bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of new‐onset diabetes mellitus and worsening glycaemic variables for established diabetes in men undergoing androgen‐deprivation therapy for prostate cancer
Authors: Derweesh Ithaar H. , DiBlasio Christopher J. , Kincade Matt C. , Malcolm John B. , Lamar Kimberly D. , Patterson Anthony L. , Kitabchi Abbas E. , Wake Robert W.
Published: September 2007

OBJECTIVE

To investigate the incidence of new‐onset diabetes mellitus (NODM) and of worsening glycaemic control in established DM after starting androgen‐deprivation therapy (ADT) for prostate cancer, as ADT is associated with altered body composition, potentially influencing insulin sensitivity.

PATIENTS AND METHODS

We retrospectively reviewed patients receiving ADT for prostate cancer at our institution between January 1989 and July 2005; those with incomplete information and those receiving only neoadjuvant ADT were excluded. Variables examined included age, race, body mass index (BMI), pretreatment prostate‐specific antigen, Gleason sum, clinical stage, ADT type (medical vs surgical) and schedule (continuous vs intermittent), presence of pre‐existing DM, serum glucose and glycosylated haemoglobin (HbA1c) levels before and after ADT, and receipt of vitamin D or bisphosphonate supplementation. Data were analysed statistically and P < 0.05 considered to indicate significance.

RESULTS

In all, 396 patients (median age 73.2 years; median BMI of 26.7 kg/m2 at ADT initiation) were analysed. Of these, 59.1% were African‐American and 40.9% were Caucasian/other. At a median follow‐up of 60.1 months, 36 (11.3%) patients developed NODM. In 77 patients with pre‐existing DM, there was an increase of ≥10% in serum HbA1c or fasting glucose levels in 15 (19.5%) and 22 (28.6%), respectively. On multivariate analysis, a BMI of ≥30 kg/m2 was associated with an increased risk of developing NODM (odds ratio 4.65, P = 0.031). Receipt of vitamin D had a protective effect (odds ratio 5.75, P = 0.017).

CONCLUSIONS

Patients receiving ADT for prostate cancer with or with no history of DM should have routine surveillance of glycaemic control, particularly when their BMI is ≥ 30 kg/m2, with appropriate preventive and treatment measures.
Overlap of different urological symptom complexes in a racially and ethnically diverse, community‐based population of men and women
Authors: Barry Michael J. , Link Carol L. , McNaughton‐Collins Mary F. , McKinlay John B. ,   for the Boston Area Community Health (BACH) Investigators
Published: September 2007

OBJECTIVE

To define the prevalence and overlap of symptom patterns traditionally associated with benign prostatic hyperplasia, chronic prostatitis/chronic pelvic pain syndrome, interstitial cystitis/painful bladder syndrome, and incontinence among men and women in a racially and ethnically diverse, community‐based population.

SUBJECTS AND METHODS

In all, 5506 men and women aged 30–79 years were recruited to participate in the Boston Area Community Health Survey, using a stratified‐cluster sampling technique to obtain roughly similar representative samples by age group, gender and race/ethnicity (White, Black, Hispanic). Survey data were collected by bilingual interviewers in subjects’ homes. Scales measuring symptom patterns were derived from validated instruments, with minor changes to eliminate different recall periods and overlap in items that might have confused subjects.

RESULTS

About a quarter of men and women of all ages met the definition for one or more of the target symptom patterns; there was no significant variation in the prevalence of any of the symptom patterns by race/ethnicity. Overall, ≈16% of men and women had one symptom pattern, while 7% had overlap patterns. Except for urinary incontinence and interstitial cystitis/painful bladder syndrome in both men and women, the prevalence of all symptom complexes were associated with one another significantly more often that would be expected by chance.

CONCLUSIONS

Overlapping patterns of lower urinary tract symptoms and pelvic pain are common. These overlapping patterns present challenges for clinical practice and research, and require further investigation of their causes, diagnosis and optimum treatment.
Erythropoietin receptor expression in the human urogenital tract: immunolocalization in the prostate, neurovascular bundle and penis
Authors: Liu Tongyun , Allaf Mohamad E. , Lagoda Gwen , Burnett Arthur L.
Published: September 2007

Associate Editor

Michael G. Wyllie

Editorial Board

Ian Eardley, UK

Jean Fourcroy, USA

Sidney Glina, Brazil

Julia Heiman, USA

Chris McMahon, Australia

Bob Millar, UK

Alvaro Morales, Canada

Michael Perelman, USA

Marcel Waldinger, Netherlands

OBJECTIVE

To investigate whether the erythropoietin (EPO) receptor is expressed in human periprostatic (including the neurovascular bundles) and penile tissues, and define its distribution in these tissues, as the administration of exogenous EPO in cavernous nerve injury promoted the recovery of erectile function in a rat model.

MATERIALS AND METHODS

Human prostate (six samples) and penile (two) tissue were collected and paraffin‐embedded. Tissue was sectioned and processed for immunohistochemical studies using an antibody for the EPO receptor; immunolocalization was assessed using light microscopy.

RESULTS

There was prominent staining for the EPO receptor in neuronal cell bodies of the periprostatic neurovascular bundles, and in the axons emanating from these ganglia. The glandular epithelium of the prostate also had weak staining. There was EPO receptor immunoreactivity in the penile specimens in the penile dorsal nerves, sinusoidal endothelium of the corpus cavernosum, and endothelial cells lining the dorsal veins and arteries. All slides processed with no primary antibody or blocking peptide showed no staining.

