K/PKB/GSK3β and NFAT pathway.
Light‐induced reactions of Escherichia coli DNA photolyase monitored by Fourier transform infrared spectroscopy
Authors: Schleicher Erik , Heßling Benedikt , Illarionova Viktoria , Bacher Adelbert , Weber Stefan , Richter Gerald , Gerwert Klaus
Published: April 2005

Cyclobutane‐type pyrimidine dimers generated by ultraviolet irradiation of DNA can be cleaved by DNA photolyase. The enzyme‐catalysed reaction is believed to be initiated by the light‐induced transfer of an electron from the anionic FADH− chromophore of the enzyme to the pyrimidine dimer. In this contribution, first infrared experiments using a novel E109A mutant of Escherichia coli DNA photolyase, which is catalytically active but unable to bind the second cofactor methenyltetrahydrofolate, are described. A stable blue‐coloured form of the enzyme carrying a neutral FADH radical cofactor can be interpreted as an intermediate analogue of the light‐driven DNA repair reaction and can be reduced to the enzymatically active FADH− form by red‐light irradiation. Difference Fourier transform infrared (FT‐IR) spectroscopy was used to monitor vibronic bands of the blue radical form and of the fully reduced FADH− form of the enzyme. Preliminary band assignments are based on experiments with 15N‐labelled enzyme and on experiments with D2O as solvent. Difference FT‐IR measurements were also used to observe the formation of thymidine dimers by ultraviolet irradiation and their repair by light‐driven photolyase catalysis. This study provides the basis for future time‐resolved FT‐IR studies which are aimed at an elucidation of a detailed molecular picture of the light‐driven DNA repair process.
Biochemical and spectroscopic characterization of the bacterial phytochrome of Pseudomonas aeruginosa
Authors: Tasler Ronja , Moises Tina , Frankenberg‐Dinkel Nicole
Published: April 2005

Phytochromes are photochromic biliproteins found in plants as well as in some cyanotrophic, photoautotrophic and heterotrophic bacteria. In many bacteria, their function is largely unknown. Here we describe the biochemical and spectroscopic characterization of recombinant bacterial phytochrome from the opportunistic pathogen Pseudomonas aeruginosa (PaBphP). The recombinant protein displays all the characteristic features of a bonafide phytochrome. In contrast with cyanobacteria and plants, the chromophore of this bacterial phytochrome is biliverdin IXα, which is produced by the heme oxygenase BphO in P. aeruginosa. This chromophore was shown to be covalently attached via its A‐ring endo‐vinyl group to a cysteine residue outside the defined bilin lyase domain of plant and cyanobacterial phytochromes. Site‐directed mutagenesis identified Cys12 and His247 as being important for chromophore binding and photoreversibility, respectively. PaBphP is synthesized in the dark in the red‐light‐absorbing Pr form and immediately converted into a far‐red‐light‐absorbing Pfr‐enriched form. It shows the characteristic red/far‐red‐light‐induced photoreversibility of phytochromes. A chromophore analog that lacks the C15/16 double bond was used to show that this photoreversibility is due to a 15Z/15E isomerization of the biliverdin chromophore. Autophosphorylation of PaBphP was demonstrated, confirming its role as a sensor kinase of a bacterial two‐component signaling system.
Syndecan‐4 is a signaling molecule for stromal cell‐derived factor‐1 (SDF‐1)/ CXCL12
Authors: Charnaux Nathalie , Brule Séverine , Hamon Morgan , Chaigneau Thomas , Saffar Line , Prost Catherine , Lievre Nicole , Gattegno Liliane
Published: April 2005

