bluuebunny/crossref_metadata_2025 huggingface dataset:
SIZE‐DISTRIBUTION OF EARNINGS AND HOUSEHOLD INCOMES IN SMALL SOCIALIST COUNTRIES
Authors: Michal Jan M.
Published: April 2005

Part I: Availability and meaning of East European distributional statistics are discussed.

Part II: Measures of inequality to be used in this study are examined: the Gini coefficient of concentration, though superior to some other single indicators, is found to be an unreliable comparative measure of inequality, and is therefore supplemented by a set of ratios of selected percentiles to the median.

Part III: Inequality of full‐time gross monthly earnings is measured for (almost) the whole civilian working population and for some subpopulations (selected industries, men, women) in Czechoslovakia and Yugoslavia through 1970, in Hungary through 1968: the observed inequality appears to be less than in small capitalist countries, in spite of the reversal of the socialist egalitarian trend in the 'sixties. The main factor of equalization of socialist earnings are small interoccupational and interregional differentials and a very flat age profile.

Part IV: The socio‐economic structure of households, the size of samples underlying the distributional statistics, and the composition of household “revenues” (wage and salary earnings, agricultural incomes, social security payments, relatively unimportant property incomes, as well as non‐income cash flows) are examined. Inequality coefficients are estimated for per capita revenues of all households as well as subpopulations of households in Czechoslovakia and Hungary, and some information is given on the distribution of household incomes in Yugoslavia.

Part V: Limits of desirable equalization of earnings are discussed. With very narrowly dispersed short‐term earnings, lifetime earnings tend to be rather unequally distributed because of the variation of earning years among occupations. With largely equalized primary incomes, per capita household incomes tend to be more unequally distributed, in spite of massive transfers, because of the varying ratio of earners to dependents within households. The need of income differentials as incentives to work, the probable trade‐off between income equality and economic growth, and socialist distributive principles are outlined.
HOUSEHOLD PRODUCTION AND NATIONAL PRODUCTION: AN IMPROVEMENT OF THE RECORD
Authors: Weinrobe Maurice
Published: April 2005

Man may work from sun to sun, But woman's work is never done. Anon.

It has become almost a cliché that measured growth in the U.S. is being overstated. The classic on the subject is by Mishan [5], who argues persuasively that the (uncounted) externalities from production in industrialized economies are overtaking the production which these economies are counting. But externalities are not the only problems in measuring economic activity and economic growth. Two other problems of equal importance, but more amenable to measurement, are the distinction between final and intermediate production, and the quantification of nonmarket productive behavior. In this paper, we concentrate on one aspect of the measurement of nonmarket behavior—the value of production at home by housewives.1

Specifically, we will present estimates of the value of home based nonmarket production by housewives. These estimates will then be used to supplement various national product aggregates in order to calculate more accurate growth rates for the U.S. economy. We find that the value of nonmarket production by married women during the 1960's has averaged approximately thirty percent of the GNP and close to 40 percent of the national income. The inclusion of the nonmarket work of housewives in GNP would reduce the measured rate of growth of real GNP per potential worker by about ten percent, the exact amount depending on how the value of nonmarket work is estimated. Our estimates indicate a reduction in the absolute rate of growth of almost 0.25 percent.
PERSPECTIVE ON PRODUCTIVITY RESEARCH*
Authors: Fabricant Solomon
Published: April 2005

Radical changes, up and down, have taken place in the estimates of growth in total factor productivity in the U.S. made by different economists, or by the same economists at different times. If such estimates provide “some sort of measure of our ignorance,” as Abramovitz once put it, we seemed to be a lot less ignorant in 1927 (when Cobb and Douglas published their famous paper), or in 1967 (when Jorgenson and Griliches published theirs), than we were in the years between (when Schmookler, Abramovitz, Kendrick, and Denison completed their studies), or than we are today (when we have, or will soon have, revised estimates by Denison and by Kendrick, and new estimates by Christensen and Jorgenson). Viewed in this perspective, many questions may be raised about the significance of the current estimates that something like a third or more of the rate of increase in U.S. national output is “due” to increase in productivity, as well as about the concepts, data, and methods that underlie the estimates. A list of particular subjects worth considering for research is given and each is briefly discussed.
Plasmodium falciparum hypoxanthine guanine phosphoribosyltransferase
Authors: Raman Jayalakshmi , Ashok Chethan S. , I.N. Subbayya Sujay , Anand Ranjith P. , T. Selvi Senthamizh , Balaram Hemalatha
Published: April 2005

Hypoxanthine guanine phosphoribosyltransferases (HGPRTs) catalyze the conversion of 6‐oxopurine bases to their respective nucleotides, the phosphoribosyl group being derived from phosphoribosyl pyrophosphate. Recombinant Plasmodium falciparum HGPRT, on purification, has negligible activity, and previous reports have shown that high activities can be achieved upon incubation of recombinant enzyme with the substrates hypoxanthine and phosphoribosyl pyrophosphate [Keough DT, Ng AL, Winzor DJ, Emmerson BT & de Jersey J (1999) Mol Biochem Parasitol98, 29–41; Sujay Subbayya IN & Balaram H (2000) Biochem Biophys Res Commun279, 433–437]. In this report, we show that activation is effected by the product, Inosine monophosphate (IMP), and not by the substrates. Studies carried out on Plasmodium falciparum HGPRT and on a temperature‐sensitive mutant, L44F, show that the enzymes are destabilized in the presence of the substrates and the product, IMP. These stability studies suggest that the active, product‐bound form of the enzyme is less stable than the ligand‐free, unactivated enzyme. Equilibrium isothermal‐unfolding studies indicate that the active form is destabilized by 2–3 kcal·mol−1 compared with the unactivated state. This presents a unique example of an enzyme that attains its active conformation of lower stability by product binding. This property of ligand‐mediated activation is not seen with recombinant human HGPRT, which is highly active in the unliganded state. The reversibility between highly active and weakly active states suggests a novel mechanism for the regulation of enzyme activity in P. falciparum.
MANAGERIAL INCENTIVES AND CORPORATE DIVERSIFICATION STRATEGIES
Authors: Denis David J. , Denis Diane K. , Sarin Atulya
Published: April 2005