CONCLUSIONS

EPO receptor expression was identified and localized in human penile tissues and in the periprostatic neurovascular bundles responsible for erectile function. This suggests a likely role for endogenous EPO within these tissues, and provides the rationale for its clinical use as a protective agent locally.
Effect of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin on testicular spermatogenesis‐related panels and serum sex hormone levels in rats
Authors: Choi Jong‐Soon , Kim Il‐Woong , Hwang Seock‐Yeon , Shin Bong‐Jeong , Kim Si‐Kwan
Published: September 2007

OBJECTIVES

To determine the detrimental role of tetrachlorodibenzo‐p‐dioxin (TCDD) in testicular histology, spermatogenesis‐related panels and proteome, and serum sex hormone levels.

MATERIALS AND METHODS

In all, 40 male rats were divided into equal groups: a normal control (NC) group that received vehicle and saline, and a TCDD‐treated (TT) group injected intraperitoneally with TCDD (one dose, 50 µg/kg body weight). The rats were killed 4 weeks after TCDD exposure and testicular weight, histopathology, proteome and variables related to spermatogenesis, and serum sex hormone levels were investigated.

RESULTS

TCDD induced a significant decrease in testicular weight, Johnsen’s score, seminiferous tubular size, percentage of tubules containing sperm, sperm counts, germ cell counts and Sertoli cell index. In addition, there was a significant decrease in serum testosterone level (P < 0.01) and a remarkable increase in oestradiol (P < 0.01), follicle‐stimulating hormone (P < 0.05) and luteinizing hormone (P < 0.05) levels in the TT group. The expression of six testicular proteins including testis‐specific heat shock protein (Hsp70), protein disulphide isomerase A3 precursor, 3‐phosphoglycerate dehydrogenase, nonmuscle myosin heavy‐chain type B‐like protein, and superoxide dismutase 1 were significantly up‐regulated (P < 0.05–0.01). Interestingly, fertility protein SP22 and phosphatidylethanolamine‐binding protein were down‐regulated but this was only significant for fertility protein SP22 (P < 0.05).

CONCLUSION

TCDD induces marked histological changes in the testis, impairs variables related to spermatogenesis, and increases serum oestradiol levels but decreases testosterone levels. In particular, TCDD disturbs testicular proteome profiles in rats.
Microarray analysis of exstrophic human bladder smooth muscle
Authors: Hipp Jason , Andersson Karl‐Erik , Kwon Tae Gyun , Kwak Eun Kyoung , Yoo James , Atala Anthony
Published: September 2007

OBJECTIVE

To compare the genetic profiles of ‘healthy’ bladder smooth muscle cells (SMCs) and exstrophic SMCs (ESMCs) to identify genes that are over‐ and under‐expressed in ESMCs, thus providing a molecular evaluation of the quality and therapeutic potential of ESMC tissue.

PATIENTS, MATERIAL AND METHODS

Classical bladder exstrophy is a rare disorder, occurring in 1 in 30 000 live births. Studies have shown that exstrophic bladders are developmentally immature at birth. After surgical closure, the bladder typically undergoes abnormal remodelling (such as over‐expression of collagen III) throughout early development. We hypothesized that the predominant genetic differences between normal SMCs and ESMCs are in the developmental genes. This hypothesis was tested by the use of microarray analysis. Bladder SM biopsies were taken from ‘healthy’ subjects undergoing bladder surgeries for other conditions (for example, urinary reflux) and patients with bladder exstrophy. Cells were expanded in vitro, and total RNA was isolated and hybridized to the Affymetrix U133A GeneChip® (Affymetrix Inc., Santa Clara, CA, USA) by the Wake Forest University School of Medicine Affymetrix core facility, using standard protocols.

RESULTS

We created a genetic signature consisting of 961 genes that are over‐expressed and 432 genes that are under‐expressed in ESMCs. Analysis of these signatures identified an over‐expression of inflammatory genes and an under‐expression of developmental genes.

CONCLUSION

Our data is in concordance with previous studies and histological data showing that ESMCs are developmentally immature relative to healthy bladder SM. The clinical implication of the ESMC genetic signature is that it provides a list of targets that can be (i) manipulated ex vivo and/or in vivo to induce differentiation (the completion of development) and (ii) used as biomarkers to explain the variability of the clinical symptoms after surgical closure.
Liquidity commonality and the intervalling effect
Authors: Hillier David , Hillier Joe , Kyaw Khine
Published: September 2007

Past studies of liquidity commonality have reported conflicting findings regarding the relationship between market liquidity and firm size. The present paper provides empirical evidence that underlying estimation problems might be responsible for these results. We develop a model of information and spreads that provides some insights into the firm size–liquidity relationship. Our empirical evidence confirms the main testable implications of the model and presents evidence that the presence and strength of common covariability in liquidity depends upon the interval over which liquidity movements are measured. These intervalling effects are caused by delays in information being incorporated into bid and ask spreads.
The horse has bolted: revisiting the market reaction to going concern modifications of audit reports
Authors: Herbohn Kathleen , Ragunathan Vanitha , Garsden Robert
Published: September 2007