Stromal cell‐derived factor‐1 (SDF‐1)/CXCL12, the ligand for CXCR4, induces signal transduction. We previously showed that CXCL12 binds to high‐ and low‐affinity sites expressed by primary cells and cell lines, and forms complexes with CXCR4 as expected and also with a proteoglycan, syndecan‐4, but does not form complexes with syndecan‐1, syndecan‐2, CD44 or beta‐glycan. We also demonstrated the occurrence of a CXCL12‐independent heteromeric complex between CXCR4 and syndecan‐4. However, our data ruled out the glycosaminoglycan‐dependent binding of CXCL12 to HeLa cells facilitating the binding of this chemokine to CXCR4. Here, we demonstrate that CXCL12 directly binds to syndecan‐4 in a glycosaminoglycan‐dependent manner. We show that upon stimulation of HeLa cells by CXCL12, CXCR4 becomes tyrosine phosphorylated as expected, while syndecan‐4 (but not syndecan‐1, syndecan‐2 or beta‐glycan) also undergoes such tyrosine phosphorylation. Moreover, tyrosine‐phosphorylated syndecan‐4 from CXCL12‐stimulated HeLa cells physically coassociates with tyrosine phosphorylated CXCR4. Pretreatment of the cells with heparitinases I and III prevented the tyrosine phosphorylation of syndecan‐4, which suggests that the heparan sulfate‐dependent binding of SDF‐1 to this proteoglycan is involved. Finally, by reducing syndecan‐4 expression using RNA interference or by pretreating the cells with heparitinase I and III mixture, we suggest the involvement of syndecan‐4 and heparan sulfate in p44/p42 mitogen‐activated protein kinase and Jun N‐terminal/stress‐activated protein kinase activation by action of CXCL12 on HeLa cells. However, these treatments did not modify the calcium mobilization induced by CXCL12 in these cells. Therefore, syndecan‐4 behaves as a CXCL12 receptor, selectively involved in some transduction pathways induced by SDF‐1, and heparan sulfate plays a role in these events.
The multifarious short‐term regulation of ammonium assimilation of Escherichia coli: dissection using an in silico replica
Authors: Bruggeman Frank J. , Boogerd Fred C. , Westerhoff Hans V.
Published: April 2005

Ammonium assimilation in Escherichia coli is regulated through multiple mechanisms (metabolic, signal transduction leading to covalent modification, transcription, and translation), which (in‐)directly affect the activities of its two ammonium‐assimilating enzymes, i.e. glutamine synthetase (GS) and glutamate dehydrogenase (GDH). Much is known about the kinetic properties of the components of the regulatory network that these enzymes are part of, but the ways in which, and the extents to which the network leads to subtle and quasi‐intelligent regulation are unappreciated. To determine whether our present knowledge of the interactions between and the kinetic properties of the components of this network is complete − to the extent that when integrated in a kinetic model it suffices to calculate observed physiological behaviour − we now construct a kinetic model of this network, based on all of the kinetic data on the components that is available in the literature. We use this model to analyse regulation of ammonium assimilation at various carbon statuses for cells that have adapted to low and high ammonium concentrations. We show how a sudden increase in ammonium availability brings about a rapid redirection of the ammonium assimilation flux from GS/glutamate synthase (GOGAT) to GDH. The extent of redistribution depends on the nitrogen and carbon status of the cell. We develop a method to quantify the relative importance of the various regulators in the network. We find the importance is shared among regulators. We confirm that the adenylylation state of GS is the major regulator but that a total of 40% of the regulation is mediated by ADP (22%), glutamate (10%), glutamine (7%) and ATP (1%). The total steady‐state ammonium assimilation flux is remarkably robust against changes in the ammonium concentration, but the fluxes through GS and GDH are completely nonrobust. Gene expression of GOGAT above a threshold value makes expression of GS under ammonium‐limited conditions, and of GDH under glucose‐limited conditions, sufficient for ammonium assimilation.
Small exterior hydrophobic cluster contributes to conformational stability and steroid binding in ketosteroid isomerase from Pseudomonas putida biotype B
Authors: Yun Young S. , Nam Gyu H. , Kim Yeon‐Gil , Oh Byung‐Ha , Choi Kwan Y.
Published: April 2005