Because the break‐up of conglomerates typically produces substantial increases in shareholder wealth, many commentators have argued that the conglomerate form of organization is inefficient. This article reports the findings of a number of recent academic studies, including the authors' own, that examine the causes and consequences of corporate diversification.

Although theoretical arguments suggest that corporate diversification can have benefits as well as costs, several studies have documented that diversified firms trade at a significant discount from their single‐segment peers. Estimates of this discount range from 10–15% of firm value, and are larger for “unrelated” diversification than for “related” diversification.

If corporate diversification has generally been a value‐reducing managerial strategy, why do firms remain diversified? One possibility, which the authors label the “agency cost” hypothesis, is that top executives without substantial equity stakes may have incentives to maintain a diversification strategy even if doing so reduces shareholder wealth. But, as top managers' ownership stakes increase, they bear a greater fraction of the costs associated with value‐reducing policies and are therefore less likely to take actions that reduce shareholder wealth. Also, to the extent that outside blockholders monitor managerial behavior, the agency cost hypothesis predicts that diversification will be less prevalent in firms with large outside blockholders. Consistent with this argument, the authors find that companies in which managers own a significant fraction of the firm's shares, and in which blockholders own a large fraction of shares, are significantly less likely to be diversified.

If agency problems lead managers to maintain value‐reducing diversification strategies, what is it that leads some of these same firms to refocus? The agency cost hypothesis predicts that managers will reduce diversification only if pressured to do so by internal or external mechanisms that reduce agency problems. Consistent with this argument, the authors find that decreases in diversification appear to be precipitated by market disciplinary forces such as block purchases, acquisition attempts, and management turnover.
Picking Your Tick: Toward a New Theory of Stock Splits
Authors: Angel James J.
Published: April 2005

Thanks to stock splits, the average nominal share price has been amazingly stable in the United States. The average NYSE share price has fluctuated within the $30 to $40 range since the late 1930s—a period in which most consumer prices have increased by a factor of 10 and the S&P index has risen over 1,500%. Why has this nominal price been so stable when every other price has increased so much?

And why do typical stock prices vary so greatly among different countries? For example, the median nominal stock price ranges from about $2 in Hong Kong and $7 in the U.K., to $103 in France and over $600 in Switzerland.

The author's recent research suggests that typical stock prices vary across countries in ways that reflect primarily differences in how markets in each country set their “tick” rules—the rules governing the minimum price variation that can occur in a stock (in the U.S., for example, the tick was recently reduced from $1/8 to $1/16). Companies, on average, appear to respond to the resulting differences in tick size by adjusting the number of their shares outstanding so that the tick size relative to the nominal share price remains relatively constant. In fact, a tick size equal to about 25 basis points of the median share price “appears to be a universal norm” across global markets.

This article explores how and why a company might wish to affect the relative tick size for its stock by splitting—and, in so doing, it suggests a “new theory” of stock splits. The theory also suggests that the optimal tick size for any given company will vary according to its size, visibility, and riskiness.
Reforming the Bookbuilding Process for IPOs
Authors: Jagannathan Ravi , Sherman Ann E.
Published: April 2005

The controversy over IPOs has raised questions about whether retail investors are being unfairly denied access to shares in IPOs and whether the new Internet auction methods might provide a fairer and more efficient way to allocate shares. This article argues that much of the popular concern may be misdirected. By and large, bookbuilding is well designed to accomplish price discovery in a cost‐effective way. And standard auctions, which have been all but abandoned in a number of countries, have generally proved disappointing for equity IPOs (although they have been successful for bond offerings). The authors propose a “hybrid” form of securities issuance that would retain the advantages of bookbuilding while incorporating a public offer “tranche” for retail investors and other measures designed to increase transparency.
How To Choose a Capital Structure: Navigating the Debt‐Equity Decision
Authors: Shivdasani Anil , Zenner Marc
Published: April 2005

In corporate offices as well as the classroom, there continues to be significant debate about the costs and benefits of debt financing. There is also considerable variation in corporate credit ratings, even among companies as large and successful as those that make up the S&P 500. Many companies have been reassessing how they manage their balance sheet and their rating agency relationships; and with the market's generally favorable response to recapitalizations and dividend increases, such financing issues are likely to receive even more attention.

Underlying the diversity of corporate credit ratings is widespread disagreement about the “right” credit rating—a matter that is complicated by the fact that the cost of debt varies widely among companies with the same rating. Although credit ratings are clearly tied to measures of indebtedness such as leverage and coverage ratios, the most important factor in most industries is a company's size. For many mid‐sized companies, an investment‐grade rating can be attained only by making a large, equity‐financed acquisition—or by making minimal use of debt. In this sense, the corporate choice of credit rating can be as much a strategic issue as a financial decision.