This paper examines what value is added by an audit report through an investigation of the information content for first‐time going concern modifications (GCMs). Consistent with prior research, we find no evidence of a short‐term market reaction to the public announcement of a first‐time GCM. We document a significant adverse medium‐term market reaction in the 12 months prior to a first‐time GCM announcement, but find no evidence of a persistent market underreaction in the 12 months following the announcement. These results are consistent with an audit opinion fulfilling an attestation function and confirming the deteriorating financial condition of a firm.
Use of loan loss provisions for capital, earnings management and signalling by Australian banks
Authors: Anandarajan Asokan , Hasan Iftekhar , McCarthy Cornelia
Published: September 2007

This study examines whether and to what extent Australian banks use loan loss provisions (LLPs) for capital, earnings management and signalling. We examine if there were changes in the use of LLPs as a result of the implementation of banking regulations consistent with the Basel Accord of 1988, which made loan loss reserves no longer part of Tier I capital in the numerator of the capital adequacy ratio. We find some evidence to indicate that Australian banks use LLPs for capital management, but we find no evidence of a change in this behaviour after the implementation of the Basel Accord. Our results indicate that banks in Australia use LLPs to manage earnings. Furthermore, listed commercial banks engage more aggressively in earnings management using LLPs than unlisted commercial banks. We also find that earnings management behaviour is more pronounced in the post‐Basel period. Overall, we find a significant understating of LLPs in the post‐Basel period relative to the pre‐Basel period. This indicates that reported earnings might not reflect the true economic reality underlying those numbers. Finally, Australian banks do not appear to use LLPs for signalling future intentions of higher earnings to investors.
A Dynamic Model of Cracks Development Based on a 3D Discrete Shrinkage Volume Propagation
Authors: Valette Gilles , Prévost Stéphanie , Lucas Laurent , Léonard Joël
Published: September 2007

We attempt to model and visualize the main characteristics of cracks produced on the surface of a desiccating crusted soil: their patterns, their different widths and depths and their dynamics of creation and evolution. In this purpose we propose a method to dynamically produce three‐dimensional (3D) quasi‐static fractures, which takes into account the characteristics of the soil. The main originality of this method is the use of a 3D discrete propagation of ‘shrinkage volumes’ with respect to 2D precalculated paths. In order to get realistic cracks, we newly propose to take into account a possibly inhomogeneous thickness of the shrinking layer by using a watershed transformation to compute these paths. Moreover, we use the waterfall algorithm in order to introduce in our simulation a hierarchy notion in the cracks appearance, which is therefore linked with the initial structure of the surface. In this paper, this method is presented in detail and a validation of the cracks patterns by a comparison with real ones is given.
Defining Globalisation
Authors: Scholte Jan Aart
Published: September 2007

A clear and precise definition of globalisation is crucial to advance contemporary knowledge and policy. When taken to mean internationalisation, liberalisation, universalisation or westernisation, ideas of globalisation reveal little new. Important novel insight is opened when globalisation is understood as the spread of transplanetary – and in recent times also increasingly supraterritorial – connections between people. That said, this conception needs to be carefully qualified in order to avoid globalist excesses.
Globalisation and Values
Authors: Whalley John
Published: September 2007

This paper discusses a central element in globalisation debate little addressed by economists, namely the interactions at global, national and community levels between globalisation and societally based values. Social values refer to wider notions of collective identity; religious values, attitudes towards materialism, moral beliefs, and a sense of collective awareness and are a broader and more encompassing concept than social capital discussed in recent economics and sociology literature. Social capital relates to trust, honesty and the social fabric of accepted norms central to the successful implementation of individual optimising decisions and denotes a communal asset reflecting strength of joint collective commitment whose amount can be increased or improved upon through investment of time and resources. Social values are much discussed in sociological literature going back to Comte, Durkheim, Parsons, and others. The issues taken up here are how different social values might interact and change as societies and their economies integrate (globalise). Processes of value competition, displacement and joint assimilation occur naturally to economists, but seem little studied by sociologists who seemingly place less stress on analytical comparative statics. Scenarios for how values can interact under globalisation are discussed in the text.
On Some Effects of International Fragmentation of Production on Comparative Advantages, Trade Flows and the Income of Countries
Authors: Baldone Salvatore , Sdogati Fabio , Tajoli Lucia
Published: September 2007

In traditional trade models, whether based on technological differences or on relative factor endowments, merchandise composition and directions of trade are derived from closed‐economy conditions. But nowadays one of the basic assumptions of traditional trade models, i.e. that production processes are integrated within just one country, is being increasingly violated as previously integrated productive activities are segmented and spread over an international network of production sites: as a result, an increasingly large share of trade flows is made up of intermediate and unfinished goods being transferred from one country to another in order to be processed. In this paper we submit that such new configuration of production processes has important effects on at least three dimensions of economic research. First, we show that international disintegration of production processes leads to a lessening of the power of comparative advantages when it comes to explaining both merchandise composition and directions of trade, while it is the concept of absolute advantage to become increasingly relevant; second, we show that empirical measures of revealed comparative advantages are inherently misleading if they do not account for differences in the stage‐of‐processing of traded goods; third, we estimate a simple model of aggregate demand accounting for international trade in intermediates: results of estimation lend support to our prior that participation of a country in the process of international fragmentation of production plays a specific and significant role in determining its year‐over‐year change in GDP.
PUBLIC PROTECTION OR PRIVATE EXTORTION?
Authors: BUENO DE MESQUITA ETHAN , HAFER CATHERINE
Published: September 2007