A structural motif called the small exterior hydrophobic cluster (SEHC) has been proposed to explain the stabilizing effect mediated by solvent‐exposed hydrophobic residues; however, little is known about its biological roles. Unusually, in Δ5‐3‐ketosteroid isomerase from Pseudomonas putida biotype B (KSI‐PI) Trp92 is exposed to solvent on the protein surface, forming a SEHC with the side‐chains of Leu125 and Val127. In order to identify the role of the SEHC in KSI‐PI, mutants of those amino acids associated with the SEHC were prepared. The W92A, L125A/V127A, and W92A/L125A/V127A mutations largely decreased the conformational stability, while the L125F/V127F mutation slightly increased the stability, indicating that hydrophobic packing by the SEHC is important in maintaining stability. The crystal structure of W92A revealed that the decreased stability caused by the removal of the bulky side‐chain of Trp92 could be attributed to the destabilization of the surface hydrophobic layer consisting of a solvent‐exposed β‐sheet. Consistent with the structural data, the binding affinities for three different steroids showed that the surface hydrophobic layer stabilized by SEHC is required for KSI‐PI to efficiently recognize hydrophobic steroids. Unfolding kinetics based on analysis of the ΦU value also indicated that the SEHC in the native state was resistant to the unfolding process, despite its solvent‐exposed site. Taken together, our results demonstrate that the SEHC plays a key role in the structural integrity that is needed for KSI‐PI to stabilize the hydrophobic surface conformation and thereby contributes both to the overall conformational stability and to the binding of hydrophobic steroids in water solution.
Solution structure and internal dynamics of NSCP, a compact calcium‐binding protein
Authors: Rabah Ghada , Popescu Razvan , Cox Jos A. , Engelborghs Yves , Craescu Constantin T.
Published: April 2005

The solution structure of Nereis diversicolor sarcoplasmic calcium‐binding protein (NSCP) in the calcium‐bound form was determined by NMR spectroscopy, distance geometry and simulated annealing. Based on 1859 NOE restraints and 262 angular restraints, 17 structures were generated with a rmsd of 0.87 Å from the mean structure. The solution structure, which is highly similar to the structure obtained by X‐ray crystallography, includes two open EF‐hand domains, which are in close contact through their hydrophobic surfaces. The internal dynamics of the protein backbone were determined by studying amide hydrogen/deuterium exchange rates and 15N nuclear relaxation. The two methods revealed a highly compact and rigid structure, with greatly restricted mobility at the two termini. For most of the amide protons, the free energy of exchange‐compatible structural opening is similar to the free energy of structural stability, suggesting that isotope exchange of these protons takes place through global unfolding of the protein. Enhanced conformational flexibility was noted in the unoccupied Ca2+‐binding site II, as well as the neighbouring helices. Analysis of the experimental nuclear relaxation and the molecular dynamics simulations give very similar profiles for the backbone generalized order parameter (S2), a parameter related to the amplitude of fast (picosecond to nanosecond) movements of NH‐H vectors. We also noted a significant correlation between this parameter, the exchange rate, and the crystallographic B factor along the sequence.
Actin mutations in hypertrophic and dilated cardiomyopathy cause inefficient protein folding and perturbed filament formation
Authors: Vang Søren , Corydon Thomas J. , Børglum Anders D. , Scott Melissa D. , Frydman Judith , Mogensen Jens , Gregersen Niels , Bross Peter
Published: April 2005

Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most common hereditary cardiac conditions. Both are frequent causes of sudden death and are often associated with an adverse disease course. Alpha‐cardiac actin is one of the disease genes where different missense mutations have been found to cause either HCM or DCM. We have tested the hypothesis that the protein‐folding pathway plays a role in disease development for two actin variants associated with DCM and six associated with HCM. Based on a cell‐free coupled translation assay the actin variants could be graded by their tendency to associate with the chaperonin TCP‐1 ring complex/chaperonin containing TCP‐1 (TRiC/CCT) as well as their propensity to acquire their native conformation. Some variant proteins are completely stalled in a complex with TRiC and fail to fold into mature globular actin and some appear to fold as efficiently as the wild‐type protein. A fraction of the translated polypeptide became ubiquitinated and detergent insoluble. Variant actin proteins overexpressed in mammalian cell lines fail to incorporate into actin filaments in a manner correlating with the degree of misfolding observed in the cell‐free assay; ranging from incorporation comparable to wild‐type actin to little or no incorporation. We propose that effects of mutations on folding and fiber assembly may play a role in the molecular disease mechanism.
Quaternary structure and functional properties of Penaeus monodon hemocyanin
Authors: Beltramini Mariano , Colangelo Nadia , Giomi Folco , Bubacco Luigi , Di Muro Paolo , Hellmann Nadja , Jaenicke Elmar , Decker Heinz
Published: April 2005

The hemocyanin of the tiger shrimp, Penaeus monodon, was investigated with respect to stability and oxygen binding. While hexamers occur as a major component, dodecamers and traces of higher aggregates are also found. Both the hexamers and dodecamers were found to be extremely stable against dissociation at high pH, independently of the presence of calcium ions, in contrast to the known crustacean hemocyanins. This could be caused by only a few additional noncovalent interactions between amino acids located at the subunit–subunit interfaces. Based on X‐ray structures and sequence alignments of related hemocyanins, the particular amino acids are identified. At all pH values, the p50 and Bohr coefficients of the hexamers are twice as high as those of dodecamers. While the oxygen binding of hexamers from crustaceans can normally be described by a simple two‐state model, an additional conformational state is needed to describe the oxygen‐binding behaviour of Penaeus monodon hemocyanin within the pH range of 7.0 to 8.5. The dodecamers bind oxygen according to the nested Monod–Whyman–Changeaux (MWC) model, as observed for the same aggregation states of other hemocyanins. The oxygen‐binding properties of both the hexameric and dodecameric hemocyanins guarantee an efficient supply of the animal with oxygen, with respect to the ratio between their concentrations. It seems that under normoxic conditions, hexamers play the major role. Under hypoxic conditions, the hexamers are expected not to be completely loaded with oxygen. Here, the dodecamers are supposed to be responsible for the oxygen supply.
Hyperthermal stability of neuroglobin and cytoglobin
Authors: Hamdane Djemel , Kiger Laurent , Dewilde Sylvia , Uzan Julien , Burmester Thorsten , Hankeln Thomas , Moens Luc , Marden Michael C
Published: April 2005

Neuroglobin (Ngb) and cytoglobin (Cygb), recent additions to the globin family, display a hexa‐coordinated (bis‐histidyl) heme in the absence of external ligands. Although these proteins have the classical globin fold they reveal a very high thermal stability with a melting temperature (Tm) of 100 °C for Ngb and 95 °C for Cygb. Moreover, flash photolysis experiments at high temperatures reveal that Ngb remains functional at 90 °C. Human Ngb may have a disulfide bond in the CD loop region; reduction of the disulfide bond increases the affinity of the iron atom for the distal (E7) histidine, and leads to a 3 °C increase in the Tm for ferrous Ngb. A similar Tm is found for a mutant of human Ngb without cysteines. Apparently, the disulfide bond is not involved directly in protein stability, but may influence the stability indirectly because it modifies the affinity of the distal histidine. Mutation of the distal histidine leads to lower thermal stability, similar to that for other globins. Only globins with a high affinity of the distal histidine show the very high thermal stability, indicating that stable hexa‐coordination is necessary for the enhanced thermal stability; the CD loop which contains the cysteines appears as a critical region in the neuroglobin thermal stability, because it may influence the affinity of the distal histidine.