Maintaining the right amount of financial fl exibility is a key consideration when determining the right credit rating for a given company (although what management views as value‐preserving flexibility may be viewed by the market as value‐reducing financial “slack”). A BBB rating will accommodate considerably more leverage (30–60%) in companies with fairly stable cash flows and limited investment requirements than in more cyclical or growth‐oriented companies (10–20%). When contemplating taking on more leverage, companies should examine all major operating risks and view their capital structure in the context of an enterprisewide risk management framework.
Effects of Glucose and Plasminogen Activator Inhibitor‐1 on Collagen Metabolism in the Peritoneum
Authors: Higuchi Chieko , Tanihata Yoko , Nishimura Hideki , Naito Takashi , Sanaka Tsutomu
Published: April 2005

Abstract:  Nonphysiological solutions containing high glucose levels have been considered an important factor in the etiology of fibrotic changes in long‐term continuous ambulatory peritoneal dialysis (CAPD) patients. At the same time, increased Plasminogen Activator Inhibitor (PAI)‐1 secretion has been reported to correlate with fibrotic changes. We suspected that the high glucose content of peritoneal dialysis solution may induce peritoneal sclerosis via up‐regulation of PAI‐1 gene expression. In this study, we evaluated the effects of glucose on PAI‐1 activity in peritoneal fibrosis in a rat model of CAPD. The effects of glucose on the expressions of PAI‐1 and several other genes correlated with collagen metabolism were also examined in cultured rat peritoneal mesothelial cells and fibroblasts. Sprague‐Dawley rats were intraperitoneally injected twice daily for 28 days with phosphate‐buffered saline (PBS) (control group), PBS containing 4% glucose (glucose group), or PBS containing 4% glucose plus a PAI‐1 inhibitor (PAI‐1 inhibitor group). Thickening of the peritoneum with increase the deposition of collagens type I and III in the submesothelial interstitium were observed in the glucose and the PAI‐1 inhibitor group, but these were less severe in the PAI‐1 inhibitor group. Glucose stimulated expression of the mRNA of PAI‐1, collagen type I and III, and tissue inhibitor of metalloproteinase (TIMP)‐1 in fibroblasts but not in mesothelial cells. Glucose stimulated matrix metalloproteinase (MMP)‐13 mRNA expression in both cell types. The PAI‐1 inhibitor suppressed expression of the mRNAs induced by glucose. In conclusion, glucose induces peritoneal fibrosis, including changes in collagen metabolism, by stimulating PAI‐1 expression.
Homeward Sound
Authors: Simpson Stephen D. , Meekan Mark , Montgomery John , McCauley Rob , Jeffs Andrew
Published: April 2005

Despite spending weeks at sea as larvae, potentially scattered over many kilometers, young coral reef fish find suitable settlement habitat and in some cases return to their natal reefs. We report that some dominant families of larval reef fish use the sounds made by fish and shrimp resident on reefs to help them locate and settle on reefs and that some fish groups use specific components of the reef sound to guide their behavior. These findings could offer potential for active management of reef fisheries.
The Floral Regulator LEAFY Evolves by Substitutions in the DNA Binding Domain
Authors: Maizel Alexis , Busch Maximilian A. , Tanahashi Takako , Perkovic Josip , Kato Masahiro , Hasebe Mitsuyasu , Weigel Detlef
Published: April 2005

The plant-specific transcription factor LEAFY controls general aspects of the life cycle in a basal plant, the moss
Physcomitrella patens
. In contrast, LEAFY has more specialized functions in angiosperms, where it specifically induces floral fate during the reproductive phase. This raises the question of a concomitant change in the biochemical function of LEAFY during the evolution of land plants. We report that the DNA binding domain of LEAFY, although largely conserved, has diverged in activity. On the contrary, other, more rapidly evolving portions of the protein have few effects on LEAFY activity.
Kinesin and Dynein Move a Peroxisome in Vivo: A Tug-of-War or Coordinated Movement?
Authors: Kural Comert , Kim Hwajin , Syed Sheyum , Goshima Gohta , Gelfand Vladimir I. , Selvin Paul R.
Published: April 2005

We used fluorescence imaging with one nanometer accuracy (FIONA) to analyze organelle movement by conventional kinesin and cytoplasmic dynein in a cell. We located a green fluorescence protein (GFP)–tagged peroxisome in cultured
Drosophila
S2 cells to within 1.5 nanometers in 1.1 milliseconds, a 400-fold improvement in temporal resolution, sufficient to determine the average step size to be ∼8 nanometers for both dynein and kinesin. Furthermore, we found that dynein and kinesin do not work against each other in vivo during peroxisome transport. Rather, multiple kinesins or multiple dyneins work together, producing up to 10 times the in vitro speed.
The Real-Time Stellar Evolution of Sakurai's Object
Authors: Hajduk Marcin , Zijlstra Albert A. , Herwig Falk , van Hoof Peter A. M. , Kerber Florian , Kimeswenger Stefan , Pollacco Don L. , Evans Aneurin , Lopéz José A. , Bryce Myfanwy , Eyres Stewart P. S. , Matsuura Mikako
Published: April 2005