We analyze the strategic interaction between a firm, an extortionary mafia, and a potentially corrupt government. The model identifies several results. First, government spending is not monotonic in revenues. Second, although the firm wants the government to challenge the mafia (it uses the threat of electoral sanctions to induce the government to do so), in equilibrium, the firm does not directly appeal to the government for protection even though it is extorted. The more likely the government is to uncover mafia extortion independent of an appeal from the firm, the more effective the firm's threat of electoral sanction is at motivating the government to invest in law enforcement. This is because the electoral threat to punish failure on the government's part is only a compelling reason to invest in law enforcement when the government actually expects to confront the mafia. This same logic also implies that the relationship between mafia strength and government corruption is somewhat counterintuitive. When the mafia is strong in equilibrium (i.e. pervasive and extorting large fees), the government is not very corrupt. When the mafia is weak, the government is highly corrupt. Finally, an extension shows that if the mafia and government can collude, then the harsher the threatened sanctions against the mafia, the less likely the government is to challenge the mafia because the mafia is more willing to bribe the government.
INFLUENCE, ELECTIONS, AND THE VALUE OF A VOTE IN THE U.S. HOUSE OF REPRESENTATIVES
Authors: MAGEE CHRISTOPHER S. P.
Published: September 2007

This paper investigates the extent to which interest groups use their campaign contributions to affect election outcomes as opposed to influencing candidate policy choices directly. It also reveals how much value interest groups place on gaining one more favorable vote in the House of Representatives. The empirical estimates suggest that gaining influence dominates helping favored candidates win the election as a means to affect defense spending policies. Political action committees differ in interesting ways, however, with the more ideological peace groups placing greater emphasis on changing electoral outcomes than do investor lobbies representing the defense industry.
THE COMMON EXTERNAL TARIFF IN A CUSTOMS UNION: VOTING, LOGROLLING, AND NATIONAL GOVERNMENT INTERESTS
Authors: TAVARES SAMIA COSTA
Published: September 2007

Missing from the analysis of customs unions has been a consideration of collective decision‐making by countries regarding the union's common trade policy. In the case of the common European external tariff, how governments voted was not public information. This paper uses a unique dataset to derive member states' tariff preferences, which are then used to establish the decision rule before 1987, when individual governments had veto power. Results indicate a principle of unanimity, as well as the presence of logrolling. The political equilibrium for the common external tariff is also illustrated to have shifted as a result of union enlargements.
Health security for the rural poor? A case study of a health insurance scheme for rural farmers and peasants in India
Authors: Kuruvilla Sarosh , Liu Mingwei
Published: September 2007

This is a case study of an important innovation in providing healthcare for the rural poor: the Yeshasvini Health Insurance Scheme for rural farmers and peasants in Karnataka, India. Arguably the world's largest health insurance scheme for the rural poor, the scheme commenced in 2003. Designed in ways that overcome several obstacles to providing health security for rural populations, the scheme covered, in its second year, about 2.2 million widely dispersed peasant farmers for surgical and out patient care for a low annual premium of approximately US$ 2. In this paper, we describe and evaluate the scheme in its first year of operation, and explore its potential to be a model for the developing world generally.
The impact of HIV/AIDS on social security contributions: The case of Zimbabwe
Authors: Chikova Henry N. , Chinamasa Camillo F.
Published: September 2007

Significant early retirement from work due to HIV/AIDS‐related illness is reducing the gainfully employed population and threatening the viability of the statutory social security schemes run by the National Social Security Authority in Zimbabwe. The economy has been in recession for a decade, with high inflation and significant job losses also impacting negatively on contributions to the National Pension and Other Benefits Scheme (NPOBS), and government imposes ceilings on insurable earnings from which contributions are drawn. There are currently no consistent strategies to mitigate attritional effects of these factors on the social security schemes. The aim of this study was to prospectively project the potential impact of HIV/AIDS and imposed ceilings on NPOBS revenue in the presence of high inflation. It was found that HIV/AIDS will reduce projected contributions to the scheme by more than 30 per cent by 2030. Policy strategies to adjust and frequently review levels of growth of imposed ceilings on insurable earnings in line with inflation growth and to invest in HIV/AIDS prevention could be adopted to ameliorate the negative impact of HIV/AIDS and/or ceiling caps on social security contributions in Zimbabwe.
Social protection and poverty in Azerbaijan, a low‐income country in transition: Implications of a household survey
Authors: Habibov Nazim , Fan Lida
Published: September 2007

Using a nationally representative survey, this study examines the performance of social protection in Azerbaijan from the perspective of poverty reduction. Empirical evidence presented suggests that social protection programmes have an important impact on poverty alleviation. However, poverty is still widespread. The findings demonstrate that the current system of social protection has several important limitations. First, a significant proportion of the poor population is not covered by the social protection system. Second, the poor typically receive a smaller share of total benefits than the non‐poor. Finally, most social transfers are too small to lift households out of poverty. The current system of social protection in Azerbaijan requires further strengthening. In particular, the government should develop and implement new social assistance programmes specifically directed towards poverty reduction.
Notional defined contributions (NDC): Solvency and risk in Spain
Authors: Del Carmen Boado‐Penas María , Domínguez‐Fabiá Inmaculada , Vidal‐Meliá Carlos
Published: September 2007