After a hot white dwarf ceases its nuclear burning, its helium may briefly and explosively reignite. This causes the star to evolve back into a cool giant, whereupon it experiences renewed mass ejection before reheating. A reignition event of this kind was observed in 1996 in V4334 Sgr (Sakurai's object). Its temperature decrease was 100 times the predicted rate. To understand its unexpectedly fast evolution, we have developed a model in which convective mixing is strongly suppressed under the influence of flash burning. The model predicts equally rapid reheating of the star. Radio emission from freshly ionized matter now shows that this reheating has begun. Such events may be an important source of carbon and carbonaceous dust in the Galaxy.
Transcriptional Response of
Saccharomyces cerevisiae
to the Plasma Membrane-Perturbing Compound Chitosan
Authors: Zakrzewska Anna , Boorsma Andre , Brul Stanley , Hellingwerf Klaas J. , Klis Frans M.
Published: April 2005

Chitosan is a plasma membrane-perturbing compound consisting of linear chains of β-1,4-linked glucosamine residues, which at acidic pHs become positively charged. It is extensively used as an antimicrobial compound, yet its mode of action is still unresolved. Chitosan strongly affected the growth of the yeast
Saccharomyces cerevisiae
, the food spoilage yeast
Zygosaccharomyces bailii
, and two human-pathogenic yeasts,
Candida albicans
and
Candida glabrata
. Microarray analysis of yeast cells treated with sublethal concentrations of chitosan revealed induction of the environmental stress response and three more major transcriptional responses. The first was a rapid and stable Cin5p-mediated response. Cin5p/Yap4p is a transcription factor involved in various stress responses. Deletion of
CIN5
led to increased chitosan sensitivity. The second was a Crz1p-mediated response, which is delayed compared to the Cin5p response. Crz1p is a transcription factor of the calcineurin pathway. Cells deleted for
CRZ1
or treated with the calcineurin inhibitor FK506 became hypersensitive to chitosan, supporting the notion that the Crz1p-controlled response offers protection against chitosan. The third was a strong Rlm1p-mediated response which ran parallel in time with the Crz1p-regulated response. Rlm1p is a transcription factor of the cell wall integrity pathway, which is activated by cell wall stress. Importantly, chitosan-treated cells became more resistant to β-1,3-glucanase, which is a well-known response to cell wall stress. We propose that the transcriptional response to chitosan may be representative of other plasma membrane-perturbing compounds.
Role of Snf1p in Regulation of Intracellular Sorting of the Lactose and Galactose Transporter Lac12p in
Kluyveromyces lactis
Authors: Wiedemuth Christian , Breunig Karin D.
Published: April 2005

The protein kinase Snf1/AMPK plays a central role in carbon and energy homeostasis in yeasts and higher eukaryotes. To work out which aspects of the Snf1-controlled regulatory network are conserved in evolution, the Snf1 requirement in galactose metabolism was analyzed in the yeast
Kluyveromyces lactis
. Whereas galactose induction was only delayed,
K. lactis snf1
mutants failed to accumulate the lactose/galactose H
+
symporter Lac12p in the plasma membran,e as indicated by Lac12-green fluorescent protein fusions. In contrast to wild-type cells, the fusion protein was mostly intracellular in the mutant. Growth on galactose and galactose uptake could be restored by the
KHT3
gene, which encodes a new transporter of the
HXT
subfamily of major facilitators These findings indicate a new role of Snf1p in regulation of sugar transport in
K. lactis
.
Effect of the Major Repeat Sequence on Chromosome Loss in
Candida albicans
Authors: Lephart Paul R. , Chibana Hiroji , Magee Paul T.
Published: April 2005

The major repeat sequence (MRS) is found at least once on all but one chromosome in
Candida albicans
, but as yet it has no known relation to the phenotype. The MRS affects karyotypic variation by serving as a hot spot for chromosome translocation and by expanding and contracting internal repeats, thereby changing chromosome length. Thus, MRSs on different chromosomes and those on chromosome homologues can differ in size. We proposed that the MRS's unique repeat structure and, more specifically, the size of the MRS could also affect karyotypic variation by altering the frequency of mitotic nondisjunction. Subsequent analysis shows that both natural and artificially induced differences in the size of the chromosome 5 MRS can affect chromosome segregation. Strains with chromosome 5 homologues that differ in the size of the naturally occurring MRSs show a preferential loss of the homologue with the larger MRS on sorbose, indicating that a larger MRS leads to a higher risk of mitotic nondisjunction for that homologue. While deletion of an MRS has no deleterious effect on the deletion chromosome under normal growth conditions and leads to no obvious phenotype, strains that have the MRS deleted from one chromosome 5 homologue preferentially lose the homologue with the MRS remaining. This effect on chromosome segregation is the first demonstration of a phenotype associated with the MRS.
A Point Mutation in the Cargo-Binding Domain of Myosin V Affects Its Interaction with Multiple Cargoes
Authors: Pashkova Natasha , Catlett Natalie L. , Novak Jennifer L. , Weisman Lois S.
Published: April 2005

Class V myosins move diverse intracellular cargoes, which attach via interaction of cargo-specific proteins to the myosin V globular tail. The globular tail of the yeast myosin V, Myo2p, contains two structural and functional subdomains. Subdomain I binds to the vacuole-specific protein, Vac17p, while subdomain II likely binds to an as yet unidentified secretory vesicle-specific protein. All functions of Myo2p require the tight association of subdomains I and II, which suggests that binding of a cargo to one subdomain may inhibit cargo-binding to a second subdomain. Thus, two types of mutations are predicted to specifically affect a subset of Myo2p cargoes: first are mutations within a cargo-specific binding region; second are mutations that mimic the inhibited conformation of one of the subdomains. Here we analyze a point mutation in subdomain I,
myo2-2
(
G1248D
), which is likely to be this latter type of mutation.
myo2-2
has no effect on secretory vesicle movement. The secretory vesicle binding site is in subdomain II. However,
myo2-2
is impaired in several Myo2p-related functions. While subdomains I and II of myo2-2p tightly associate, there are measurable differences in the conformation of its globular tail. Based solely on the ability to restore vacuole inheritance, a set of intragenic suppressors of
myo2-2
were identified. All suppressor mutations reside in subdomain I. Moreover, subdomain I and II interactions occurred in all suppressors, demonstrating the importance of subdomain I and II association for Myo2p function. Furthermore, 3 of the 10 suppressors globally restored all tested defects in
myo2-2
. This large proportion of global suppressors strongly suggests that
myo2-2
(
G1248
) causes a conformational change in subdomain I that simultaneously affects multiple cargoes.
PROTON-INDUCED X-RAY EMISSION STUDIES OF TWO REPRESENTATIVE FERROMANGANESE OXIDE ORES FROM EASTERN INDIA
Authors: NAYAK P. K. , CHAKRAVORTTY V. , VIJAYAN V. , SINGH P. P.
Published: April 2005

Precambrian ferromanganese oxide deposits of India and Brazil were formed in optimum favorable geological situations at specific period of evolution. Two representative ferromanganese oxide ore samples have been collected from different mines of Precambrian Bonai-Keonjhar belt, Eastern India, and were irradiated with 3 MeV proton beam from a 3 MV pelletron accelerator at Institute of Physics, Bhubaneswar, India. The spectral data were analyzed by using GUPIX software package. About 20 major, minor and trace elements including Ca , Ti , V , Cr , Co , Ni , Cu , Zn , Ga , As , Se , Rb , Sr , Y , Zr , Mo and Pb were quantified in these ores. The obtained Mn/Fe ratio and the content of the trace elements were used in interpreting the initial formation environment of the depositional basin.
ANALYSIS OF COPPER COINS BY EDXRF TECHNIQUE
Authors: RAUTRAY T. R. , VIJAYAN V. , NAYAK P. K. , JENA S.
Published: April 2005

Coins are important archaeological objects that can provide useful information regarding preparation methodology and provenance. Their classification plays a fundamental role in dating historical events, in constructing trade routes and in establishing the welfare of population. Several Indian copper coins of different periods have been studied using Energy Dispersive X-ray Fluorescence (EDXRF) spectroscopic technique. The method is rapid, efficient, multi elemental and non-destructive in nature. Concentrations of the major and trace elements like Ca , Ti , V , Cr , Mn , Fe , Co , Ni , Cu , Zn , As and Pb have been estimated in these copper coins. In the present investigation, an attempt has been made to characterize some Indian copper coins of different periods using EDXRF technique.
GREEN FUNCTIONS WITH SINGULARITIES ALONG COMPLEX SPACES
Authors: RASHKOVSKII ALEXANDER , SIGURDSSON RAGNAR
Published: April 2005

We study properties of a Green function GAwith singularities along a complex subspace A of a complex manifold X. It is defined as the largest negative plurisubharmonic function u satisfying locally u≤ log |ψ|+C, where ψ=(ψ1,…,ψm), ψ1,…,ψmare local generators for the ideal sheaf ℐAof A, and C is a constant depending on the function u and the generators. A motivation for this study is to estimate global bounded functions from the sheaf ℐAand thus proving a "Schwarz lemma" for ℐA.
MEROMORPHIC FUNCTIONS SHARING SMALL FUNCTIONS AS TARGETS
Authors: THAI DO DUC , TAN TRAN VAN
Published: April 2005

The purpose of this article is twofold. The first is to prove the unicity theorem with truncated multiplicities of meromorphic functions sharing five small functions. This gives a remarkable improvement of the results of Yuhua–Jianyong, Yao and Yi. The second is to generalize the unicity theorem of Fujimoto to meromorphic functions sharing four small functions with truncated multiplicities.
COMPLEX GENETICS OF GLAUCOMA SUSCEPTIBILITY
Authors: Libby Richard T. , Gould Douglas B. , Anderson Michael G. , John Simon W.M.
Published: April 2005

▪ Abstract  Glaucoma describes a group of diseases that kill retinal ganglion cells. There are different types of glaucoma, and each appears to be genetically heterogeneous. Different glaucoma genes have been identified, but these genes account for only a small proportion of glaucoma. Most glaucoma cases appear to be multifactorial, and are likely affected by multiple interacting loci. A number of genetic susceptibility factors have been suggested to contribute to glaucoma. These factors fit into two broad groups, those affecting intraocular pressure and those important in modulating retinal ganglion cell viability. Defining the complex genetics of glaucoma will require significant further study of the human disease and animal models. Genetic approaches are essential and will be enhanced by recently developed genomic and proteomic technologies. These technologies will provide valuable clues about pathogenesis for subsequent testing. In this review, we focus on endogenous genetic susceptibility factors and on how experimental studies will be valuable for dissecting the multifactorial complexity of their interactions.
Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men
Authors: Kok Simon W. , Roelfsema Ferdinand , Overeem Sebastiaan , Lammers Gert Jan , Frölich Marijke , Meinders A. Edo , Pijl Hanno
Published: April 2005

Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. Injection of hypocretin-1 acutely suppresses TRH and TSH release in rats. In contrast, subchronic administration does not appear to affect the hypothalamo-pituitary-thyroid ensemble in animals. We explored (in 7 patients and 7 controls) whether hypocretin deficiency impacts circulating TSH levels and circadian timing of TSH release in narcoleptic humans. Plasma TSH concentration profiles (blood samples taken at 10-min intervals during 24 h) and TSH levels in response to TRH injection were analyzed by Cluster, robust regression, approximate entropy (ApEn), and deconvolution. Circulating TSH levels were lower in patients, which was primarily attributable to lower pulse amplitude and nadir concentrations. TSH secretion correlated positively with mean 24-h leptin levels ( R2 = 0.46, P = 0.02) and negatively with amount of sleep ( R2 = 0.29, P = 0.048). Pattern-synchrony between 24-h leptin and TSH concentrations was demonstrated by significant cross-correlation and cross-ApEn analyses with no differences between controls and patients. Sleep onset was closely associated with a fall in circulating TSH. Features of diurnal rhythmicity of circulating TSH fluctuations were similar in patients and controls, with the acrophase occurring shortly after midnight. Thyroxine and triiodothyronine concentrations were similar in patients and controls and did not display a diurnal rhythm. The response of plasma TSH levels to TRH was also similar in both groups. Sleep patterns in narcoleptics were significantly disorderly compared with controls, as measured by ApEn ( P = 0.006). In summary, circulating TSH concentrations are low in hypocretin-deficient narcoleptic men, which could be attributable to their low plasma leptin levels and/or their abnormal sleep-wake cycle.
Attenuation of extracellular ATP response in cardiomyocytes isolated from hearts subjected to ischemia-reperfusion
Authors: Saini Harjot K. , Elimban Vijayan , Dhalla Naranjan S.
Published: April 2005

Extracellular ATP is known to augment cardiac contractility by increasing intracellular Ca2+concentration ([Ca2+]i) in cardiomyocytes; however, the status of ATP-mediated Ca2+mobilization in hearts undergoing ischemia-reperfusion (I/R) has not been examined previously. In this study, therefore, isolated rat hearts were subjected to 10–30 min of global ischemia and 30 min of reperfusion, and the effect of extracellular ATP on [Ca2+]iwas measured in purified cardiomyocytes by fura-2 microfluorometry. Reperfusion for 30 min of 20-min ischemic hearts, unlike 10-min ischemic hearts, revealed a partial depression in cardiac function and ATP-induced increase in [Ca2+]i; no changes in basal [Ca2+]iwere evident in 10- or 20-min I/R preparations. On the other hand, reperfusion of 30-min ischemic hearts for 5, 15, or 30 min showed a marked depression in both cardiac function and ATP-induced increase in [Ca2+]iand a dramatic increase in basal [Ca2+]i. The positive inotropic effect of extracellular ATP was attenuated, and the maximal binding characteristics of35S-labeled adenosine 5′-[γ-thio]triphosphate with crude membranes from hearts undergoing I/R was decreased. ATP-induced increase in [Ca2+]iin cardiomyocytes was depressed by verapamil and Cibacron Blue in both control and I/R hearts; however, this response in I/R hearts, unlike control hearts, was not affected by ryanodine. I/R-induced alterations in cardiac function and ATP-induced increase in [Ca2+]iwere attenuated by treatment with an antioxidant mixture and by ischemic preconditioning. The observed changes due to I/R were simulated in hearts perfused with H2O2. The results suggest an impairment of extracellular ATP-induced Ca2+mobilization in I/R hearts, and this defect appears to be mediated through oxidative stress.
Hemodynamic profile, responsiveness to anandamide, and baroreflex sensitivity of mice lacking fatty acid amide hydrolase
Authors: Pacher Pál , Bátkai Sándor , Osei-Hyiaman Douglas , Offertáler László , Liu Jie , Harvey-White Judy , Brassai Attila , Járai Zoltán , Cravatt Benjamin F. , Kunos George
Published: April 2005

The endocannabinoid anandamide exerts neurobehavioral, cardiovascular, and immune-regulatory effects through cannabinoid receptors (CB). Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the in vivo degradation of anandamide. Recent experimental studies have suggested that targeting the endocannabinergic system by FAAH inhibitors is a promising novel approach for the treatment of anxiety, inflammation, and hypertension. In this study, we compared the cardiac performance of FAAH knockout (FAAH−/−) mice and their wild-type (FAAH+/+) littermates and analyzed the hemodynamic effects of anandamide using the Millar pressure-volume conductance catheter system. Baseline cardiovascular parameters, systolic and diastolic function at different preloads, and baroreflex sensitivity were similar in FAAH−/− and FAAH+/+ mice. FAAH−/− mice displayed increased sensitivity to anandamide-induced, CB1-mediated hypotension and decreased cardiac contractility compared with FAAH+/+ littermates. In contrast, the hypotensive potency of synthetic CB1 agonist HU-210 and the level of expression of myocardial CB1 were similar in the two strains. The myocardial levels of anandamide and oleoylethanolamide, but not 2-arachidonylglycerol, were increased in FAAH−/− mice compared with FAAH+/+ mice. These results indicate that mice lacking FAAH have a normal hemodynamic profile, and their increased responsiveness to anandamide-induced hypotension and cardiodepression is due to the decreased degradation of anandamide rather than an increase in target organ sensitivity to CB1 agonists.
Diverse phenotypes of outward currents in cells that have survived in the 5-day-infarcted heart
Authors: Dun Wen , Boyden Penelope A.
Published: April 2005