The aim of this article is twofold: to demonstrate the actuarial imbalance in the Spanish pension system in its current form; and to measure the degree of aggregate economic risk to which pensioners are exposed when applying formulas for the calculation of retirement pensions based on notional accounts. The model used generates scenarios for various periods encompassing some 10,000 different permutations of the macroeconomic indices needed to calculate such parameters as initial pension, earnings replacement rate, or internal rate of return and value at risk. The findings are analysed both objectively and subjectively. The main conclusions are that if the projections for the macroeconomic indices used bear only a minimal resemblance to reality, the pension system will accumulate further financial imbalance in the future that will force it either to reduce initial pensions considerably or to make some radical adjustments to the parameters. In terms of risk, for beneficiaries with high risk aversion the preferred formulas would be those based on future variations in wages with a constant pension amount in real terms; on the other hand, those less averse to risk would prefer formulas that generate a smaller initial pension but one which grows in real terms with subsequent changes in wage levels.
Differential regulation of the Cdk5‐dependent phosphorylation sites of inhibitor‐1 and DARPP‐32 by depolarization
Authors: Nguyen Chan , Hosokawa Tomohisa , Kuroiwa Mahomi , Ip Nancy Y. , Nishi Akinori , Hisanaga Shin‐ichi , Bibb James A.
Published: September 2007

While cyclin‐dependent kinase 5 (Cdk5) is of growing importance to neuronal signaling, its regulation remains relatively unexplored. Examination of the mechanism by which NMDA modulates the phosphorylation of protein phosphatase inhibitor‐1 at Ser6 and Ser67 and dopamine‐ and cAMP‐regulated phosphoprotein Mr 32 000 at Thr75 revealed that generalized depolarization, rather than specific activation of NMDA receptors, was sufficient to induce decreases in these Cdk5 sites. Although no evidence for the involvement of the Cdk5 cofactors p35 or p39, or for L‐ and T‐type voltage‐gated Ca2+ channels, was found, evaluation of the role of phosphatases and extracellular cations revealed differential regulation of the three sites. NMDA‐induced decreases in the phosphorylation of Thr75 of dopamine‐ and cAMP‐regulated phosphoprotein Mr 32 000 required protein phosphatase 1/2A activity and extracellular Ca2+. In contrast, the effects on Ser6 and Ser67 of inhibitor‐1 were not cation specific; either Na+ or Ca2+ sufficed. Furthermore, while the decrease in phosphorylation of Ser6 was partially dependent on protein phosphatase 2B, that of Ser67 was independent of the major protein serine/threonine phosphatases, likely indicating the presence of a pathway by which NMDA inhibits Cdk5 activity. Thus, in the striatum the regulation of phosphorylation of Cdk5‐dependent sites by NMDA occurs through multiple distinct pathways.
P2Y2 nucleotide receptors inhibit trauma‐induced death of astrocytic cells
Authors: Burgos Michelle , Neary Joseph T. , González Fernando A.
Published: September 2007

Nucleotides as well as other neurotransmitters are known to be released to the extracellular space upon injury. To determine whether nucleotides acting on P2Y2 nucleotide receptors promote protective or degenerative events after trauma in astrocytic cells, a well‐established model of in vitro brain trauma was applied to 1321N1 cells expressing recombinant P2Y2 nucleotide receptors (P2Y2R‐1321N1). Cellular death was examined by measuring DNA fragmentation and caspase activation. Fragmented DNA was observed 48 h post‐injury in 1321N1 cells, while P2Y2 nucleotide receptor expressing cells did not show DNA fragmentation. A laddering pattern of fragmented DNA following injury was observed upon inhibition of P2Y2 nucleotide receptors with suramin. Time‐dependent increases of cleaved caspase‐9, a mitochondrial‐associated caspase, correlated with injury‐induced cellular death. A decreased bax/bcl‐2 gene expression ratio was observed in P2Y2R‐1321N1 cells after traumatic injury, while untransfected 1321N1 cells showed a significant time‐dependent increase of the bax/bcl‐2 gene expression ratio. Activation of protein kinases was assessed to determine the signaling pathways involved in cell death and survival responses following traumatic injury. In P2Y2R‐1321N1 and 1321N1 cells p38 phosphorylation was stimulated in a time‐dependent manner but the phosphatidylinositol 3‐kinase‐dependent activation of extracellular signal‐regulated kinase 1/2 and protein kinase B (PKB)/Akt was only observed in P2Y2R‐1321N1 cells after injury. The stress‐activated protein kinase/c‐Jun NH2‐terminal kinase (SAPK/JNK) signaling pathway was not activated by traumatic injury in either astrocytic cell line. Inhibition of p38 kinase signaling pathway by treatment with PD1693, a MKK3/6 inhibitor, abolished the expression of cleaved caspase‐9, the increase in the bax/bcl‐2 gene expression ratio, as well as the fragmentation of DNA that followed injury of 1321N1 cells. Taken together, our results demonstrate a novel role for P2Y2 nucleotide receptors and extracellular nucleotides in mediating survival responses to glial cells undergoing cellular death induced by trauma.
Constitutive endocytosis and recycling of the neuronal glutamate transporter, excitatory amino acid carrier 1
Authors: González Marco I. , Susarla Bala T. S. , Fournier Keith M. , Sheldon Amanda L. , Robinson Michael B.
Published: September 2007

The neuronal glutamate transporter, excitatory amino acid carrier 1 (EAAC1), has a diverse array of physiologic and metabolic functions. There is evidence that there is a relatively large intracellular pool of EAAC1 both in vivo and in vitro, that EAAC1 cycles on and off the plasma membrane, and that EAAC1 cell surface expression can be rapidly regulated by intracellular signals. Despite the possible relevance of EAAC1 trafficking to both physiologic and pathologic processes, the cellular machinery involved has not been defined. In the present study, we found that agents that disrupt clathrin‐dependent endocytosis or plasma membrane cholesterol increased steady‐state levels of biotinylated EAAC1 in C6 glioma cells and primary neuronal cultures. Acute depletion of cholesterol increased the Vmax for EAAC1‐mediated activity and had no effect on Na+‐dependent glycine transport in the same system. These agents also impaired endocytosis as measured using a reversible biotinylating reagent. Co‐expression with dominant‐negative variants of dynamin or the clathrin adaptor, epidermal growth factor receptor pathway substrate clone 15, increased the steady‐state levels of biotinylated myc‐EAAC1. EAAC1 immunoreactivity was found in a subcellular fraction enriched in early endosome antigen 1 (EEA1) isolated by differential centrifugation and partially co‐localized with EEA1. Co‐expression of a dominant‐negative variant of Rab11 (Rab11 S25N) reduced steady‐state levels of biotinylated myc‐EAAC1 and slowed constitutive delivery of myc‐EAAC1 to the plasma membrane. Together, these observations suggest that EAAC1 is constitutively internalized via a clathrin‐ and dynamin‐dependent pathway into early endosomes and that EAAC1 is trafficked back to the cell surface via the endocytic recycling compartment in a Rab11‐dependent mechanism. As one defines the machinery required for constitutive trafficking of EAAC1, it may be possible to determine how intracellular signals regulate EAAC1 cell surface expression.
Brain‐to‐blood elimination of 24S‐hydroxycholesterol from rat brain is mediated by organic anion transporting polypeptide 2 (oatp2) at the blood–brain barrier
Authors: Ohtsuki Sumio , Ito Shingo , Matsuda Akihiro , Hori Satoko , Abe Takaaki , Terasaki Tetsuya
Published: September 2007

24S‐Hydroxycholesterol (24S‐OH‐chol), a major cerebral cholesterol metabolite, is an endogenous ligand for the liver X receptor and is a potential stimulant of cholesterol release from glial cells. The elimination mechanism of 24S‐OH‐chol from the brain is one of the key issues for understanding cerebral cholesterol homeostasis. The purpose of the present study was to clarify the molecular mechanism of the elimination process of 24S‐OH‐chol across the blood–brain barrier (BBB). After an intracerebral injection in rats, [3H]24S‐OH‐chol was eliminated from the brain and the radioactivity derived from [3H]24S‐OH‐chol was detected in the plasma, while [3H]cholesterol was not significantly eliminated from the brain. Co‐administration of unlabeled 24S‐OH‐chol significantly inhibited the [3H]24S‐OH‐chol elimination, while no inhibitory effect was seen at the same concentration of cholesterol. The [3H]24S‐OH‐chol elimination was inhibited by co‐administration of probenecid, but not by benzylpenicillin. Pre‐administration of digoxin completely inhibited the elimination.Xenopus laevisoocytes expressing rat oatp2 exhibited significant transport of [3H]24S‐OH‐chol, and this was inhibited by unlabeled 24S‐OH‐chol and digoxin, indicating that rat oatp2 transports 24S‐OH‐chol. These results are the first direct demonstration that 24S‐OH‐chol undergoes elimination from the brain to blood across the BBB via a carrier‐mediated process, which involves oatp2 expressed at the BBB in rats.
Cellular prion protein expression in astrocytes modulates neuronal survival and differentiation
Authors: Lima Flavia R. S. , Arantes Camila P. , Muras Angelita G. , Nomizo Regina , Brentani Ricardo R. , Martins Vilma R.
Published: September 2007

The functions of cellular prion protein (PrPC) are under intense debate and PrPC loss of function has been implicated in the pathology of prion diseases. Neuronal PrPC engagement with stress‐inducible protein‐1 and laminin (LN) plays a key role in cell survival and differentiation. The present study evaluated whether PrPC expression in astrocytes modulates neuron‐glia cross‐talk that underlies neuronal survival and differentiation. Astrocytes from wild‐type mice promoted a higher level neuritogenesis than astrocytes obtained from PrPC‐null animals. Remarkably, neuritogenesis was greatly diminished in co‐cultures combining PrPC‐null astrocytes and neurons. LN secreted and deposited at the extracellular matrix by wild‐type astrocytes presented a fibrillary pattern and was permissive for neuritogenesis. Conversely, LN coming from PrPC‐null astrocytes displayed a punctate distribution, and did not support neuronal differentiation. Additionally, secreted soluble factors from PrPC‐null astrocytes promoted lower levels of neuronal survival than those secreted by wild‐type astrocytes. PrPC and stress‐inducible protein‐1 were characterized as soluble molecules secreted by astrocytes which participate in neuronal survival. Taken together, these data indicate that PrPC expression in astrocytes is critical for sustaining cell‐to‐cell interactions, the organization of the extracellular matrix, and the secretion of soluble factors, all of which are essential events for neuronal differentiation and survival.
Superoxide dismutase/catalase mimetics but not MAP kinase inhibitors are neuroprotective against oxygen/glucose deprivation‐induced neuronal death in hippocampus
Authors: Zhou Miou , Dominguez Reymundo , Baudry Michel
Published: September 2007