We have shown reduced density and altered kinetics in slowly activating K+ currents ( IKs) in epicardial border zone (EBZ) cells (IZs) of the 5-day-infarcted canine heart (Jiang M, Cabo, C, Yao J-A, Boyden PA, and Tseng G-N. Cardiovasc Res 48: 34–43, 2000). β-Adrenergic stimulation with isoproterenol increases IKs in normal cells (NZs). In this study, we used a voltage-clamp protocol with an external solution to isolate IKs from contaminating currents to determine the effects of 1 μM isoproterenol on IKs in IZs and NZs. Under our recording conditions, 10 μM azimilide-sensitive currents were stimulated with isoproterenol to compare responsiveness of IKs to isoproterenol in the two cell groups. IKs tail density was reduced 67% in IZs ( group I, n = 26) compared with NZs ( n = 24, P < 0.05). Isoproterenol-stimulated azimilide-sensitive tail currents were increased 1.72 ± 0.2-fold in NZs and 2.2 ± 0.3-fold in IZs ( P > 0.05). In 33% of IZs ( group II, n = 13), native currents showed no tail currents; however, isoproterenol-stimulated azimilide-sensitive currents were voltage dependent, fast activating, and large in amplitude compared with group I IZs, similar to “lone” KCNQ1 currents. Using short clamp pulses, we also found an increase in sustained currents sensitive to tetraethylammonium chloride (TEA) and no change in C-9356-sensitive currents in IZs with little or no transient outward current. In some IZs where IKs is downregulated, the effect of isoproterenol on IKs was similar to that on IKs in NZs. In others, the existence of lone KCNQ1-type currents, which are sensitive to β-adrenergic stimulation, is consistent with our findings of an increased KCNQ1-to-KCNE1 mRNA ratio (Jiang et al.). Accompanying altered IKs in IZs are an enhanced TEA-sensitive current and a normal C-9356-sensitive current.
Daily administration of interleukin-18 causes myocardial dysfunction in healthy mice
Authors: Woldbæk Per Reidar , Sande Jørn Bodvar , Strømme Tævje Andreas , Lunde Per Kristian , Djurovic Srdjan , Lyberg Torstein , Christensen Geir , Tønnessen Theis
Published: April 2005

Although increased levels of circulating interleukin (IL)-18 have been demonstrated in patients with cardiovascular diseases, the functional consequences of chronically increased circulating IL-18 with respect to myocardial function have not been defined. Thus we aimed to examine the effects of chronic IL-18 exposure on left ventricular (LV) function in healthy mice. Moreover, to clarify whether IL-18 has direct effects on the cardiomyocyte, we examined effects of IL-18 on cardiomyocytes in vitro. After 7 days of daily intraperitoneal injections of 0.5 μg IL-18 in healthy mice, a 40% ( P < 0.05) reduction in the LV maximal positive derivative, a 25% ( P < 0.05) reduction in the LV maximal rate of pressure decay, and a 2.8-fold ( P < 0.001) increase in the LV end-diastolic pressure were measured, consistent with myocardial dysfunction. Furthermore, we measured a 75% ( P < 0.05) reduction in β-adrenergic responsiveness to isoproterenol. IL-18 induced myocardial hypertrophy, and there was a 2.9-fold increase ( P < 0.05) in atrial natriuretic peptide mRNA expression in the LV myocardium. In vitro examinations of isolated adult rat cardiomyocytes being stimulated with IL-18 (0.1 μg/ml) exhibited an increase in peak Ca2+transients ( P < 0.05) and in diastolic Ca2+concentrations ( P < 0.05). In conclusion, this study shows that daily administration of IL-18 in healthy mice causes LV myocardial dysfunction and blunted β-adrenergic responsiveness to isoproterenol. A direct effect of IL-18 on the cardiomyocyte in vitro was demonstrated, suggesting that IL-18 reduces the responsiveness of the myofilaments to Ca2+. Finally, induction of myocardial hypertrophy by IL-18 indicates a role for this cytokine in myocardial remodeling.
Hyperoxia enhances brain-derived neurotrophic factor and tyrosine kinase B receptor expression in peribronchial smooth muscle of neonatal rats
Authors: Yao Qin , Haxhiu Musa A. , Zaidi Syed I. , Liu Shijian , Jafri Anjum , Martin Richard J.
Published: April 2005

Airway hyperreactivity is one of the hallmarks of hyperoxic lung injury in early life. As neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are potent mediators of neuronal plasticity, we hypothesized that neurotrophin levels in the pulmonary system may be disturbed by hyperoxic exposure. We therefore evaluated the effects of hyperoxia on the expression of BDNF, NGF, and their corresponding high-affinity receptors, TrkB and TrkA, respectively, in the lung of rat pups. Five-day-old Sprague-Dawley rat pups were randomized to hyperoxic or control groups and then continuously exposed to hyperoxia (>95% oxygen) or normoxia over 7 days. At both mRNA and protein levels, BDNF was detected in lung but not in trachea; its level was substantially enhanced in lungs from the hyperoxia-exposed rat pups. Distribution of BDNF mRNA by in situ hybridization indicates that peribronchial smooth muscle was the major source of increased BDNF production in response to hyperoxic exposure. Interestingly, hyperoxia-induced elevation of BDNF was not accompanied by any changes of NGF levels in lung. Furthermore, hyperoxic exposure increased the expression of TrkB in peribronchial smooth muscle but had no effect on the distribution of the specific NGF receptor TrkA. These findings indicate that hyperoxic stress not only upregulates BDNF at mRNA and protein levels but also enhances TrkB within peribronchial smooth muscle. However, there was no corresponding effect on NGF and TrkA receptors. We speculate that the increased level of BDNF may contribute to hyperoxia-induced airway hyperresponsiveness in early postnatal life.
PKC-dependent, burn-induced adherens junction reorganization and barrier dysfunction in pulmonary microvascular endothelial cells
Authors: Tinsley John H. , Breslin Jerome W. , Teasdale Nicole R. , Yuan Sarah Y.
Published: April 2005