Although oxygen/glucose deprivation (OGD) has been widely used as a model of ischemic brain damage, the mechanisms underlying acute neuronal death in this model are not yet well understood. We used OGD in acute hippocampal slices to investigate the roles of reactive oxygen species and of the mitogen‐activated protein kinases (MAPKs) in neuronal death. In particular, we tested the neuroprotective effects of two synthetic superoxide dismutase/catalase mimetics, EUK‐189 and EUK‐207. Acute hippocampal slices prepared from 2‐month‐old or postnatal day 10 rats were exposed to oxygen and glucose deprivation for 2 h followed by 2.5 h reoxygenation. Lactate dehydrogenase (LDH) release in the medium and propidium iodide (PI) uptake were used to evaluate cell viability. EUK‐189 or EUK‐207 applied during the OGD and reoxygenation periods decreased LDH release and PI uptake in slices from 2‐month‐old rats. EUK‐189 or EUK‐207 also partly blocked OGD‐induced ATP depletion and extracellular signal‐regulated kinases 1 and 2 (ERK1/2) dephosphorylation, and completely eliminated reactive oxygen species generation. The MEK inhibitor U0126 applied together with EUK‐189 or EUK‐207 completely blocked ERK1/2 activation, but had no effect on their protective effects against OGD‐induced LDH release. U0126 alone had no effect on OGD‐induced LDH release. EUK‐207 had no effect on OGD‐induced p38 or c‐Jun N‐terminal kinase dephosphorylation, and when the p38 inhibitor SB203580 was applied together with EUK‐207, it had no effect on the protective effects of EUK‐207. SB203580 alone had no effect on OGD‐induced LDH release either. In slices from p10 rats, OGD also induced high‐LDH release that was partly reversed by EUK‐207; however, neither OGD nor EUK‐207 produced significant changes in ERK1/2 and p38 phosphorylation. OGD‐induced spectrin degradation was not modified by EUK‐189 or EUK‐207 in slices from p10 or 2‐month‐old rats, suggesting that their protective effects was not mediated through inhibition of calpain activation. Thus, both EUK‐189 and EUK‐207 provide neuroprotection in acute ischemic conditions, and this effect is related to elimination of free radical formation and partial reversal of ATP depletion, but not mediated by the activation or inhibition of the MEK/ERK or p38 pathways, or inhibition of calpain activation.
Catecholamine exocytosis is diminished in R6/2 Huntington’s disease model mice
Authors: Johnson Michael A. , Villanueva Melissa , Haynes Christy L. , Seipel Andrew T. , Buhler Leah A. , Wightman R. Mark
Published: September 2007

In this work, the mechanisms responsible for dopamine (DA) release impairments observed previously in Huntington’s disease model R6/2 mice were evaluated. Voltammetrically measured DA release evoked in striatal brain slices from 12‐week old R6/2 mice by a single electrical stimulus pulse was only 19% of wild‐type (WT) control mice. Iontophoresis experiments suggest that the concentration of released DA is not diluted by a larger striatal extracellular volume arising from brain atrophy, but, rather, that striatal dopaminergic terminals have a decreased capacity for DA release. This decreased capacity was not due to an altered requirement for extracellular Ca2+, and, as in WT mice, the release in R6/2 mice required functioning vesicular transporters. Catecholamine secretion from individual vesicles was measured during exocytosis from adrenal chromaffin cells harvested from R6/2 and WT mice. While the number of exocytotic events was unchanged, the amounts released per vesicle were significantly diminished in R6/2 mice, indicating that vesicular catecholamines are present in decreased amounts. Treatment of chromaffin cells with 3‐nitropropionic acid decreased the vesicular release amount from WT cells by 50%, mimicking the release observed from untreated R6/2 cells. Thus, catecholamine release from tissues isolated from R6/2 mice is diminished because of impaired vesicle loading.
Expression level and activity profile of membrane bound guanylate cyclase type 2 in rod outer segments
Authors: Helten Andreas , Säftel Werner , Koch Karl‐Wilhelm
Published: September 2007

Rod and cone cells of the mammalian retina harbor two types of a membrane bound guanylate cyclase (GC), rod outer segment guanylate cyclase type 1 (ROS‐GC1) and ROS‐GC2. Both enzymes are regulated by small Ca2+‐binding proteins named GC‐activating proteins that operate as Ca2+ sensors and enable cyclases to respond to changes of intracellular Ca2+after illumination. We determined the expression level of ROS‐GC2 in bovine ROS preparations and compared it with the level of ROS‐GC1 in ROSs. The molar ratio of a ROS‐GC2 dimer to rhodopsin was 1 : 13 200. The amount of ROS‐GC1 was 25‐fold higher than the amount of ROS‐GC2. Heterologously expressed ROS‐GC2 was differentially activated by GC‐activating protein 1 and 2 at low free Ca2+ concentrations. Mutants of GC‐activating protein 2 modulated ROS‐GC2 in a manner different from their action on ROS‐GC1 indicating that the Ca2+ sensitivity of the Ca2+ sensor is controlled by the mode of target–sensor interaction.
PERMANENT GENETIC RESOURCES: Development of polymorphic microsatellite loci for the common vampire bat, Desmodus rotundus (Chiroptera: Phylostomidae)
Authors: PIAGGIO ANTOINETTE J. , JOHNSTON JOHN J. , PERKINS SUSAN L.
Published: September 2007

The common vampire bat (Desmodus rotundus) is one of three haematophagous species of bats and the only species in this genus. These New World bats prey on mammals and create significant economic impacts through transmission of rabies in areas where livestock are prevalent. Furthermore, in some portions of their range, it is not uncommon for them to prey upon humans. It is critical to the management of this species and for understanding the spread of bat rabies that detailed studies of D. rotundus population structure be conducted. To further such studies, we have characterized 12 microsatellite loci for this species.
PERMANENT GENETIC RESOURCES: Development of microsatellite markers for the ecosystem bioengineer mussel Perumytilus purpuratus and cross‐priming testing in six Mytilinae genera
Authors: PÉREZ M. , GUIÑEZ R. , LLAVONA A. , TORO J. E. , ASTORGA M. , PRESA P.
Published: September 2007

Eight microsatellite markers have been characterized from the Perumytilus purpuratus genome. Their gene diversity ranged from 0.057 to 0.873 and significant interpopulation genic heterogeneity was observed between two populations of southeastern Pacific (Chile) and southwestern Atlantic (Argentine). Distinct cross‐priming amplification rates were recovered on nine additional species belonging to six Mytilinae genera. The microsatellites developed herein would likely be a powerful intraspecific genetic tool to undertake fine population studies in the intertidal ecosystem bioengineer P. purpuratus along the South American shoreline.
PERMANENT GENETIC RESOURCES: Identification of microsatellite loci for parentage analysis in roach Rutilus rutilus and eight other cyprinid fish by cross‐species amplification, and a novel test for detecting hybrids between roach and other cyprinids
Authors: HAMILTON P. B. , TYLER C. R.
Published: September 2007

In order to identify microsatellite loci for parentage analysis in roach Rutilus rutilus, 59 published primer sets were tested on roach and eight other cyprinid fish. Twenty polymorphic loci were identified for roach, of which the polymerase chain reaction products of seven could be pooled for sequencer analysis. Together, these seven loci have an exclusion probability of 0.997 for parentage, when no parents are known. We also describe a novel test for hybrids between roach and four other cyprinids, based on intraspecies length differences of internal transcribed spacer region 1.
The Distribution of Top Incomes in Australia*
Authors: ATKINSON ANTHONY B. , LEIGH ANDREW
Published: September 2007

Using taxation statistics, we estimate the income share held by top income groups in Australia over the period 1921–2003. We find that the income share of the richest fell from the 1920s until the mid‐1940s, rose briefly in the postwar decade, and then declined until the early 1980s. During the 1980s and 1990s, top income shares rose rapidly. At the start of the twenty‐first century, the income share of the richest was higher than it had been at any point in the previous 50 years. Among top income groups, recent decades have also seen a rise in the share of top income accruing to the super‐rich. Trends in top income shares are similar to those observed among other elite groups, such as judges, politicians, top bureaucrats and chief executive officers.
Some Ethnic Dimensions of Income Distribution from Pre‐ to Post‐reform New Zealand, 1984–1998*
Authors: CHATTERJEE SRIKANTA , PODDER NRIPESH
Published: September 2007

Based on unit record data from four household surveys conducted by Statistics New Zealand for the years 1983/1984, 1991/1992, 1995/1996 and 1997/1998, this paper addresses some ethnic dimensions of income inequality among New Zealanders over the period of the surveys. It applies alternative techniques of decomposition of the Gini coefficient of inequality by subgroups of population. It then analyses how changes in the incomes of specific population subgroups affect the overall inequality. The results help quantify the economic distances among the different ethnic populations of New Zealand, and indicate how and why these distances have been changing over time.
Unemployment and Psychological Well‐being*
Authors: CARROLL NICK
Published: September 2007

Who records the largest drops in life satisfaction when they move into unemployment? Do men experience a larger drop in life satisfaction? Do Australians and Americans record a larger drop than Europeans? Using panel data, this paper finds that the unemployed in Australia report lower life satisfaction than observationally equivalent employed people (holding current income constant). Being unemployed is estimated to be equivalent to the loss of $A42 100 annual income for men and even more for women. It is found that unemployment is less painful for men in Australia than for men in Germany and the UK.
Trade Liberalisation, Poverty and Inequality in South Africa: A Computable General Equilibrium‐Microsimulation Analysis*
Authors: HERAULT NICOLAS
Published: September 2007

This paper studies the effects of trade liberalisation on poverty and income inequality in South Africa. The main issue of interest is the effect of international trade on households (especially their income). The approach presented in this paper relies on combining a macro‐orientated computable general equilibrium model with a microsimulation model. The main concern regarding poor households is whether the decrease in nominal earnings for formal low‐skilled and skilled workers is offset by the upward trend in formal employment levels. The analysis indicates that such a trade‐off occurs, implying a decrease in poverty due to trade liberalisation.