Rat lung microvascular endothelial cell monolayers were exposed to donor plasma from burned rats (25% total body surface area) at 1:3 dilution for 30 min. Immunofluorescence analysis revealed that concomitant with gap formation alterations were seen in the adherens junction (AJ) proteins β-catenin and vascular endothelial-cadherin. Both of these components were shown to exist in a smooth, uniform arrangement at the cell periphery in untreated cells. However, upon exposure to burn plasma, this uniformity was lost, and the AJ proteins showed a disrupted, zipper-like pattern at the cells' edge. In addition, these proteins were absent from areas of gap formation between the cells, and an increase in punctate staining throughout the cells suggests they were internalized in response to burn plasma. Measurements of both transendothelial electrical resistance and FITC-albumin flux across the cell monolayer were used to assess barrier integrity. Our study found that exposure to burn plasma rapidly caused the electrical resistance across confluent monolayers to decrease and albumin flux to increase, phenomena associated with barrier dysfunction. Furthermore, all the above responses to burn plasma were attenuated when cells were pretreated with the PKC inhibitor bisindolylmaleimide, suggesting that PKC is required for burn-induced pulmonary endothelial dysfunction.
Isoproterenol induces actin depolymerization in human airway smooth muscle cells via activation of an Src kinase and GS
Authors: Hirshman Carol A. , Zhu Defen , Pertel Thomas , Panettieri Reynold A. , Emala Charles W.
Published: April 2005

In a previous study, we showed that isoproterenol induced actin depolymerization in human airway smooth muscle cells by both protein kinase A (PKA)-dependent and -independent signaling pathways. We now investigate the signaling pathway of PKA-independent actin depolymerization induced by isoproterenol in these cells. Cells were briefly exposed to isoproterenol or PGE1in the presence and absence of specific inhibitors of Src-family tyrosine kinases, phosphatidylinositol-3-kinase (PI3 kinase), or MAP kinase, and actin depolymerization was measured by concomitant staining of filamentous actin with FITC-phalloidin and globular actin with Texas red DNase I. Isoproterenol, cholera toxin, and PGE1induced actin depolymerization, indicated by a decrease in the intensity of filamentous/globular fluorescent staining. Pretreatment with the Src kinase inhibitors 4-amino-5-(4-chlorophenyl)-7-( t-butyl)pyrazolo[3,4-d]pyriimidine (PP2) or geldanamycin or the PKA inhibitor Rp-cAMPS only partly inhibited isoproterenol- or PGE1-induced actin depolymerization. In contrast, PP2 and geldanamycin did not inhibit forskolin-induced actin depolymerization, and AG-213 (an EGF receptor tyrosine kinase inhibitor) did not inhibit isoproterenol- or PGE1-induced actin depolymerization. PI3 kinase or MAP kinase inhibition did not inhibit isoproterenol-induced actin depolymerization. Moreover, isoproterenol but not forskolin induced tyrosine phosphorylation of an Src family member at position 416. These results further confirm that both PKA-dependent and PKA-independent pathways mediate actin depolymerization in human airway smooth muscle cells and that the PKA-independent pathway by which isoproterenol induces actin depolymerization in human airway smooth muscle cells involves Src protein tyrosine kinases and the Gsprotein.
Mechanisms of insulin-dependent glucose transport into porcine and bovine skeletal muscle
Authors: Duhlmeier Reinhard , Hacker Anja , Widdel Andrea , von Engelhardt Wolfgang , Sallmann Hans-Peter
Published: April 2005

Euglycemic, hyperinsulinemic clamp tests have shown that adult ruminants are less insulin-sensitive than monogastric omnivores. The present study was carried out to elucidate possible cellular mechanisms contributing to this impaired insulin sensitivity of ruminants. Western blotting was used to measure glucose transporters 1 and 4 (GLUT1, GLUT4) in oxidative (musculus masseter and diaphragm) and glycolytic (musculus longissimus dorsi and semitendinosus) skeletal muscle in the crude membranes of pigs and cows. Muscles were characterized biochemically. To determine insulin-stimulated 3- O-d-[3H]-methylglucose (3- O-MG) uptake and GLUT4 translocation, porcine and bovine musculus semitendinosus strips were removed by open muscle biopsy and incubated without and with 0.1 or 20 mIU insulin/ml. GLUT4 translocation was analyzed using subcellular fractionation techniques to isolate partially purified plasma membranes and cytoplasmic vesicles and using Western blotting. GLUT4 protein contents were significantly higher in oxidative than in glycolytic muscles in pigs and cows. GLUT1 protein contents were significantly higher in glycolytic than in oxidative muscles in bovines but not in porcines. The 3- O-MG uptake into musculus semitendinosus was similar in both species. Maximum insulin-induced GLUT4 translocation into musculus semitendinosus plasma membrane was significantly lower in bovines than in porcines. These results indicate that GLUT1 is the predominant glucose transporter in bovine glycolytic muscles and that a reinforced insulin-independent glucose uptake via GLUT1 may compensate for the impaired insulin-stimulated GLUT4 translocation, resulting in a similar 3- O-MG uptake in bovine and porcine musculus semitendinosus. These findings may explain at least in part the impaired in vivo insulin sensitivity of adult ruminants compared with that of omnivorous monogastric animals.